Effect Of Chronic Renal Failure Research Articles

Connections in chronic kidney disease: connexin 43 and connexin 37 interaction

the prevalence of chronic kidney disease is rising sharply worldwide and affects 13.1% of the population in the US ([3][1]). Patients with chronic kidney disease represent a population not only at risk of progression to end-organ failure but also at higher risk for cardiovascular diseases ([22][2

Coronary risk factors in maintenance hemodialysis patients: Who is the culprit - hemodialysis or chronic renal failure?

Objective:Dyslipidemia, common in uremic patients subjected to maintenance hemodialysis (HD), represents an independent risk factor for atherosclerosis; but the association between long-term HD and uremic dyslipidemia is not crystal clear. The present study was aimed to ascertain any association.Materials and Methods:The effects of chronic renal failure (CRF) and HD duration on serum lipids, lipoproteins and homocysteine (HC) were studied in 84 patients suffering from CRF subjected to maintenance HD and were compared with 68 healthy, age-, sex- and race-matched control cohorts.Results:Increase in serum free cholesterol (FC), triglycerides, very low-density lipoprotein cholesterol and HC levels, and decrease in esterified cholesterol (EC), EC/FC ratio, high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol levels were highly significant (P < 0.001) in pre-dialysis patients compared to controls. Further disturbances were observed (P < 0.05) by repeated HD, resulting in further significant increase in FC, and decrease in EC/FC ratio and HDL-C levels after 40 dialysis schedules.Conclusion:Levels of HDL-C, plasma FC, and ratio of EC/FC appeared to be clearly altered by HD duration, submitting patients to a greater risk of atherosclerosis due to maintenance HD.

Effects of Chronic Renal Failure on L-arginine-Nitric Oxide Pathway and Arginase in Erythrocytes

Effects of Chronic Renal Failure on L-arginine-Nitric Oxide Pathway and Arginase in Erythrocytes

Post‐fertilization effects of chronic renal failure in male rats

We evaluated the potential for growth and intrauterine development of embryos generated from the fertilization of oocytes with spermatozoa recovered from animals with chronic renal failure (CRF). Group A included sham-operated rats (n = 28), group B1 involved CRF rats that had undergone erythropoietin plus bromocryptine treatment (n = 28), and group B2 included CRF rats that had received normal saline. Embryos derived from the in vitro fertilization of oocytes with spermatozoa recovered from rats of group A or group B1 or group B2 were transferred to female recipients. We induced CRF in a group of rats (group B; n = 56; the total kidney volume was reduced to one-sixth with two operations). One week after the second operation, the rats of group B were randomly divided into group B1 (they subsequently received bromocryptine plus erythropoietin) and group B2 (they received injections of saline). Nine weeks after the second operation, the fertility of each male rat was assessed by mating tests and in vitro fertilization of oocytes. The mean litter size was significantly smaller in the subpopulation of fertile animals in group B2 than in the fertile rats of group B1 and in the fertile rats of group B1 than in the fertile rats of group A. Per cent of transferred blastocysts that developed into alive offspring were significantly lower in group B2 than in group B1 and in group B1 than in group A. Epididymal spermatozoa demonstrated a significantly larger DNA-oxidative damage in group B2 than in group B1 and in group B1 than in group A. These findings demonstrate that sperm-DNA damage because of CRF development is accompanied by a defect in the development of embryos generated in vitro. We may suggest that bromocryptine and erythropoietin protecting sperm DNA from oxidative damage improve reproductive potential in rats with CRF.

The curative effect study on 35 cases of Chronic Renal Failure by retention enema with the traditional Chinese medicine

Objective To discuss the curative effect of Chronic Renal Failure by retention enema with the traditional Chinese medicine.Methods 70 CRF patients were randomly divided into.two groups:the treatment group with conventional treatment and retention enema,the control group treated with conventional treatment,the therapeutic effect was observed.Results The symptoms of the two groups were improved in different degree and had significant differences comparatively.The effect of the treatment group was better than the control group.The two groups both had fewer side effects during the period of the treatment.Conclusion Retention enema with the traditional Chinese medicine has the effect of retarding the progress of CRF and also has significantly improved the symptoms and signs of patient.Therefore,it is a relatively safe and efficient means. Key words: Chronic renal failure; Traditional Chinese medicine; Retention enema

