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PubMed1965

FIBROGEN PRECIPITATION BY STREPTOCOCCAL M PROTEIN. II. RENAL LESIONS INDUCED BY INTRAVENOUS INJECTION OF M PROTEIN INTO MICE AND RATS.

Intravenous injection of Type 1 streptococcal M protein into mice and rats produced lesions confined to renal glomeruli. Thrombi of eosinophilic amorphous material, seen to occlude glomerular capillaries, were shown to contain M protein and fibrinogen. Gradual regression of the morphological lesions was observed during the 3 weeks following injection. Initial abnormal proteinuria and azotemia returned to control levels by the end of the 1st week; a second rise in urinary protein excretion and urea retention was demonstrated in some rats coincident with appearance of anti-M antibodies. The mechanism of renal localization of streptococcal M protein by means of a complex with fibrinogen was suggested, which may comprise an initial phase in the pathogenesis of acute poststreptococcal glomerulonephritis.

Animals↗
PubMed1968

The experimental induction of glomerulonephritis like that in man by infection with group A streptococci.

106 rabbits received one or more courses of inoculations, spaced 1-4 months apart, with Group A streptococci, usually of strains isolated from patients with acute glomerulonephritis. 8 days to a few weeks after onset of a given infection with streptococci known to have been nephritogenic for man, marked proteinuria, often with hematuria and occasionally with azotemia, was detected in 22 of the animals. 15 of these were sacrificed a few days to a few weeks thereafter, and 10 showed renal changes like those of acute or recurrent acute glomerulonephritis in man. Such changes occurred in three other rabbits whose urine was not examined that died or were sacrificed 1-3 wk after onset of infection with streptococci of a serotype known to include a strain nephritogenic for man. The remaining seven animals in which marked proteinuria had occurred died or were sacrificed many months later, in some cases after additional infections. Two of these had become azotemic and two convulsed and died after giving birth; in these animals, there were renal changes like those that occur in man in chronic latent glomerulonephritis, toxemia of pregnancy super-imposed on chronic latent glomerulonephritis, or chronic active glomerulonephritis. Anatomical changes in the kidneys in the experimentally induced and in naturally occurring glomerulonephritis, from acute to chronic stages, are compared and illustrated. The pathogenesis of poststreptococcal glomerulonephritis is discussed.

Acute Disease↗
PubMed2001

Laparoscopic orthotopic ileal neobladder.

BACKGROUND AND PURPOSE: Orthotopic ileal neobladder is currently the preferred continent urinary diversion in suitable patients undergoing radical cystectomy for muscle-invasive bladder cancer. To our knowledge, presented herein is the initial report of laparoscopic orthotopic ileal neobladder following cystectomy that was performed completely intracorporeally in a porcine model. MATERIALS AND METHODS: The laparoscopic technique was developed in seven pigs. Subsequently, a long-term survival study was performed in 12 consecutive animals. Laparoscopic cystectomy was performed, preserving the urethral sphincter. An ileal segment of 35 cm (first three animals), 45 cm (next four), or 55 cm (final five animals) with adequate mesentery was isolated; and ileal continuity was restored intracorporeally by a stapled anastomosis. Ileal detubularization for construction of an ileal neobladder, urethroileal anastomosis, and bilateral stented ileoureteral anastomoses to a tubular Studer limb extension were all created completely intracorporeally using only laparoscopic free-hand suturing and knot-tying. Biochemical data (preoperative and serial postoperative hemoglobin, renal panel, blood gases), radiologic studies (intravenous urogram, retrograde pouchgram), functional measures (neobladder urodynamics, Whitaker pressure-flow study of both ureters), and microscopic evaluation of the neobladder and ureteroileal and urethroileal anastomotic sites were obtained to evaluate the long-term functional and anatomic outcome. RESULTS: Completely intracorporeal laparoscopic construction of an ileal orthotopic neobladder was successful in all 12 animals without intraoperative or early postoperative complications or open conversion. The mean operating time was 5.4 hours (range 4.5-6.5 hours), and the blood loss was minimal. All study pigs survived their predetermined follow-up period, ranging from 1 to 3 months. Late complications occurred in three animals: one port-site abscess and two cases of E. coli pyelonephritis and azotemia, leading to one death at 2 months. The mean serum creatinine concentrations were 1.33 mg/dL, 1.61 mg/dL, and 1.55 mg/dL at 1, 2, and 3 months, respectively. The mean neobladder capacity was 420 mL (range 250-700 mL) with pressures < or = 20 cm H2O (range 17-20 cm H2O). Pre-euthanasia Whitaker testing confirmed excellent drainage in all 24 ureters. No ileoureteral or ileourethral anastomotic strictures or leaks were noted on intravenous urography, retrograde pouchgram, or postmortem physical calibration of the anastomotic sites. Histologic examination confirmed excellent healing without obvious fibrosis. CONCLUSION: Laparoscopic construction of an orthotopic neobladder is feasible. The anatomic and functional outcome is excellent and comparable to that of open surgery. Clinical application is imminent.

