Evidence Of Acute Tubular Necrosis Research Articles

Тип сосудистого анастомоза и ближайшие результаты трансплантации почки

There are usually two main techniques of vessel anastomosis called as; end-to-end or end-to-side. The aim of this study was to investigate surgical vascular anastomotic and its correlation with early outcome after kidney transplantation. Data including gender, age, hospital stay, living or deceased donor, evidence of acute tubular necrosis, preference of artery or vein in addition to biochemical variables were noted analysed by SPSS. The study population was comprised of 84 females and 176 males (174 living versus 86 deceased donor). Surgical vascular anastomic techniques were based on; first artery second vein (FASV; n=209) or first vein second artery (FVSA; n=51). Vascular anastomic were performed as follow; group 1 (FASV with end-to-end; n= 52%), group 2 (FASV with end-to-side; n=29%), group 3 (FVSA with end-to-end; n=15%) and group 4 (FVSA with end-to-side; n= 5%). Comparison of groups showed that; deceased/living donor (group 1 versus group 3; p=0.02), ATN (group 1 versus group 2; p=0.002, group 1 versus group 4; p=0.03). Despite the higher use of deceased donors, those with vascular anastomic technique based on FASV (end-to-end) revealed a lower rate of ATN when compared to other techniques. Further studies in this direction recommended.

Role of Blood Oxygen Level-dependent MRI in Differentiation of Acute Renal Allograft Dysfunction.

Early graft dysfunction after renal transplantation manifests as acute rejection (AR) or acute tubular necrosis (ATN). Blood oxygen level-dependent (BOLD) magnetic resonance (MR) imaging is a noninvasive method of assessing tissue oxygenation, which may be useful for predicting acute allograft dysfunction. This was a prospective study involving 40 patients scheduled for renal transplantation from August 2012 to August 2014. In addition, 15 healthy donors were also enrolled in this study. All recipients underwent BOLD MR imaging (MRI) and R2* mapping 10–20 days after transplant, and additionally within 48 h of biopsy if there was any evidence of graft dysfunction. The healthy donors underwent BOLD MRI 1–2 days before surgery. The biopsies were grouped into AR, ATN, and no evidence of AR or ATN. The mean medullary R2*, cortical R2*, corticomedullary gradient, and medullary: cortical R2* ratio were compared between groups using one-way analysis of variance. Spearman's correlation and multinomial linear regression were applied to determine the influence factors of R2* value. Overall, nine patients had graft dysfunction. Six were reported as AR, two as ATN, and one as no evidence of ATN or rejection. The mean medullary and cortical R2* were significantly higher in ATN group compared with AR and normal group, whereas the mean medullary and cortical R2* of AR group were significantly lower than normal group. The corticomedullary gradient of AR group was significantly lower compared with ATN and normal group. Medullary R2*:cortical R2* ratio was significantly lower in AR group compared with normal group. No significant difference was noted between the 15 donors and patients with normal graft function. R2* values on BOLD MRI are significantly decreased in AR allografts and increased in an early stage of ATN allografts, suggesting that BOLD MRI can become a valuable tool for discriminating between AR and ATN.

