BUN Concentrations Research Articles

Toxicity studies in rats fed nature cure bitters

Graded doses of Nature Cure Bitters (NCB) were administered daily (100, 200 and 400 mg/kg p.o) to rats for 28 days and the effects on body weight, organ weight, clinical signs, gross pathology, haematology, histology and serum biochemical parameters were evaluated. The relative weights of the heart, liver and testes of treated rats were unaffected in contrast to a significant increase in the relative weights of the lungs, kidneys and spleen. The packed cell volume and haemoglobin concentrations were significantly reduced whereas total leucocyte counts and glucose levels were remarkably increased. A significant decrease in alkaline phosphatase occurred in all the groups but alanine aminotransferase and albumin levels were significantly elevated. NCB elicited hypo-cholesterolaemic effects in addition to lowering urea, uric acid, BUN and total protein concentrations. Histological findings did not reveal any treatment-related effects. The calculated therapeutic index was >37.5. These preliminary results suggest that NCB was not likely to produce severe toxicological effects on organ weights, haematological and biochemical indices when given at normal therapeutic doses. Key words: Nature Cure Bitters, organ weight; pathology, haematology; serum biochemistry.

Thirteen-Week Oral Toxicity Study of l,4-Dichloro-2-Nitrobenzene in Rats and Mice

Subchronic toxicity of 1,4-dichloro-2-nitrobenzene (DCNB) was examined by feeding F344 rats and BDF mice of both sexes a diet containing 1,481, 2,222, 3,333, 5,000 or 7,500 ppm DCNB (w/w) for 13 wk. Oral administration of DCNB in feed to rats and mice retarded growth rates and induced subchronic toxicity affecting the liver, kidney, testes and blood. Liver and kidney were most responsive to DCNB. BMDL10 values for relative liver weight were 12.0 and 22.6 mg/kg/d for male and female rats, respectively, and 88.7 and 94.4 mg/kg/d for male and female mice, respectively. Increased liver weights and centrilobular hypertrophy of hepatocytes were observed in the DCNB-fed rats and mice of both sexes. Both increased serum activities of AST and ALT and liver necrosis occurred in the DCNB-fed mice. Increased incidences of hyaline droplets and granular casts in the proximal renal tubules were observed only in the DCNB-fed male rats, indicating alpha2v-globulin nephropathy. Eosinophilic droplets in the renal tubular cells and increased BUN concentrations occurred in the DCNB-fed female rats. DCNB-induced testicular and hematologic changes were noted in rats and mice. On the basis of these results, the highest dose level for the 2-yr bioassay study of rodent carcinogenicity was determined to be 2,000 ppm.

Acquired Portosystemic Shunting in 2 Cats Secondary to Congenital Hepatic Fibrosis

Case 1. A 2-year-old female crossbred cat was referred to Utrecht University Companion Animal Clinic with a 2-month history of episodic vomiting, constipation, decreased appetite, apathy, and decreased activity. The vomiting was treated successfully with cisapride (0.25 mg/kg PO q8h). Physical examination disclosed no abnormalities and a full CBC and serum biochemistry tests were performed. These evaluations showed a leukocytosis (18.6 3 109/L; reference range, 4.3–16.2 3 109/L), increased bile acid concentration (132 mmol/L [53.88 mg/mL]; reference range, 1– 13 mmol/L) and a low BUN concentration (3.6 mmol/L [10.08 mg/dL]; reference range, 6.1–12.8 mmol/L). The combination of high bile-acid concentration and low BUN concentration indicated possible portosystemic shunting. Fasting venous blood ammonia concentration was measured and was increased (196 mmol/L [354 mg/dL]; reference range, ,50 mmol/L). Abdominal ultrasonography was performed for the further diagnosis and identification of portosystemic shunting. Abdominal ultrasonography revealed several small cortical cysts in both kidneys compatible with polycystic kidney disease (PKD). Otherwise, the size and structure of both kidneys and the liver were considered normal. An anomalous tortuous vessel with hepatofugal flow was seen originating from the portal vein in the region where the splenic vein enters the trunk of the portal vein. It was not possible to follow the shunting vessel to its termination. The direction of blood flow was hepatofugal in the portal vein cranial to the origin of the anomalous vein and was hepatopetal caudal to it. The left ovarian vein was dilated. A very small amount of free abdominal fluid was seen. The spleen was ultrasonographically normal. The tortuous anomalous vein was suspected to be an acquired portosystemic collateral, therefore ultrasound-guided core biopsiesa of the liver were taken. The liver biopsies were processed routinely and stained with hematoxylin-eosin, Von Gieson, and a reticulin stain according to the method of Gordon and Sweet. Histological

Is Berlina grandiflora (Leguminosae) toxic in rats?

