Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0022672 (acute tubular necrosis)
 2,175 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Male adult Sprague-Dawley rats were treated for 14 days with either rapamycin (RAP, 1.5 mg/kg/d i.p.) in carboxymethylcellulose (RAP/CMC) or polyethyleneglycol (RAP/PEG), cyclosporine (CsA, 15 mg/kg/d by gavage) or with the appropriate drug vehicles. Biochemical indices of renal function and integrity were determined throughout the experimental period, at the end of which the rats were killed and kidneys examined histologically. All animals gained weight at a similar rate to untreated animals except those treated with RAP; RAP/PEG animals were lighter on day 14 compared with day 0 values, whilst RAP/CMC animals were lighter only in comparison with CMC-only controls on day 14. Significant increases in urinary flow rate (UFR) were found in each drug treatment group. RAP/CMC, RAP/PEG and CsA caused mild renal functional impairment, but only with CsA was there a significant reduction in 51Cr-EDTA clearance. Significant enzymuria, resulting from drug but not vehicle administration, was observed only in the CsA-treatment group. Increased plasma and urinary glucose levels, elevated in all drug-treatment groups, were related to increased UFR. Kidneys of RAP-treated rats appeared normal, whereas mild, focal, acute tubular necrosis was evident in all CsA-tested animals. Pancreases of all drug-treated animals were histologically normal.
 ...
PMID:The effect of rapamycin on renal function in the rat: a comparative study with cyclosporine. 168 33

Sprague-Dawley rats were treated for 14 days with rapamycin (RAP; 1.5 mg/kg/day i.p.), cyclosporine (15 mg/kg/day by gavage), both drugs in combination, or appropriate drug vehicles. Hematological parameters and biochemical indices of renal and hepatic function were determined throughout the experimental period, at the end of which the rats were killed and tissues examined histologically. There was a significant reduction in weight gain in RAP- but not CsA-treated animals, while rats given both drugs showed a reduction in body weight over the 14-day experimental period. There were no significant alterations in absolute or differential white blood cell counts or in T or B cell numbers, except in the drug combination group, in which an absolute lymphopenia was detected on day 14. Small but significant increases in urinary flow rate (UFR) were found with either drug alone, and there was a marked (4-fold) increase in UFR in response to drug combination. Both RAP and CsA caused a small elevation in serum creatinine concentrations, but only with CsA was there a significant elevation in urinary enzyme activity and reduction in 51Cr. EDTA clearance. The drug combination exacerbated renal impairment, the extent of which was greater than the additive effect of either drug alone. Hyperbilirubinemia of similar magnitude was observed in rats receiving either CsA alone or in combination with RAP. In contrast to its effect on renal function, however, the CsA+RAP combination was without additional effect on liver function compared with the minor changes seen with either drug alone. Plasma and urinary glucose levels were elevated in all drug treatment groups and especially in animals given both drugs. RAP administration did not significantly affect whole-blood CsA concentrations, although the possibility of a pharmacokinetic interaction cannot be totally excluded. Histological studies revealed striking thymic medullary atrophy in all drug-treated animals. In addition, all rats given RAP showed focal myocardial necrosis of overall mild-moderate severity. Kidneys of RAP-treated rats appeared normal, whereas mild, focal, acute tubular necrosis was evident in all CsA-treated animals. Pancreases of all drug-treated animals were normal.
 ...
PMID:Toxicity of rapamycin--a comparative and combination study with cyclosporine at immunotherapeutic dosage in the rat. 187 90

