Chronic Renal Failure Kidney Research Articles

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

Upregulation of cytochrome P450 1A2 in chronic renal failure: does oxidized tryptophan play a role?

Earlier studies from this laboratory have shown that L-tryptophan, after oxidation by either UV-irradiation or ozone induces aryl hydrocarbon receptor (AhR) transformation and binding of the liganded AhR complex to its specific DNA recognition site, thereby inducing transcription of Cyp1a1 gene with concomitant increase of CYP1A1 protein and activity in cells in culture. In the present investigation, we investigated the expression of CYP1A2 in the liver and kidney in chronic renal failure (CRF). The results demonstrate that CYP1A2 protein abundance was upregulated in both the liver and kidney tissues of the CRF group compared to the sham-operated controls.

Effect of hemodialysis on carnitine levels in children with chronic renal failure.

Impaired structural and metabolic integrity of the kidney in chronic renal failure (CRF) effects carnitine metabolism by means of many factors. Depletion due to hemodialysis (HD) is one of the major concerns. The aim of the study was to investigate the effects of chronic renal failure and HD on plasma free carnitine (FC) concentrations in children. Plasma FC concentrations were measured in age-matched 14 undialyzed patients, 20 dialyzed patients and 12 healthy children. In the HD group, measurements were done pre- and postdialysis and an hour after ceasing HD. None of the children have been receiving exogenous l-carnitine replacement. Plasma FC concentrations on either HD or conservative treatment were found to be decreased as compared to the healthy subjects (P < 0.001 and P = 0.001, respectively). The patients on HD had lower levels of plasma FC at the predialysis period than those on conservative treatment (P = 0.01). The FC levels significantly dropped at the postdialysis period as compared to those at the predialysis period (P < 0.001), but recovered at 1 h after ceasing HD. The mean duration of HD did not correlate with plasma FC levels at predialysis period. Children with CRF, either dialyzed or undialyzed, have decreased plasma FC levels. Hemo-dialysis treatment significantly depletes plasma FC concentrations during the procedure, but predialysis levels are reached 1 hr after ceasing HD.

Radiographic techniques in renal parenchymal disease.

In his or her practice, the nephrologist usually has a substantial number of patients on dialysis for chronic renal failure. The longer a patient remains on either peritoneal dialysis or hemodialysis, the more at risk he or she is of developing acquired cystic disease of the kidney and renal cell carcinoma. Due to recent developments such as lower osmolar intravenous contrast media, sonography, and magnetic resonance imaging, the radiologist has the ability to assess the kidney in chronic renal failure with a growing number of less-invasive modalities. The lower osmolar agents appear to be less toxic to the kidney. Thus, they can be used when the benefit of the information obtained from a necessary procedure, eg, computed tomography or coronary arteriography, surpasses the risk. Duplex Doppler sonography can assess the pressure of flow in the arcuate vessels of the kidney with measurements of the resistive index. The resistive index is a proven tool for assessing rejection of the renal allograft--another newer application is in the diagnosis of obstruction. An elevated resistive index found in a kidney with a dilated collecting system confirms the diagnosis of obstruction. Studies are being made on its application in other renal disease processes as well.

慢性腎不全腎のCT

慢性腎不全腎のCT

Amidation of C3 at the thiolester site: stimulation of chemiluminescence and phagocytosis by a new inflammatory mediator.

We studied the ability of particle-bound and fluid-phase C3b monomers and monomeric amidated C3 (prepared by treatment of purified human C3 with ammonium chloride or methylamine) to stimulate chemiluminescence of human polymorphonuclear leukocytes (PMN) and monocytes and to promote phagocytosis in the absence of antibody. Particle-bound C3b evoked chemiluminescence from both PMN and monocytes, and fluid-phase C3b (0.5 mg/ml) elicited significant chemiluminescence from PMN but not from monocytes. Amidated forms of C3, both particle bound and fluid phase, were potent stimulators of chemiluminescence from phagocytic cells and caused a significantly greater response than did C3b. The phagocytosis of 1-micron microspheres by PMN and monocytes was enhanced by coating them with purified C3b in an antibody-free system. Microspheres coated with amidated C3 were avidly phagocytized, and to a greater degree than were C3b-coated microspheres. In a direct binding assay with tritiated monomeric C3b and amidated C3, the affinity of the PMN complement receptor type 1 for C3b (Ka = 4.9 X 10(7) L/M) was similar to that for amidated C3 (Ka = 5.7 X 10(7) L/M). However, there was a fourfold increase in the number of apparent binding sites for amidated C3. This increase did not reflect binding of amidated C3 to the complement receptor type 3, because blocking of CR3 with the monoclonal antibody OKM 10 failed to decrease binding of amidated C3. In sites of increased ammoniagenesis, such as the kidney in chronic renal failure, amidated C3 may play a role as an inflammatory mediator by stimulating oxidative metabolism in phagocytic cells.

The artificial kidney in chronic renal failure.

Hemodialysis has proved valuable in improving and stabilizing patients in terminal chronic uremia.In this analysis of 71 patients in whom hemodialysis was used, the diagnosis and therapeutic response were definitely correlated. The highest percentage of favorable responses was obtained in cases of polycystic renal disease; none of the patients with subacute glomerulonephritis responded favorably.The prognosis was worse in chronic glomerulonephritis when hypertension or extensive glomerular destruction was present. Factors such as age, congestive heart failure and active infection were not significant in predicting a response.

3 hardly classical indications for blod purification by the artificial kidney

SummaryThe indications for using the artificial kidney in 3 cases (crush syndrome, severe diabetic acidosis and chronic kidney disease) are discussed.In the patient with crush syndrome recovery followed 4 haemodialyses. It was demonstrated that prolonged dialysis drain large amounts of cellular electrolytes.In the diabetic patient, 3 hours-haemodialysis entirely corrected the marked acid-base imbalances.The use of the artificial kidney in chronic renal failure is discussed in the light of the results obtained in our case and in those previously reported in the literature.