ATP-MgCl2 restores renal microcirculation following trauma and severe hemorrhage.

Although ATP-MgCl2 enhances the recovery of renal function after ischemia and reperfusion, it is not known whether this agent has any beneficial effects on renal microcirculation and function in a nonheparinized model of trauma and severe hemorrhage. To study this, a midline laparotomy was performed (i.e., trauma induced) and the rats were bled to and maintained at a mean arterial pressure of 40 mmHg (1 mmHg = 133.32 Pa) until 40% of the maximum shed blood volume was returned in the form of Ringer's lactate (RL) solution. Animals were then resuscitated with 4 times the volume of the shed blood in the form of RL. ATP-MgCl2, 50 mumol/kg body weight, or an equivalent volume of saline, was infused intravenously during and following resuscitation. Renal microcirculation was examined by using colloidal carbon infusion and laser Doppler flow-metry. Glomerular filtration rate (GFR) was assessed with [3H]inulin clearance and cardiac output (CO) was determined by dye dilution technique. The results indicate that the depressed renal microcirculation following hemorrhage and resuscitation was restored by ATP-MgCl2 treatment. GFR was significantly higher in ATP-MgCl2-treated than saline-treated rats. ATP-MgCl2 also increased urine output, restored the decreased CO, and prevented the occurrence of renal edema after hemorrhage and resuscitation. Thus, ATP-MgCl2 appears to be a useful adjunct to crystalloid resuscitation following trauma and severe hemorrhagic shock even in the absence of blood resuscitation.     

Mannitol

Mannitol may be useful clinically both as a diuretic and as an obligate extracellular solute. As a diuretic it can be used to treat patients with intractable edema states, to increase urine flow and flush out debris from the renal tubules in patients with acute tubular necrosis, and to increase toxin excretion in patients with barbiturate, salicylate or bromide intoxication. As an obligate extracellular solute it may be useful to ameliorate symptoms of the dialysis disequilibrium syndrome, to decrease cerebral edema following trauma or cerebrovascular accident, and to prevent cell swelling related to renal ischemia following cross-clamping of the aorta. Largely unexplored uses for mannitol include its use as an osmotic agent in place of dextrose in peritoneal dialysis solutions, its use to maintain urine output in patients newly begun on hemodialysis, and its use to limit infarct size following acute myocardial infarction.     

Hemorrhagic fever with renal syndrome: clinical aspects

Hemorrhagic fever with renal syndrome (HFRS) is an acute viral fever which typically progresses through five stages: an acute grippe, followed by hemorrhage and shock, acute renal insufficiency from tubulo-interstitial nephritis, and recovery. Death from circulatory or renal failure occurs in 5%-15% of cases. In mild or abortive forms of the disease, associated with viral strains enzootic in Scandinavia the illness is milder. Hemorrhage and shock occur with lower frequency and the fatality rate is less than 1%. Pathologic examination of HFRS cases from Asia discloses generalized congestion, hyperemia, and hemorrhage, with scattered foci of necrosis in numerous organs. Congestion and hemorrhage are most evident in the kidney medulla. Widespread microscopic evidence of capillary and vascular dysfunction is found, with endothelial cell swelling, perivascular edema, diapadesis of erythrocytes and mononuclear cell infiltration. Hemorrhage and inflammation in the renal interstitium and tubular epithelial degeneration characterize the kidney pathology. Limited data indicate pathogenic roles for cell destruction from viral infection as well as immune mediated mechanisms. No specific therapy is available.     

Sheehan Syndrome Presenting as Central Diabetes Insipidus: A Rare Presentation of an Uncommon Disorder