The toxicity profile of the aqueous methanolic extract of Berlina grandiflora (BG) stem bark was studied in rats. The rats were administered graded doses (125-500 mg/kg p.o) of the extract daily for 21 days and the effects on body weight, organ weight, clinical signs, gross pathology, hematology, histology and serum biochemical parameters were measured. The relative weights of the heart, liver, kidneys and lungs of treated rats were unaffected but there were significant changes in the relative weights of the spleen and testes. The packed cell volume and hemoglobin concentrations were slightly reduced whereas total leucocytes counts were increased remarkably. Alkaline phosphatase and Creatine Kinase levels were reduced in all the groups but Glutamate oxaloacetate was significantly elevated. Total proteins and albumin levels remained normal. BG elicited a significant increase in gamma glutamyl transferase concentrations at 250 mg/kg. No significant changes occurred in urea, uric acid and BUN concentrations but calcium levels shot up remarkably. Histological findings did not reveal any treatment-related effects. The acute toxicity LD50 was estimated to be >2000 mg/kg but dose-related mortality rates of 16.7, 33.4 and 50% were observed during the sub-acute toxicity studies. These findings have once more highlighted the limitations of acute toxicity LD50 testing and suggest that BG may exert varied toxicological effects when administered orally in rats.

Antegrade pyelography for suspected ureteral obstruction in cats: 11 cases (1995-2001).

To determine sensitivity and specificity of radiography, ultrasonography, and antegrade pyelography for detection of ureteral obstructions in cats. Retrospective study. 11 cats. Medical records of cats that had radiography, ultrasonography, and antegrade pyelography performed for suspected ureteral obstructions were examined. Ultrasound-guided pyelocentesis and fluoroscopic-assisted antegrade pyelography were performed on 18 kidneys in 11 cats. Obstructive ureteral lesions were confirmed in all cats by surgical or necropsy examination. Sensitivity and specificity of survey radiography, ultrasonography, and antegrade pyelography for identification of ureteral obstructions were calculated. Surgical or necropsy findings were used as the standard for comparison. All cats were azotemic. Mean +/- SD serum creatinine and BUN concentrations were 10.2 +/- 6.1 and 149 +/- 82 mg/dL, respectively. Fifteen of 18 ureters were found to be obstructed at surgery or necropsy. Sensitivity and specificity were 60 and 100% for radiography and 100 and 33% for ultrasonography, respectively, in identification of ureteral obstructions. Leakage of contrast material developed in 8 of 18 kidneys during antegrade pyelography and prevented diagnostic interpretation in 5 of 18 studies. For the 13 diagnostic studies, specificity and sensitivity were 100% by use of the antegrade pyelography technique. Correct identification of the anatomic location of the ureteral obstruction was obtained in 100% of diagnostic antegrade pyelography studies and in 60% of radiography or ultrasonography studies. Antegrade pyelography can be a useful alternative in the diagnosis and localization of ureteral obstructions in azotemic cats, although leakage of contrast material may prevent interpretation of the study.

Effects of the anaesthetic/tranquillizer treatments on selected plasma biochemical parameters in NZW rabbits.

