Radio frequency-based renal denervation: a story of simplicity?

Radio frequency-based renal denervation is a safe and effective way of lowering blood pressure, a common condition associated with high cardiovascular risk. Several catheters have been developed to administer energy to the renal arteries and their side branches, thereby modulating sympathetic renal activity. The Symplicity Flex™ and Symplicity Spyral™ are first- and second-generation devices, respectively, for radio frequency-based renal denervation. There is a continuous need to further improve and adjust interventional antihypertensive therapies. Several randomized controlled trials have been conducted to investigate the safety and efficacy of these catheters and most were able to show radio frequency-based renal denervation to be feasible, safe and effective in lowering blood pressure in hypertensive patients with and without concomitant antihypertensive medication. Herein, the authors discuss the pathophysiologic concepts of renal denervation and its procedural approaches, report catheter designs, summarize clinical trials outcomes and, finally, discuss real-world evidence.

High blood pressure causes illness and death worldwide. Treatment of high blood pressure is usually based on lifestyle modification and blood pressure-lowering drugs. Renal denervation represents a minimally invasive approach to lower blood pressure by interrupting the nerves surrounding the renal arteries. These nerves are involved in the body's fight-or-flight and rest-and-digest systems, the so-called autonomous nervous system. The Spyral™ catheter system uses radio frequency energy to modulate renal nerve activity. Trials have consistently shown that renal denervation is safe. The first-generation catheter was a monoelectrode catheter called Symplicity Flex™ and several points in the renal artery had to be treated. The second-generation device called the Symplicity Spyral™ catheter, on the other hand, has a multielectrode design and consequently fewer ablation points are sufficient for complete denervation. Caused by the positive effects on blood pressure and the consistent safety reports, renal denervation is considered by current guidelines as an alternative and additive treatment approach in patients with high blood pressure.

Estimated Glomerular Filtration Rate in Chronic Kidney Disease: A Critical Review of Estimate-Based Predictions of Individual Outcomes in Kidney Disease.

Chronic kidney disease (CKD) is generally regarded as a final common pathway of several renal diseases, often leading to end-stage kidney disease (ESKD) and a need for renal replacement therapy. Estimated GFR (eGFR) has been used to predict this outcome recognizing its robust association with renal disease progression and the eventual need for dialysis in large, mainly cross-sectional epidemiological studies. However, GFR is implicitly limited as follows: (1) GFR reflects only one of the many physiological functions of the kidney; (2) it is dependent on several non-renal factors; (3) it has intrinsic variability that is a function of dietary intake, fluid and cardiovascular status, and blood pressure especially with impaired autoregulation or medication use; (4) it has been shown to change with age with a unique non-linear pattern; and (5) eGFR may not correlate with GFR in certain conditions and disease states. Yet, many clinicians, especially our non-nephrologist colleagues, tend to regard eGFR obtained from a simple laboratory test as both a valid reflection of renal function and a reliable diagnostic tool in establishing the diagnosis of CKD. What is the validity of these beliefs? This review will critically reassess the limitations of such single-focused attention, with a particular focus on inter-individual variability. What does science actually tell us about the usefulness of eGFR in diagnosing CKD?

Effect of Geumgwe-Sinkihwan on Renal Dysfunction in Ischemia/Reperfusion-Induced Acute Renal Failure Mice.

Renal ischemia-reperfusion (I/R) injury is an important cause of acute renal failure (ARF). Geumgwe-sinkihwan (GSH) was recorded in a traditional Chines medical book named "Bangyakhappyeon" in 1884. GSH has been used for treatment for patients with diabetes and glomerulonephritis caused by deficiency of kidney yang and insufficiency of kidney gi. Here we investigate the effects of GSH in mice model of ischemic acute kidney injury. The mice groups are as follows; sham group: C57BL6 male mice, I/R group: C57BL6 male mice with I/R surgery, GSH low group: I/R + 100 mg/kg/day GSH, and GSH high group: I/R + 300 mg/kg/day GSH. Ischemia was induced by clamping both renal arteries and reperfusion. Mice were orally given GSH (100 and 300 mg/kg/day) during 3 days after surgery. Treatment with GSH significantly ameliorated creatinine clearance, creatinine, and blood urea nitrogen levels. Treatment with GSH reduced neutrophil gelatinase associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1), specific renal injury markers. GSH also reduced the periodic acid-Schiff and picro sirius red staining intensity in kidney of I/R group. Western blot and real-time RT-qPCR analysis demonstrated that GSH decreased protein and mRNA expression levels of the inflammatory cytokines in I/R-induced ARF mice. Moreover, GSH inhibited protein and mRNA expression of inflammasome-related protein including NLRP3 (NOD-like receptor pyrin domain-containing protein 3, cryoprin), ASC (Apoptosis-associated speck-like protein containing a CARD), and caspase-1. These findings provided evidence that GSH ameliorates renal injury including metabolic dysfunction and inflammation via the inhibition of NLRP3-dependent inflammasome in I/R-induced ARF mice.

