Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.3.1 (alkaline phosphatase)
 47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A young man receiving high dose cytosine arabinoside (3g/m2 every 12 hours) for promyelocytic leukemia developed rapidly increasing hyperbilirubinemia and hepatorenal syndrome. The patient had been treated previously with courses of standard dose cytosine arabinoside without hepatic or renal complications. His condition rapidly deteriorated, and he required hemodialysis. The total bilirubin increased to 45.4 mg/dL, but alkaline phosphatase remained normal. Twelve days after starting chemotherapy, the patient died of hepatorenal failure. Liver necropsy revealed mild bile stasis and microvesicular steatosis. We suspect high dose cytosine arabinoside played a major role in causing impairment of bilirubin transport within the hepatocyte in this patient.
 ...
PMID:Jaundice and hepatorenal syndrome associated with cytosine arabinoside. 231 16

A 15-yr-old girl presented with complaints of right upper quadrant pain and jaundice. Elevation of serum alkaline phosphatase, signs of protal hypertension, and computed tomographic scan findings suggested a diagnosis of primary sclerosing cholangitis. However, cultures of the bile and of the common bile duct specimen obtained during a surgical procedure grew Cryptococcus neoformans. Treatment with amphotericin B was begun. An episode of upper gastrointestinal bleeding, however, led to the hepatorenal syndrome, and the patient died before antifungal therapy was completed. At autopsy, active sclerosing cholangitis associated with cryptococci involved the common bile duct. We suggest that opportunistic infection of the biliary tree should be considered in pediatric patients with presumed primary sclerosing cholangitis.
 ...
PMID:Cholangitis associated with Cryptococcus neoformans. 397 25

Clinical observations indicate an increased number of post-operative complications and deaths in jaundiced patients. The patient may require some simultaneous treatment of concomitant ailments, among which cardiovascular diseases occur rather frequently. Some of the drugs administered then, like digoxin, are, in spite of being predominantly eliminated via the kidneys, metabolized in the liver, secreted into the bile or participating in the enterohepatic circulation. The changed pharmacokinetics of such drugs, in the case of mechanical jaundice, may be due to an altered liver status which can affect the function of the kidneys. The aim of the study was to evaluate the pharmacokinetics of digoxin administered both intravenously and into the stomach, in the state of mechanical, extrahepatic cholestasis. The study was carried out on male rabbits, divided randomly into four groups: the first two (experimental and control) were administered digoxin intragastrically and the next two groups (experimental and control)-intravenously (Tab. 1). The animals of the experimental groups had the bile ducts ligated, whereas the controls were sham-operated on. Digoxin was given to all the animals 4 days before the operation and 6 days after the surgery, in a dose of 0.02 mg/kg. Blood samples were collected ten times for 24 hours after the drug administration. Digoxin concentrations were determined by FPIA method, and pharmacokinetic parameters were calculated by the two compartment open model for intragastric drug administration, and by the noncompartmental analysis for intravenous route. The levels of serum total bilirubin, creatinine, urea, glucose, albumin and activities of alanine, aspartate aminotransferases and alkaline phosphatase were estimated in all of the animals. The rabbits were sacrificed at the end of the study i.e. on the 7th day after the operation. The kidneys and the livers were weighed and examined macro- and microscopically. The laboratory tests as well as the anatomopathological investigations showed the symptoms of cholestasis and the hepatorenal syndrome (Tab. 2, 3). The blood serum concentrations of digoxin, both after intragastric and intravenous administration, were statistically higher during the whole observation period in the animals with obstructive cholestasis versus the controls (Tab. 4, 6). There were no significant alterations of digoxin parameters in the animals of the control groups, measured prior to and after the surgery. In the jaundiced animals, however, most of the pharmacokinetic parameters were markedly changed as compared with the preoperative values. In the rabbits which were given digoxin intragastrically, an increase in area under the plasma concentration-time curve (AUC) and in the peak concentration of the drug (Cmax) was noted (Tab. 5). Besides, the prolongation of mean residence time (MRT) and decrease in total body clearance (Cl) as well as apparent volume of distribution (Vz), were observed, as compared to the sham-operated controls. After the intravenous administration the following changes took place (Tab. 7): an increase in AUC, the prolongation of elimination half-life (t1/2 lambda z) and decrease in the total body clearance. All the above differences were statistically significant. Thus, digoxin, a drug predominantly eliminated via the kidney undergoes an impaired elimination in obstructive cholestasis. Basing on the results of the present study, the following statements could be expressed: (1) experimental, extrahepatic jaundice alters the pharmacokinetics of digoxin given intragastrically as well as intravenously; (2) the administration of therapeutic dose of digoxin in the state of mechanical jaundice may lead to its overdose; (3) obstruction of the common bile duct should indicate the necessity of monitoring the serum concentration of digoxin; (4) extrahepatic cholestasis may induce hepatorenal syndrome.
 ...
PMID:[The effect of experimental extrahepatic cholestasis on absorption, distribution and elimination of digoxin]. 919 26