ObjectiveTo add to the current scant literature on rare clinical presentations of Sheehan syndrome.MethodsWe describe the study patient’s clinical, laboratory, and imaging findings and review the literature for publications regarding varied clinical presentations of Sheehan syndrome.ResultsA 36-year-old multigravida woman developed severe postpartum hemorrhage and disseminated intravascular coagulation followed by Sheehan syndrome, with central diabetes insipidus as the primary presenting feature. This was diagnosed when, postoperatively, she developed polyuria with a urine output of 11 L in 24 hours with an accompanying rise in creatinine. She had laboratory evidence of diabetes insipidus, with serum osmolality greater than urine osmolality. Her clinical status improved significantly with intranasal desmopressin supplementation, thus confirming the diagnosis of Sheehan syndrome. Although Sheehan syndrome is a known complication of postpartum hemorrhage, central diabetes insipidus is seldom considered or suspected. Hypovolemia is usually presumed to be secondary to blood loss and polyuria resulting from a diuretic phase of acute renal failure.ConclusionsIt is important to consider posterior pituitary ischemia resulting from Sheehan syndrome presenting as central diabetes insipidus as a cause of polyuria because appropriate hormonal replacement initiated early can possibly improve clinical status and patient outcomes. (Endocr Pract. 2011;17:108-114)     

OCRL1 Modulates Cilia Length in Renal Epithelial Cells

Lowe syndrome is an X-linked disorder characterized by cataracts at birth, mental retardation and progressive renal malfunction that results from loss of function of the OCRL1 (oculocerebrorenal syndrome of Lowe) protein. OCRL1 is a lipid phosphatase that converts phosphatidylinositol 4,5-bisphosphate to phosphatidylinositol 4-phosphate. The renal pathogenesis of Lowe syndrome patients has been suggested to result from alterations in membrane trafficking, but this cannot fully explain the disease progression. We found that knockdown of OCRL1 in zebrafish caused developmental defects consistent with disruption of ciliary function, including body axis curvature, pericardial edema, hydrocephaly and impaired renal clearance. In addition, cilia in the proximal tubule of the zebrafish pronephric kidney were longer in ocrl morphant embryos. We also found that knockdown of OCRL1 in polarized renal epithelial cells caused elongation of the primary cilium and disrupted formation of cysts in three-dimensional cultures. Calcium release in response to ATP was blunted in OCRL1 knockdown cells, suggesting changes in signaling that could lead to altered cell function. Our results suggest a new role for OCRL1 in renal epithelial cell function that could contribute to the pathogenesis of Lowe syndrome.     

Lipid peroxidation--an initial event in experimental acute renal failure

A method was developed to monitor the occurrence of lipid peroxidation (LPO) during ischemia and Na-maleate-induced acute renal failure (ARF) on male rats in vivo by measuring malondialdehyde (MDA) levels in arterial and renal venous blood and in urine. No signs of LPO could be detected under control conditions. In ischemic ARF produced by 45 min of renal artery clamping a steep increase of MDA was found in the renal venous effluent immediately after starting reperfusion. This effect was nearly abolished after 5 min of blood reflow while glomerular filtration remained at 5% of control value during a 90-min postischemic observation period. Intoxication with Na-maleate leads to enhanced LPO in combination with an impaired renal function 2 h after administration. These findings would well explain cellular damage and some aspects of renal dysfunction associated with the initiation phase of ARF.     

Uterine prolapse with an interesting vascular anomaly in a cheetah: a case report

A 5-year-old cheetah suffered a complete prolapse of the left uterine horn after the birth of her second litter. Two attempts to reduce the prolapse transvaginally failed. The animal was hospitalized 13 days after the prolapse first occurred, and an ovariohysterectomy was performed to resolve the prolapse. The prolapsed uterine horn had been mutilated: its tip, together with the ipsilateral ovary was absent. Laparotomy revealed no sign of recent or past hemorrhage or adhesions, or any signs of the left ovarian artery or left ovarian vein in the remnants of the left mesovarium. A large vein crossed the uterine body from the left uterine horn to join the right uterine vein, presumably serving as the only route of venous drainage for the prolapsed uterine horn. A possible cause for the prolapse is excessive mobility of the uterus due to prior rupture of its mesial support. The animal died 24 days after surgery due to chronic renal failure, as a result of severe renal amyloidosis.     