Secondary Sclerosing Cholangitis in the Setting of Elective Bariatric Surgery

Secondary sclerosing cholangitis (SSC) is a rare, chronic, progressive condition of biliary tree fibrosis after an insult. It is a rare cause of preventable liver cirrhosis. Of 31 reported cases in the past decades most presented after surgical trauma, other causes include chronic cholestatis, cholangitis or ischemia.1 A 45-year-old female with a history of idiopathic pulmonary fibrosis presented with prolonged hyperbilirubinemia after gastric sleeve bypass, cholecystectomy, and hiatal hernia repair three months prior to admission. She presented with jaundice and elevated total bilirubin, direct bilirubin and alkaline phosphatase at 3.6 mg/dL, 3.0 mg/dL, and 217 U/L, respectively. MRCP revealed a stricture near the level of the cystic duct. ERCP showed a focal stricture at the distal common hepatic duct (CHD) requiring stent (Image 1). Due to worsened hyperbilirubinemia, a repeat ERCP was completed which revealed a highgrade stricture at the CHD that required dilation and another stent. Liver biopsy was also performed and showed canalicular cholestatis without intra-hepatic granulomas or ductal lesions, suggesting extrahepatic ductal obstruction (Image 2). She then underwent hepaticojejunostomy with surgical pathology of the common bile duct revealing a post-cholecystectomy traumatic neuroma. She was discharged after HIDA scan revealed no evidence of biliary leak, but returned to clinic 14 days later with progressive jaundice, new ascites, bilateral lower extremity edema, and acute kidney injury (AKI) with elevated creatinine of 1.76 mg/dL (baseline 0.4 mg/dL). A third liver biopsy was performed which showed findings consistent with portal edema, mixed inflammation, cholestasis and fibrosis (Image 3). Her bilirubin slowly improved without further intervention, but remained elevated at 14.2 mg/dL and she ultimately required dialysis. This patient was diagnosed with SSC in the setting of biliary tract fibrosis subsequent to traumatic injury of the biliary tract after cholecystectomy. Our presentation is unique as SSC was complicated by hemodialysis dependent renal dysfunction with microscopic evidence of acute tubular necrosis. This case is consistent with the common cause, histological characteristics and chronic nature of SSC. Future research is required to elucidate other organ complications that management of this disease may be optimized. 1- Ruemmele et. al. Secondary sclerosing cholangitis. Nat. Rev. Gastroenterol. Hepatol. 6, 287-295 (2009).Figure: ERCP showing common hepatic duct stricture.Figure: Cholestasis and edema.Figure: Portal tract with edema and fibrosis.

047 COMBINATION OF TENOFOVIR/EMTRICITABINE WITH PROTEASE INHIBITOR - BASED REGIMEN INDUCED ACUTE KIDNEY INJURY REQUIRING HAEMODIALYSIS: A CASE REPORT

Category: Other Presenter: Dr CHUI MUNN ANG Keywords: Human Immunodeficiency Virus, Tenofovir, Protease Inhibitor, Acute Kidney Injury 51 years old with Human Immunodeficiency Virus and Hepatitis C; non compliant to medication, was switched to Tenofovir/Emtricitabine (TDF/FTC) and Lopinavir/ Ritonavir (LPV/r). Renal profile (RP) was normal and urine FEME showed protein 2+ with viral load of 311 748 copies/ml and CD 4 count of 55 cell/ul prior to initiation of therapy. He presented with uraemia after 4 months; normotensive, afebrile with no evidence of fluid overload or infection. Blood parameters showed acute kidney injury with severe metabolic acidosis (ph 7.052, HCO3 9.6mmol/L, urea 48.7mmol/L, creatinine 1771umol/L); Urine showed microscopic haematuria, proteinuria and glycosuria. Ultrasound showed no evidence of obstruction. TDF/FTC and LPV/r were withheld. Regular hemodialysis was only required for 1 month. RP after 3 months showed urea 5.8mmol/L, creatinine 209 umol/L. Renal biopsy showed 33% of focal global glomerulosclerosis with moderate chronic tubulointerstitial damage and acute tubular necrosis. TDF is eliminated by a combination of glomerular filtration and proximal tubular secretion with 20 - 30% of the drug actively transported into renal proximal tubule cells by anion transporters; hence drug interaction of LPV/r with these transporters favours intracellular accumulation and increases risk of renal toxicity (AUC of TDF increased by 32%). The proximal tubular cells injury leads to failure of reabsorption of low molecular weight proteins, glucose, amino acids, phosphate and uric acid; as well as failure of H+ secretion which reflects on the proteinuria, glycosuria, acute kidney injury with renal tubular acidosis requiring renal replacement; supported by evidence of acute tubular necrosis with interstitium occasionally infiltrated by eosinophils from renal biopsy which suggest a case of drug induced nephropathy likely TDF. The combination of TDF/FTC with LPV/r is associated with greater declines in renal function hence patient should be closely monitored to look for any early signs of renal impairment.

Anti-LG3 Antibodies Aggravate Renal Ischemia-Reperfusion Injury and Long-Term Renal Allograft Dysfunction.