Trimetazidine an emerging paradigm in renal therapeutics: Preclinical and clinical insights.

Trimetazidine (TMZ) is a well-known anti-ischemic agent used for the treatment of angina pectoris. In the past decades, the efficacy of this drug has been tested in a wide range of kidney injuries, including drug-induced nephrotoxicity (DIN), radio-contrast agent-induced nephropathy, and surgically induced renal ischemic injury. TMZhas renoprotective effects by attenuating oxidative stress, inflammatory cytokine release, maintaining oxygen and energy balance. Moreover, TMZ administration prevented kidney graft rejection in the porcine model by suppressing the infiltration of mononuclear cells, preserving mitochondrial functions, and maintaining Ca+ homeostasis. In DIN and diabetic kidney diseases,TMZ treatment prevents renal injury by inactivating immune cells, attenuating renal fibrosis, inflammation, apoptosis, and histological abnormalities. Interestingly, the clinical therapeutic efficacy of TMZ has also been documented in pre-existing kidney disease patients undergoing contrast exposure for diagnostic intervention. However, the mechanistic insights into the TMZ mediated renoprotective effects in other forms of renal injuries, including type-2 diabetes, drug-induced nephrotoxicity, and hypertension-induced chronic kidney diseases, remain uninvestigated and incomplete. Moreover, the clinical utility of TMZ as a renoprotective agent in radio-contrast-induced nephrotoxicity needs to be tested in a large patient population. Nevertheless, the available pieces of evidence suggest that TMZ is a promising and emerging renal therapy for the treatment and management of kidney diseases of variable etiologies. This review discusses the various pre-clinical and clinical findings and provides mechanistic insights into the TMZ mediated beneficial effects in various kidney diseases.

Pomegranate extract ameliorates renal ischemia/reperfusion injury in rats via suppressing NF-κB pathway.

Inflammation and oxidative stress are the major pathways involved in ischemia-reperfusion (I/R)-induced renal injury. This study was designed to evaluate the potential effect of pomegranate against I/R-induced renal injury. I/R injury was induced in nephrectomized rats by unilateral occlusion of the left renal pedicle for 45 min followed by 24 h of perfusion. Pomegranate succeeded to decrease serum levels of creatinine, potassium, and urea nitrogen, along with increasing creatinine clearance. Pomegranate also decreased I/R-induced changes in histopathological examination. Pomegranate attenuated the renal inflammatory response reflected by the suppression of nuclear factor κB p65 DNA binding activity, the upregulation of inhibitory protein kappa B-alpha mRNA expression, the downregulation of mRNA and protein expression of tumor necrosis factor α, in addition to the reduced myeloperoxidase activity and mRNA expression. Additionally, pomegranate attenuated oxidative stress likely through the modulation of lipid peroxidation and antioxidant levels reflected by the decreased MDA content and the increased glutathione level and superoxide dismutase activity. Results confirm the potential protective effect of pomegranate against I/R-induced renal injury through its anti-inflammatory and anti-oxidant effects mediated through the upregulation of inhibitory protein kappa B-alpha, the inhibition of NF-κB activity, and the associated TNF-α release, neutrophil infiltration, and oxidative stress.

Fully hydrogenated canola oil extends lifespan in stroke-prone spontaneously hypertensive rats.

