Early acute rejection of renal homografts: a characteristic clinical syndrome

Seven of 74 patients with early functioning cadaveric renal homografts developed acute oliguric renal failure after the second but before the ninth day post-transplantation. The syndrome characteristically begins with an abrupt and simultaneous decrease in creatinine clearance, urine volume and urine sodium concentration. After a variable period and despite a reduction in immunosuppressive therapy, a diuretic phase ensues and renal function is restored. Complications associated with the syndrome include groin hematoma, pulmonary edema and renal rupture with shock. Renal rupture does not require nephrectomy: if the hemorrhage is controlled, the transplanted organ will resume function. Angiographic studies show normal nephrograms, stretched arterial vasculature and filling defects in the veins. Percutaneous renal biopsy shows interstitial edema and hemorrhage, venous congestion and tubular necrosis. Evidence is presented to support the hypothesis that this is a form of rejection occurring as the result of injury to the renal venous system.     

Effect of diuretic use on 30-day postdialysis mortality in critically ill patients receiving acute dialysis

Background

The impact of diuretic usage and dosage on the mortality of critically ill patients with acute kidney injury is still unclear.

Methods and Results

In this prospective, multicenter, observational study, 572 patients with postsurgical acute kidney injury receiving hemodialysis were recruited and followed daily. Thirty-day postdialysis mortality was analyzed using Cox''s proportional hazards model with time-dependent covariates. The mean age of the 572 patients was 60.8±16.6 years. Patients with lower serum creatinine (p = 0.031) and blood lactate (p = 0.033) at ICU admission, lower predialysis urine output (p = 0.001) and PaO₂/FiO₂ (p = 0.039), as well as diabetes (p = 0.037) and heart failure (p = 0.049) were more likely to receive diuretics. A total of 280 (49.0%) patients died within 30 days after acute dialysis initiation. The analysis of 30-day postdialysis mortality by fitting propensity score-adjusted Cox''s proportional hazards models with time-dependent covariates showed that higher 3-day accumulated diuretic doses after dialysis initiation (HR = 1.449, p = 0.021) could increase the hazard rate of death. Moreover, higher time-varying 3-day accumulative diuretic doses were associated with hypotension (p<0.001) and less intense hemodialysis (p<0.001) during the acute dialysis period.

Background and Significance

Higher time-varying 3-day accumulative diuretic dose predicts mortality in postsurgical critically ill patients requiring acute dialysis. Higher diuretic doses are associated with hypotension and a lower intensity of dialysis. Caution should be employed before loop diuretics are administered to postsurgical patients during the acute dialysis period.     

Body Water and Electrolyte Composition in Acute Renal Failure

Body water and electrolyte contents have been measured by means of muscle biopsy analysis in 11 patients with untreated acute renal failure and in one patient during the diuretic recovery phase of his illness. Patients with acute oliguric renal failure show two main types of imbalance. One group shows evidence of a reduction in extracellular sodium and chloride with normal intracellular water and electrolytes. These findings are thought to be due to a combination of excess urinary salt loss during the development of oliguric renal failure, and inadequate replacement of extrarenal electrolyte losses. A second group shows overhydration of both extra- and intracellular phases, associated with an excess of sodium and chloride. The intracellular potassium concentration is reduced, owing to the intracellular water excess. The patient studied during the diuretic recovery phase of acute renal failure showed a marked loss of sodium and chloride, which emphasizes the necessity to replace urinary electrolyte losses at this stage of the illness. It is often extremely difficult to assess fluid and electrolyte balance in patients presenting with acute renal failure, and muscle biopsy analysis or isotope dilution studies may be required before accurate replacement therapy is possible.     

Diuretic treatment of resistant hypertension.

In patients with hypertension resistant to three or four drugs including a thiazide diuretic substitution of frusemide for the thiazide, or the addition of spironolactone, produced significant reductions in blood pressure and body weight. The response did not depend on the presence of overt fluid retention, renal impairment, or the use of antihypertensive drugs of high potency. Women had larger responses than men. Expansion of the plasma or extracellular fluid volume is an important cause of resistance to treatment even when a thiazide diuretic is used. An increase in diuretic treatment should be tried before using the postganglionic adrenergic blockers or minoxidil in resistant hypertension.     