Pretransplant autoantibodies to LG3 and angiotensin II type 1 receptors (AT1R) are associated with acute rejection in kidney transplant recipients, whereas antivimentin autoantibodies participate in heart transplant rejection. Ischemia-reperfusion injury (IRI) can modify self-antigenic targets. We hypothesized that ischemia-reperfusion creates permissive conditions for autoantibodies to interact with their antigenic targets and leads to enhanced renal damage and dysfunction. In 172 kidney transplant recipients, we found that pretransplant anti-LG3 antibodies were associated with an increased risk of delayed graft function (DGF). Pretransplant anti-LG3 antibodies are inversely associated with graft function at 1 year after transplantation in patients who experienced DGF, independent of rejection. Pretransplant anti-AT1R and antivimentin were not associated with DGF or its functional outcome. In a model of renal IRI in mice, passive transfer of anti-LG3 IgG led to enhanced dysfunction and microvascular injury compared with passive transfer with control IgG. Passive transfer of anti-LG3 antibodies also favored intrarenal microvascular complement activation, microvascular rarefaction and fibrosis after IRI. Our results suggest that anti-LG3 antibodies are novel aggravating factors for renal IRI. These results provide novel insights into the pathways that modulate the severity of renal injury at the time of transplantation and their impact on long-term outcomes.

Lesão Renal Aguda e Rabdomiólise como Apresentação da Doença de Mcardle

McArdle disease typically presents in childhood or young adults with myalgia, exercise intolerance, cramps and myoglobinuria. Deficiency of myophosphorylase enzyme results in inability to degrade glycogen stores, causing glycogen accumulation in muscle tissue and energy deficit. Evolution with rhabdomiolysis may occur and can be complicated with acute kidney injury but rarely, in about 11% of cases, is the initial disease manifestation. We report a case of McArdle Disease in a 38-year-old male patient. The disease went unrecognized despite previous symptoms (myalgia, exercise intolerance and single myoglobinuria episode) until an episode of rhabdomyolisis complicated with oliguric acute kidney injury requiring hemodialysis. The kidney biopsy showed evidence of acute tubular necrosis. Despite normalization of renal function, muscle lysis markers remained abnormal. Metabolic myopathy was suspected and a muscle biopsy was performed. It showed subsarcolemic glycogen deposition and absence of myophosphorylase activity. This case-report underlines the importance of considering metabolic myopathy in patients with acute kidney injury and severe rhabdomyolisis.

Cell cycle arrest in a model of colistin nephrotoxicity

Colistin (polymixin E) is an antibiotic prescribed with resurging frequency for multidrug resistant gram negative bacterial infections. It is associated with nephrotoxicity in humans in up to 55% of cases. Little is known regarding genes involved in colistin nephrotoxicity. A murine model of colistin-mediated kidney injury was developed. C57/BL6 mice were administered saline or colistin at a dose of 16 mg/kg/day in 2 divided intraperitoneal doses and killed after either 3 or 15 days of colistin. After 15 days, mice exposed to colistin had elevated blood urea nitrogen (BUN), creatinine, and pathologic evidence of acute tubular necrosis and apoptosis. After 3 days, mice had neither BUN elevation nor substantial pathologic injury; however, urinary neutrophil gelatinase-associated lipocalin was elevated (P = 0.017). An Illumina gene expression array was performed on kidney RNA harvested 72 h after first colistin dose to identify differentially expressed genes early in drug treatment. Array data revealed 21 differentially expressed genes (false discovery rate < 0.1) between control and colistin-exposed mice, including LGALS3 and CCNB1. The gene signature was significantly enriched for genes involved in cell cycle proliferation. RT-PCR, immunoblot, and immunostaining validated the relevance of key genes and proteins. This murine model offers insights into the potential mechanism of colistin-mediated nephrotoxicity. Further studies will determine whether the identified genes play a causative or protective role in colistin-induced nephrotoxicity.