Animals↗
PubMed2001

Treatment of HIV-associated nephropathy.

HIV-associated nephropathy (HIVAN) is the most common cause of renal failure in patients infected with type 1 human immunodeficiency virus (HIV-1). The renal prognosis for HIVAN is poor and is typically associated with rapid progression to renal death. We report a patient with biopsy-proven HIVAN who was successfully treated with corticosteroids and review the currently available evidence supporting the specific treatments of this condition. A 34-year-old African-American male with a 2-year history of uncomplicated HIV disease developed progressive azotemia despite treatment with highly active antiretroviral therapy (HAART). He was treated with an uncomplicated 4-month course of prednisone, which improved his serum creatinine from 2.9 to 1.9 mg/dl and decreased his degree of proteinuria from 8 to 2.1 g/day. Two years post-steroid treatment his renal function remains stable. Increasing evidence supports that both ACE inhibitors and HAART are effective in preventing and in some cases of reversing HIVAN induced renal failure. In selected patients who progress despite these measures, a limited course of corticosteroid may achieve long-standing disease remissions. In general, with adequate supervision, corticosteroid therapy appears to be well tolerated and has an acceptable side effect profile. Although persuasive in view of the abysmal natural history of HIVAN, the currently available studies are subject to major methodological limitations. Appropriate randomized controlled trials are urgently required in order to further examine the efficacy, optimal timing, and potential side effects of these treatments.

AIDS-Associated Nephropathy↗
PubMed1993

Endourologic management of ureteric complications after live-donor kidney transplantation.

Among 620 consecutive live-donor kidney transplants, 40 patients (6.5%) developed ureteric complications in the form of fistula (N = 16) or obstruction (N = 24). Patients with these complications were stratified into two consecutive groups according to the use of graft percutaneous nephrostomy (PCN) in their initial management. Group A was comprised of 17 patients (8 fistulas and 9 obstructions) treated by conventional open surgery without graft PCN. In Group B, 23 patients (8 fistulas and 15 obstructions) were initially treated by graft PCN until resolution of azotemia and control of infection, then treated definitively by endourologic procedures or open surgery. Patients of Group B demonstrated significantly better graft function 2 weeks after treatment, better 1-year graft survival, a shorter hospital stay, and a lower incidence of secondary post-treatment complications. Moreover, in this group of patients, endourologic procedures provided definitive management in 3 of 8 patients with ureteric fistula and in 9 of 15 patients with ureteric obstruction. These data supplement the growing evidence that endourologic techniques are good adjuncts to or substitutes for open surgery in renal allograft recipients with ureteric complications.

Adult↗
PubMedDate not supplied

In vivo and in vitro degradation of urea and uric acid by encapsulated genetically modified microorganisms.