Renal Failure in Cirrhosis of the Liver

The clinical course and autopsy findings of three patients with acute renal failure terminating the course of cirrhosis of the liver are presented. Review of the literature demonstrated that where decompensated cirrhosis is present the renal blood flow is characteristically low, although the total cardiac output is elevated. This circulatory disturbance results in the production of urine low in sodium, although normal in solute content. It also renders the kidney more vulnerable to further, sometimes minor, reductions in renal blood flow. As more patients with hepatic cirrhosis live through episodes of gastrointestinal bleeding and hepatic coma, death in acute renal failure will undoubtedly become more common.     

蝮蛇咬伤10885例救治分析

目的：探讨提高蝮蛇咬伤的救治水平。方法,回性总结我院１９７２－１９９９年蝮蛇咬伤患者１０８８５年,采用抗蝮蛇毒血清结合中药蛇伤合剂治疗;对合并急性呼吸衰竭的８５例患者,早期气管切开保持气管畅通,同时正压人工呼吸;对合并急性肾功能衰竭的１０３例患者,早期碱化尿液,应用足量利尿剂,必须时进行腹膜透析;对合并急性心功能衰竭的４３例患者,在应用强心、利尿、扩血管药物的同时,早期静脉给予山莨菪碱（６５４－２     

Experiences with High Doses of Furosemide in Renal Disease and Resistant Edematous States

Six cases of edema, three due to the nephrotic syndrome, one to congestive heart failure and two to chronic renal failure, are reported in which furosemide was administered in oral doses higher than those usually prescribed (up to 720 mg. a day), in order to obtain a satisfactory diuresis. In one case of severe prerenal failure secondary to cardiogenic shock and in one case of acute tubular necrosis secondary to hypotension at the time of operation, intravenous doses up to 990 and 1400 mg. per day respectively were able to reverse the oliguria. In eight additional patients who were on chronic hemodialysis, furosemide was administered to the amount of 1000 mg. per day orally in divided doses for two weeks, and produced a moderate diuretic response.The use of high doses of furosemide in edema and renal failure resistant to the usual therapeutic measures appears to be safe and effective.     

Acute and chronic influence of hemodialysis according to the membrane used on phagocytic function of neutrophils and monocytes and pro-inflammatory cytokines production in chronic renal failure patients

This work evaluated the phagocytic capacity of monocytes and neutrophils, and tumor necrosis factor-alpha, interleukin 6, 1 and 8 serum levels in chronic renal failure patients under peritoneal dialysis and hemodialysis treatment, compared with chronic renal failure patients without dialysis treatment and healthy individuals, in order to contribute to a better understanding of the action of these therapies on the evolution of chronic renal failure patients. All patients with chronic renal failure (under dialysis or not) showed decreased phagocytic capacity of neutrophils and monocytes. All those in hemodialysis (cellulose acetate or polysulfone membranes) showed a decreased phagocytic capacity. The phagocytic index for neutrophil was 13 times lower than that of the control group for both membranes, whereas for monocytes, only those using polysulfone membrane showed a significant decrease of 4.9 times in phagocytic capacity. There was an acute stimulation of the phagocytosis by neutrophils after a single session of dialysis with both types of membrane, while only cellulose acetate membrane decreased the phagocytic index of monocytes after the hemodialysis session. Patients using cellulose acetate showed a chronic increase in tumor necrosis factor-alpha serum levels, while those using polysulfone showed a chronic increase in interleukin 6. After a single hemodialysis procedure, no acute effect of the treatment on tumor necrosis factor-alpha and interleukin 6 levels was identified. The decreased phagocytic function of neutrophils and monocytes may account for the high levels of susceptibility of chronic renal failure patients to infections with pyogenic bacteria and tuberculosis. Furthermore, inflammatory activity may occur with both types of membrane studied, suggesting that it will be useful for these patients to evaluate some anti-inflammatory or anti-cytokine therapies against tumor necrosis factor-alpha and interleukin 6, in order to avoid cardiovascular complication.     