Effect of Milrinone on Ischemia-Reperfusion Injury in the Rat Kidney

Background Milrinone (MIL), a phosphodiesterase (PDE) 3 inhibitor, exhibits cardiotonic and angioectatic effects. Various PDE inhibitors have been shown to suppress inflammatory cytokines. In this study, we evaluated the angioectatic and anti-inflammatory cytokine effects of MIL on renal function after warm ischemia in a rat ischemia-reperfusion (I-R) injury model. Materials and methods MIL or control solution was perfused from the left renal artery to the right kidney, and the left kidney was excised. The right renal artery, vein, and ureter were clamped and then released after 50 minutes to produce warm ischemia. We evaluated control ( n = 7), MIL ( n = 7), and sham operation ( n = 7) groups for serum creatinine, blood urea nitrogen (BUN), blood flow, expression of tumor necrosis factor (TNF)-α mRNA, apoptosis index, and histological evidence of acute tubular necrosis. Results Serum creatinine and BUN concentrations peaked at 24 hours after reperfusion. MIL treatment significantly reduced serum creatinine (control group 1.27 ± 0.45 mg/dL vs MIL group 0.77 ± 0.19 mg/dL, P < .05; sham 0.35 ± 0.2 mg/dL) and BUN (control 67.6 ± 13.6 mg/dL vs MIL 51.0 ± 8.8 mg/dL, P < .05; sham 23.0 ± 4.2 mg/dL) levels at 24 hours. Thereafter, serum creatinine and BUN concentrations in the MIL group remained significantly lower compared with the control group for 120 hours ( P < .05). MIL group exhibited significantly higher tissue blood flow, less acute tubular necrosis, lower expression of TNF-α mRNA in renal tissue, and lower apoptotic index ( P < .05). Conclusions MIL maintained renal tissue blood flow by its vasodilatory effect, suppressed expression of TNF-α mRNA by increasing intracellular cyclic adenosine monophosphate, and ultimately decreased tubular cell apoptosis, thus protecting renal function after warm I-R injury.

Prevention of post-cardiopulmonary bypass acute kidney injury by endothelin A receptor blockade*

The aim of this study was to determine whether administration of a specific endothelin A receptor antagonist, sitaxsentan sodium, would prevent the development of post-cardiopulmonary bypass acute kidney injury in swine. Experimental study. Cardiovascular Research Institute. Adult pigs (n = 8 per group) were randomized to undergo a sham procedure, cardiopulmonary bypass, or cardiopulmonary bypass plus administration of endothelin A receptor antagonist (RA), with recovery and reassessment at 24 hrs. Cardiopulmonary bypass resulted in a significant reduction in creatinine clearance relative to sham pigs (mean difference for cardiopulmonary bypass vs. sham, -50.3 mL/min [95% confidence interval -89.2 to -11.4 mL/min], p = .008). This was reversed by the administration of endothelin A RA during cardiopulmonary bypass (mean difference for cardiopulmonary bypass + endothelin A RA vs. cardiopulmonary bypass, +43.3 mL/min [95% confidence interval +3.3 to +83.4 mL/min], p = .030). Cardiopulmonary bypass also resulted in a significant rise in the specific urinary biomarker of acute kidney injury interleukin-18 compared to sham procedures (mean difference +209 pg/mL [95% confidence interval +119 to +299 pg/mL], p < .001) that was reversed by endothelin A receptor antagonist administration. Post-cardiopulmonary bypass kidney injury was associated with vascular endothelial injury and dysfunction, reduced nitric oxide bioavailability, inflammation, and a significant increase in the expression of the paracrine vasoconstrictors adenosine and endothelin-1. In post-cardiopulmonary bypass kidneys at 24 hrs there was persistent hypoxia at the level of the outer medulla, cortical adenosine triphosphate depletion, and evidence of proximal tubule epithelial cell stress manifest as phenotypic change. There was no evidence of acute tubular necrosis. Administration of endothelin A RA to cardiopulmonary bypass pigs reversed endothelial dysfunction, regional hypoxia, inflammation, and tubular changes. In this model, post-cardiopulmonary bypass acute kidney injury is associated with endothelial dysfunction, regional tissue hypoxia, and proximal tubular epithelial cell stress but not acute tubular necrosis. Antagonism of the endothelin-1 A receptor reversed these changes and may represent a therapeutic target for the prevention of post-cardiac surgery acute kidney injury.

Pulmonary and systemic toxicity following exposure to nickel nanoparticles

Nanoparticles are being used in ever increasing numbers in a range of industrial and medical products. Questions surrounding their potential to cause toxic effects in humans have been raised. Although animal experiments predict that nanoparticles are more toxic than their larger counterparts there are few descriptions in the literature of human exposure. A case described in 1994 has been re-examined from a pathology perspective. The subject, a 38-year-old previously healthy male, inhaled nanoparticles of nickel while spraying nickel onto bushes for turbine bearings using a metal arc process. He died 13 days after being exposed and the cause of death at autopsy was adult respiratory distress syndrome (ARDS). Nickel particles <25 nm in diameter were identified in lung macrophages using transmission electron microscopy. High levels of nickel were measured in his urine and his kidneys showed evidence of acute tubular necrosis.

