Renal response of the starling (Sturnus ;ulgaris) to an intravenous salt load

Total kidney GFR's, urine flow, inorganic ion excretion, and single nephron glomerular filtration rates (SNGFRs) were evaluated in anesthetized starlings under control conditions (2.5% mannitol infusion) and in starlings subjected to an osmotic stress induced by the intravenous infusion of 5.8% sodium chloride. Under control conditions the GFR was 2.92 ml/kg per min, urine flow 0.20 ml/kg per min, 63% of filtered sodium was reabsorbed, mean mammalian type (MT) SNGFR was 15.6 nl/min, and mean reptilian type (RT) SNGFR was 7.0 nl/min. During osmotic stress the GFR did not change, urine flow increased to 3 times the control level, the percentage of filtered sodium reabsorbed did not change, both the mean MT SNGFR (24.3 nl/min) and the mean RT SNGFR (10.3 nl/min) were significantly higher than the control levels. During the osmotic stress more MT and fewer RT nephrons were filtering than during control conditions. Under control conditions 98.5% of the sodium excreted by the kidney was associated with uric acid. This percentage decreased as the osmotic stress increased. The starlings tended to excrete the osmotic load imposed by the infusion of NaCl to prevent the plasma osmolality from increasing.     

Uric acid excretion by the pig kidney.

The handling of uric acid by the pig kidney has been investigated during continuous urate infusion in unrestrained, unanesthetized animals. Urate-to-inulin clearance rates in excess of 1 were found under all experimental conditions, demonstrating only net secretion by the pig kidney. The demonstration of a secretory maximum was precluded owing to a progressive reduction in the GFR associated with high rates of urate infusion. Urate clearance was independent of urine flow rate up to 10 ml/min. The administration of probenecid inhibited urate secretion, but urate-to-inulin clearance ratios below unity were not observed. Pyrazinamide or pyrazinoic acid, at doses which either inhibited secretion or promoted uricosuria in other species, did not alter urate excretion in the pig. Probenecid together with pyrazinamide exerted the same inhibitory effect on urate secretion as probenecid alone. Pyrazinoic acid was reabsorbed at all infusion rates. It is concluded that the pig kidney eliminates uric acid by filtration and secretion only.     

纳米细菌肾结石模型血、尿生化的动态观测

目的 构建纳米细菌Wistar雄性大鼠肾结石模型,动态监测血、尿生化各项指标,旨在为进一步研究纳米细菌在肾结石发生发展过程中所起的作用,提供数据支持,进而为肾结石病因学的下一步探索提供新思路。方法 将60只大鼠随机分为纳米细菌组和空白对照组,每组30只。纳米细菌组给予尾静脉注射1.2 ml NB悬液,空白对照组给予尾静脉注射1.2 ml生理盐水,实验周期为10周,每周每组各处死大鼠3只,处死前采集大鼠血、尿标本,供生化分析,并取两侧鲜活肾脏标本,用于病理结晶情况检测及计算肾体比。结果 自第8周开始,纳米细菌组肾体比值大于空白对照组,差异有统计学意义（P＜0.05）。截至第10周末,纳米细菌组大鼠肾脏晶体阳性11只,空白对照组均为阴性,纳米细菌组大鼠肾脏晶体阳性率高于空白对照组,差异有统计学意义（P＜0.05）。与空白对照组相比,纳米细菌组第4~8周血肌酐、第3~8周血尿酸、第3~9周尿素氮及尿钙水平均升高,第8周纳米细菌组尿pH高于空白对照组差,第6~7周纳米细菌组血钙高于空白对照组,差异均有统计学意义（P＜0.05）。结论 肾体比、结晶阳性率、血肌酐、血尿酸、血尿素、尿钙等重要指标的有效升高,均显示纳米细菌Wistar雄性大鼠肾结石实验模型的成功制备,这为进一步揭示NB在结石形成过程中所起的作用以及后续对肾结石病因学的进一步研究提供了良好的实验基础与数据支持。     

Intense exercise induces the degradation of adenine nucleotide and purine nucleotide synthesis via de novo pathway in the rat liver