Peritoneal Dialysis in Chronic Renal Failure

The long-term results of intermittent peritoneal dialysis in long-term treatment of renal disease have yet to equal those of intermittent hemodialysis. However, further exploration and refinement of this technique is justified.Performed in acute stages of disease, both peritoneal dialysis and hemodialysis relieve the symptoms of uremia and specifically “buy time” for the patient so that proper medical or surgical therapy may be instituted. In acute situations, peritoneal dialysis is the procedure of choice, and is an important adjunct to more conventional treatment for chronic renal disease. It may be useful sometimes even in chronically hemodialyzed patients—for example, when the hemodialysis cannula for one reason or another is inaccessible because of clots, replacement, or infection. It is especially valuable when the hemorrhagic complications of uremia contraindicate hemodialysis treatment.Its use in chronic uremia remains sharply limited in time, but for brief periods chronic peritoneal dialysis appears to be a reasonably satisfactory means of prolonging life while awaiting homotransplant or decision for maintenance hemodialysis therapy.     

体外循环中急性肺水肿分析

目的：强调重视和加强体外循环中对肺功能的保护。方法：分析16例在体外循环中发生肺水肿患者术前的肺动脉高压,血红蛋白,肾功能和心功能情况,经PEEP＋利尿药＋激素和超滤器为主,辅以强心,扩血管药的协同治疗。结果：所有患者经治疗后气道阻力下降,均减小至术前水平,无酸中毒,尿量＞100ml/min。平均2．5天拔管停呼吸机,11例患者术后第一天均顺利脱离呼吸机。15例患者出院,1例死于MOF。结论：中度肺动脉高压、贫血和心肾功能功能不全可能是体外循环中急性肺水肿的诱发因素,体外循环时应采取措施预防预防和减轻肺功能损伤。     

Clinical Experience with an Oral Diuretic,Trichlormethiazide

The main objective of this study was to observe the long-term effects of the administration of trichlormethiazide on the urine and blood. Fourteen patients suffering from essential hypertension or edema requiring diuretic therapy were treated for periods of one to 12 months (mean 5.4 months). There were no significant changes in urine values, blood counts, or serum sodium or potassium levels. Additional nitrogen retention occurred in two patients with renal failure, but no significant changes in blood urea nitrogen occurred in the remainder. Serum uric acid levels were lower at the end of treatment than before. The blood pressure fell in nine patients. No toxic effects were observed.     

A Clinical Evaluation of Peritoneal Dialysis

A total of 18 peritoneal dialyses were performed on 14 patients at the Hamilton Civic Hospital over a period of 11 months. Nine of these patients were in uremia, four had non-nephrotoxic intoxication, and one had hepatic coma. Patients with chronic uremia may present with acute renal failure which may be treated by peritoneal dialysis with resultant significant prolongation of life. A decreased mortality rate might be expected in acute renal failure if dialysis is implemented before the classical picture of uremia develops. Many non-nephrotoxic intoxicating substances are readily dialysable. Considerable benefit to the patient and decreased time in hospital may result from the use of this procedure in cases of intoxication with such substances. Peritoneal dialysis may be of value in treatment of intractable congestive heart failure. This procedure may eventually provide another means of treating hepatic coma.     

低剂量多巴胺对急性心衰合并肾功能不全患者的影响

目的:探讨低剂量多巴胺能否通过利尿作用改善急性左心衰患者的充血症状以及肾功能。方法:将2013年9月至2013年12月我院收治的80例急性心衰合并肾功能不全的患者随机分为对照组和治疗组,每组各40例。对照组给予常规治疗,治疗组在常规治疗的基础上加用小剂量多巴胺静脉泵入48小时。观察和比较两组患者48小时内的总尿量及血清胱抑素C的变化、充血症状、肾功能及临床疗效的差异。结果:与对照组相比,治疗组48小时总尿量、血清胱抑素C的变化、体重变化、BNP变化、肌酐变化、进展性心衰发生率、死亡率、治疗失败患者比例均无明显差异(P0.05)。结论:低剂量多巴胺不能在利尿治疗基础上减轻急性心力衰竭并发肾功能不全患者的充血症状或改善肾功能。     

Urinary excretion of furosemide in rats with HgCl2-induced acute renal damage.