老年患者脓毒性休克液体复苏速度与预后的关系

目的探讨老年患者脓毒性休克液体复苏过程中输液速度与预后的相关性。方法回顾性分析92例严重感染病人液体复苏效果。按液体复苏期间的输液速度分为慢速组（〈500ml/h）和快速组（≥500ml/h）,并对两组患者的心率、有创及无创血压、血氧饱和度、呼吸、中心静脉压（CVP）、每小时尿量、尿比重、血乳酸、ScVO2及有无发生肺水肿、急性心功能不全、急性肾功能不全、MODS和7天死亡率、28天死亡率及入住ICU时间、住院时间等指标进行分析比较。结果两组患者在液体复苏过程中CVP和MAP两项指标比较无统计学意义。慢速组的尿量达标时间耗时较长（P〈0.05）;ScVO2及乳酸清除率比较无明显差异。快速组对液体的需求量多,而应用血管活性药物的病例数则少于慢速组;发生肺水肿、急性心功能不全的比例高于慢速组（P〈0.05）。两组急性肾功能不全的发生率相近,但慢速组出现MODS的例数少（P〈0.05）。7天死亡率和28天死亡率比较,慢速组低于快速组,但无统计学意义。两组患者住院时间无显著统计学意义,入住ICU时间慢速组明显短于快速组（P〈0.05）。结论在脓毒性休克复苏过程中不可一味靠加快输液速度来保证组织灌注,尤其对于老年患者,更应控制单位时间内的输液量,避免给储备能力较差的心功能造成更大的负担。在保证主要脏器灌注的情况下可以适当应用血管活性药物。     

Protein concentration in the arterial and venous renal blood serum of the rabbit

In normal rabbits, under Nembutal anesthesia, the total protein and albumin content of the arterial blood serum are significantly higher than the same fractions of the renal venous blood serum. This condition is reversed in the rabbits after removal of more than 15 ml. blood/kg.Renal innervation plays a role in the regulation of the protein concentration in the renal venous blood, after hemorrhage.No significant difference of protein fractions in the arterial and renal venous blood sera has been observed in a series of rabbits with experimental renal hypertension.Parallel estimations of color intensity of previously injected Evans Blue, and of the protein fractions (by electrophoretic and turbidimetric methods) in the arterial and renal venous blood specimens of normal rabbits corroborate the possibility of a renal mechanism of albumin storage.     

Replacement therapy of acquired antithrombin III deficiency in experimental nephrotic syndrome

The influence of antithrombin III on hemostasis and renal function was studied in experiments on rats with nephrotic syndrome. The development of nephrotic syndrome was accompanied by the activation of blood coagulation and appearance of acquired antithrombin III deficiency due to its loss with the urine. The replacement therapy by bovine antithrombin III at a dose of 25 U/kg a day for 10 days decreased the signs of excessive thrombinogenesis in experimental animals and increased the amount of thrombin-antithrombin III complexes in the blood flow. The activation of coagulation in rats with nephrotic syndrome predominantly induced the disturbances of the excretory renal function which could be efficiently corrected by antithrombin III.     

Effects of short-term hypothermic perfusion and cold storage on function of the isolated-perfused dog kidney

The isolated-perfused dog kidney was used as a model to measure the effects of short-term hypothermic preservation on renal function and metabolism. Kidneys were cold-stored in Collins' solution, hypotonic citrate, or phosphate-buffered sucrose for 4 and 24 hr, or were continuously perfused for 4 and 24 hr with a synthetic perfusate. Following preservation kidneys were perfused with an albumin-containing perfusate at 37 degrees C for 60 min for determination of renal function. The results indicate that many of the effects of short-term preservation on renal function in dog kidneys are similar to results reported for rat and rabbit kidneys. Cold storage for 4 hr resulted in a large decrease in GFR (57%), but only a small decrease in Na reabsorption (from 97 to 87%). Cold storage for 24 hr caused a further decline in renal function (GFR = 95% decrease, Na reabsorption = 49-64%). Results were similar for all cold storage solutions tested. Perfusion for 4 hr was less damaging to renal function than cold storage. The GFR decreased only 14% and urine formation and Na reabsorption were practically normal. After 24 hr of hypothermic perfusion, the GFR was reduced by 79%, urine flow was normal, and Na reabsorption was 78%. There were no obvious biochemical correlates (adenine nucleotides, tissue edema, or electrolyte concentration) with the loss of renal function during short-term preservation. The results suggest that the isolated-perfused dog kidney can be used to test the effects of preservation on renal function, and yields results similar to those obtained using small animal models.(ABSTRACT TRUNCATED AT 250 WORDS)     