BACKGROUND: Canola oil (Can) and several vegetable oils shorten the lifespan of stroke-prone spontaneously hypertensive rats (SHRSP). Although similar lifespan shortening has been reported for partially hydrogenated Can, the efficacy of fully hydrogenated oils on the lifespan remains unknown. The present study aimed to investigate the lifespan of SHRSP fed diets containing 10 % (w/w) of fully hydrogenated Can (FHCO) or other oils. METHODS: Survival test: Upon weaning, male SHRSP were fed a basal diet for rodents mixed with one of the test oils -i.e., FHCO, Can, lard (Lrd), and palm oil (Plm) throughout the experiment. The animals could freely access the diet and drinking water (water containing 1 % NaCl), and their body weight, food intake, and lifespan were recorded. Biochemical analysis test: Male SHRSP were fed a test diet with either FHCO, Can, or soybean oil (Soy) under the same condition, except to emphasize effects of fat, that no NaCl loading was applied. Soy was used as a fat source in the basal diet and was set the control group. Blood pressures was checked every 2 weeks, and serum fat levels and histological analyses of the brain and kidney were examined after 7 or 12 weeks of feeding. RESULTS: During the survival study period, the food consumption of FHCO-fed rats significantly increased (15-20 % w/w) compared with that of rats fed any other oil. However, the body weight gain in the FHCO group was significantly less (10-12 %) than that in the control group at 9-11 weeks old. The FHCO (> 180 days) intervention had the greatest effect on lifespan, followed by the Lrd (115 ± 6 days), Plm (101 ± 2 days), and Can (94 ± 3 days) diets. FHCO remarkably decreased the serum cholesterol level compared with Can and the systolic blood pressure from 12 to 16 weeks of age. In addition, while some rats in the Can group exhibited brain hemorrhaging and renal dysfunction at 16 weeks old, no symptoms were observed in the FHCO group. CONCLUSION: This current study suggests that complete hydrogenation decreases the toxicity of Can and even prolongs the lifespan in SHRSP.

Acute Beetroot Juice Ingestion Does Not Alter Renal Hemodynamics during Normoxia and Mild Hypercapnia in Healthy Young Adults.

Arterial hypercapnia reduces renal perfusion. Beetroot juice (BRJ) increases nitric oxide bioavailability and may improve renal blood flow. We tested the hypothesis that acute consumption of BRJ attenuates both decreases in blood velocity and increases in vascular resistance in the renal and segmental arteries during acute hypercapnia. In fourteen healthy young adults, blood velocity and vascular resistance were measured with Doppler ultrasound in the renal and segmental arteries during five minutes of breathing a carbon dioxide gas mixture (CO2) before and three hours after consuming 500 mL of BRJ. There was no difference between pre- and post-BRJ consumption in the increase in the partial pressure of end-tidal CO2 during CO2 breathing (pre: +4 ± 1 mmHg; post: +4 ± 2 mmHg, p = 0.4281). Segmental artery blood velocity decreased during CO2 breathing in both pre- (by -1.8 ± 1.9 cm/s, p = 0.0193) and post-BRJ (by -2.1 ± 1.9 cm/s, p = 0.0079), but there were no differences between pre- and post-consumption (p = 0.7633). Segmental artery vascular resistance increased from room air baseline during CO2 at pre-BRJ consumption (by 0.4 ± 0.4 mmHg/cm/s, p = 0.0153) but not post-BRJ (p = 0.1336), with no differences between pre- and post-consumption (p = 0.7407). These findings indicate that BRJ consumption does not attenuate reductions in renal perfusion during acute mild hypercapnia in healthy young adults.

Renal Denervation in Hypertension.

The column in this issue is supplied by Drs. Benjamin Lee, MD, and Usman Ansari, DO. Dr. Lee is an assistant professor of clinical medicine at the Houston Methodist Institute for Academic Medicine and Weill Cornell Medical College. After earning his medical degree at Harvard Medical School, Dr. Lee completed a residency in internal medicine and a nephrology fellowship at the University of California San Francisco (UCSF) while simultaneously obtaining a master of advanced study in clinical research from the UCSF departments of Epidemiology and Biostatistics. He maintains his clinical practice with the Houston Kidney Consultants. Dr. Ansari earned a Doctor of Osteopathy from Touro University College of Osteopathic Medicine in California and is completing his internal medicine residency at Houston Methodist.

Renal denervation prevents myocardial structural remodeling and arrhythmogenicity in a chronic kidney disease rabbit model.

