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PubMed1982

The metabolic disposition of flucloxacillin in patients with impaired kidney function.

The fate of flucloxacillin and its active metabolite hydroxyflucloxacillin was studied in a group of patients with impaired kidney function. Flucloxacillin was administered orally or intravenously. Peak levels of hydroxyflucloxacillin were obtained between 150 and 250 min after the administration of flucloxacillin. The plasma concentrations obtained after a therapeutic dose of flucloxacillin were well above the concentration (i.e. 1-2 microgram/ml) generally considered to be the effective minimum for isoxalyl penicillins. The plasma half life of the metabolite was twice as long as that of flucloxacillin (295 min and 154 min, respectively). The nonprotein-bound fraction of hydroxyflucloxacillin in plasma from patients was twice as large as that of its parent compound (16.2 vs. 8.1%). This was also observed in normal human plasma, although protein binding in the latter was higher than in uraemic plasma. Some accumulation of hydroxyflucloxacillin may occur during flucloxacillin therapy with dosage intervals of 6 h.

Adult↗
PubMed1982

Kidney function and size in type 1 (insulin-dependent) diabetic patients before and during growth hormone administration for one week.

Kidney function and size were studied in seven well-controlled male Type 1 (insulin-dependent) diabetic patients before and after administration of highly purified human growth hormone for one week. Glomerular filtration rate, renal plasma flow (steady state infusion technique with urinary collections using 125I-iothalamate and 131I-hippuran), kidney size (ultrasonic scanning) and urinary excretion rates of albumin and beta-2-microglobulin were measured. Highly purified growth hormone was injected subcutaneously, 2 IU in the morning and 4 IU in the evening. The growth hormone dosage applied induced an elevation in plasma growth hormone concentration from the normal level seen in these very well controlled diabetics to levels within the range previously demonstrated in normally controlled Type 1 diabetic patients. During the week of growth hormone administration, glycaemic control was maintained unchanged by increasing the insulin dose by 79 +/- 9% (mean +/- SEM). Glomerular filtration rate increased from 122 +/- 3 to 131 +/- 3 ml/min X 1.73 m2 (p less than 0.05) and renal plasma flow increased from 535 +/- 10 to 569 +/- 22 ml/min x 1.73 m2 (p less than 0.05). Kidney size changed from 128 +/- 5 to 133 +/- 5 ml/1.73 m2 (NS). Urinary excretion rates of albumin and beta-2-microglobulin were unchanged. The present findings suggest that the growth hormone elevation typically found in Type 1 diabetic patients with reasonable clinical control, contributes to the enhanced glomerular filtration rate and renal plasma flow present in that disease.

Adult↗
PubMed1981

Correlation of changes in blood chemistry with pathological changes in the animal's body: II Electrolytes, kidney function tests, serum enzymes, and liver function tests.

The numerous physiological and nutritional factors which influence the concentration of serum calcium are considered. The causes of hypercalcaemia and hypocalcaemia are briefly discussed, with particular reference to the clinical symptoms and pathology. The effect of the acid-base status on the serum-ionized calcium level is stressed. The causes of changes in the serum concentrations of phosphorus and magnesium are briefly reviewed, along with the abnormalities of lactate, pyruvate, and hydrogen ion concentrations. The kidney function tests, blood urea nitrogen, serum creatinine, and the renal clearance tests are discussed, with emphasis placed on correlating their results with the findings from repeated urinalyses. The important physiologic influences and pathological processes which result in changes in the concentrations of these parameters are delineated. The causes of increases in the serum enzymes, alkaline phosphatase, alanine transaminase, asparate transaminase, lactic dehydrogenase, sorbitol dehydrogenase, glutamic dehydrogenase, gamma glutamyl transpeptidase, creatinine phosphokinase, amylase and lipase are discussed. The changes in serum bilirubin concentration and its components are fully described, with emphasis placed on the correlation of the findings with urinalysis data and the complexities resulting from the numerous pathologic conditions causing jaundice. These conditions are listed for each of the domestic animals. The other liver function tests, bromosulphthalein dye retention or excretion, serum uric acid and blood ammonia concentration are briefly considered. All the tests described are very useful, and frequently essential, in aiding the veterinary practitioner to arrive at a diagnosis and prognosis, but they never replace clinical acumen.

Animals↗
PubMed2003

Kidney function during and after withdrawal of long-term irbesartan treatment in patients with type 2 diabetes and microalbuminuria.