Differential Renal Function Study—An Aid in Preoperative Evaluation of Hypertensive Patients

Non-occlusive ureteral catheters were placed bilaterally in the renal pelves of 30 patients known to have hypertension. Samples of urine were collected under conditions of normal hydration, of urea-PAH-saline diuresis and, in some cases, mannitol diuresis. The samples were analyzed for indications of impaired flow of blood to the kidneys. Aortograms were obtained in all cases.This placement of non-occlusive catheters up into the renal pelves was felt to have caused only minimal disturbance of renal function, and was not accompanied by ureteral edema with the concomitant complications caused by occlusive catheters. Under conditions of normal hydration, leakage was insignificant.Of the 20 patients in whom urea-PAH-saline infusion revealed an ischemic pattern, 19 had an ischemic pattern under conditions of normal hydration. Since in the one exception an aortographic examination did not show a surgically reparable renal lesion, it may be inferred that the use of urea-PAH-saline diuresis is not essential in the preoperative evaluation of hypertensive renal disease.Correlation of the results of differential renal function studies and aortographic findings was possible in 19 of the 30 patients. Lack of correlation in the remaining 11 patients emphasized the importance of obtaining both types of study.Aortographic examination combined with differential renal function studies, using small ureteral catheters under conditions of normal hydration, should give the urologist a practical and yet accurate method of determining differential renal blood flow. If desired, further verification could be obtained by administering contrast medium and performing serial measurements of urine density.     

Monitoring the critically ill surgical patient.

Critically ill surgical patients account for approximately half the patients in an active multidisciplinary critical care unit. Hypovolemia and sepsis are common in such patients and affect a number of organ systems. Monitoring these systems provides therapeutically relevant information that may decrease morbidity and improve patient survival. Circulatory hemodynamics may be assessed by direct measurement of the arterial blood pressure, central venous and pulmonary artery pressure monitoring and cardiac output determination; the data thus obtained are valuable in guiding fluid replacement in the hypovolemic individual. The respiratory status may be assessed by bedside spirometry and measurement of arterial blood gas tensions to gauge pulmonary function and the need for assisted ventilation. Renal dysfunction is common in such patients; careful analysis of both urine and blood may identify prerenal as opposed to renal and postrenal factors. Monitoring of the gastrointestinal tract, especially for hemorrhage, is important. Finally, careful attention to nutritional status and provision of adequate protein and energy intake by mouth or by vein is a vital component of the optimal care of these patients.     

Partition of PGE between renal venous plasma and urine during renal ischemia

Radioimmunoassay was used to study the effects of renal ischemia on the distribution of PGE-like material between renal venous plasma and urine in anesthetized dogs. Renal venous and urinary concentrations of these substances were equal during control, ischemia and recovery periods. This relationship obtained despite significant increases in the concentration of PGE of both compartments during the ischemic insult. The renal secretion rates of PGE, calculated as the product of renal plasma flow and renal venous concentrations, was reduced during ischemia while urinary excretion, calculated as the product of urine flow and concentration, was unchanged. The evidence suggests that the increased PGE concentrations observed in both compartments during renal ischemia are primarily due to a dilutional factor rather than an increased synthesis. Furthermore, the data suggest that the net secretion of renal PG's per unit time may, in fact, be reduced during renal ischemia.     

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.     

The molecular basis of renal tubular transport disorders

Sodium and water homeostasis are key to the survival of organisms. Reabsorption of sodium and water occurs throughout the tubule structure of the nephron, the basic functional unit of the kidney, by various transport mechanisms. Altered transport protein function can lead to renal tubular disorders resulting in metabolic alkalosis, hypokalemia, hypertension, and decreased capacity to concentrate urine, for instance. However, recent advances in molecular physiology, molecular genetics and expression cloning systems have aided in unraveling the molecular basis of some renal tubular disorders. This review will examine the molecular basis of Bartter's syndrome, Gitelman's syndrome, Liddle's syndrome, and autosomal nephrogenic diabetes insipidus. An understanding of the molecular basis of these disorders of the human kidney can give us a better understanding of basic renal function of lower mammals and other vertebrates.     