This study was undertaken to characterize the capacity of a combination of genetically modified bacteria to lower elevated levels of urea and uric acid and thus to serve as a potential adjunct to maintenance dialysis in patients with chronic renal failure. Two strains of genetically modified bacteria expressing enzymes, urease to degrade urea and uricase to degrade uric acid, were identified, combined, and dispersed in 600-microm alginate microcapsules suitable for oral administration. In 24 h in vitro experiments, 5 mL of these capsules completely cleared 95% of the urea and >99% of the uric acid from 100 mL of a challenge solution formulated to the concentration of these solutes in a presenting hemodialysis patient. The process of urea degradation was found to be intracellular and each bacterial strain was specific for its substrate. Solute degradation in vivo was evaluated with a chemically induced model of acute renal failure, using Sprague-Dawley rats. Orally administered capsules were found to remain in the gastrointestinal tract for at least 6 h. The severity of azotemia and hyperuricaemia after chemical induction of acute renal failure was reduced by 64 and 31%, respectively, on administration of the capsules. Reduction of urea concentration (but not uric acid concentration) in vivo required coadministration of an ion-exchange resin to adsorb ammonia. Oral delivery of a combination of genetically modified microorganisms should be further explored in chronic renal failure models as a useful adjunct to dialysis or to immunosorption for the treatment of uremia.

Acute Kidney Injury↗
PubMed1977

Oxygen consumption in the azotemic rat.

To test the hypothesis that basal energy expenditure may be abnormal in azotemia, oxygen consumption was studied in partially nephrectomized, azotemic male Sprague-Dawley rats and sham operated control rats 10, 16, and 31 days after surgery. Observed decreased oxygen consumption in the azotemic group was related to their decreased body weight. There was no significant difference in oxygen consumption between groups when oxygen consumption values were related to weight.75.

Animals↗
PubMed1978

Increased histidine and histamine content in the brain of chronic uremic rats. Cause of enhanced cerebral cyclic adenosine monophosphate in uremia?

In rats with experimental chronic renal insufficiency (90% nephrectomy) the histidine content in brain was increased (+ 35%) in spite of normal plasma values and decreased concentrations in the striated muscle (-23%). The finding of a raised histidine level in the brain seems to be a uremia specific disorder, probably cuased by a local disturbance in histidine metabolism. In addition an increase of the histidine decarboxylation product histamine could be observed in the brain of rats with chronic renal insufficiency, as compared to pair-fed controls. This increase was directly related to the severity of azotemia. In the pathogenesis of the histamine alteration the increased histidine content in the brain of uremic rats must be considered, since the specific histidine decarboxylase is not saturated by the normal endogenous level of the amino acid precursor. Probably the increased histamine contributes to the raised cerebral cyclic AMP in the brain of uremic rats.

Animals↗
PubMed1980

Skeletal muscle amino acid metabolism in chronic uremia.

The kinetics and factors regulating acid release were studied in epitrochlaris preparations of control and chronically uremic rats. These data were correlated with abnormal glucose and glucose precursor kinetics of azotemic patients and the impact of hemodialysis on these precursor-product interrelationships. In chronically uremic rat skeletal muscle, a subsensitivity to catecholamines was evident. A 1000-fold greater concentration of epinephrine was required in uremic muscle to inhibit alanine release compared to control preparations. The dose-response curve for cAMP formation stimulated by epinephrine was shifted 1 log unit to the right in uremic muscle and adenylyl cyclase stimulation by epinephrine was shifted 1 log unit. Using simultaneous primed-injection-continuous infusions [U-14C]-alanine and [2-3H]glucose, rates of metabolite turnovers were calculated from the plateau portions of the specific activity curves. In 14 azotemic patients, alanine and glucose turnover rates were found to be increased 276 and 154%, respectively, over that of the control group of 17 subjects. Glucose production was found to be 3-fold greater. Hemodialysis decreased alanine turnover by 35% and glucose production by 19%. However, glucose turnover was not affected by dialysis. Although the percentage of glucose produced from alanine approached normal levels, the percent of alanine used for gluconeogenesis increased 60%. These studies demonstrate that abnormal carbohydrate metabolism in uremia is a result of multiple factors. Diminished response of adenylyl cyclase and decreased levels of cAMP contributes to, but does not entirely account for, increased amino acid release. The increased alanine synthesis in skeletal muscle supports glucose overproduction found in chronic azotemia. Hemodialysis ameliorates but does not fully normalize glucose and alanine metabolism and may actually introduce additional abnormalities.

Adult↗
PubMed1980

Charcoal sorbent-induced hypolipidemia in uremia and diabetes.