In order to assess the response of plasma biochemical parameters to anaesthesia, 40 New Zealand White (NZW) rabbits were assigned to four treatment groups (n = 10): control (1 ml i.v. saline solution), fentanyl-droperidol (FD) (0.4 ml/kg s.c. of 'thalamonal' solution; 2.5 mg/ml droperidol, 0.05 mg/ml fentanyl), ketamine (K) (10 mg/kg i.v.) with either xylazine (X) (3 mg/kg i.v.) or diazepam (D) (2 mg/kg i.v.). Blood samples were obtained from the central ear artery at six time points: before injection, and at 10, 30, 60, 120 min and 24 h after injection of the anaesthetics/saline. Plasma ALT, AST, ALP, GGT, BUN, creatinine, phosphate and potassium levels were measured by the Hitachi 747 autoanalyser. The administration of K-X increased (P < 0.05) plasma ALT (from 11.4 +/- 0.9 to 20.2 +/- 1.7 IU/l, at 10 min), AST (from 10.5 +/- 3.3 to 34 +/- 2.1 IU/l, at 120 min), BUN (from 17.2 +/- 0.9 to 25.8 +/- 1.8 mg/dl, at 60 min) and creatinine concentrations (from 1 +/- 0.1 to 1.6 +/- 0.2 mg/dl, at 10 min). After K-D administration, we observed an increase (P < 0.05) in plasma ALT (from 11.4 +/- 0.9 to 20.2 +/- 1.1 IU/l, at 10 min), AST (from 11.4 +/- 1.6 to 28 +/- 3.7 IU/l, at 10 min), BUN (from 15.8 +/- 0.8 to 30 +/- 1.5 mg/dl, at 10 min) and creatinine levels (from 1 +/- 0.08 to 2.2 +/- 0.2 mg/dl, at 120 min). No significant changes were seen in the FD group. We conclude that K-X and K-D may affect plasma concentration of select serum enzymes and biochemical parameters. These results should be taken into account when blood samples are evaluated in treated rabbits.

Hematologic and serum biochemical changes in Salmonella ser Typhimurium-infected calves.

To evaluate hematologic and serum biochemical changes in Salmonella ser Typhimurium-infected calves. 16 male 3- to 4-week-old dairy calves. 13 calves were experimentally infected with S Typhimurium (strains IR715 and CS401, which are derivatives of ATCC 14028), and 3 calves were uninfected controls. Several hematologic and serum biochemical parameters were measured. Hematologic changes included increases in PCV, RBC count, and hemoglobin concentration, associated with a transitory leukopenia characterized by neutropenia and lymphopenia. Biochemical findings included hypoglycemia, increased BUN, creatinine, and fibrinogen concentrations, and decreased sodium, total CO2, calcium, total protein, and albumin concentrations. Increased total bilirubin concentration associated with decreased conjugated bilirubin concentration was also observed. No significant changes in aspartate aminotransferase, gamma-glutamyltranspeptidase, alkaline phosphatase, and creatinine kinase activities were detected. Experimental salmonellosis of calves results in marked to severe dehydration, accompanied by metabolic acidosis, hypoglycemia, and an acute inflammatory response associated with increased fibrinogen concentrations and severe neutropenia immediately after inoculation.

Clinical availability of urinary N-acetyl-beta-D-glucosaminidase index in dogs with urinary diseases.

Urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG) was examined in healthy dogs and dogs with urinary diseases, and its clinical usefulness as an indicator of urinary diseases was discussed. Twenty-eight healthy dogs and 20 dogs with urinary diseases were used. Urinary NAG activity was measured using p-nitrophenyl N-acetyl-beta-D-glucosaminide as substrate, and expressed as units per gram of urinary creatinine (NAG index). Urinary NAG index in urine of healthy dogs was 3.2+/-2.4 U/g, and NAG index in the dogs with chronic renal failure or lower urinary tract infection accompanied by pyelonephritis was higher than that in healthy dogs. However, the dogs with lower urinary tract infection without pyelonephritis showed normal values of NAG index. Some dogs with diabetic mellitus showed elevated values of NAG index when control of blood sugar was not successful. Increase of NAG index was observed in some dogs with pyometra before increases of BUN and serum creatinine concentration. Therefore, NAG index in urine seems to be a good indicator for urinary diseases in dogs.

Chronic ingestion of high concentrations of cholecalciferol in cats.