The purpose of this study was to investigate the influence of intense exercise on the metabolism of adenine nucleotides in the liver. In the first experiment, to determine the degradation of adenine nucleotides, hepatic adenine nucleotides of rats were labeled by an intraperitoneal administration of ¹⁵N-labeled adenine the day before treadmill running to exhaustion. In the second experiment, to determine the de novo synthesis of purine nucleotides after intense exercise, ¹⁴C-glycine was intraperitoneally administered to rats performing intense running on a treadmill. In the first experiment, hepatic levels of ATP and total adenine nucleotides showed a reduction immediately after exercise. In contrast, hepatic levels of AMP, adenosine, hypoxanthine and uric acid showed an increase immediately after exercise. The hepatic ¹⁵N level continued to decline during the recovery period after exercise. Urinary excretion of ¹⁵N-urate was 40% higher in the exercised rats than in the control rats. In the second experiment, the radioactivity of ¹⁴C detected in the fraction of hepatic urate and allantoin was approximately 300% higher in the exercised rats than in the control rats. ¹⁴C-radioactivity that excreted into urine as urate and allantoin was approximately 200% higher in the exercised rats. Intense exercise led to the degradation of hepatic adenine nucleotides, which were not utilized for the re-synthesis of nucleotide and further degraded to hypoxanthine or uric acid. Intense exercise induced the synthesis of purine nucleotides in the liver via a de novo pathway and these synthesized nucleotides were also degraded to nucleosides and excreted into urine.     

Uric acid excretion by the rat kidney.

The renal excretion of uric acid was studied in nondiuretic (ND) male Wistar rats and in the same animals subsequently made diuretic (D) by the infusion of hypertonic saline. Clearances of endogenous urate and of inulin, determined chemically, were compared with the simultaneous clearance of 14C infused as [6(-14)C]urate or [2(-14)C]urate. In rats infused with [6(-14)C]urate the isotope/inulin clearance ratios were 0.29 +/- 0.09 (ND) and 0.31 +/- 0.11 (D) ml/min; the simultaneous urate (chemical)/inulin ratios were 0.21 +/- 0.07 (ND) and 0.24 +/- 0.08 (D) ml/min. In rats infused with [2(-14)C]urate the isotope/inulin clearance ratios were 1.02 +/- 0.5 (ND) and 1.13 +/- 0.9 ml/min (D); the simultaneous urate (chemical)/inulin clearance ratios were much lower-0.19 +/- 0.09 (ND) and 0.32 +/- 0.19 (D) ml/min. Thin-layer chromatography of urine after [6(-14)C]urate inl uric acid. In contrast, a similar analysis of urinary radioactivity after [2(-14)C]urate infusion revealed that more than 70% of the 14C was excreted as allantoin and not as uric acid.     

Kidney volume expansion and prostaglandin release by bradykinin. The effect of indomethacin pretreatment

100 ng/kg/min bradykinin was infused into the left renal artery in anaesthetized dogs which were loaded with 10% mannitol in saline to produce a diuresis of approximately 1 ml/min. Bradykinin initially increased renal blood flow (70%), kidney volume (20%), subcapsular pressure (85%), urine PG-excretion (410%), diuresis (80%) and decreased urine osmolarity (20%). Kidney volume, diuresis and urine osmolarity remained equally changed during continuous kinin infusion, while other parameters subsided toward the control levels. When renal blood flow was maintained constant during the infusion of bradykinin, urine PG-excretion increased (330%), the glomerular filtration decreased (60%) and this was accompanied by decreased kidney volume, diuresis/natriuresis with unchanged urine osmolarity. Indomethacin treatment (2.5 mg/kg i.v.) decreased renal blood flow (35%) and inhibited urine PG-excretion. Bradykinin after indomethacin showed effects which were very similar to those observed before indomethacin treatment. It is concluded that increased intratubular volume is a main determinant of bradykinin induced increase of whole kidney volume. The accompanying increase of intrarenal pressure does not apparently contribute to the kinin induced PG-release. The vasodilation by bradykinin seems independent of released prostaglandins. The diuresis/natriuresis and decreased urine osmolarity are probably of hemodynamic origin.     

Recirculation and reutilization of micellar bile lecithin.