Effects of erythropoietin, bromocryptine and hydralazine on testicular function in rats with chronic renal failure

We evaluated the effects of chronic renal failure (CRF) on testicular function and semen physiology. A CRF model was created in 48 male rats by performance of five-sixths nephrectomies in two-stage procedures, and a control (group A) by two-stage sham operation on six male rats. Seven weeks later, serum urea and creatinine concentrations were assessed, and the nephrectomized rats were then equally divided into four groups, B, C, D and E, and treated with saline, erythropoietin, bromocryptine and hydralazine, respectively. Seventeen weeks after the first surgical procedure, the number of fertile rats, the mean values of epididymal sperm content and motility, the outcome of in vitro fertilization, and peripheral serum testosterone concentrations and responses to human chorionic gonadotropin were significantly higher (P < 0.05) in groups A, C and D than in groups B and E. Serum prolactin concentration was significantly higher (P < 0.05) in all groups of nephrectomized rats than in group A. Our results indicate that bromocryptine and erythropoetin improve Leydig cell function, spermatogenesis epididymal sperm maturation, and sperm fertilizing capacity in rats with CRF.

Psychotropic drugs and renal failure: Translating the evidence for clinical practice

The kidney is a primary route of drug elimination; abnormal kidney function is predicted to alter the pharmacokinetics of agents metabolized and/or excreted predominantly through this route. The high prevalence of mental disorders associated with psychotropic drug use in individuals with deteriorating renal function suggests there is a need to investigate the effects of renal failure on psychotropic pharmacokinetics. The aim of this review is to provide a clinically accessible overview of the effect of chronic renal failure on the pharmacokinetics for each of the major classes of prescribed psychotropic agents. All English language articles published between 1977 and 2008 were searched through PubMed, using the following keywords: "renal," "kidney," "pharmacokinetics," "renal impairment," "renal insufficiency," and "renal failure." Each of these search words was cross-referenced with the non-proprietary name of each psychotropic agent. The manufacturer's product insert was also reviewed for some agents for updated dosing. Owing to the lack of adequately powered studies, an inclusive manner was used. Chronic renal failure variably affects the pharmacokinetic parameters of psychotropic drugs. A review of each psychotropic drug is provided, with an emphasis on the individual pharmacokinetic parameters and recommended dosing. The adjudication of safe and effective doses for any psychotropic agent needs to be individualized. Tactics including dosage adjustment, slow titration, and careful monitoring for serious adverse events should be incorporated into practice.

The effect of chronic renal failure on drug metabolism and transport

Background: Chronic renal failure (CRF) has been shown to significantly reduce the nonrenal clearance and alter bioavailability of drugs predominantly metabolized by the liver and intestine. Objectives: The purpose of this article is to review all significant animal and clinical studies dealing with the effect of CRF on drug metabolism and transport. Methods: A search of the National Library of Medicine PubMed was done with terms such as chronic renal failure, cytochrome P450 [CYP], liver metabolism, efflux drug transport and uptake transport, including relevant articles back to 1969. Results: Animal studies in CRF have shown a significant downregulation (40 – 85%) of hepatic and intestinal CYP metabolism. High levels of parathyroid hormone, cytokines and uremic toxins have been shown to reduce CYP activity. Phase II reactions and drug transporters such as P-glycoprotein and organic anion transporting polypeptide are also affected. Conclusion: CRF alters intestinal, renal and hepatic drug metabolism and transport producing a clinically significant impact on drug disposition and increasing the risk for adverse drug reactions.

Effects of chronic renal failure on the expression of connexin 43 in the rat's corpus cavernosum

To explore the mechanism of chronic renal failure (CRF)-related erectile dysfunction (ED). CRF experimental models were established by 5/6 nephrectomy from male Sprague-Dawley rats. Both the rats from the control group (NCRF group, n=6) and the experimental group (CRF group, n=30) were injected with a low dose (80 microg/kg) of apomorphine in the 12th week after resection surgery to measure corresponding penile erections. Western blot method was thereafter conducted to measure the expression of connexin 43 (CX43) in the rat corpus cavernosum in the 12th week after the resection surgery. There was one death in the NCRF group and five in the CRF group. The penile erection ratio of the CRF group was 28% (7/25), whereas that of the NCRF group was 100% (5/5), which presents a significant difference between the two groups (P < 0.05). In terms of penile erection frequency, the average of the CRF group was 1.0 +/- 0.0, which was significantly different from that of the NCRF group (2.2 +/- 0.8) (P < 0.05). As for the expression of CX43 in the rat corpus cavernosum, a notable difference existed between the CRF group (0.21 +/- 0.07) and the NCRF group (0.53 +/- 0.27) (P < 0.01). CRF significantly reduces the erectile function of rats. A close correlation exists between the expression of CX43 in rats' corpus cavernosum and CRF-related ED.