To determine whether ingestion of 63 times the recommended amount of vitamin D3 (cholecalciferol) results in renal calcification or damage in cats. 20 four-month-old kittens, 17 queens, and 20 kittens born to these queens. 4-month-old kittens and queens were given a purified diet with 846 microg of cholecalciferol/kg of diet (high vitamin D3 diet) or 118 microg of cholecalciferol/kg of diet (control diet) for 18 months. Kittens born to queens were weaned onto the same diet given to dams. There were no apparent adverse effects of the high vitamin D3 diet. Plasma cholecalciferol and 25-hydroxycholecalciferol (25-OHD3) concentrations of queens and 4-month-old kittens given the high vitamin D3 diet significantly increased with time. At 6 months, plasma cholecalciferol concentrations in these kittens and queens were 140.0+/-7.3 nmol/L and 423.6+/-26.6 nmol/L, respectively (10 times initial values). Corresponding 25-OHD3 concentration in queens was 587.5+/-59.4 nmol/L (2.5-fold increase over initial values). At 3 months of age, kittens born to queens given the high vitamin D3 diet had an increase in serum BUN and calcium concentrations and a decrease in RBC and serum total protein, albumin, and hemoglobin concentrations. By 18 months, these kittens had an increase in plasma cholecalciferol (276.0+/-22.2 nmol/L) and 25-OHD3 (1,071.9+/-115.3 nmol/L) concentrations. However, all indices of renal function and the appearance of renal tissue on histologic evaluation were normal. These results indicate that cats are resistant to cholecalciferol toxicosis when the diet is otherwise complete and balanced.

Fasting metabolism in Antarctic fur seal ( Arctocephalus gazella) pups

The metabolism of 52–73-day old Antarctic fur seal pups from Bird Island, South Georgia, was investigated during fasting periods of normal duration while their mothers were at sea foraging. Body mass decreased exponentially with pups losing 3.5–3.8% of body mass per day. Resting metabolic rate also decreased exponentially from 172–197 ml (O 2)·min −1 at the beginning of the fast and scaled to M b 0.74 at 2.3 times the level predicted for adult terrestrial mammals of similar size. While there was no significant sex difference in RMR, female pups had significantly higher ( F 1,18=6.614, P<0.019) mass-specific RMR than male pups throughout the fasting period. Fasting FMR was also significantly ( t 15=2.37, P<0.035) greater in females (823 kJ·kg −1·d −1) than males (686 kJ·kg −1·d −1). Average protein turnover during the study period was 19.3 g·d −1 and contributed to 5.4% of total energy expenditure, indicating the adoption of a protein-sparing strategy with a reliance on primarily lipid catabolism for metabolic energy. This is supported by observed decreases in plasma BUN, U/C, glucose and triglyceride concentrations, and an increase in β-HBA concentration, indicating that Antarctic fur seals pups adopt this strategy within 2–3 days of fasting. Mean RQ also decreased from 0.77 to 0.72 within 3 days of fasting, further supporting a rapid commencement of protein-sparing. However, RQ gradually increased thereafter to 0.77, suggesting a resumption of protein catabolism which was not substantiated by changes in plasma metabolites. Female pups had higher TBL (%) than males for any given mass, which is consistent with previous findings in this and other fur seal species, and suggests sex differences in metabolic fuel use. The observed changes in plasma metabolites and protein turnover, however, do not support this.

Iatrogenic copper deficiency associated with long-term copper chelation for treatment of copper storage disease in a Bedlington Terrier

A 9-year-old Bedlington Terrier was evaluated because of weight loss, inappetence, and hematemesis. Copper storage disease had been diagnosed previously on the basis of high hepatic copper concentration. Treatment had included dietary copper restriction and administration of trientine for chelation of copper. A CBC revealed microcytic hypochromic anemia. High serum activities of liver enzymes, high bile acid concentrations, and low BUN and albumin concentrations were detected. Vomiting resolved temporarily with treatment, but the clinicopathologic abnormalities persisted. Results of transcolonic portal scintigraphy suggested an abnormal shunt fraction. Results of liver biopsy and copper quantification revealed glycogen accumulation and extremely low hepatic copper concentration. Serum and hair copper concentrations were also low. Chelation and dietary copper restriction were tapered and discontinued. Clinical signs and all clinicopathologic abnormalities improved during a period of several months.

Evaluation of water and electrolyte transport of tubular epithelial cells under osmotic and hydraulic pressure for development of bioartificial tubules.