BACKGROUND: The electrophysiological (EP) effects and safety of renal artery denervation (RDN) in chronic kidney disease (CKD) are unclear. OBJECTIVE: The purpose of this study was to investigate the arrhythmogenicity of RDN in a rabbit model of CKD. METHODS: Eighteen New Zealand white rabbits were randomized to control (n = 6), CKD (n = 6), and CKD-RDN (n = 6) groups. A 5/6 nephrectomy was selected for the CKD model. RDN was applied in the CKD-RDN group. All rabbits underwent cardiac EP studies for evaluation. Immunohistochemistry, myocardial fibrosis, and renal catecholamine levels were evaluated. RESULTS: The CKD group (34.8% ± 9.2%) had a significantly higher ventricular arrhythmia (VA) inducibility than the control (8.6% ± 3.8%; P <.01) and CKD-RDN (19.5% ± 6.3%; P = .01) groups. In the CKD-RDN group, ventricular fibrosis was significantly decreased compared to the CKD group (7.4% ± 2.0 % vs 10.4% ± 3.7%; P = .02). Sympathetic innervation in the CKD group was significantly increased compared to the control and CKD-RDN groups [left ventricle: 4.1 ± 1.8 vs 0.8 ± 0.5 (102 µm2/mm2), P <.01; 4.1 ± 1.8 vs 0.9± 0.6 (102 µm2/mm2), P <.01; right ventricle: 3.6 ± 1.0 vs 1.0 ± 0.4 (102 µm2/mm2), P <.01; 3.6 ± 1.0 vs 1.0 ± 0.5 (102 µm2/mm2), P <.01]. CONCLUSION: Neuromodulation by RDN demonstrated protective effects with less structural and electrical remodeling, leading to attenuated VAs. In a rabbit model of CKD, RDN plays a therapeutic role by lowering the risk of VA caused by autonomic dysfunction.

Hyperbaric Oxygen Preconditioning Upregulates Heme OxyGenase-1 and Anti-Apoptotic Bcl-2 Protein Expression in Spontaneously Hypertensive Rats with Induced Postischemic Acute Kidney Injury.

Renal ischemia and reperfusion (I/R) injury is the most common cause of acute kidney injury (AKI). Pathogenesis of postischemic AKI involves hemodynamic changes, oxidative stress, inflammation process, calcium ion overloading, apoptosis and necrosis. Up to date, therapeutic approaches to treat AKI are extremely limited. Thus, the aim of this study was to evaluate the effects of hyperbaric oxygen (HBO) preconditioning on citoprotective enzyme, heme oxygenase-1 (HO-1), pro-apoptotic Bax and anti-apoptotic Bcl-2 proteins expression, in postischemic AKI induced in normotensive Wistar and spontaneously hypertensive rats (SHR). The animals were randomly divided into six experimental groups: SHAM-operated Wistar rats (W-SHAM), Wistar rats with induced postischemic AKI (W-AKI) and Wistar group with HBO preconditioning before AKI induction (W-AKI + HBO). On the other hand, SHR rats were also divided into same three groups: SHR-SHAM, SHR-AKI and SHR-AKI + HBO. We demonstrated that HBO preconditioning upregulated HO-1 and anti-apoptotic Bcl-2 protein expression, in both Wistar and SH rats. In addition, HBO preconditioning improved glomerular filtration rate, supporting by significant increase in creatinine, urea and phosphate clearances in both rat strains. Considering our results, we can also say that even in hypertensive conditions, we can expect protective effects of HBO preconditioning in experimental model of AKI.

Evaluation of Temperature Distribution Around the Probe in Cryoablation of Lipiodol-Mixed-Tissue Phantom.

PURPOSE: To determine whether lipiodol, which has low thermal conductivity, influences ice ball formation during cryoablation of a lipiodol-mixed-tissue phantom. MATERIALS AND METHODS: Lipiodol-mixed-tissue phantoms were created by injecting lipiodol (4-6 ml) into the renal arteries of ex vivo porcine kidneys (lipiodol group). A cryoprobe (CryoHit™ Needle S) with a holder that was set with thermocouples at various positions around the cryoprobe was inserted. After freezing for 300 s, the followings were evaluated: ice ball size on CT, temperature distribution around the cryoprobe, and calculated distances at 0 °C and - 20 °C. Each variable was compared between lipiodol group (n = 6) those obtained in a control group without lipiodol injection (n = 6). RESULTS: Mean ice ball diameter (width/length) on CT was 22.1 ± 2.3/22.9 ± 2.3 mm in the lipiodol group and 21.6 ± 0.7/22.2 ± 1.3 mm in the control group. Mean cryoprobe temperature was - 118 ± 3.0 °C in the lipiodol group and - 117 ± 2.6 °C in the control group. In both groups, temperature at the 3 mm thermocouple reached approximately - 50 °C and was < 0 °C within ~ 10 mm of the cryoprobe. Temperature of 0/- 20 °C occurred at a mean distance from the cryoprobe of 11.1 ± 0.5/6.9 ± 0.4 mm in the lipiodol group and 11.0 ± 0.2/6.9 ± 0.2 mm in the control group. There was no significant difference in any variable between the groups. CONCLUSION: The inclusion of lipiodol in a tissue phantom had no negative effects on ice ball formation that were related to thermal conductivity.