Acute kidney injury in human leptospirosis: an immunohistochemical study with pathophysiological correlation

Tubulointerstitial nephritis is a common clinicopathological finding in leptospirosis. Clinically, nonoliguric acute kidney injury (AKI), hypokalemia, sodium, and magnesium wasting frequently occur in leptospirosis. The exact mechanisms of renal involvement remain largely unclear. Immunohistochemistry to detect expression of the endogenous sodium/hydrogen exchanger isoform 3 (NHE 3), aquaporin 1 and 2, alpha-Na(+)K(+)ATPase, and sodium-potassium-chloride cotransporter in its NKCC2 isoform was performed on kidneys removed during autopsy of human leptospirosis cases and kidneys removed during autopsy of human non-leptospirosis cases with and without evidence of acute tubular necrosis (ATN). A decrease in NHE 3, aquaporin 1, and alpha-Na(+)K(+)ATPase expression occurred in proximal convoluted tubule cells. Expression of aquaporin 1 was preserved along the descending thin limb of the loop of Henle in the outer medulla. alpha-Na(+)K(+)ATpase expression was essentially preserved in the distal tubules, i.e., the thick ascending limb of the loop of Henle, macula densa, and distal convoluted tubule. Aquaporin 2 expression in the collecting tubules was enhanced compared to those of non-leptospirotic kidneys. NKCC2 cotransport isoform was expressed in the thick ascending limb of the loop of Henle and was essentially preserved in leptospirotic kidneys. Primary injury of the proximal convoluted tubules is regarded as the hallmark of the kidney in leptospirosis. Sodium and water transport are particularly affected with increased distal potassium excretion, hypokalemia, and polyuria. Enhanced expression of aquaporin 2 in medullary collecting tubules is probably an attempt to retain water during the nonoliguric phase of renal failure.

Severe malaria - a case of fatal Plasmodium knowlesi infection with post-mortem findings: a case report

BackgroundZoonotic malaria caused by Plasmodium knowlesi is an important, but newly recognized, human pathogen. For the first time, post-mortem findings from a fatal case of knowlesi malaria are reported here.Case presentationA formerly healthy 40 year-old male became symptomatic 10 days after spending time in the jungle of North Borneo. Four days later, he presented to hospital in a state of collapse and died within two hours. He was hyponatraemic and had elevated blood urea, potassium, lactate dehydrogenase and amino transferase values; he was also thrombocytopenic and eosinophilic. Dengue haemorrhagic shock was suspected and a post-mortem examination performed. Investigations for dengue virus were negative. Blood for malaria parasites indicated hyperparasitaemia and single species P. knowlesi infection was confirmed by nested-PCR. Macroscopic pathology of the brain and endocardium showed multiple petechial haemorrhages, the liver and spleen were enlarged and lungs had features consistent with ARDS. Microscopic pathology showed sequestration of pigmented parasitized red blood cells in the vessels of the cerebrum, cerebellum, heart and kidney without evidence of chronic inflammatory reaction in the brain or any other organ examined. Brain sections were negative for intracellular adhesion molecule-1. The spleen and liver had abundant pigment containing macrophages and parasitized red blood cells. The kidney had evidence of acute tubular necrosis and endothelial cells in heart sections were prominent.ConclusionsThe overall picture in this case was one of systemic malaria infection that fit the WHO classification for severe malaria. Post-mortem findings in this case were unexpectedly similar to those that define fatal falciparum malaria, including cerebral pathology. There were important differences including the absence of coma despite petechial haemorrhages and parasite sequestration in the brain. These results suggest that further study of knowlesi malaria will aid the interpretation of, often conflicting, information on malaria pathophysiology in humans.

Intravascular Hemolysis and Acute Renal Failure After Mitral and Aortic Valve Repair

Intravascular Hemolysis and Acute Renal Failure After Mitral and Aortic Valve Repair

Acute tubular necrosis is characterized by activation of the alternative pathway of complement

Studies in animal models have shown that the alternative pathway of complement is activated in the kidney after ischemia/reperfusion. In addition, mice deficient in complement factor B, a necessary component of the alternative pathway, are protected from ischemic acute renal failure. The purpose of this study was to determine whether alternative pathway activation also occurs during the development of ischemic acute tubular necrosis in the human kidney. Biopsies were identified from nine patients with morphologically normal kidneys and seven patients with evidence of acute tubular necrosis by light microscopy. Immunofluorescence microscopy was used to quantify and localize the complement activation products C3d and C4d. The results were correlated with available clinical data. Similar to mice, small amounts of activated C3d were present along the tubular basement membrane in normal kidneys. However, kidneys from patients with acute tubular necrosis had C3d complement deposition along a significantly greater number of tubules, and many of the tubules were completely circumscribed. In contrast, C4d was not detectable, indicating that complement activation occurred primarily via alternative pathway activation. Complement activation occurs in human ischemic acute tubular necrosis. As in rodents, complement activation along the tubular basement membrane after ischemia appears to occur principally via the alternative complement pathway. Because of this, an inhibitor of the alternative pathway might limit complement activation and inflammation after ischemia/reperfusion, thereby protecting the kidney from ischemic acute renal failure.

