PGl2 analogue mitigates the progression rate of renal dysfunction improving renal blood flow without glomerular hyperfiltration in patients with chronic renal insufficiency.

Renal blood flow decreases with the progression of chronic glomerulonephritis (CGN). This disease induces medullary ischemia and further renal dysfunction in patients with chronic renal insufficiency (CRI). Prostacyclin (PGI2), with its vasodilative action, increases renal blood flow (RBF) without increasing glomerular filtration rate (GFR). We therefore examined the possibility that PGI2 would mitigate the progression of renal dysfunction by increasing RBF in patients with CRI. Sixteen patients with progressive renal insufficiency (serum creatinine: 2.14+/-0.89 mg/dl) due to CGN were prospectively chosen for this study. The blood pressure was already under control using calcium channel blockers before and during this study in nine hypertensive patients. In the first 6 months the patients received a low-protein (0.6 g/kg/day) and low-salt (5.0 g/day) diet. In the next 6 months they received 60 microg/day of PGI2 analogue (Beraprost sodium) orally. GFR was determined by 24-hour creatinine clearance, and effective renal plasma flow (ERPF) was determined by 99mTc-MAG3 scintigraphy. Glomerular capillary pressure, the resistance ratio of afferent and efferent arterioles (R(A)/R(E)), and the other hemodynamic parameters from Gomez's estimation equation were determined at the start of this study, just before the administration of Beraprost and at the end of the study. The levels of GFR and ERPF were 34.6+/-12.4 and 140.6+/-52.1 ml/min at the start of this study respectively, and decreased to 28.0+/- 12.0 and 115.6+/-45.3 ml/min after the first 6 months without Beraprost. The levels of GFR and ERPF stayed at 28.1+/-15.7 and 119.2+/-57.6 ml/min after the next 6 months with Beraprost in the same patients. R(A)/R(E) increased in the first 6 months from 7.9+/-3.6 to 10.8+/-8.6, but remained constant during 6 months of Beraprost administration, at 10.5+/-8.0. These data indicate that PGI2 analogue diminishes the vascular resistance of glomerular afferent and efferent arterioles regulating the decrease of renal blood flow without glomerular hyperfiltration, thus mitigating the progression rate of renal dysfunction.     

The glomerular filtration rate,effective renal plasma flow,and renal blood flow in the adult male chacma baboon (Papio ursinus)

Abstract: The radionuclide determination of glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) has been validated in man, but not in the primate. GFR, ERPF, and renal blood flow (RBF) were measured in a group of 12 adult male chacma baboons using radiopharmaceuticals. GFR was determined using ^99mtechnetium-labelled diethylenetriamine-pentacetic acid. ERPF was measured with ¹³¹iodine-labelled hippuran. RBF, body surface area, and kidney weights were calculated using standard formulae. GFR was 49 ± 11 ml/min and ERPF was 237.9 ± 54.2 ml/min. Calculated RBF was 430.7 ± 111.9 ml/min and 507.4 ± 138.4 ml/min/100g of renal tissue. The results are in agreement with those obtained using more laborious nonradioisotopic techniques such as para-aminohippurate (PAH) and creatinine clearance and could serve as baseline normal values in the adult male chacma baboon.     

The effect of glucagon on glomerular filtration rate in dogs during reduction of renal blood flow.

Glucagon in small intravenous (i.v.) doses markedly increases glomerular filtration rate (GFR) in normal anesthetized dogs. In this study, the effects of glucagon 5 mug/min (i.v.) on renal hemodynamics was tested in four canine models of acute pre-renal failure (hemorrhage, barbiturate overdose; renal arterial clamping and renal arterial infusions of noradrenaline) and in a model of unilateral acute tubular necrosis at 4 h and 6-7 days following completion of the ischemic insult. Following hemorrhage and barbiturate excess, with arterial blood pressure maintained at 65-70 mm Hg, whole-kidney GFR and clearance rate of p-aminohippurate decreased by 50-70%. During this reduction of perfusion pressure, the subsequent infusion of glucagon increased GFR by 90-130%. In models where arterial pressure was normal during the period of ischemia (clamping and noradrenaline infusion), not only did glucagon significantly increase renal perfusion, but the ischemic kidney proved to be far more sensitive to the hemodynamic effects of glucagon (delta GFR - 120-160%) than the contralateral control (deltaGFR = 30-40%). In three dogs completely anuric following renal arterial clamping, glucagon was able to improve blood flow and restart urine formation. Glucagon, but not dopamine, was able to simulate the beneficial effects of hypertonic mannitol on renal function in dogs with hemorrhagic hypotension. Glucagon was without effect in established acute tubular necrosis. This study, therefore, indicates that, during renal ischemia, glucagon may be quite effective in preserving urine output and perfusion of the kidneys.     