Rats of Long-Evans Cinnamon (LEC) strain were used as a hepatorenal syndrome model of fulminant Wilson's disease. Copper levels in the kidneys increased markedly from 16 to 126 microg Cu/g from 12 to 16 weeks, and remained at the same level at 16 and 19 weeks when the rats suffered from severe renal dysfunction and also at 20 weeks in some other normal rats. The above findings imply that the renal dysfunction may have been induced independently of the copper level in the kidneys. The present study suggested the following mechanism: immediately after copper-induced hepatic dysfunction, plasma copper-metallothionein (CuMT), which was released from the liver, became elevated. The elevation was closely related to the increases in alkaline phosphatase, glucose and amino acids, all in the urine. The above findings suggest that plasma CuMT, which was released from the liver into the blood upon copper-induced hepatic dysfunction, was subsequently filtered at the glomeruli due to its smaller molecular weight, and then caused dysfunction of the brush border membrane of the renal proximal tubules probably after splitting into radical copper and amino acids in acidic vesicles close to the membrane. The critical concentration of plasma CuMT required to induce renal dysfunction was estimated as 1 microg Cu/l.
 ...
PMID:Mechanism of hepatorenal syndrome in rats of Long-Evans Cinnamon strain, an animal model of fulminant Wilson's disease. 1043 83

We describe a case of calciphylaxis in a 47-year-old man with alcohol-induced end-stage liver disease and acute renal failure secondary to hepatorenal syndrome. Possible contributing factors included transiently impaired renal function, protein C and S deficiencies, elevated calcium-phosphate product, hyperphosphatemia, low serum albumin, repeated albumin infusions, and elevated alkaline phosphatase level.
 ...
PMID:Calciphylaxis associated with acute, reversible renal failure in the setting of alcoholic cirrhosis. 1509 47

Impairment of renal function often occurs in patients with liver disease. Hepatorenal syndrome is a significant cause of acute kidney injury (AKI) in patients with cirrhosis (HRS-AKI, type 1). Causes of non-HRS-AKI include cholemic nephropathy (CN), a disease that is characterized by intratubular bile casts and tubular injury. As data on patients with CN are obtained primarily from case reports or autopsy studies, we aimed to investigate the frequency and clinical course of CN. We identified 149 patients who underwent kidney biopsy between 2000 and 2016 at the Department of Gastroenterology, Hepatology and Endocrinology at Hannover Medical School. Of these, 79 had a history of liver disease and deterioration of renal function. When applying recent European Association for the Study of the Liver criteria, 45 of 79 patients (57%) presented with AKI, whereas 34 patients (43%) had chronic kidney disease (CKD). Renal biopsy revealed the diagnosis of CN in 8 of 45 patients with AKI (17.8%), whereas none of the patients with CKD was diagnosed with CN. Univariate analysis identified serum bilirubin, alkaline phosphatase, and urinary bilirubin and urobilinogen as predictive factors for the diagnosis of CN. Histological analysis of AKI patients with normal bilirubin, elevated bilirubin, and the diagnosis of CN revealed loss of aquaporin 2 (AQP2) expression in collecting ducts in patients with elevated bilirubin and CN. Biopsy-related complications requiring medical intervention occurred in 4 of 79 patients (5.1%). Conclusion: CN is a common finding in patients with liver disease, AKI, and highly elevated bilirubin. Loss of AQP2 in AKI patients with elevated bilirubin and CN might be the result of toxic effects of cholestasis and in part be responsible for the impairment of renal function.
 ...
PMID:Cholemic Nephropathy Causes Acute Kidney Injury and Is Accompanied by Loss of Aquaporin 2 in Collecting Ducts. 3074 31