Bile lecithins, solubilized in micellar bile salt and radiolabeled in the 1-acyl fatty acid, phosphorus, and choline positions, were infused in the small bowel of fasted rats. Absorption of each label was virtually complete after 24 h. However, these lecithins were extensively hydrolyzed in the bowel lumen as well as after absorption, and neither the fatty acid nor phosphorus was significantly retained in the enterohepatic circulation or reutilized for biliary lecithin synthesis. In contrast, while choline was also dissociated from absorbed lecithin, choline was instead retained in the liver, reincorporated into newly synthesized hepatic lecithin, and sercreted in biliary lecithin in 10-fold greater amounts than either the fatty acid or phosphorus. However, the extent of choline incorporation into bile lecithin was limited and was not further increased when free choline was directly injected into the portal vein. The data therefore suggest that although only choline of absorbed lecithin is retained in the enterohepatic circulation and preserved for new biliary lecithin synthesis, exogenous choline utilization is regulated by the size of the available hepatic pool.     

Partial hypoxanthine-guanine phosphoribosyl transferase deficiency without elevated urinary hypoxanthine excretion

Partial hypoxanthine-guanine phosphoribosyl transferase (HGPRT) deficiency, also known as the Kelley-Seegmiller syndrome, can give rise to a wide range of neurological symptoms, and renal insufficiency. Biochemically, it is characterized by high uric acid concentrations in blood, high uric acid and hypoxanthine excretion in urine, and decreased activity of hypoxanthine-guanine phosphoribosyl transferase activity (HGPRT). However, normal uric acid concentrations in blood and uric acid excretions in urine have been reported. Here, a boy is presented with normal development and suffering from recurrent attacks of acute renal failure with slightly to clearly increased urinary uric acid excretion. Between these attacks, episodes of elevated urinary excretion of uric acid were observed with normal blood concentrations of uric acid and normal urinary excretion of hypoxanthine. HGPRT activity in erythrocytes, leukocytes, and fibroblasts was found to be strongly decreased. This case shows that not only normal blood uric acid but also normal urinary hypoxanthine concentrations do not exclude the diagnosis of partial HGPRT deficiency.     

Denervated and intact kidney responses to saline load in awake and anesthetized dogs.

The function of the innervated and denervated kidney was examined in clearance studies with unilaterally renal-denervated conscious and anesthetized dogs before and after saline loading. Barbiturate anesthesia distinctly depressed hemodynamics and excretory function of both kidneys and increased the difference between the denervated and innervated organ. In conscious moderately hydrated dogs the denervated kidney excreted slightly more sodium and water, while after saline loading higher excretion was observed on the innervated side. The denervated-to-innervated kidney ratios for UNaV, UNaV/100 ml GFR, and urine flow fell significantly from mean control values of 1.27, 1.27, and 1.20, respectively, to 0.80, 0.87, and 0.77 after extracellular volume expansion. Similar alterations of the ratios were observed in anesthetized dogs, but higher excretion of the denervated kidney persisted after saline loading. It is concluded that the greater natriuretic response of the intact kidney to saline infusion was due to inhibition of sodium-retaining action of renal efferent nerve activity by acute extracellular volume expansion.     

Aggravation of subclinical diabetes insipidus during pregnancy

BACKGROUND. Transient polyuria and polydipsia during pregnancy are rare, and their cause is not entirely clear. Possible explanations include the exacerbation of preexisting abnormalities in the secretion or action of vasopressin and abnormally large increases in plasma vasopressinase activity. METHODS. We studied two women in whom overt polyuria and polydipsia developed during the third trimester of pregnancy and disappeared after delivery. The secretion and action of vasopressin were studied both when the women had polyuria and polydipsia and later, when their water intake and urine volume were normal. RESULTS. One patient had partial nephrogenic diabetes insipidus. She had little increase in urine osmolality in response to water deprivation, hypertonic-saline infusion, and vasopressin injection and no response to desmopressin acetate (1-deamino-8-D-arginine vasopressin) during the immediate postpartum period. Her basal and stimulated plasma vasopressin concentrations were high (16.5 to 203.4 pmol per liter) before and during hypertonic-saline infusion 30 months post partum. The other patient had partial neurogenic diabetes insipidus. She had subnormal basal plasma vasopressin concentrations, a subnormal increase in the plasma vasopressin level and a subnormal decrease in urine flow in response to the administration of vasopressin, and a normal response to desmopressin. After pregnancy, when her urine volume was normal, she had no increase in plasma vasopressin in response to hypertonic-saline infusion, but she had a normal rise in the plasma vasopressin level and a normal renal response to vasopressin administration. CONCLUSIONS. Pregnancy may unmask subclinical forms of both nephrogenic and neurogenic diabetes insipidus. This exacerbation may result from both increased vasopressinase activity and diminished renal responsiveness to vasopressin.     