Commentary on Some Recent Theses Relevant to Combating Aging: December 2020.

Theses reviewed in this issue include "Advances on Chip-In-Cell Wireless Platform for Continuous Monitoring of Physiological Parameters in Single Cells," "Design and Delivery of Synthetic mRNA by a Peptide Nanoparticle," "Inflammation Alters Endothelial Progenitor Cell-derived Exosome Contents and Therapeutic Effect on Myocardial Repair," "Partial Reprogramming: A Shortcut to Rejuvenation," "Renal Angioplasty and Therapeutic Angiogenesis for Renovascular Disease: A Novel Treatment Strategy," and "Targeted EDTA Chelation Therapy with Albumin Nanoparticles to Reverse Arterial Calcification and Restore Vascular Health in Chronic Kidney Disease."

Effect of Renal Denervation on Cardiac Function and Inflammatory Factors in Heart Failure After Myocardial Infarction.

Heart failure (HF) affects around 100 million people and is a staggering burden for health care system worldwide. Rapid and sustained activation of inflammatory response is an important feature of HF after myocardial infarction. Sympathetic overactivation is also an important factor in the occurrence and progression of HF. The beneficial effect of renal denervation (RDN) has been demonstrated in HF. In the current study, we hypothesized that RDN improves cardiac function in HF canine models due to acute myocardial infarction (AMI) and reduced inflammation might be involved. Twenty-four beagles were randomized into the control (n = 8), HF (n = 8), and HF + RDN group (n = 8). The HF model after AMI was established by embolization the anterior descending distal artery with anhydrous ethanol in the HF and HF + RDN group. Bilateral renal artery ablation was performed in the HF + RDN group. Cardiac function, serum creatine kinase, creatine kinase-MB and NT-Pro BNP level, and expression of inflammation-related proteins in myocardial were examined. Because the paraventricular nucleus of the hypothalamus might be involved in inflammation-induced central neural excitation in HF and plays an important role in regulating extracellular fluid volume and sympathetic activity, expression of inflammation-related proteins in hypothalamus was also examined. AMI and post-AMI HF model was created successfully. Compared with the HF group, dogs in the HF + RDN group showed better cardiac function 4 weeks after AMI: lower left ventricular end-diastolic pressure, left ventricular end-diastolic dimension, and left ventricular end-systolic dimension and higher LEVF and left ventricular systolic pressure (P < 0.05 for all) were observed in the HF + RDN group. In addition, dogs in the HF + RDN group had slightly less ventricular fibrosis. Interestingly, RDN had lower expression of inflammation-related proteins including interleukin-6, tumor necrosis factors-α, nuclear factor κB, and monocyte chemotactic protein 1 (P < 0.05 for all) in both myocardial tissue and hypothalamus. RDN can improve cardiac function in dogs with HF after myocardial infarction. Our results suggested that RDN might affect cytokine-induced central neural excitation in HF and later affect sympathetic activity. Our results suggested a potential beneficial mechanism of RDN independent of mechanism involving renal afferent and efferent sympathetic nerves.

Anti-inflammatory and antioxidant activity of essential amino acid α-ketoacid analogues against renal ischemia-reperfusion damage in Wistar rats. / Actividad antiinflamatoria y antioxidante de los α-cetoanálogos de aminoácidos esenciales en un modelo de daño por isquemia-reperfusión en ratas Wistar