Rats with hyperlipidemia associated with streptozotocin-induced diabetes or azotemia after subtotal nephrectomy were administered a diet containing 5% activated charcoal. Significant lowering of nonfasting serum cholesterol and triglyceride levels resulted. Charcoal-feeding also altered the abnormal high density lipoprotein electrophoresis pattern of diabetic rats toward normal.

Animals↗
PubMed1983

Growth of rats with severe renal insufficiency fed a formula designed to minimize urinary solutes.

Experiments were designed to test the hypothesis that growth depression and azotemia in chronic renal failure can be minimized by providing a nutritional formula that is adequate is essential nutrients but minimizes urinary excretion of all solutes. Unrestrained rats were fed exclusively by continuous intragastric infusion with a mixture containing sucrose, essential amino acids, N-free analogues thereof, minerals, corn oil, and vitamins, designed to minimize urinary solute excretion while permitting growth. After 5 days, renal excretory function was reduced to 1/10 by reinfusing 90% of each day's urinary output intragastrically for the next 3 wk. Weight gain (3.6 +/- 0.1 g/day), linear growth and carcass N accretion were the same as in nonreinfused rats receiving substantially the same formula by intragastric catheter. Except for sight acidosis (CO2 18.5 mM) accumulation of electrolytes did not occur. Average final serum urea N was only 42.5 +/- 7.1 mg/dl. The results are considered as supporting the hypothesis.

Amino Acids↗
PubMed1985

Skeletal muscle function in chronic renal failure: an index of nutritional status.

To determine whether skeletal muscle function testing (SMF) provides an index of nutritional status in patients with chronic renal failure (CRF), two groups with comparable CRF were studied. In 48 well-nourished (WN) and 17 malnourished (MN) patients with stable CRF, and in 33 WN nonazotemic controls, adductor pollicis function was assessed. The force at 10 Hz was expressed as a % of force at 100 Hz (F10/F100), and maximal relaxation rate (MRR) as % force loss/10 ms. Standard nutritional assessment was also performed. The WN group was not significantly different from controls for either F10/F100 or MRR. The F10/F100 of the MN group was significantly greater than either the WN group or controls (p less than 0.001), while MRR was less (p less than 0.001). Significant malnutrition by conventional parameters was shown in patients with abnormal F10/F100, and also in patients with abnormal MRR. Hence, SMF as described is unaffected by azotemia, and provides a functional measure of nutritional status in CRF.

Adult↗
PubMed1980

Significance of a sixth lactate dehydrogenase isoenzyme (LDH6).

An unusual band on the cathodic side of the membrane was found on lactate dehydrogenase electrophoresis of blood specimens from 18 patients. Fifteen patients died shortly after the finding. No specific cause was found for the unique band, but most of the patients had arteriosclerotic cardiovascular disease with acute passive hyperemia of the liver, and prerenal azotemia.

Aged↗
PubMed1987

The pathology of fatal Mediterranean spotted fever.

A 77-year-old woman from rural Spain had a febrile summertime disease develop with rash, eschar, and pulmonary, abdominal, and neurologic signs and symptoms. Mediterranean spotted fever (MSF) was diagnosed late in the course, and antirickettsial treatment was given only during the last 30 hours of life. Clinical manifestations of severe disseminated vascular injury included thrombocytopenia, hypoalbuminemia, edema of the lungs and legs, and severe prerenal azotemia. The diagnosis was documented by specific serology. Necropsy revealed vascular injury with perivascular lymphohistiocytic infiltrates suggestive of rickettsiosis in the central nervous system, lung, heart, kidneys, esophagus, stomach, colon, pancreas, spleen, and thyroid. Gastric hemorrhage and acute pneumonia contributed to the patient's death on day 18 of illness. Antimicrobial treatment and host defenses apparently reduced rickettsiae to an undetectable quantity. MSF has increased in incidence in the Mediterranean basin and has been reported in travelers returning to the United States.

Aged↗
PubMed1989

Histopathology and immunohistologic demonstration of the distribution of Rickettsia typhi in fatal murine typhus.