Effect of chronic renal failure on foregut smooth muscle reactivity: an experimental study

Purpose An association between chronic renal failure (CRF) and gastroesophageal reflux (GER) is well known. The aim of this study was to pharmacologically characterize and investigate the possible contribution of smooth muscle reactivity pathways involving GER on the CRF rat model. Material and Methods Chronic renal failure was created in Sprague-Dawley rats by 5 of 6 nephrectomy. The rats were divided into 2 groups: the CRF-induced group (CRF group) and the sham-operated group (control group). Esophageal smooth muscle strips were studied in vitro for their contractile (KCl, carbachol) and relaxant (isoproterenole, serotonin, and papaverine) response to receptor activation in the organ chambers set up. Subsequently, the in vitro lower esophageal sphincter (LES) smooth muscle study was generated by KCl, carbachol, isoproterenole, nicotine, sodium nitroprusside (SNP), and papaverine. Results Compared with controls, esophageal strips taken from CRF-induced rats associated with decreased smooth muscle responses to carbachol, serotonin, and increased response to KCl. Isoproterenole- and papaverine-induced relaxant responses were not affected. Contractility of the isolated LES strips were significantly increased to KCl and carbachol in the CRF group compared with the control group. Similar relaxant responses were obtained in LES strips stimulated by isoproterenole, SNP, and papaverine in the CRF and control group. Nicotine-induced relaxant responses were decreased in the CRF group compared with the control group. Conclusions Our study revealed alterations of receptor-dependent esophageal and LES smooth muscle reactivity in the CRF-induced rats. Impaired foregut smooth muscle reactivity may contribute to the development of GER-related functional abnormalities in patients with CRF.

Differential effect of chronic renal failure on the pharmacokinetics of lidocaine in patients receiving and not receiving hemodialysis

The effect of chronic renal failure (CRF) on the pharmacokinetics of lidocaine, a drug cleared almost exclusively by hepatic metabolism, has thus far only been evaluated in patients undergoing regular hemodialysis. This study had 2 objectives: (1) to investigate the effect of CRF on the pharmacokinetics of lidocaine in both patients undergoing hemodialysis and patients not undergoing hemodialysis and (2) to test the effects of plasma from the patients examined and of lidocaine metabolites possibly accumulated in vivo on lidocaine biotransformation in vitro. In a clinical investigation we studied the kinetics of lidocaine and its metabolites, monoethylglycinexylidide (MEGX) and glycinexylidide (GX), after intravenous injection of 1 mg/kg lidocaine in 15 healthy volunteers (creatinine clearance [CL(cr)] >80 mL/min x 1.73 m(-2)), 10 subjects with moderate renal insufficiency (CL(cr) between 30 and 60 mL/min x 1.73 m(-2)), 10 subjects with severe renal insufficiency (CL(cr) <30 mL/min x 1.73 m(-2)), and 10 functionally anephric patients undergoing long-term hemodialysis. In experiments in vitro we determined the effects of plasma and GX on the formation rate of the primary lidocaine metabolite, MEGX, by use of human liver microsomes. In patients not undergoing hemodialysis, lidocaine kinetic parameters were altered in proportion to the degree of renal function impairment, but only in patients with severe renal insufficiency were differences statistically significant: clearance was about half that of control subjects (mean +/- SD, 6.01 +/- 2.54 mL/min x kg versus 11.87 +/- 2.97 mL/min x kg; P < .001), and half-life was approximately doubled (4.55 +/- 1.71 hours versus 2.24 +/- 0.55 hours, P < .001). No such alterations were observed in patients undergoing regular hemodialysis, whose values were similar to those of the control group. The steady-state volume of distribution and MEGX levels were independent of renal function, whereas GX levels were more than double those of control subjects (P < .05) in all CRF groups. No inhibitory effect of plasma was observed, for any of the subjects examined, on lidocaine biotransformation in vitro. GX was found to be a competitive inhibitor, but its apparent inhibition constant value (52 +/- 6 micromol/L) was 2 orders of magnitude higher than its concentrations in vivo. Our in vivo findings have both clinical and methodologic implications: (1) Lidocaine dose adjustment may be required in patients with severe renal insufficiency who are not receiving hemodialysis. (2) Results of studies evaluating the effect of CRF on metabolic drug disposition are not of general validity, unless both patients undergoing hemodialysis and patients not undergoing hemodialysis have been examined. Our in vitro observations exclude that impairment of lidocaine disposition is the result of direct inhibition of metabolizing enzymes by accumulated metabolites or uremic toxins. Alternative mechanisms, suggested by the results of recent in vitro studies, are discussed.