INTRODUCTION: Essential amino acid α-keto acid analogs are used in the treatment of chronic kidney disease to delay the symptoms of uremia. However, it is unknown whether essential amino acid α-keto acid analogs affect the oxidative stress and the inflammation in acute renal injury such as those produced by ischemia-reperfusion. OBJECTIVE: To evaluate the effect of essential amino acid α-keto acid analogs on renal ischemia-reperfusion injury in Wistar rats. MATERIALS AND METHODS: Rats were divided into 11 groups (n=6/group): Two groups received physiological saline with or without ischemia-reperfusion injury (45 min/24 h), six groups received essential amino acid α-keto acid analogs (400, 800, or 1,200 mg/kg/24 h/7d) with or without ischemia-reperfusion injury (essential amino acid α-keto acid analogs + ischemia-reperfusion), and two groups received allopurinol (50 mg/kg/24 h/7d) with or without ischemia-reperfusion injury. Biochemical markers included creatinine and blood urea nitrogen (BUN), proinflammatory cytokines (IL-1ß, IL-6, and TNF-α), renal damage markers (cystatin C, KIM-1, and NGAL), and markers of oxidative stress such as malondialdehyde (MDA) and total antioxidant activity. RESULTS: The essential amino acid α-keto acid analog- and allopurinol-treated groups had lower levels of creatinine, BUN, renal damage markers, proinflammatory cytokines, and MDA than their corresponding ischemia-reperfusion groups. These changes were related to the essential amino acid α-keto acid analogs dosage. Total antioxidant activity was lower in essential amino acid α-keto acid analog- and allopurinol-treated groups than in the corresponding ischemia-reperfusion groups. CONCLUSIONS: This is a new report on the nephroprotective effects of essential amino acid α-keto acid analogs against ischemia-reperfusion injury. Essential amino acid α-keto acid analogs decreased the levels of biochemical markers, kidney injury markers, proinflammatory cytokines, and MDA while minimizing total antioxidant consumption.

Introducción. Los α-cetoanálogos de aminoácidos esenciales se utilizan en el tratamiento de la enfermedad renal crónica para retrasar los síntomas de la uremia. Sin embargo, se desconoce si los α-cetoanálogos de aminoácidos esenciales afectan el estrés oxidativo y la inflamación en la lesión renal aguda tal como en la producida por la isquemia-reperfusión. Objetivo. Evaluar el efecto de las α-cetoanálogos de aminoácidos esenciales sobre la lesión renal por isquemia-reperfusión en ratas Wistar. Materiales y métodos. Se emplearon 11 grupos de ratas (n=6): dos grupos recibieron solución salina fisiológica con lesión isquemia-reperfusión o sin ella (45 min/24 h), seis grupos recibieron α-cetoanálogos de aminoácidos esenciales (400, 800 o 1.200 mg/kg/24 h/7d) con lesión isquemia-reperfusión o sin ella (α-cetoanálogos de aminoácidos esenciales + isquemia-reperfusión), y dos grupos recibieron (50 mg/kg/24 h/7d) con lesión isquemia-reperfusión o sin ella. Los marcadores bioquímicos incluyeron creatinina y nitrógeno ureico en sangre (BUN), citocinas proinflamatorias (IL-1ß, IL-6 y TNF-α), marcadores de daño renal (cistatina C, KIM-1 y NGAL) y marcadores del estrés oxidativo como el malondialdehído (MDA) y la actividad antioxidante total. Resultados. Los grupos tratados con α-cetoanálogos de aminoácidos esenciales y alopurinol tuvieron niveles inferiores de creatinina, BUN, marcadores de daño renal, citocinas proinflamatorias, actividad antioxidante total y MDA que los grupos isquemia-reperfusión correspondientes. Estos cambios se asociaron con la dosis. La actividad antioxidante total fue menor en los grupos tratados con α-cetoanálogos de aminoácidos esenciales que en los grupos isquemia-reperfusión correspondientes. Conclusiones. Este es un nuevo informe de los efectos nefroprotectores de las α-cetoanálogos de aminoácidos esenciales contra la lesión isquemia-reperfusión. Los α-cetoanálogos de aminoácidos esenciales disminuyeron los niveles de los marcadores bioquímicos, de los de lesión renal, de las citocinas proinflamatorias y el MDA, a la vez que minimizaron el consumo total de antioxidantes.

Beneficial Effects of Isoflavones in the Kidney of Obese Rats Are Mediated by PPAR-Gamma Expression.

