OXGR1-Dependent (Pro)Renin Receptor Upregulation in Collecting Ducts of the Clipped Kidney Contributes to Na+ Balance in Goldblatt Hypertensive Mice.

The two-kidney, one-clip (2K1C) Goldblatt rodent model elicits a reduction in renal blood flow (RBF) in the clipped kidney (CK). The reduced RBF and oxygen bio-ability causes the accumulation of the tricarboxylic cycle intermediary, α-ketoglutarate, which activates the oxoglutarate receptor-1 (OXGR1). In the kidney, OXGR1 is abundantly expressed in intercalated cells (ICs) of the collecting duct (CD), thus contributing to sodium transport and electrolyte balance. The (pro)renin receptor (PRR), a member of the renin-angiotensin system (RAS), is a key regulator of sodium reabsorption and blood pressure (BP) that is expressed in ICs. The PRR is upregulated in 2K1C rats. Here, we tested the hypothesis that chronic reduction in RBF in the CK leads to OXGR1-dependent PRR upregulation in the CD and alters sodium balance and BP in 2K1C mice. To determine the role of OXGR1 in regulating the PRR in the CDs during renovascular hypertension, we performed 2K1C Goldblatt surgery (clip = 0.13 mm internal gap, 14 days) in two groups of male mice: (1) mice treated with Montelukast (OXGR1 antagonist; 5 mg/Kg/day); (2) OXGR1-/- knockout mice. Wild-type and sham-operated mice were used as controls. After 14 days, 2K1C mice showed increased systolic BP (SBP) (108 ± 11 vs. control 82 ± 5 mmHg, p < 0.01) and a lower natriuretic response after the saline challenge test. The CK group showed upregulation of erythropoietin, augmented α-ketoglutarate, and increased PRR expression in the renal medulla. The CK of OXGR1 knockout mice and mice subjected to the OXGR1 antagonist elicited impaired PRR upregulation, attenuated SBP, and better natriuretic responses. In 2K1C mice, the effect of reduced RBF on the OXGR1-dependent PRR upregulation in the CK may contribute to the anti-natriuretic and increased SBP responses.

A peptide fraction from hardened common beans (Phaseolus vulgaris) induces endothelium-dependent antihypertensive and renal effects in rats.

Beans reached the research spotlight as a source of bioactive compounds capable of modulating different functions. Recently, we reported antioxidant and oxidonitrergic effect of a low molecular weight peptide fraction (<3 kDa) from hardened bean (Phaseolus vulgaris) in vitro and ex vivo, which necessitate further in vivo assessments. This work aimed to evaluate the hypotensive effect and the involved physiological mechanisms of the hardened common bean peptide (Phaseolus vulgaris) in normotensive (Wistar) and hypertensive (SHR) animals. Bean flour was combined with a solution containing acetonitrile, water and formic acid (25: 24: 1). Protein extract (PV3) was fractioned (3 kDa membrane). We assessed PV3 effects on renal function and hemodynamics of wistar (WT-normotensive) and spontaneously hypertensive rats (SHR) and measured systemic arterial pressure and flow in aortic and renal beds. The potential endothelial and oxidonitrergic involvements were tested in isolated renal artery rings. As results, we found that PV3: I) decreased food consumption in SHR, increased water intake and urinary volume in WT, increased glomerular filtration rate in WT and SHR, caused natriuresis in SHR; II) caused NO- and endothelium-dependent vasorelaxation in renal artery rings; III) reduced arterial pressure and resistance in aortic and renal vascular beds; IV) caused antihypertensive effects in a dose-dependent manner. Current findings support PV3 as a source of bioactive peptides and raise the potential of composing nutraceutical formulations to treat renal and cardiovascular diseases.

Resilience to acute kidney injury in offspring of maternal protein restriction.