Effect of Chronic Renal Failure on Arginase and Argininosuccinate Synthetase Expression

Background:L-arginine (L-arg) participates in numerous biological functions including urea and nitric oxide synthesis. Sources of L-arg include dietary proteins and endogenous synthesis by argininosuccinate synthetase and argininosuccinate lyase. L-arg is converted to urea by arginase I in the liver and arginase II in the kidney. Normally, the liver fully consumes L-arg for urea generation and does not contribute to its circulating pool. Instead, much of the circulating L-arg is produced by the kidney. If true, plasma L-arg should be severely reduced in chronic renal failure (CRF); however, plasma L-arg is frequently unchanged in CRF. We hypothesized that preservation of plasma L-arg in CRF may be, partly, due to downregulation/inhibition of arginase. Methods: Argininosuccinate synthetase, arginase I and II protein abundance and activity were measured in the liver and kidneys of rats 6 weeks after 5/6 nephrectomy or sham operation. In addition, arginase activity was measured in the presence of different urea concentrations to simulate azotemia in vitro. Results: Arginases I and II protein abundance as well as arginase activity in the liver, measured in the physiological buffer, were similar among the CRF and control groups. However, in vitro experiments simulating a uremic milieu revealed a marked concentration-dependent inhibition of arginase activity by urea in the tissue lysates. CRF had no significant effect on argininosuccinate synthetase abundance in the kidney, liver, spleen or intestine. Conclusions: Although CRF does not change the abundance or intrinsic properties of arginase, the inherent rise in urea concentration inhibits its enzymatic activity. The latter, in turn, attenuates L-arg catabolism and urea production and, thereby, mitigates the fall in plasma L-arg.

Effects of Chronic Renal Failure on the Pharmacokinetics of Ruboxistaurin and its Active Metabolite 338522

Ruboxistaurin, a specific inhibitor of the beta(1) and beta(2) isoforms of protein kinase C, is currently in clinical development for the treatment of several diabetic microvascular complications. The major metabolite, N-desmethyl ruboxistaurin (metabolite 338522), is equipotent in its inhibitory activity. The elimination of ruboxistaurin and its metabolites is primarily through bile and the faecal route, with urinary excretion constituting only a minor route. To assess the effects of chronic renal insufficiency on the pharmacokinetics of ruboxistaurin and metabolite 338522. Six healthy subjects (creatinine clearance >80 mL/min/1.73 m(2)) and six end-stage renal disease (ESRD) subjects requiring long-term haemodialysis were studied. All subjects received a single oral dose of ruboxistaurin 32 mg followed by serial blood sampling up to 72 hours. ESRD subjects underwent haemodialysis approximately 58 hours after dosing, with blood samples obtained immediately before and after dialysis. No differences were observed in the pharmacokinetic parameters (area under the plasma concentration-time curve from time zero to infinity [AUC(infinity)], maximum plasma concentration [C(max)] and elimination half-life [t(1/2)]) of ruboxistaurin and metabolite 338522 between healthy and ESRD subjects Plasma concentrations of ruboxistaurin were below the lower limit of quantification by the time of haemodialysis. The predicted post-dialysis plasma concentrations of metabolite 338522 were not statistically different from the observed values (p=0.163). Ruboxistaurin was well tolerated in both groups of subjects. These results indicate that the kidney is not an important route of metabolism or excretion for ruboxistaurin and metabolite 338522. Based on the pharmacokinetic and tolerability findings, no formal dosage adjustment of ruboxistaurin should be required for patients with any degree of renal impairment who are undergoing haemodialysis.