Several studies have demonstrated an important association between altered lipid metabolism and the development of kidney injury because of a high-fat diet. Fructose is also closely associated with renal injury. We opted for a combination of fructose and saturated fats in a diet (DH) that is a model known to induce renal damage in order to evaluate whether soy isoflavones could have promising use in the treatment of renal alterations. After two months of ingestion, there was an expansion of visceral fat, which was associated with long-term metabolic disorders, such as sustained hyperglycemia, insulin resistance, polyuria, dyslipidemia, and hypertension. Additionally, we found a decrease in renal blood flow and an increase in renal vascular resistance. Biochemical markers of chronic kidney disease were detected; there was an infiltration of inflammatory cells with an elevated expression of proinflammatory cytokines (tumor necrosis factor-α, interleukin (IL)-6, and IL-1ß), the activation of the renin-angiotensin system, and oxidative/nitrosative stress. Notably, in rats exposed to the DH diet for 120 days, the concomitant treatment with isoflavones after 60 days was able to revert metabolic parameters, renal alterations, and oxidative/nitrosative stress. The beneficial effects of isoflavones in the kidney of the obese rats were found to be mediated by expression of peroxisome proliferator-activated receptor gamma (PPAR-γ).

Effects of Monomeric and Oligomeric Flavanols on Kidney Function, Inflammation and Oxidative Stress in Runners: A Randomized Double-Blind Pilot Study.

Nonsteroidal anti-inflammatory drugs are frequently used by athletes in order to prevent musculoskeletal pain and improve performance. In combination with strenuous exercise, they can contribute to a reduction of renal blood flow and promote development of kidney damage. We aimed to investigate whether monomeric and oligomeric flavanols (MOF) could reduce the severity of kidney injuries associated with the intake of 400-mg ibuprofen followed by the completion of a half-marathon in recreational athletes. In this double-blind, randomized study, the original MOF blend of extracts from grape seeds (Vitis vinifera L.) and pine bark (Pinus pinaster L.) or placebo were taken for 14 days preceding the ibuprofen/half-marathon. Urine samples were collected before and after the ibuprofen/half-marathon, and biomarkers of kidney injury, inflammation and oxidative stress were assessed. Intake of MOF significantly reduced the incidence of post-race hematuria (p = 0.0004) and lowered concentrations of interleukin (IL)-6 in the urine (p = 0.032). Urinary neutrophil-associated lipocalin, creatine, albumin, IL-8 and malondialdehyde tended to decrease. The supplementation with MOF in recreational runners appears to safely preserve kidney function, reduce inflammation and promote antioxidant defense during strenuous exercise and intake of a single dose of ibuprofen.

Effect of Hyperbaric Oxygen on Tissue Damage and Expression of Adhesion Molecules and C3 in a Rat Model of Renal Ischemia-Reperfusion Injury After Kidney Transplantation.

BACKGROUND The aim of this study was to investigate the protective effect and mechanism of hyperbaric oxygen (HBO) in a rat model of renal ischemia-reperfusion injury following kidney transplantation. MATERIAL AND METHODS Sprague Dawley rats were randomly divided into 3 groups (n=18): sham group, kidney transplantation group, and HBO treatment group. Six rats in each group were sacrificed at 1, 3, and 5 hours after reperfusion, and serum and renal tissue were then collected. The serum creatinine levels and histopathological changes of the renal tissue were detected. ICAM-1, VCAM-1, and C3 expression levels were also detected by immunohistochemical staining or real-time polymerase chain reaction. RESULTS Renal function was damaged in the kidney transplantation group and the HBO treatment group compared with sham group (P<0.05). Renal histopathological changes, including tubular cell swelling, tubular dilatation, and hyaline casts, were remarkably reduced in the HBO treatment group compared to the kidney transplantation group. In the immunohistochemical examination, the expression levels of ICAM-1, VCAM-1, and C3 were obviously increased in the kidney transplantation group and the HBO treatment group; moreover, the levels in the HBO treatment group were significantly lower than in the kidney transplantation group (P<0.05). In addition, the ICAM-1 and C3 mRNA levels were increased in the kidney transplantation group and HBO treatment group, but the levels of in the HBO treatment group them were significantly decreased compared to the kidney transplantation group that at 3 and 5 hours after reperfusion (P<0.05). CONCLUSIONS HBO treatment exerted a protective effect on renal function through inhibition of adhesion molecule overexpression and complement system activation in a rat model of renal ischemia-reperfusion injury after kidney transplantation.

Acute on chronic kidney disease in cats: Etiology, clinical and clinicopathologic findings, prognostic markers, and outcome.