To examine the influence of mercuric chloride (HgCl2)-induced acute renal damage on urinary excretion of furosemide, HgCl2 (1 mg/kg) or its vehicle alone was given intraperitoneally to Wistar rats. The following two experiments were done. Study I: Three percent body weight (b.w.) of 1% NaCl solution or furosemide (30 mg/kg) in 3% b.w. of 1% NaCl solution was given orally before and after HgCl2 treatment, and an 8-hour urine was collected. Study II: Furosemide (30 mg/kg) was given orally, and blood samples were obtained at 1, 2, 3, 4, 6 and 8 hours after administration. Urinary excretion of N-acetyl-beta-D-glucosaminidase increased, and urine volume and urinary excretions of furosemide and sodium decreased in the HgCl2-treated rats. There were significant correlations between the urinary furosemide and its diuretic effects. Regression lines after HgCl2 were significantly different from those before treatment. The values of absorption as well as elimination rate constant were smaller, while the time to maximum concentration and the elimination half-life were longer in the HgCl2-treated rats compared to vehicle-treated animals. These results suggest that the urinary excretion of furosemide and the responsiveness of renal tubular cells to this agent are impaired in rats with HgCl2-induced acute renal damage.     

Cytometric bead array (CBA) for the measurement of cytokines in urine and plasma of patients undergoing renal rejection

Renal rejection is associated with an active immune response regulated by cytokines and in which immunocompetent cells are involved. Previous studies have measured high levels of cytokines in the urine and plasma in various renal dysfunction states. However, some methods used to measured cytokines hinder their use as a diagnostic tool in renal rejection. In this report, cytokine levels were determined in the plasma and urine of kidney transplant patients, with renal rejection and without it, using a cytometric bead array (CBA) technique. Concentrations of six human cytokines (IL-2, IL-4, IL-5, IL-10, TNF-alpha and INF-gamma) were established. Results show that patients who develop renal rejection presented high levels of IL-10 and IFN-gamma cytokines in plasma and urine compared to patients without renal rejection. The CBA technique displayed greater sensitivity in the determination of cytokines in urine than the conventional ELISA technique. Finally, when standard cytokines in plasma and in urine were compared, it was observed that, in plasma, levels of IL-4, IL-5, IL-10, TNF-alpha and IFN-gamma were detected, whereas in urine the levels detected were of IL-4, IL-5, IL-10 and IFN-gamma. These results indicate that the CBA assay is a sensitive method to measure cytokines in urine. In kidney transplant patients undergoing acute renal rejection, the presence of cytokines in urine reflects renal damage and could be a useful method in the diagnosis of renal rejection.     

The "valve" of the ductus arteriosus--an enigma.

The urine/plasma creatinine ratio (U/P Cr), the urine sodium concentration (UNa), and the diuretic response to mannitol infusion in 23 patients were reviewed in an attempt to differentiate functional renal failure (FRF) from acute tubular necrosis (ATN). FRF was diagnosed if the plasma urea nitrogen (PUN) or serum creatinine stabilized within 72 hours. When renal failure persisted longer, patients had ATN. Subjects dying within 72 hours were excluded. Ten patients had ATN and five survived. The minimum duration of renal failure among survivors was 10 days. None responded to mannitol. Of 13 patients with FRF, 11 survived. Seven of 12 who received mannitol responded with a diuresis. The mean UNa in the patients with ATN was 51.4 mEq./1. ± 9.48 (SE). The mean U/P Cr was 11.2 ± 1.12. In patients with FRF, the mean UNa was 14.0 mEq./1. ± 4.2 and the mean U/P Cr was 42.5 ± 11.5. A significant overlap was present between the two groups. When UNa was factored by the U/P Cr, the resultant ratio was significantly different for the two groups of patients (P < 0.01), and this proved to be a useful clinical index with which to distinguish FRF from established ATN.     