Our aim was to develop bioartificial tubules using tubular epithelial cells and artificial membranes and evaluate the function of water and electrolyte transport by various tubular epithelial cells. The cells were cultivated onto extracellular matrix (ProNectin F) coating polycarbonate membrane. Water transport from the apical to the basolateral site of cells was examined using a modified Ussing chamber module. Water transport under colloidal osmotic pressure on the apical site and hydraulic pressure on the basolateral site were higher in JTC-12, LLC-PK1 cells than in MDCK cells. Water transport under osmotic plus hydraulic pressure was highest in LLC-PK1 cells. We made bioartificial tubules using LLC-PK1 cells and polysulfone hollow fiber cartridges. Water and Na ion transport function was high, and BUN and creatinine passage was recognized in these bioartificial tubules. BUN and creatinine concentrations of reabsorption fluid in these bioartificial tubules were significantly lower than those concentrations of control media and of noncell attached polysulfone hollow fiber cartridges. Though LLC-PK1 cells were more preferable cells for the use of bioartificial tubules in terms of water and electrolyte transport, the passage of BUN and creatinine was not appropriate for clinical use. To select more preferable cells for bioartificial tubules which transport water and electrolytes and do not induce passage of uremic toxins is necessary.

Effect of excess degradable intake protein on early embryonic development, ovarian steroids, and blood urea nitrogen on days 2, 3, 4, and 5 of the estrous cycle in mature ewes.

Two trials were conducted to determine whether feeding excess degradable intake protein (DIP) during a synchronized estrous cycle and the first 5 d after breeding alters early embryonic development, ovarian steroids, or BUN concentrations in ewes. Ewes were group-fed in Trial 1 (T1) and individually fed in Trial 2 (T2) either 100 (control; T1, n = 15; T2, n = 12) or 200% (high-protein; T1, n = 16; T2, n = 12) of the NRC protein recommendation for maintenance during a synchronized estrous cycle until surgery in the next cycle. Ampullae (AMP), isthmi (IST), and uterine horns (UT) of high-protein and control ewes were removed on d 2 (T1), 3 (T2), 4 (T1), or 5 (T2) after breeding. In T1, jugular blood samples were taken once daily starting on d 2 of the synchronized cycle, and in T2 on d 2, 9, 15, 16, and 17, and in both trials from estrus (d 0) to the day of surgery. Ampullae, IST, and UT flushings were examined microscopically for the presence of embryos, embryo condition, and embryo cell number. There was no trial x treatment interaction (P > or = 0.10), so data for both trials were pooled. Concentrations of BUN were higher (P < 0.05) in high-protein-fed ewes than in control ewes during the synchronized cycle and the first 5 d of the next cycle. Progesterone concentrations of the synchronized cycle did not differ (P > 0.10) between treatments. During the first 5 d of the next cycle, estradiol-17beta concentrations were lower (P = 0.06) in high-protein-fed than in control ewes. Progesterone increased (P < 0.05) to higher concentrations by d 5 in high-protein-fed ewes than in control ewes. More (P < 0.05) embryos were found in AMP of high-protein-fed ewes than in AMP of control ewes on d 4. Fewer (P = 0.05) embryos were found in UT of high-protein-fed ewes than in UT of control ewes on d 4. More embryos were found in UT of high-protein-fed ewes than in UT of control ewes on d 5. Fewer (P = 0.05) embryos were found in IST of high-protein ewes than in the IST of control ewes on d 5. Embryos of high-protein-fed ewes had more (P < 0.05) cells than embryos from control fed ewes on d 5. Feeding ewes excess DIP protein during an estrous cycle and the first 5 d after breeding initially impeded embryo transport; thereafter, embryo transport and development through the oviduct was accelerated.

Effect of dopamine on excretory urographic image quality and the prevention of contrast-induced nephropathy in dogs.

The effect of low dose dopamine on the excretory urographic image quality and contrast media-induced nephropathy in normal dogs (experiment 1) and the dogs with decreased renal function (experiment 2) were assessed. In experiment 2, decreased renal function was induced by gentamicin overdose. In each experiment, animals were divided into 3 groups. In group 1, only contrast medium (iohexol) was administered. In group 2, contrast medium plus intravenous fluid (0.9% saline) were administered. And in group 3, contrast medium plus intravenous fluid and low dose dopamine were administered. Investigated parameters included intrarenal resistive index (RI), serum BUN and creatinine concentrations, contrast medium elimination time and radiographic image quality. In experiment 1, RI of group I increased at 80 min after contrast medium administration (p<0.05), but RI of group 3 decreased at 48 and 72 hr (p<0.05). Serum BUN concentration of group 1 was higher than that of group 2 and 3 (p<0.05); in radiographic examination, contrast medium elimination time decreased in group 2 and 3, but image quality of group 2 was inferior to that of group 3. In experiment 2, image quality of group 3 only provided adequate visualization of renal structures. The formula of contrast medium plus low dose dopamine was found to provide good nephrogram and pyelogram image quality without supplemental contrast medium, and to protect renal tubules from prolonged exposure to concentrated contrast medium.