The localization of thromboxane synthase in normal and pathological human kidney tissue using a monoclonal antibody Tü 300

Thromboxane, excreted in the urine in increased amounts in glomerular, vascular and tubulo-interstitial diseases, is considered to originate from the kidney. The localization of thromboxane synthase, a key enzyme of arachidonic acid metabolism, was studied in the human kidney by immunohistology using the monoclonal antibody Tü 300. In the interstitial tissue dendritic reticulum cells surrounding the tubules expressed high concentrations of the enzyme. In glomeruli the enzyme was weakly expressed in podocytes. This was confirmed by co-localization with an antiserum directed to podocalyxin, a marker of the visceral epithelial cells. In the study of various kidney diseases, massive accumulation of thromboxane synthase containing cells was observed in interstitial diseases, whereas in glomerular diseases there were no differences from normal kidney; in a case of thrombotic microangiopathy podocytes exhibited an increase in thromboxane-synthase. The thromboxane-synthase positive infiltrating interstitial cells were shown by conventional light microscopy to be mononuclear phagocytic cells. The physiological sources of renal thromboxane are dendritic reticular cells and podocytes. In interstitial renal disease infiltrating cells of the monocyte/macrophage system constitute the major site of thromboxane synthesis. In glomerular disease, a characteristic alteration of thromboxane-synthase was not found.     

Renal handling of dopa, dopamine, norepinephrine, and epinephrine in the dog

The uptake and excretion of endogenous dopa, dopamine, norepinephrine, and epinephrine by the kidney were studied. Blood samples were taken from the aorta at the origin of the renal artery and from the renal vein during a timed urine collection in each of six anesthetised greyhound dogs. Arterial plasma dopa (1,043 +/- 129 pg/ml) and epinephrine (218 +/- 96 pg/ml) were consistently higher than venous levels of dopa (591 +/- 80) and epinephrine (54 +/- 16 pg/ml), showing extraction of these by the kidney, whereas arterial plasma norepinephrine (329 +/- 89 pg/ml) and dopamine (64 +/- 9 pg/ml) were lower than the venous levels of norepinephrine (695 +/- 161 pg/ml) and dopamine (239 +/- 45 pg/ml), indicating secretion of these catecholamines into the circulation. The dopa extracted did not appear in the urine. Norepinephrine (7.2 +/- 1.7 ng/min), epinephrine (4.5 +/- 1.7 ng/min), and dopamine (3.2 +/- 0.7 ng/min) were excreted in the urine. These rates of urinary excretion could be accounted for by glomerular filtration and tubular secretion of the three catecholamines. The kidney extracts circulating dopa. It extracts and excretes epinephrine, norepinephrine, and dopamine, and, in addition, secretes both dopamine and norepinephrine into the circulation. These observations emphasize the important relationship between renal function and the peripheral sympathetic nervous system.     

Stimulation of renin release by PGE2 and PGI2 infusion in the dog: enhancing effect of ureteral occlusion or administration of ethacrynic acid

This study on 19 anaesthetized dogs had two objectives. The first was to compare the potencies of PGE2 and PGI2 as stimulators of renin release and demonstrate their dependency on activation of intrarenal mechanisms for renin release. The second objective was to demonstrate that ethacrynic acid (ECA) increases renin release not as a stimulator, but by activating intrarenal mechanisms. After inhibiting renal prostaglandin synthesis by indomethacin, PGE2 and PGI2 infused into the aorta proximal to the renal arteries exerted no significant effects on renin release, but increased renin release during ureteral occlusion. At equimolar infusion rates, PGI2 increased renin release twice as much as PGE2, but this difference in potency may reflect differences in degradation since 86% of PGE2 and 29% of PGI2 (measured as 6-keto-PGF1 alpha) were degraded during one passage through the kidney. By infusing PGF2 at 8 nmol min-1 and PGI2 at 2 nmol min-1 renin release increased equally and the prostaglandin outputs increased to the same levels as during ureteral occlusion before indomethacin administration. ECA did not increase renin release after indomethacin administration. However, infusion of PGE2 during continuous ECA administration increased renin release in a dose-dependent manner similar to the experiments performed during ureteral occlusion. We conclude that PGI2 and PGE2 in the amounts synthesized in the kidney seem to be equally important stimulators of renin release but their relative potencies cannot be determined because the site of degradation is uncertain. Renin release is enhanced by intrarenal mechanisms activated by ECA infusion or ureteral occlusion, which both cause autoregulatory vasodilation and reduce NaCl reabsorption at the macula densa.     