Positron emission tomography (PET) is perfectly suited for quantitative imaging of the kidneys, and the recent improvements in detector technology, computer hardware, and image processing software add to its appeal. Multiple positron emitting radioisotopes can be used for renal imaging. Some, including carbon-11, nitrogen-13, and oxygen-15, can be used at institutions with an on-site cyclotron. Other radioisotopes that may be even more useful in a clinical setting are those that either can be obtained from radionuclide generators (rubidium-82, copper-62) or have a sufficiently long half-life for transportation (fluorine-18). The clinical use of functional renal PET studies (blood flow, glomerular filtration rate) has been slow, in part because of the success of concurrent technologies, including single-photon emission computed tomography (SPECT) and planar gamma camera imaging. Renal blood flow studies can be performed with O-15-labeled water, N-13-labeled ammonia, rubidium-82, and copper-labeled PTSM. With these tracers, renal blood flow can be quantified using a modified microsphere kinetic model. Glomerular filtration can be imaged and quantified with gallium-68 EDTA or cobalt-55 EDTA. Measurements of renal blood flow with PET have potential applications in renovascular disease, in transplant rejection or acute tubular necrosis, in drug-induced nephropathies, ureteral obstruction, before and after revascularization, and before and after the placement of ureteral stents. The most important clinical application for imaging glomerular function with PET would be renovascular hypertension. Molecular imaging of the kidneys with PET is rather limited. At present, research is focused on the investigation of metabolism (acetate), membrane transporters (organic cation and anion transporters, pepT1 and pepT2, GLUT, SGLT), enzymes (ACE), and receptors (AT1R). Because many nephrological and urological disorders are initiated at the molecular and organelle levels and may remain localized at their origin for an extended period of time, new disease-specific molecular probes for PET studies of the kidneys need to be developed. Future applications of molecular renal imaging are likely to involve studies of tissue hypoxia and apoptosis in renovascular renal disease, renal cancer, and obstructive nephropathy, monitoring the molecular signatures of atherosclerotic plaques, measuring endothelial dysfunction and response to balloon revascularization and restenosis, molecular assessment of the nephrotoxic effects of cyclosporine, anticancer drugs, and radiation therapy. New radioligands will enhance the staging and follow-up of renal and prostate cancer. Methods will be developed for investigation of the kinetics of drug-delivery systems and delivery and deposition of prodrugs, reporter gene technology, delivery of gene therapy (nuclear and mitochondrial), assessment of the delivery of cellular, viral, and nonviral vectors (liposomes, polycations, fusion proteins, electroporation, hematopoietic stems cells). Of particular importance will be investigations of stem cell kinetics, including local presence, bloodborne migration, activation, seeding, and its role in renal remodeling (psychological, pathological, and therapy induced). Methods also could be established for investigating the role of receptors and oncoproteins in cellular proliferation, apoptosis, tubular atrophy, and interstitial fibrosis; monitoring ras gene targeting in kidney diseases, assessing cell therapy devices (bioartificial filters, renal tubule assist devices, and bioarticial kidneys), and targeting of signal transduction moleculas with growth factors and cytokines. These potential new approaches are, at best, in an experimental stage, and more research will be needed for their implementation.
 ...
PMID:Future direction of renal positron emission tomography. 1635 95

The heavy metal lead (Pb) is a major environmental and occupational hazard. Epidemiological studies have demonstrated a strong association between lead exposure and the presence of chronic kidney injury. Some studies have suggested that chelation therapy with calcium disodium ethylenediaminetetraacetic acid (calcium disodium EDTA) might help decrease the progression of chronic kidney disease among patients with measurable body lead burdens. However, calcium disodium EDTA chelation in lead exposure is controversial due to the potential for adverse effects such as acute tubular necrosis. Therefore, we investigated the available randomized controlled trials assessing the renoprotective effects of calcium disodium EDTA chelation therapy. Our meta-analysis shows that calcium disodium EDTA chelation therapy can effectively delay the progression of chronic kidney disease in patients with measurable body lead burdens reflected by increasing the levels of estimated glomerular filtration rate (eGFR) and creatinine clearance rate (Ccr). There appears to be no conclusive evidence that calcium disodium EDTA can decrease proteinuria.
...
PMID:Is lead chelation therapy effective for chronic kidney disease? A meta-analysis. 2434 61