Role of the paraventricular nucleus in renal excretory responses to acute volume expansion: role of nitric oxide

Acute volume expansion (VE) produces a suppression of renal sympathetic nerve discharge (RSND) resulting in diuresis and natriuresis. Recently, we have demonstrated that the endogenous nitric oxide (NO) system within the paraventricular nucleus (PVN) produces a decrease in RSND. We hypothesized that endogenous NO in the PVN is involved in the suppression of RSND leading to diuretic and natriuretic responses to acute VE. To test this hypothesis, we first measured the VE-induced increase in renal sodium excretion and urine flow with and without blockade of NO, with microinjection of NG-monomethyl-L-arginine (L-NMMA; 200 pmol in 200 nl), within the PVN of Inactin-anesthetized male Sprague-Dawley rats. Acute VE produced significant increases in urine flow and sodium excretion, which were diminished in rats treated with L-NMMA within the PVN. This effect of NO blockade within the PVN on VE-induced diuresis and natriuresis was abolished by renal denervation. Consistent with these data, acute VE induced a decrease in RSND (52% of the baseline level), which was significantly blunted by prior administration of L-NMMA into the PVN (28% of the baseline level) induced by a comparable level of acute VE. Using the push-pull perfusion technique, we found that acute VE induced a significant increase in NOx concentration in the perfusate from the PVN region. Taken together, these results suggest that acute VE induces an increase in NO production within the PVN that leads to renal sympathoinhibition, resulting in diuresis and natriuresis. We conclude that NO within the PVN plays an important role in regulation of sodium and water excretions in the volume reflex via modulating renal sympathetic outflow.     

Renal interstitial hydrostatic pressure and sodium excretion during acute volume expansion in diabetic rats

Experiments were performed to test the hypothesis that the renal interstitial hydrostatic pressure (RIHP) response to acute volume expansion is suppressed in diabetes mellitus. Sprague-Dawley rats received streptozotocin (STZ rats; 65 mg/kg ip) or vehicle (Sham rats). Two weeks later, RIHP and Na(+) excretion responses to acute graded volume expansion with isotonic saline were quantified under Inactin anesthesia (0.1 mg/kg ip). In Sham rats, acute graded volume expansion to 10% body wt produced increases in RIHP (Delta = 12.2 +/- 2.4 mmHg), urine flow (Delta = 54 +/- 8 microliter. min(-1). g(-1)), and Na(+) excretion (Delta = 11.5 +/- 1.9 mueq. min(-1). g(-1)). In STZ rats, these volume expansion-induced responses were significantly blunted (RIHP by 50%, urine flow by 81%, and Na(+) excretion by 76%). Renal decapsulation eliminated the differences between STZ and Sham rats with regard to volume expansion-induced increases in RIHP, urine flow, and Na(+) excretion. Renal denervation normalized the RIHP response to volume expansion and improved the diuretic and natriuretic responses in STZ rats. Moreover, diuretic and natriuretic responses to direct changes in RIHP (induced by renal interstitial volume expansion) were blunted in STZ rats. We conclude that diminished alterations in RIHP, as well as a reduced impact of RIHP on Na(+) excretion, contribute to the impaired diuretic and natriuretic responses to acute volume expansion during the early stage of diabetes.     

The Kolff-Merrill artificial kidney; clinical application in acute renal insufficiency

Acute renal insufficiency is often called "lower nephron nephrosis." Its recognition, its prognostic significance, and its therapy by conservative measures are receiving increasing clinical emphasis. The mortality rate in this complicated syndrome still remains unduly high. One method of therapy of anuric patients whose lives are in jeopardy because of fulminating uremia or critical potassium intoxication is use of an artificial kidney to "purify" the blood stream by means of extracorporeal dialysis.The author describes clinical (and laboratory) experience with ten such dialyzed patients, eight of whom presented the classical picture of acute renal insufficiency. Four died, one from unrecognized coronary occlusion, another from antecedent, overwhelming peritonitis. Two other patients with chronic kidney disorders received no benefit from dialysis and died of renal disease. Good biochemical and clinical response was brought about in six cases of lower nephron nephrosis. Presumably, these six patients would have died had they not been subjected to artificial dialysis.