PGE2 concentrations in renal venous plasma and renal lymph during basal and stimulated conditions in the dog

PGE₂ concentration (pg/ml ± SEM) was measured in canine renal lymph (394±115), renal venous plasma (276±55), arterial plasma (172±34) and urine (1290±934). Control periods were followed by an infusion of the sodium salt of arachidonic acid (AA) (40 g/kg min) into the renal artery to stimulate prostaglandin synthesis. During infusion of AA PGE₂ concentrations increased significantly in renal lymph (672±155) renal venous plasma (549±123), and urine (6768±1420), but not in the arterial plasma (176±31). Concentrations in renal lymph and renal venous plasma were not significantly different under either condition. These findings indicate that PGE₂ concentration in renal venous plasma is, by and large, representative of mean PGE₂ concentrations in the cortical renal interstitium, although focal inhomogeneities in PGE₂ concentration in the different areas of the renal interstitium cannot be excluded. Since flow rate of renal lymph is insignificant in comparison with renal venous plasma flow rate total renal PGE₂ output can be estimated from measurements in renal venous plasma and urine.This work was supported by the Friedrich-Baur-Stiftung, München     

Effects of ureteral occlusion and ethacrynic acid infusion on renal prostaglandin degradation in the dog

The two major renal prostaglandins PGE2 and PGI2 are partly metabolized during a single passage of the kidney. To examine whether stopping glomerular filtration affected the renal degradation, PGE2 and PGI2 were infused into the suprarenal aorta of dogs during ureteral occlusion. Prostaglandin synthesis was blocked by indomethacin, 10 mg kg-1 b.w. i.v. About 20% of PGI2 and 80-90% of PGE2 were metabolized during one passage through the kidney. Prostaglandin degradation and arterial input were proportional (r greater than 0.95). Compared to control conditions at free urine flow, PGI2 degradation was not changed, whereas the degradation of PGE2 was slightly increased by ureteral occlusion. Ethacrynic acid might reduce degradation of PGE2 by inhibiting two degradation enzymes. To examine the influence of ethacrynic acid, PGE2 was infused in different doses into the suprarenal aorta of dogs before and after administration of ethacrynic acid 3 mg kg-1 b.w. i.v. At all dose levels of PGE2, 75-80% was degraded by one passage through the kidney, whether ethacrynic acid was administered or not. However, although ethacrynic acid did not alter the total renal output, the urinary fraction was reduced from 20-30% to 10-15%. We conclude that degradation of both PGE2 and PGI2 is mainly confined to the blood vessels, and that ethacrynic acid in conventional doses does not prevent degradation of PGE2, but redistributes PGE2 output from urine to renal venous blood.     

The targeting of anionized polyvinylpyrrolidone to the renal system

We reported that the co-polymer composed of vinylpyrrolidone and maleic acid selectively distributed into the kidneys after i.v. injection. To further optimize the renal drug delivery system, we assessed the renal targeting capability of anionized polyvinylpyrrolidone (PVP) derivatives after intravenous administration in mice. The elimination of anionized PVP derivatives from the blood decreased with increasing anionic groups, and the clearance of carboxylated PVP and sulfonated PVP from the blood was almost similar. But carboxylated PVP efficiently accumulated in the kidney, whereas sulfonated PVP was rapidly excreted in the urine. The renal levels of carboxylated PVP were about five-fold higher than sulfonated PVP. Additionally, carboxylated PVP was effectively taken up by the renal proximal tubular epithelial cells in vivo after i.v. injection. These anionized PVP derivatives did not show any cytotoxicity against renal tubular cells and endothelial cells in vitro. Thus, these carboxylated and sulfonated PVPs may be useful polymeric carriers for drug delivery to the kidney and bladder, respectively.     

Kinetic analysis of potassium transport in bullfrog kidney.