Protein restriction (PR) during pregnancy induces morphofunctional alterations related to deficient nephrogenesis. We studied the renal functional and morphological significance of PR during pregnancy and/or lactation in adult male rat offspring and the repercussions on acute kidney injury (AKI) severity. Female rats were randomly assigned to the following groups: control diet during pregnancy and lactation (CC), control diet during pregnancy and PR diet during lactation (CR), PR during pregnancy and control diet during lactation (RC), and PR during pregnancy and lactation (RR). Three months after birth, at least 12 male offspring of each group randomly underwent either bilateral renal ischemia for 45 min [ischemia-reperfusion (IR)] or sham surgery. Thus, eight groups were studied 24 h after reperfusion: CC, CC + IR, CR, CR + IR, RC, RC + IR, RR, and RR + IR. Under basal conditions, the CR, RC, and RR groups exhibited a significant reduction in nephron number that was associated with a reduction in renal blood flow. Glomerular hyperfiltration was present as a compensatory mechanism to maintain normal renal function. mRNA levels of several vasoactive, antioxidant, and anti-inflammatory molecules were decreased. After IR, renal function was similarly reduced in all of the studied groups. Although all of the offspring from maternal PR exhibited renal injury, the magnitude was lower in the RC and RR groups, which were associated with faster renal blood flow recovery, differential vasoactive factors, and hypoxia-inducible factor-1α signaling. Our results show that the offspring from maternal PR are resilient to AKI induced by IR that was associated with reduced tubular injury and a differential hemodynamic response.

Scintigraphic Evaluation of the Impact of Pneumoperitoneum on Renal Blood Flow: A Rabbit Model.

Background: Increased intra-abdominal pressure resulting from pneumoperitoneum can cause renal physiological changes, such as oliguria and anuria, in mammals. Although videolaparoscopic operations are common, the occurrence of renal lesions due to these procedures has not been precisely documented in the literature. The aim of this study was to evaluate the impact of pneumoperitoneum on renal blood flow using renal scintigraphy in a rabbit model. Methods: Six New Zealand male rabbits weighing 3 kg, previously anesthetized, were mechanically ventilated and underwent pneumoperitoneum. Each animal served as its own control and was analyzed in two different moments: [99mTc] diethylenetriaminepentaacetic acid (DTPA) renal blood flow evaluation in baseline conditions (T0) and 30 minutes after installation of 15 mmHg-pneumoperitoneum (T1). The animals were monitored throughout the study by capnography, oximetry, and arterial pressure median, and were euthanized at the end of the experiment. Results: The quantitative analysis of the scintigraphic images of renal uptake of the radiopharmaceutical evidence reduced renal arterial blood flow during pneumoperitoneum. Compared with baseline conditions, all animals presented a reduction of renal blood flow varying from 16% to 82%, with mean [±standard deviation] of 53% [±24%]. Conclusions: Pneumoperitoneum induces a significant reduction of the renal blood flow, as determined in this experimental method in rabbits and dynamic renal scintigraphy with [99mTc] DTPA is an adequate method to investigate this event in the experimental setting.

Time-intensity curve analysis of contrast-enhanced ultrasound is unable to differentiate renal dysfunction in the early post-transplant period - a prospective study.

BACKGROUND: Contrast enhanced ultrasonography (CEUS) assessment of kidney allografts mainly focuses on graft rejection. However, studies on delayed graft function (DGF) without acute rejection are still lacking. The aim of this study was to build a time-intensity curve (TIC) using CEUS in non-immunological DGF to understand the utility of CEUS in early transplantation. METHODS: Twenty-eight patients in the short-term postoperative period (<14 days) were divided according to the need for dialysis (early graft function [EGF] and [DGF]) and 37 subjects with longer than 90 days follow-up were divided into creatinine tertiles. Time to peak [TTP] and rising time [RT were compared between groups. RESULTS: EGF and DGF were similar, except for creatinine. In comparison to the late group, medullary TTP and RT were shorter in the early group as well as the delay regarding contrast arrival in the medulla (in relation to cortex) and reaching the medullary peak (in relation to artery and cortex). In the late group, patients with renal dysfunction showed shorter temporal difference to reach medullary peak in relation to artery and cortex. CONCLUSIONS: Although it was not possible to differentiate EGF and DGF using TIC, differences between early and late groups point to blood shunting in renal dysfunction.

Curcumin prevents potassium dichromate (K2Cr2O7)-induced renal hypoxia.