腎機能低下犬に対するアンジオテンシン変換酵素阻害剤ベナゼプリル高用量投与の影響

The angiotensin-converting enzyme inhibitor, benazepril was orally administered to dogs for a period 15days before and after renal ablation. Renal ablation by right-side nephrectomy and ligation of one branch of the left renal artery were performed in the animals to impair renal function. One group of dogs received a standard dose (0.5mg/kg) of benazepril; a second group received 20 times the standard dose (10mg/kg). During the period before surgery, neither the standard nor the increased doses produced remarkable changed in clinical signs and laboratory test results. In 1 1/2 nephrectomized dogs, renal plasma flow and glomerular filtration rate decreased to approximately 1/3 of what they had been before surgery, and BUN and plasma creatinine concentrations increased. These variables remained unchanged in both dose groups during the administration period also in 11/2 nephrectomized dogs.

Complications and outcomes associated with use of gastrostomy tubes for nutritional management of dogs with renal failure: 56 cases (1994-1999).

To evaluate complications and outcomes associated with use of gastrostomy tubes in dogs with renal failure. Retrospective study. 56 dogs. Medical records were reviewed for dogs with renal failure that were treated by use of gastrostomy tubes. Mean +/- SD BUN concentration was 134 +/- 79 mg/dl and mean serum creatinine concentration was 9.0 +/- 3.8 mg/dl. Low-profile gastrostomy tubes were used for initial placement in 10 dogs, and traditional gastrostomy tubes were used in 46 dogs. Mild stoma-site complications included discharge, swelling, erythema, and signs of pain in 26 (46%) of dogs. Twenty-six gastrostomy tubes were replaced in 15 dogs; 11 were replaced because of patient removal, 6 were replaced because of tube wear, and 3 were replaced for other reasons. Six tubes were replaced by low-profile gastrostomy tubes. Gastrostomy tubes were used for 65 +/- 91 days (range, 1 to 438 days). Eight dogs gained weight, 11 did not change weight, and 17 lost weight; information was not available for 20 dogs. Three dogs were euthanatized because they removed their gastrostomy tubes, 2 were euthanatized because of evidence of tube migration, and 1 died of peritonitis. Gastrostomy tubes appear to be safe and effective for improving nutritional status of dogs with renal failure.

Expression of α-smooth muscle actin and fibronectin in tubulointerstitial lesions of cats with chronic renal failure

To examine renal expression of alpha-smooth muscle actin (alpha-SMA) and fibronectin in cats with tubulointerstitial nephritis (TIN) for use in predicting progression to renal fibrosis. 19 cats with TIN and 9 cats without nephritis. Serum creatinine and BUN concentrations were measured. Indices for glomerular extra-cellular matrix (ECM), tubular injury (TI), and fibronectin were determined in renal specimens to quantify the extent of injury and fibrotic lesions. Expression of alpha-SMA in renal tissue was immunohistochemically detected, and correlations were evaluated between the alpha-SMA index and other histologic and clinical variables. The alpha-SMA index in tubulointerstitial areas (1.63 +/- 0.78) was significantly higher in cats with TIN, especially in the periglomerular and peritubular areas, than in cats without nephritis (0.20 +/- 0.14). The alpha-SMA index was significantly associated with the TI index (r2 = 0.70), fibronectin index (r2 = 0.95), BUN concentration (r = 0.64), and serum creatinine concentration () = 0.66). Of special interest was that interstitial alpha-SMA expression appeared evident in the kidneys at an early stage of TIN, prior to the onset of ECM deposition. Analysis of results of histologic and clinical examinations revealed that interstitial alpha-SMA expression may have clinical importance and may be a useful early histologic marker for development of chronic renal failure in cats. An immunohistochemical examination for fibrogenic molecules (such as alpha-SMA expression) may provide fundamental information on the pathogenesis of early-stage renal disease and aid clinical management of cats with chronic renal failure, including TIN.