Water balance and renal function in the Australian desert rodent Notomys alexis: The effect of diet on water turnover rate,glomerular filtration rate,renal plasma flow and renal blood flow

• 1.1. Water turnover rate, glomerular nitration rate and renal plasma and blood flow rates have been measured in individuals of the Australian desert rodent Notomys alexis under conditions of acute and chronic water deprivation and high nitrogen diet.
• 2.2. When these parameters are compared with values predicted allometrically the extreme ability of the species to conserve water is apparent only in those groups subjected to water stress.
• 3.3. Whilst a reversible reduction in renal function is evident upon water deprivation, the major factor in water conservation under these conditions is the renal reabsorption of water at a post-filtration stage.

     

慢性肾衰竭患者肠道菌群改变与肾小球滤过率的关系

探究慢性肾衰竭患者肠道菌群结构改变与肾小球滤过率的关系。

选取2017年3月至2020年3月我院收治的202例慢性肾衰竭患者作为试验组, 并选取198例同期健康体检者作为对照组。收集两组入选者粪便标本并进行检测, 对比两组入选者肠道菌群数量; 同时对比两组入选者体质量、肾小球滤过率、血肌酐、血尿素氮、血胱抑素C水平, 采用Pearson相关性分析肠道菌群改变与肾小球滤过率的相关性。

相比于对照组, 试验组患者肠道双歧杆菌(t=21.915, P < 0.001)、大肠埃希菌数量显著降低(t=18.220, P < 0.001), 肠球菌数量显著增高(t=16.782, P < 0.001)。相比于对照组, 试验组患者肾小球滤过率(t=147.035, P < 0.001)显著降低, 血肌酐(t=43.129, P < 0.001)、血尿素氮(t=170.206, P < 0.001)、血胱抑素C(t=22.432, P < 0.001)水平显著增高。Spearman相关性分析显示, 慢性肾衰竭患者肠道双歧杆菌(r=-0.695, P < 0.001)和大肠埃希菌(r=-0.631, P < 0.001)与肾小球滤过率呈负相关。Logistic回归分析显示, 双歧杆菌、大肠埃希菌、肠球菌、血肌酐、血尿素氮和血胱氨酸均是慢性肾衰竭患者肾小球滤过率降低的独立危险因素。

慢性肾衰竭患者肠道双歧杆菌和大肠埃希菌数量降低、肠球菌数量升高, 且与肾小球滤过率呈显著负相关。

     

The effects of urea infusion on glomerular filtration rate and renal plasma flow in sheep fed low and high protein diets.

Reducing the dietary N intake of sheep resulted in a significant fall in GFR with no change in RPF. Intravenous of urea for 19-46 h had no effect on the high protein diet but on the low protein diet GFR and FF were increased to values approaching those observed on the high protein diet. On the low protein diet GFR was unaffected by infusion of urea for 4 h or of saline alone for 30 h. It is suggested that the observed changes in GFR are associated with changes in the quantity of protein passing to the abomasum and small intestine.     

On the correlation between composition and site-specific evolutionary rate: implications for phylogenetic inference

Model-based phylogenetic reconstruction methods traditionally assume homogeneity of nucleotide frequencies among sequence sites and lineages. Yet, heterogeneity in base composition is a characteristic shared by most biological sequences. Compositional variation in time, reflected in the compositional biases among contemporary sequences, has already been extensively studied, and its detrimental effects on phylogenetic estimates are known. However, fewer studies have focused on the effects of spatial compositional heterogeneity within genes. We show here that different sites in an alignment do not always share a unique compositional pattern, and we provide examples where nucleotide frequency trends are correlated with the site-specific rate of evolution in RNA genes. Spatial compositional heterogeneity is shown to affect the estimation of evolutionary parameters. With standard phylogenetic methods, estimates of equilibrium frequencies are found to be biased towards the composition observed at fast-evolving sites. Conversely, the ancestral composition estimates of some time-heterogeneous but spatially homogeneous methods are found to be biased towards frequencies observed at invariant and slow-evolving sites. The latter finding challenges the result of a previous study arguing against a hyperthermophilic last universal ancestor from the low apparent G + C content of its rRNA sequences. We propose a new model to account for compositional variation across sites. A Gaussian process prior is used to allow for a smooth change in composition with evolutionary rate. The model has been implemented in the phylogenetic inference software PHASE, and Bayesian methods can be used to obtain the model parameters. The results suggest that this model can accurately capture the observed trends in present-day RNA sequences.     