Effects of chronic renal failure on hypothalamo–pituitary –testicular axis function and fertility in rats and humans

Effects of chronic renal failure on hypothalamo–pituitary –testicular axis function and fertility in rats and humans

The effects of chronic renal failure on siblings

It is well recognised that chronic illness in children can have a significant effect upon siblings, but their viewpoints need to be sought if we are to change our practice. We conducted semi-structured interviews at home with 15 siblings (8 males) aged 8-12 years whose brother/sister were on chronic dialysis or had received or were waiting for a renal transplant. The interviews were analysed using a grounded theory approach. The children also completed the Spence Children's Anxiety Scale (SCAS), which revealed no statistically significant evidence that they were exhibiting chronic clinical anxiety. Qualitative data indicated that siblings had a variety of concerns concerning their own health and that of their siblings and worried about the effects on family routine and separation from parents. The siblings felt more protective towards their chronically ill sibling and felt that they themselves needed to be more grown up. The study has implications for our clinical practice in that our psychosocial assessment of families needs to include an assessment of sibling needs and siblings should be involved when preparing patients for chronic renal failure treatment. The importance of maintaining family routines should be emphasised, as well as trying to involve siblings in unit activities.

Effects of chronic renal failure on caveolin-1, guanylate cyclase and AKT protein expression

Chronic renal failure (CRF) has been documented to cause oxidative stress and alter nitric oxide (NO) metabolism. However, the effect of CRF on proteins related to NO bioactivity has not been investigated. The present study was designed to test the hypothesis that CRF would induce changes in caveolin-1 (Cav-1), soluble guanylate cyclase (sGC) and Akt, three proteins important in regulating NO synthase (NOS) functionality. Male Sprague-Dawley rats were randomized to CRF via 5/6 nephrectomy or sham-operated control groups. After 6 weeks, body weight, blood pressure, creatinine clearance, plasma creatinine, urinary cyclic guanosine monophosphate (cGMP) and immunodetectable levels of Cav-1, sGC and Akt were determined in the renal, aorta, heart and liver tissues from both groups. CRF resulted in marked decreases in body weight and creatinine clearance, and elevation of blood pressure and plasma creatinine. An apparent upregulation of sGC protein abundance in renal tissue was noted, with no change in aorta, heart and liver. This was accompanied by a reduction in urinary cGMP levels, indicative of sGC dysfunction. Cav-1 protein abundance was increased in aortic, liver and renal tissues. In contrast, CRF depressed Akt abundance in aorta, heart and liver tissues. These data document that CRF is characterized by alteration in the abundance of proteins regulating NO function in hepatic, vascular, cardiac and renal tissues, and a decrease in cGMP, which contributes to hypertension and changes in NO bioactivity previously noted in this model.

Effect of age and disease on taste perception

Abnormalities in taste function may contribute to poor dietary intake in the elderly, and in patients with renal failure or cancer. This study examined the effect of age on taste thresholds, and taste thresholds adjusted for age, in patients with renal failure with and without dialysis, and patients with cancer receiving chemotherapy and/or radiotherapy. Three groups of healthy volunteers aged 21–34 ( n = 26), 36–61 ( n = 13), and 69–94 ( n = 24), were recruited for the study on the effect of age. Nineteen patients with chronic renal failure on chronic ambulatory peritoneal dialysis (CAPD) and 11 age-matched chronic renal failure patients not yet requiring dialysis were recruited to examine the effect of chronic renal failure on taste function. Twenty-four inpatients with various types of cancer were recruited from a clinical oncology ward. Taste threshold was measured using commercial flavors supplied by Firmenich (pork, beef) and the ascending forced-choice method. Results showed that taste threshold increased with age. No abnormality in taste threshold was observed in patients with chronic renal failure with and without dialysis, and in patients with cancer. However, altered taste occurred in a large number of these patients. Abnormal taste function is present in healthy elderly people, and in patients with chronic renal failure and cancer. The nature of the abnormality differs among these groups, consisting of elevation of taste threshold in the elderly, and dysgeusia in those with disease.