Curcumin exhibits several therapeutic properties. Potassium dichromate (K2Cr2O7)-induced nephropathy is associated with oxidative stress. Reactive oxygen species production affects renal oxygenation that may participate in the progression of renal damage. The aim of the present work was to elucidate whether K2Cr2O7-induced nephropathy is associated to partial O2 pressure (pO2) impairment and if curcumin is able to prevent it. Four groups of rats were studied: control group; K2Cr2O7 group (12.5 mg/kg, s.c.); curcumin + K2Cr2O7 group, in which animals were treated with curcumin (400 mg/kg/day, p.o.) for 10 days before K2Cr2O7 injection; and curcumin group. All animals were sacrificed 48 h after the end of the treatments. K2Cr2O7 administration increased renal function markers and decreased glomerular filtration rate, pO2 and renal perfusion. Concerning hemodynamic parameters, K2Cr2O7 increased mean arterial pressure and renal vascular resistance and reduced renal blood flow. The hemodynamic changes were attributed to decreased availability of nitric oxide and increased 3-nitrotyrosine levels. Moreover, increased superoxide anion production and vascular endothelial growth factor levels were observed after K2Cr2O7 administration. Curcumin attenuated all the above-described alterations. Our results suggest that the protective effects of curcumin in K2Cr2O7-induced nephropathy are associated with its ability to prevent O2 supply reduction.

Horseshoe Kidney / Riñón en herradura

Abstract We present the clinical case of a 39 year old male that presented with a violent death in the city of Medellin. During the necropsy, a horseshoe Kidney was found, which was never diagnosed according to the patients' medical history. It is a case relevant in the medical field given the unusual vasculature that was found, because it's not a usual arrangement. The lack of symptoms and its spontaneous finding during the necropsy, shows us that it's not a rare find in our environment and that it has a big impact in the surgical fields, and in occasions, with urinary tract infections. Methodology: Descriptive. Informed consent was given by the deceased relatives for the use and analysis of the medical history.

Resumen Se expone el caso de un hombre de 39 años que presenta muerte violenta en la ciudad de Medellín. Durante la necropsia se encuentra un riñón en herradura, que no tuvo diagnóstico clínico en su momento, según los hallazgos en su historial médico. Es un caso que puede tener implicaciones en el campo médico, dada la vasculature accesoria que presenta, presentación que no es comúnmente observada. La falta de sintomatología y su hallazgo espontáneo durante la necropsia hacen ver que, a pesar de la poca incidencia, no es extraño encontrar el caso en pacientes de nuestro entorno. Este tiene mayor impacto en el campo quirúrgico y, en ocasiones, en las afecciones urinarias. Metodología: descriptivo. Se obtuvo consentimiento informado, de la familia del occiso, para el estudio de su historial médico.

Involvement of sinoaortic afferents in renal sympathoinhibition and vasodilation induced by acute hypernatremia.

Despite the abundance of evidence that supports the important role of aortic and carotid afferents to short-term regulation of blood pressure and detection of variation in the arterial PO2 , PCO2 and pH, relatively little is known regarding the role of these afferents during changes in the volume and composition of extracellular compartments. The present study sought to determine the involvement of these afferents in the renal vasodilation and sympathoinhibition induced by hypertonic saline (HS) infusion. Sinoaortic-denervated and sham male Wistar rats were anaesthetised with intravenous (i.v.) urethane (1.2 g/kg body weight (bw)) prior to the measurement of the mean arterial pressure (MAP), renal vascular conductance (RVC) and renal sympathetic nerve activity (RSNA). In the sham group, the HS infusion (3 mol/L NaCl, 1.8 mL/kg bw, i.v.) induced transient hypertension (12 ± 4 mmHg from baseline, peak at 10 min; P < 0.05), an increase in RVC (127 ± 9% and 150 ± 13% from baseline, at 20 and 60 min respectively; P < 0.05) and a decrease in RSNA (-34 ± 10% and -29 ± 5% from baseline, at 10 and 60 min respectively; P < 0.05). In sinoaortic-denervated rats, HS infusion promoted a sustained pressor response (30 ± 5 and 17 ± 6 mmHg of baseline values, at 10 and 30 min respectively; P < 0.05) and abolished the increase in RVC (85 ± 8% from baseline, at 10 min) and decrease in RSNA (-4 ± 3% from baseline, at 10 min). These results suggest that aortic and carotid afferents are involved in cardiovascular and renal sympathoinhibition responses induced by acute hypernatremia.