An 81-year-old woman had chills, fever, nausea, vomiting, and epigastric pain. On day 3 she had hematuria and was treated with trimethoprim-sulfamethoxazole. On day 5 she had a cough, hypotension, anemia, azotemia, and elevated hepatic enzyme levels. Her condition deteriorated with thrombocytopenia, anuria requiring dialysis, edema, and hypoalbuminemia. Treatment with chloramphenicol and doxycycline was started on day 10. By day 11, she was in hypotensive shock; on day 12 she had seizures and died. Murine typhus was diagnosed by demonstration of antibodies to Rickettsia typhi by indirect immunofluorescence. Necropsy revealed interstitial pneumonia, pulmonary edema, hyaline membranes, alveolar hemorrhages, petechiae and vasculitis in the central nervous system, interstitial myocarditis, multifocal interstitial nephritis and hemorrhages, splenomegaly, portal triaditis, and mucosal hemorrhages in urinary tract. Immunofluorescent R. typhi were demonstrated in the lungs, brain, kidneys, liver, and heart. This unusual death occurred in an elderly patient without rash who was treated too late with antirickettsial drugs.

Aged↗
PubMed1989

Sodium-sensitive hypertension. Implications of pathogenesis for therapy.

Fifty to sixty percent of clinical hypertension is sensitive to sodium (Na) intake: known causes, primary aldosteronism, bilateral renal artery stenosis, mild azotemia, acromegaly, and low-renin hypertension account for only a fraction. We have identified a group of normal-renin hypertensives characterized by inability to modulate normally their renal vascular and adrenal responsiveness to angiotensin II. These patients handle shifts in Na intake abnormally, show more positive balance on a high-salt diet, and raise their blood pressure when shifted to a high-salt diet. Renal blood flow does not shift with Na intake, but does respond strikingly to converting enzyme inhibition, which also corrects altered renal and adrenal responsiveness, ability to handle a sodium load, and hypertension. These patients have a striking family history of hypertension; 50% of the offspring of hypertensives show similar features, including a renal vasodilator response to converting enzyme inhibitors or calcium channel blocking agents. Accumulating evidence suggests that the abnormality is inherited and may be the most common form of hypertension.

Adrenal Glands↗
PubMed1991

Renographic diagnosis of renovascular hypertension with angiotensin converting enzyme inhibition and furosemide.

Captopril renography is a powerful tool for evaluating renovascular hypertension. In this article we examine four different protocols: 99mTc-DTPA, [131I]hippuran with captopril, [131I]hippuran with enalaprilat, and 99mTc-mercaptoacetyltriglycine (MAG3). In our experience, [131I]hippuran renograms are a reliable and reproducible test in patients both with and without azotemia. Although our experience with the new 99mTc-MAG3 technique is somewhat limited, it appears that this will also be a valuable test, which additionally has several advantages over hippuran, namely, a smaller turnaround time between test and baseline study, a smaller dose of radioactivity, better images, and more accurate counts. We look forward to the future development of this technique.

Angioplasty, Balloon↗
PubMedDate not supplied

Adverse effects of the fluoroquinolones.

Data on adverse reactions due to the quinolone antibacterial agents--ciprofloxacin, ofloxacin, pefloxacin, norfloxacin, and enoxacin--observed in a patient sample of approximately 30,000 are reviewed. Overall rates of adverse reactions were 4.0%-8.0%, and adverse reactions necessitated discontinuation of therapy in 1.0%-2.6% of patients. Patterns of organ-system involvement and of signs and symptoms were quite similar, with gastrointestinal effects predominating (nausea, vomiting, diarrhea, or abdominal pain in 1.0%-5.0% of the patients), followed by effects on the central nervous system (dizziness, headache, and/or insomnia in 0.1%-0.3% of the patients) and skin (0.5%-2.2% of the patients). Elevation in levels of hepatic enzymes occurred in 1.8%-2.5% of the patients, azotemia in 0.2%-1.3%, and eosinophilia in 0.2%-2.0%. These adverse effects were reversible after drug withdrawal and were generally not dose-dependent. Within the constraints of the relatively small number of well-documented patients and the unique mechanism of action of these antimicrobial agents, the safety profile of these drugs seems to make them acceptable for use when their administration is well directed and specific. In addition, close surveillance for new phenomena should be maintained.

Anti-Infective Agents↗