Effect of chronic renal failure with metabolic acidosis on alanine metabolism in isolated liver cells

<h2>Abstract</h2> <i>Background & aims</i>: Decreased ureagenesis and gluconeogenesis from alanine have been reported during chronic renal failure in rat. This study addressed the respective roles of plasma-membrane transport and intracellular metabolism in these abnormalities of alanine pathways. <i>Methods</i>: In hepatocytes isolated from uremic and control rats, we investigated: (1) the influence of uremia on gluconeogenesis and ureagenesis during incubations with alanine; (2) the kinetics of alanine plasma-membrane transport; (3) the relationships between intracellular alanine concentrations and its metabolism. Plasma-membrane alanine transport was assessed after addition of alanine (2mM) by measuring its intracellular accumulation from 0 to 10min, in the presence of a transaminase inhibitor. Alanine metabolism was studied in perifused hepatocytes by measuring intracellular alanine concentration together with urea, glucose and lactate production in the presence of increasing concentrations of alanine (0–8mM). <i>Results</i>: Uremic rats showed decreased plasma bicarbonate. Uremia induced (<i>P</i><0.05) a decrease in both gluconeogenesis (36%) and ureagenesis (22%). Alanine plasma-membrane transport decreased by 20% during uremia. During perifusions, uremia induced a 30–40% decrease in urea, glucose, and lactate production without modifying intracellular alanine concentration. <i>Conclusions</i>: In uremic rats with acidosis, hepatocyte alanine utilization was impaired at both plasma-membrane transport and intracellular transamination steps.

Effect of chronic renal failure with metabolic acidosis on alanine metabolism in isolated liver cells

Background & aims: Decreased ureagenesis and gluconeogenesis from alanine have been reported during chronic renal failure in rat. This study addressed the respective roles of plasma-membrane transport and intracellular metabolism in these abnormalities of alanine pathways. Methods: In hepatocytes isolated from uremic and control rats, we investigated: (1) the influence of uremia on gluconeogenesis and ureagenesis during incubations with alanine; (2) the kinetics of alanine plasma-membrane transport; (3) the relationships between intracellular alanine concentrations and its metabolism. Plasma-membrane alanine transport was assessed after addition of alanine (2 mM) by measuring its intracellular accumulation from 0 to 10 min, in the presence of a transaminase inhibitor. Alanine metabolism was studied in perifused hepatocytes by measuring intracellular alanine concentration together with urea, glucose and lactate production in the presence of increasing concentrations of alanine (0–8 mM). Results: Uremic rats showed decreased plasma bicarbonate. Uremia induced ( P<0.05) a decrease in both gluconeogenesis (36%) and ureagenesis (22%). Alanine plasma-membrane transport decreased by 20% during uremia. During perifusions, uremia induced a 30–40% decrease in urea, glucose, and lactate production without modifying intracellular alanine concentration. Conclusions: In uremic rats with acidosis, hepatocyte alanine utilization was impaired at both plasma-membrane transport and intracellular transamination steps.

Effect of chronic renal failure on UDP-glucuronosyltransferase (UGT) enzymes in liver and kidney

In Chronic Renal Failure (CRF) patients, the hepatic clearance of many drugs is altered, which could be due to downregulation of hepatic enzymes. UGT1A6 is an important Phase II enzyme involved in the glucuronidation of planar phenols. The purpose of this study was to determine the catalytic activity and protein levels of rat hepatic and renal UGT1A6. CRF was induced in male Sprague-Dawley rats (n=4) by 5/6th Nephrectomy model in which two-thirds of left kidney and complete right kidney were excised and animals were sacrificed after 5 weeks; control animals (n=5) were sham operated and pair fed. UGT1A6 activity was determined by the glucuronidation of 4-methylumbelliferone (4MU) and Vmax and Km values were determined for hepatic UGT1A6. Protein content of UGT1A6 was examined by Western blot using a polyclonal antibody. There was no difference between CRF and CPF rats in hepatic and renal 4MU UGT activity (CRF liver: 32.08±4.82 nmole/min/mg, CPF liver: 30.26±5.54 nmole/min/mg; CRF kidney: 14.30±5.04 nmole/min/mg, CPF kidney: 13.63±5.55 nmole/min/mg) and UGT1A6 protein level. No difference was observed in the Vmax and Km values between the two groups. UGT1A6 protein levels were similar between the liver and the kidney. However the UGT1A6 activity was ~2-fold higher in the liver than the kidney, suggesting that 4MU may also be metabolized by other UGT isozymes in liver. CRF does not appear to influence the protein levels or catalytic activity of UGT1A6. Clinical Pharmacology & Therapeutics (2004) 75, P86–P86; doi: 10.1016/j.clpt.2003.11.327