Cardiac edema in dogs: distribution of renal blood flow and glomerular filtrate.

The injection of Freund's adjuvant into the pericardial sac of 29 dogs resulted in chronic pericardial tamponade with persistent sodium retention. Micropuncture, clearance, and radioactive microsphere experiments were initiated 6--13 days after pericardial injection and 60 min after pericardiocentesis. Pericardiocentesis increased sodium excretion (from 12.2 to 41.3 microequiv./min) and mean arterial pressure (+ 20 mmHg (1 mmHg = 133.322 Pa)). Central venous pressure decreased 6.5 mmHg, as did hematocrit (from 45.7 to 39.8%) and plasma protein concentration (from 5.88 to 5.15 g%). Pericardiocentesis had no significant effect on renal blood flow (RBF), nor plasma flow. Redistribution of glomerular filtrate was suggested by the observation that superficial nephron glomerular filtration rate increased (from 91 to 108 nL/min) while glomerular filtration rate remained unaltered. Determination of intrarenal distribution of RBF revealed that cortical blood flow also distributed superficially. A significant increase in the fraction of RBF perfusing zone 1 (outer cortex) and a decrease in fractional perfusion of zones 2, 3 and 4 (juxtamedullary cortex) were observed in each experiment following pericardiocentesis. RBF distribution examined in a series of six animals prior to and during the development of pericardial tamponade showed the opposite effect. These results indicate that pericardiocentesis causes redistribution of both glomerular filtrate and RBF to superficial nephrons. The development of pericardial tamponade was associated with increased fractional juxtamedullary blood flow. These changes may have been the result of altered blood pressure, hematocrit, plasma protein concentration, or altered renal resistance.     

The glomerular apparatus and renal blood flow in rats during postnatal ontogenesis

In anesthetized Wistar rats of the age of 4, 12, 30 and 65 days, the renal blood flow (RBF) with laser-Doppler flowmetry, diameter, number and density of glomeruli, diameter of afferent and efferent arterioles were measured. We found that during rat development the RBF increased 2.8-fold, the diameter of glomeruli--3.6-fold, diameter of afferent arterioles--1.8-fold, and the efferent arterioles--rose 1.3-fold. The number of glomeruli increased 1.3-fold, but their density decreased 16-fold.     

Increased glomerular filtration rate in early metabolic syndrome is associated with renal adiposity and microvascular proliferation

Metabolic syndrome (MetS) is associated with glomerular hyperfiltration and is a risk factor for chronic kidney disease, but the underlying mechanisms are poorly defined. This study tested the hypothesis that increased glomerular filtration rate (GFR) in early MetS is associated with renal adiposity and microvascular proliferation. Twelve MetS-prone Ossabaw pigs were randomized to 10 wk of a standard (lean, n = 6) or atherogenic (MetS, n = 6) diet. Kidney hemodynamics and function, perirenal fat volume, and tubular dynamics were assessed in vivo by multidetector computed tomography (CT) and blood oxygen level-dependent (BOLD)-MRI. Microvascular architecture was assessed ex vivo with micro-CT. Candidate injury mechanisms were evaluated in kidney tissue by Western blotting and histology. Basal GFR, renal blood flow, and renal cortical perfusion and volume were elevated in the MetS group. Perirenal and kidney tissue fat, proximal-nephron intratubular fluid concentration, and endothelial nitric oxide synthase expression were increased in MetS. GFR levels correlated with tissue triglyceride levels. Elevated spatial density of 20- to 40-μm cortical microvessels was accompanied by mild oxidative stress, inflammation, and with proximal tubular vacuolization. Medullary size and perfusion were relatively preserved, and BOLD-MRI showed intact medullary tubular response to furosemide. Increased GFR in early MetS is associated with renal adiposity and microvascular proliferation, which involve mainly the renal cortex and precede significant activation of oxidative stress and inflammation. Renal adiposity and proliferative microvessels may represent novel therapeutic targets for preserving renal function in early MetS.     

Early postischaemic renal fibrin deposition and reduction of glomerular filtration rate in the rat: effect of the defibrinating agent Arwin

The correlation between the extent of intrarenal fibrin deposition induced by 15, 20 and 30-min bilateral occlusion of the renal arteries and the reduction of glomerular filtration rate (GFR) has been studied. The tissue level of fibrin was estimated by 125I-labelled human fibrinogen. There was a significant negative correlation between cortical and medullary fibrin content and GFR. In rats pretreatment with the defibrinating agent Arwin failed to prevent postischaemic coagulation in the kidney and the reduction of GFR.