Morphofunctional reorganization of the kidneys in lymphatic outflow disturbance

In 115 Wistar male rats structures and rates of tissue blood flow have been studied in the cortical and medullary renal substance histologically, polarographically (estimation of the volumetric tissue blood flow by hydrogen clearance). Systemic arterial (peritoneal aorta), venous (caudal vena cava) and lymphatic (renal lymph nodes) pressures have been measured, normal and after ligation of the thoracic duct at early (1-3 days), middle (1 month) and late (2-3 months) periods. In 1-3 days edema and dystrophy of the renal parenchyma, decrease of the blood flow rate in the cortical and its increase in the renal medullary substance, as well as a sharp elevation of pressure in the lymph nodes are observed. In 1 month of the experiment together with dystrophy and edema moderate sclerosis, decreasing blood flow rate in the cortical and medullary substance are noted. Increase of the systemic arterial and venous pressure and decreasing pressure in the lymph nodes, as well as a sharp increase of the renal nodes mass are revealed. In 2-3 months of the experiment, together with sclerosis of the renal parenchyma, elevated blood flow rate is observed in the kidneys and decreasing pressure in the lymph nodes up to its initial value takes place.     

The contribution of prostaglandins to renal blood flow maintenance is determined by the level of activity of the renin-angiotensin system

A growing body of experimental and clinical evidence has led to the formation of the hypothesis that the contribution of intrarenal prostaglandins to the determination of renal blood flow is a function of the level of activity of renin-angiotensin system. The following is a brief review of a portion of the pertinent literature. The focus of this review is the effect of inhibition of prostaglandin synthesis on renal blood flow in diverse conditions characterized by increased activity of the renin-angiotensin system, including reduction of renal arterial pressure, ureteral obstruction, hemorrhage, the hepatorenal syndrome, and sodium depletion. Under these conditions, in contrast to the lack of effect in non-stress conditions, the renin-angiotensin system activity is high, and prostaglandin synthesis inhibition is associated with reductions in renal blood flow.     

AQP-4在几种常见类型脑水肿中的表达及其作用

脑水肿是指各种原因导致的脑组织水含量增多,可导致脑容积增大、颅内压增高,脑水肿发病机制复杂,是多种颅脑疾病如脑静脉血栓形成、脑缺血、脑出血、脑组织创伤等的主要病理生理改变之一,其形成严重影响疾病预后,是颅脑疾病中致残、致死的主要原因。水通道蛋白(Aquaporin,缩写为AQP)是一个具有高度选择性通透水的膜通道蛋白家族,包括200多个家族成员,其蛋白质分子结构中有一狭窄的亲水性孔道,通过该孔道水分子从水位势能高的一侧迅速扩散到势能低的一侧,而其它的物质则不能通过;AQP-4是脑内含量最多的水通道蛋白,最近研究表明AQP-4参与多种颅脑疾病的脑水肿的形成及消退。本文就AQP-4在几种常见类型脑水肿中的表达及作用进行综述。     

Postinfectious glomerulonephritis and Epstein-barr virus co-infection

Contrary to group A beta-hemolytic streptococcus as the most common cause of postinfectious glomerulonephritis (PIGN), Epstein-Barr virus (EBV) is only occasionally associated with acute renal involvement. We describe an 11-year-old boy who presented with clinical signs of infective mononucleosis and acute glomerulonephritis characterized by edema, hypertension and dark colored urine with diminished renal function. Serology tests confirmed streptococcal infection and acute EBV infection. Persistently depressed C3 complement and gross hematuria indicated renal biopsy which shows PIGN-type picture and, in addition, acute interstitial nephritis, both conclusive of streptococcal infection. We performed tissue DNA extraction by polymerase chain reaction (PCR) and demonstrated EBV-DNA from the kidney specimen supporting EBV involvement in renal tissue. This is the first reported case of PIGN with serologically-proven streptococcal and simultaneously, acute EBV co-infection. EBV-DNA extraction supported the EBV involvement in renal tissue suggesting that both etiologic agents might have contributed to renal inflammation. Adding serology evaluation for EBV in cases with typical clinical signs of infective mononucleosis and renal symptoms, EBV might be more commonly associated with PIGN than is currently appreciated.