Effects of polyhemoglobin-antioxidant enzyme complex on ischemia-reperfusion in kidney

Introduction The kidney suffers ischemia-reperfusion (I/R) injury during transplantation. The purpose of the present study was to investigate the therapeutic effect of artificials cells on renal I/R injury through biochemical assays and histological examination. Methods We prepared artificial cells using cross-linked hemoglobin (Hb), superoxide dismutase (SOD), and catalase. Normal male Sprague-Dawley rats were divided into 6 groups: the sham-operated control group, the group treated with polyHb,and the group treated with polyHb-SOD-catalase (PSC) (per groups were subjected to ischemia for 1 hour or 2 hours). After reperfusion for 4 hours, kidney and blood samples were obtained. Results The levels of SOD and catalase in the PSC group were 15 and 50 times higher than those of the control group, respectively. In the polyHb group, the levels of blood urea nitrogen (BUN), serum creatinine, renal hydrogen peroxide, and renal malondialdehyde were increased. However, their levels were significantly decreased by PSC administration. Renal SOD activity did not show any significant changes in the polyHb group, but renal catalase activity was decreased by polyHb treatment in comparison with the control group. The activities of renal SOD and catalase were increased using PSC treatment. In the histological findings, the PSC group showed no evidence of acute tubular necrosis in proximal convoluted tubules; their microvilli and cytoplasmic microorganelles were relatively well preserved. Conclusions These results show that PSC effectively reduces renal damage via diminished oxygen free radical-mediated injury after I/R.

Distribution of epidermal growth factor in the kidneys of rats exposed to amikacin

The distribution of epidermal growth factor (EGF) was examined by immunocytochemistry in the kidneys of rats exposed to amikacin, an aminoglycoside antibiotic causing tubular necrosis at high dose. Five-animal groups were treated for 4 or 10 days with amikacin at daily doses of 15, 40, 80 or 200 mg/kg. The drug was delivered i.p. twice a day. One hour before termination, each rat received an i.p. injection of [3H] thymidine to evaluate DNA synthesis in renal tissue. After sacrifice, the kidneys were processed for morphological (semithin and paraffin sections) and biochemical analysis (measurement of DNA synthesis by [3H] thymidine incorporation in vivo). Amikacin induced in proximal tubules a dose-related lysosomal phospholipidosis, which was assessed by the morphometric evaluation of altered lysosomes ("myeloid bodies") on semithin section. However, frank evidence of acute tubular necrosis was only observed in rats receiving amikacin at a daily dose of 200 mg/kg. Concomitantly with the development of tubular necrosis, there was a rise in the rate of cell turnover, reflected by an increase of DNA synthesis in renal tissue. This sign of tubular regeneration was accompanied by a redistribution of EGF immunoreactivity, as revealed by immunocytochemical staining. Within renal cortex of control rats, EGF immunoreactivity predominantly appeared in distal tubules and collecting ducts (97% of examined tubular sections). In contrast, in treated animals where the renal cortex displayed evidence of tubular necrosis/regeneration, EGF immunoreactivity was frequently associated with proximal tubules (more than 30% of examined tubular sections, as compared to 3% in controls).(ABSTRACT TRUNCATED AT 250 WORDS)

Pathophysiology of hemorrhagic shock

A model of acute blood loss in rats with a reproducible mortality rate over a wide range of body weights was developed by withdrawing various amounts of fixed blood volume per 100 g body weight via the left common carotid artery and observing the survival of the animals. Younger (lighter) animals survived the bleeding longer than older (heavier) animals. As early as 70 min following the shock episode there was evidence of acute tubular necrosis in kidney proximal tubules and focal centrilobular necrosis in the liver. The 84%, 50%, or 16% body weight - mortality line was: V84 = -0.17 BW + 3.25; V50 = -0.18 BW + 3.16; or V16 = -0.18 BW + 3.01 in animals ranging from 250 to 400 g body weight (where V = bleeding volume ml/100 g body weight, BW = body weight in grams X 10(-2). To produce the same mortality rate, the bleeding volume per unit body weight decreased with increased body weight. On the other hand, the bleeding volume per total blood volume or per unit body surface area increased with increased body weight. The body weight-mortality line is a useful method to calculate the bleeding volume to produce predetermined mortality rate. This method can be easily applied to various pathophysiological and metabolic studies on the nature of acute blood loss as well as in the treatment of acute blood loss.