Intra-renal transfection of heat shock protein 90 alpha or beta (Hsp90α or Hsp90ß) protects against ischemia/reperfusion injury.

BACKGROUND: We previously reported that radicicol (Hsp90 inhibitor) induced a reduction in the renal blood flow and glomerular filtration rate, in part due to a reduction in urinary NO2/NO3 excretion, suggesting that Hsp90 regulates renal vascular tone in physiological conditions. However, there is a lack of information concerning Hsp90α or Hsp90ß role on eNOS activity and their association with acute kidney injury (AKI) characterized by an inadequate NO production. This study evaluated the effects of Hsp90α or Hsp90ß intra-renal transfection under ischemia/reperfusion (IR) injury. METHODS: Uninephrectomized (Nx) rats were intra-renally transfected through injections with Hsp90α or Hsp90ß cloned into pcDNA3.1(+) or empty vector (EV) at 48 h before inducing IR, as indicated in the following groups: (i) Nx+sham, (ii) Nx+IR, (iii) Nx+IR+EV, (iv) Nx+IR+Hsp90α and (v) Nx+IR+Hsp90ß. After 24 h, physiological, histopathological, biochemical and molecular studies were performed. RESULTS: IR-induced renal dysfunction, structural injury, tubular proliferation, the elevation of urinary Hsp72 and the reduction of urinary NO2/NO3 excretion. These alterations were associated with reduced eNOS-Hsp90 coupling and changes in the eNOS phosphorylation state mediated through a reduction in PKCα and increased Rho kinase expression. In contrast, intra-renal transfection of Hsp90α or Hsp90ß prevented IR injury that was associated with the restoration of eNOS-Hsp90 coupling, eNOS activating phosphorylation and PKCα and Rho kinase levels. CONCLUSIONS: Here we showed that eNOS-Hsp90 uncoupling plays a critical role in promoting NO reduction during IR. This effect was effectively reversed through Hsp90α or Hsp90ß intra-renal transfection, suggesting their implication in regulating NO/eNOS pathway and the renal vascular tone.

Infrared Thermometer: an accurate tool for temperature measurement during renal surgery

Purpose To evaluate infrared thermometer (IRT) accuracy compared to standard digital thermometer in measuring kidney temperature during arterial clamping with and without renal cooling. Materials and Methods 20 pigs weighting 20Kg underwent selective right renal arterial clamping, 10 with (Group 1 - Cold Ischemia with ice slush) and 10 without renal cooling (Group 2 - Warm Ischemia). Arterial clamping was performed without venous clamping. Renal temperature was serially measured following clamping of the main renal artery with the IRT and a digital contact thermometer (DT): immediate after clamping (T0), after 2 (T2), 5 (T5) and 10 minutes (T10). Temperature values were expressed in mean, standard deviation and range for each thermometer. We used the T student test to compare means and considered p < 0.05 to be statistically significant. Results In Group 1, mean DT surface temperature decrease was 12.6 ± 4.1°C (5-19°C) while deep DT temperature decrease was 15.8 ± 1.5°C (15-18°C). For the IRT, mean temperature decrease was 9.1 ± 3.8°C (3-14°C). There was no statistically significant difference between thermometers. In Group 2, surface temperature decrease for DT was 2.7 ± 1.8°C (0-4°C) and mean deep temperature decrease was 0.5 ± 1.0°C (0-3°C). For IRT, mean temperature decrease was 3.1 ± 1.9°C (0-6°C). No statistically significant difference between thermometers was found at any time point. conclusions IRT proved to be an accurate non-invasive precise device for renal temperature monitoring during kidney surgery. External ice slush cooling confirmed to be fast and effective at cooling the pig model. IRT = Infrared thermometer DT = Digital contact thermometer D:S = Distance-to-spot ratio .