Techniques have been developed for studying the distribution and the rates of exchange of K among urine, the tubular cells, and the circulation in the isolated, pump-perfused, bullfrog kidney. Tubular cells were loaded with 42K via the portal circulation, and the subsequent washout of the tracer into the vena cava and into urine was measured. Analysis of the data indicated the existence of at least three cellular pools of K. Pools a and b have half times of exchange of 1.1 and 4.1 min and contain about 25 and 40% of tissue K, respectively. The remainder of cellular K is contained in one or more very slowly exchanging pools. The rate of exchange of K at the basolateral surface of tubular cells is 50-fold greater than at the luminal surface. A pulse-washout method was also devised to permit control and experimental measurements to be made in the same kidney. With this technique, we found that portal perfusion with 10 mM K increased the rate of uptake into pools a and b from the circulation and the rate constants for efflux into the urine from both pools, Acetazolamide increased uptake into pool a and the rate constants for efflux into the urine from both pools.     

血尿酸与糖尿病肾病患者肾脏功能减退的相关性分析

目的探讨尿酸与糖尿病肾病(diabetic nephropathy,DN)患者肾脏功能减退的相关性。方法纳入670例就诊于四川大学华西医院,并且诊断为糖尿病肾病的患者为研究对象,记录其年龄、性别,检测尿酸(uric acid,UA)、肌酐(creatinine,CREA)、三酰甘油(triglyceride,TG)、总胆固醇(total cholesterol,TC)、高密度脂蛋白胆固醇(high density lipoprotein cholesterol,HDL-C)、低密度脂蛋白胆固醇(low density lipoprotein cholesterol,LDL-C)、尿素(urea,UREA)和糖化血红蛋白(glycated hemoglobin,HbA1c)水平。根据尿酸水平分为高尿酸血症组和正常尿酸组。对各检测指标进行组间比较,并进行相关性分析,分析尿酸与糖尿病肾病患者肾脏进展的相关性。结果研究人群中,高尿酸组有334例,正常尿酸组有336例。高尿酸组的肌酐、尿素高于正常尿酸组,肾小球滤过率和糖化血红蛋白低于正常尿酸组,差异有统计学意义(P<0.05);尿酸水平与糖尿病肾病患者的肾小球滤过率成负相关(P<0.05)。结论糖尿病肾病患者的尿酸水平与eGFR水平成负相关,即尿酸水平越高,肾脏功能越差。糖尿病肾病患者的日常管理中,应重视尿酸水平的检测。     

Effects of maleate on carbohydrate metabolism in rats.

Intraperitoneal administration of maleate produced an increase in blood alpha-ketoacid, acetoacetate, and free fatty acids. The effect of this treatment on blood glucose levels depended on whether the rats were fed or fasted. In fed rats it was accompanied by slight, transient hyperglycemia connected with depletion of liver glycogen stores. In fasted animals moderate hypoglycemia was observed. The in vivo conversion of various precursors into blood glucose was not inhibited, suggesting that maleate does not affect hepatic gluconeogenesis. Neither was a direct effect on liver glycogenolysis observed. On the other hand, maleate inhibited renal gluconeogenesis from various substrates and stimulated anerobic glycolysis in kidney cortical alices. The data are interpreted in terms of increased utilization and decreased production of glucose by the kidney followed by secondary changes in liver carbohydrate metabolism.     

Does cadmium contribute to the development of renal parenchymal hypertension?

In our study we investigated 36 out-patients with renal disease, 22 of whom were hypertensive. In all patients proteinuria was present (4.30 +/- 5.05 g protein/day) and kidney diseases were verified by renal biopsy. Blood cadmium in non-smokers was significantly (p less than 0.05) lower than in smokers. We found a positive correlation between cadmium-concentration of blood and urine (p less than 0.01, R = 0.44) and between cadmium-concentration of blood and blood uric acid (p less than 0.01, R = 0.44). Proteinuria was weakly correlated with cadmium concentration of urine (p less than 0.05, R = 0.35). Patients with renal hypertension showed a significantly higher (p less than 0.05) urine cadmium excretion per day (1.60 +/- 1.12 micrograms/day) compared to normotensives with a disease of the kidney (1.14 +/- 1.47 micrograms/day). Our results indicate that cadmium may be involved in the development of hypertension in patients with renal disease.