BACKGROUND: Chronic kidney disease (CKD) and acute decompensation of CKD (ACKD) are common in cats. OBJECTIVES: To characterize the etiology, clinical and clinicopathologic findings, and the short- and long-term prognosis of feline ACKD. ANIMALS: One hundred cats with ACKD. METHODS: Retrospective study, search of medical records for cats with ACKD. RESULTS: Common clinical signs included anorexia (85%), lethargy (60%), weight loss (39%), and vomiting (27%). Suspected etiologies included ureteral obstruction (11%), renal ischemia (9%), pyelonephritis (8%), others (6%), or unknown (66%). Hospitalization duration was longer in survivors versus nonsurvivors (median = 7 days, range = 2-26 versus median = 3 days, range = 2-20, respectively, P < .001). The survival rate to discharge was 58%. Age, serum creatinine, urea, and phosphorous concentrations were higher and venous blood pH was lower in nonsurvivors. However, only serum phosphorus remained associated with the short-term outcome in the multivariable model (P = .02; 95% confidence interval = 1.03-1.39). Survivors had a median survival time of 66 days after discharge. Serum creatinine concentrations at presentation as well as at discharge were associated with long-term survival (P < .002 for both). CONCLUSIONS: The short-term prognosis of ACKD is comparable to acute kidney injury, while the long-term prognosis is guarded.

Device-based therapies for arterial hypertension.

Arterial hypertension is the most prevalent modifiable risk factor associated with cardiovascular morbidity and mortality. Although antihypertensive drugs are widely available, in many patients blood pressure control to guideline-recommended target values is not achieved. Several device-based approaches have been introduced to lower blood pressure; most of these strategies aim to modulate autonomic nervous system activity. Clinical trials have moved from including patients with resistant hypertension receiving intensive pharmacological treatment to including patients with mild-to-moderate hypertension in the presence or absence of antihypertensive medications. Renal sympathetic denervation is the most extensively investigated device-based therapy for hypertension, and randomized, sham-controlled trials have provided proof-of-principle data for its blood pressure-lowering efficacy. Unilateral electrical baroreflex activation, endovascular baroreflex amplification and pacemaker-mediated cardiac neuromodulation therapy have yielded promising results in observational trials, which need to be confirmed in larger, adequately powered, sham-controlled trials. Until further evidence becomes available, device-based therapy for hypertension should not be considered for routine treatment. However, when considering a device-based treatment for hypertension, the underlying pathophysiology in each patient has to be taken into consideration, and the procedural risks weighed against the cardiovascular risk attributable to the elevated blood pressure. This Review summarizes the pathophysiological rationale and the latest clinical evidence for device-based therapies for hypertension.

Notoginsenoside R1 Suppresses Inflammatory Signaling and Rescues Renal Ischemia-Reperfusion Injury in Experimental Rats.

BACKGROUND Notoginsenoside R1 (NR) is a major dynamic constituent of Panax notoginseng found to possess anti-inflammatory activity against various inflammatory diseases. However, its protective effects against renal ischemia-reperfusion (I/R) injury have not been elucidated. In male Wistar rats, we induced I/R under general anesthesia by occluding the renal artery for 60 min, followed by reperfusion and right nephrectomy. MATERIAL AND METHODS Rats were randomized to 4 groups: a sham group, an I/R group, an NR-pretreated (50 mg/kg) before I/R induction group, and an NR control group. All animals were killed at 72 h after I/R induction. Blood and renal tissues were collected, and histological and basic renal function parameters were assessed. In addition, levels of various kidney markers and proinflammatory cytokines were measured using RT-PCR, ELISA, and immunohistochemistry analysis. RESULTS After I/R induction, the onset of renal dysfunction was shown by the elevated levels of serum urea, creatinine levels, and histological evaluation, showing a 2-fold increase in the renal failure markers kim-1 and NGAL compared to control rats. Rats pretreated with NR before I/R induction had significantly better renal functions, with attenuated levels of oxidative markers, restored levels of inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha), tumor growth factor-ß1 (TGF-ß1), INF-γ, and IL-6, and increased anti-inflammatory cytokine levels (IL-10) compared to I/R-induced rats. CONCLUSIONS NR suppressed I/R-induced inflammatory cytokines production by suppressing oxidative stress and kidney markers, suggesting that NR is a promising drug candidate for prevention, progression, and treatment of renal dysfunction.