Renal allograft acute tubular necrosis. II. A light and electron microscopic study of biopsies taken at procurement and after revascularization.

The light and electron microscopic morphology of 57 cadaver renal allografts was assessed at the time of procurement and again after revascularization. Twenty-two kidneys (39%) did not function immediately after transplantation and 19 of these (86%) contained morphologic evidence of acute tubular necrosis (ATN) in the procurement biopsy. The morphology of the post-transplant biopsy was abnormal in all 22 kidneys with delayed function. There was a wide spectrum of morphologic change between the time of procurement and revascularization in all kidneys with normal function. These changes were mild in nature, were usually confined to proximal tubules, and were of unknown clinical significance. The morphology of kidneys that were damaged by the time of procurement was surprisingly different after storage with simple hypothermia (ice) than after storage with hypothermic pulsatile perfusion. The changes attributed to ice storage included endothelial swelling and vacuolation with obliteration and collapse of capillary lumens, fracture and splitting of peritubular basement membrane, and hyalinization of the renal interstitium. It was unknown whether these morphologic abnormalities were associated with delayed recovery of function of the injured kidneys.

Ethacrynic acid in acute tubular necrosis. Indications and effect on the natural course.

13 patients with oliguric acute renal failure were given ethacrynic acid to induce diuresis. Histologic evidence of acute tubular necrosis was present in all patients who died. Seven patients responded with sustained diuresis, six patients did not. The most important factor determining the efficiency of treatment was the period of time between the onset of the oliguria and the time the ethacrynic acid was given. If this delay exceeded 24 h, only one patient responded; but all patients treated within 22 h responded. Permanent hearing loss in one patient and transient loss in another were the major side effects. Ethacrynic acid profoundly influences the natural course of acute tubular necrosis if given before 24 h of oliguria.

Renal failure in patients with cirrhosis of the liver: I. Clinical and pathologic characteristics

A study was undertaken to determine the clinical course, complications and pathogenesis of renal failure in patients with cirrhosis of the liver. Azotemia was present in a high percentage of the patients who died of cirrhosis, particularly in those with hepatic coma. In patients who had cirrhosis without azotemia, impaired ability to excrete water strongly indicated that the development of renal failure was imminent and that the prognosis was grave. In some cases, elevations of blood creatinine and/or uric acid levels were apparent before elevations of blood urea nitrogen concentrations, and provided early indications that renal insufficiency existed. Serum sodium concentration was less than 125 mEq. per L. in 19 per cent of the patients who died of cirrhosis. Hyponatremia usually was due to overhydration. Despite oliguria and azotemia, serum potassium concentrations usually were normal or low rather than high. Renal function studies and fluid balances were followed serially in fifteen patients who eventually died of renal failure. Eight demonstrated clinical evidence of acute tubular necrosis and two had “prerenal” azotemia. In the remaining five patients azotemia developed following acute and apparently spontaneous reductions in glomerular filtration rate. Initially tubular functions were intact, but prior to death these also deteriorated. Decreases in the glomerular filtration rate often followed episodes of “spontaneous” hepatic precoma or coma. Hepatic coma or an associated metabolic abnormality may cause alterations in renal function, or aggravate pre-existing abnormalities in renal function associated with severe liver disease. In some patients with cirrhosis, impaired renal function is characterized by limited ability to excrete water, reductions in renal plasma flow and glomerular filtration rate, and intact tubular function. Although their exact cause and relation to hepatic disease are not established, these abnormalities are often demonstrable before renal insufficiency is overt. They may make patients with cirrhosis more susceptible to the development of progressive renal failure when intercurrent incidents known to affect renal function adversely are superimposed. In other cases the abnormalities may progress and cause renal failure that uniformly follows a clinical course ending with death.