Simian-human immunodeficiency virus-associated nephropathy in macaques.

A number of chimeric simian-human immunodeficiency virus (SHIV) viruses containing tat, rev, vpu, and env from HIV-1 (strain HXBc2) in a genetic background of simian immunodeficiency virus (SIV(mac)239) have been derived from the parental nonpathogenic SHIV-4 virus. In this article we examine the renal pathology associated with the derivation of these pathogenic SHIV strains. The first of the pathogenic SHIVs, SHIV(KU-1), is associated with rapid CD4(+) T cell loss and opportunistic infections associated with AIDS, but only one of four infected pigtail macaques examined has developed significant renal pathology. The renal pathology in this macaque consists of a diffuse increase in matrix in the core of each lobule with collapsed glomerular capillries, which is similar to the renal changes reported in HIVAN. Passage of this virus into rhesus macaques yielded SHIV(KU-2), which results in renal pathology in three of four inoculated rhesus macaques in which <10% of the glomeruli are involved. A molecular clone of SHIV(KU-2) was derived (SHIV(KU-2MC4)) that causes neurologic and renal pathology with more than 60% of the glomeruli involved and results in uremic level BUN concentrations. These results indicate that SHIV(KU-2MC4) causes severe significant glomerular pathology and should permit a detailed analysis of the molecular determinants associated with the development of SHIV-associated glomerulosclerosis in rhesus macaques.

Role of percutaneous urinary diversion in malignant and benign obstructive uropathy.

We evaluated the feasibility and effectiveness of percutaneous urinary diversion in patients with obstructive uropathy. A total of 206 percutaneous nephrostomies (PCNs) (right-sided in 54, left in 56, and bilateral in 48) were performed in 102 male and 57 female patients 18 to 94 years old. In 125 patients, malignancy was the underlying cause of the obstruction and in 30, benign disease. In four patients, the cause remained unknown. In most patients (N = 154), the access was guided with both ultrasound and fluoroscopy. Percutaneous nephrostomy was successful in 158 patients (99%). Antegrade ureteral stenting was attempted in 48 patients with a success rate of 81%. Fifteen days postprocedure, the mean urea and creatinine concentrations had declined from 160.8 mg/mL to 63 mg/mL and from 6.9 mg/dL to 2.2 mg/dL, respectively. In 66% of the patients, renal function returned to normal. In 28%, it improved with no need for hemodialysis, while in 6%, there was no improvement. Advanced age and prostate cancer were negative predictive factors for the improvement of renal function, whereas the BUN and creatinine concentrations before the procedure and performance of unilateral v bilateral nephrostomies were not. We did not have severe complications. Three patients received transfusions, and in one patient, a urinoma was drained percutaneously. Patients with malignancy had a median survival of 227 days. Percutaneous urinary diversion under radiologic guidance is a safe and effective procedure for patients with obstructive uropathy.

Impact of dialysis modality and acidosis on nutritional status.

Experimental evidence suggests that acidosis may have a deleterious effect on protein metabolism. We evaluated 124 chronic dialysis patients (59 +/- 17 years) and defined acidosis as an anion gap >18 meq/L. A direct correlation (p < 0.0001 was found between anion gap and serum albumin (R = 0.402), BUN (R = 0.488), and serum creatinine (R = 0.473) concentrations. Acidotic patients (43%), when compared with nonacidotic patients, had greater serum albumin concentrations (3.95 +/- 0.50 vs. 3.60 +/- 0.48 g/dl, p = 0.0001, respectively), higher normalized protein catabolic rates (1.12 +/- 0.27 vs. 0.96 +/- 0.26 g/kg/d, respectively; p = 0.0004), and higher BUN (70 +/- 19 vs. 55 +/- 17 mg/dl, p = 0.0001) and serum creatinine (11.1 +/- 3.4 vs. 8.3 +/- 3.2, p = 0.0001 mg/dl) concentrations. However, no differences in midarm muscle circumference, fat free mass, or body cell mass were noted between groups when assessed by dialysis modality or acidosis status. In conclusion, mild chronic metabolic acidosis, likely caused by increased dietary protein intake, does not independently and adversely impact nutritional status in chronic dialysis patients.