OBJECTIVE: Irbesartan is renoprotective in patients with type 2 diabetes and microalbuminuria. Whether the observed reduction in microalbuminuria is reversible (hemodynamic) or persistent (glomerular structural/biochemical normalization) after prolonged antihypertensive treatment is unknown. Therefore, the present substudy of the Irbesartan in Patients with Type 2 Diabetes and Microalbuminuria Study (IRMA-2) investigated the reversibility of kidney function changes after withdrawal of 2 years' antihypertensive treatment. RESEARCH DESIGN AND METHODS: The substudy included 133 hypertensive type 2 diabetic patients with persistent microalbuminuria in IRMA-2, randomized to double-masked treatment with either placebo, irbesartan 150 mg, or irbesartan 300 mg o.d. for 2 years. Arterial blood pressure, overnight urinary albumin excretion rate, and glomerular filtration rate (GFR) were determined repeatedly. RESULTS: Baseline characteristics were similar in the placebo, irbesartan 150-mg, and irbesartan 300-mg groups. At the end of the study, mean arterial blood pressure (MABP) was similarly lowered to 105 +/- 2 (mean +/- SE), 103 +/- 2, and 102 +/- 2 mmHg, respectively (P < 0.05 versus baseline), and urinary albumin excretion rate reduced by 8% (-16 to 27) (NS), 34% (95% CI 8-53), and 60% (46-70) (P < 0.05). Rates of decline in GFR were 1.3 +/- 0.7, 1.2 +/- 0.7, and 1.0 +/- 0.8 ml. min(-1). 1.73 m(-2) per month, respectively, during the initial 3 months of the study and 0.3 +/- 0.1, 0.3 +/- 0.1, and 0.4 +/- 0.1 ml. min(-1). 1.73 m(-2) per month in the remaining study period. One month after withdrawal of all antihypertensive medication, MABP remained unchanged in the placebo group, 105 +/- 2 mmHg, but increased significantly in the irbesartan groups, to 109 +/- 2 and 108 +/- 2 mmHg, respectively. Compared with baseline, urinary albumin excretion rate was increased by 14% (-17 to 54) in the placebo group and by 11% (-26 to 65) in the irbesartan 150-mg group but was persistently reduced by 47% (24-73) in the irbesartan 300-mg group (P < 0.05). GFR levels increased to baseline values in the placebo group and approached initial levels in irbesartan groups. CONCLUSIONS: Persistent reduction of microalbuminuria after withdrawal of all antihypertensive treatment suggests that high-dose irbesartan treatment confers long-term renoprotective effects.

Albuminuria↗
PubMed1987

[The significance of renal prostaglandins for kidney function in early childhood].

When comparing iatrogenic inhibition with endogenous stimulation of renal prostaglandin production, the role of this mediator and modulator system for renal function becomes apparent. Renal perfusion and glomerular filtration as well as modulation of tubular function with respect to electrolyte and water excretion is significantly influenced by renal prostaglandin activity. Treatment with the prostaglandin cyclooxygenase inhibitor indomethacin reduces the endogenous creatinine clearance by about fifty percent in a state of a diminished circulatory blood volume, such as may exist during left-to-right shunting across a persistent ductus arteriosus in preterm infants. In addition, urinary electrolyte and water excretion is reduced by increased tubular absorption leading to marked oliguria. In contrast, electrolytes and water are lost in congenital renal tubular disorders associated with increased prostaglandin E2 (PGE2) activity (a so called hyperprostaglandin E syndrome). Patients with this renal disorder require a permanent high dosed indomethacin therapy. After this pharmacotherapy has brought electrolyte and water metabolism into balance, no deterioration of glomerular filtration and renal perfusion was observed. This is in accordance with the general principle that renal function only becomes dependent on the vasodilatory activity of renal prostaglandins in a stress situation resulting in the threat of hypoperfusion. It is essential to bear in mind the physiological and pathophysiological role of renal prostaglandins, when prescribing frequently administered prostaglandin cyclooxygenase inhibitors like aspirin, paracetamol or indomethacin in pediatrics. Otherwise, renal function may deteriorate or the kidney will be irreversibly damaged.

Angiotensin II↗
PubMed1996

Evaluation of gamma camera-based measurement of individual kidney function using iodine-123 orthoiodohippurate.

Gamma camera-based clearance techniques which use the renal uptake ratio (RUR) of the radiotracer are available to estimate the effective renal plasma flow (ERPF) and glomerular filtration rate. To evaluate the accuracy of these techniques, we measured RUR by an optimized procedure and compared it with standard ERPF. Iodine-123 orthoiodohippurate (OIH) scintigraphy and simultaneous para-aminohippurate clearance study for measuring standard ERPF were performed in three hospitals in 24 patients with normal or mildly impaired renal function. 123I-OIH was injected intravenously and 10-s consecutive imaging of the kidneys was started when the abdominal aorta was seen. The attenuation coefficient for 123I was measured in each hospital using the same water-equivalent absorption materials and used for the attenuation correction. After subtracting background radioactivity, RURs were defined as the count ratios of fractional renal uptakes based on the integral from 1 to 2, 2 to 3, 1.5 to 2.5 and 1 to 3 min after the injection of 123I-OIH in relation to injected doses using the following three procedures in respect of attenuation correction: (1) RUR without attenuation correction, (2) RUR with fractional renal uptake corrected by the measured attenuation coefficient, (3) RUR with the total injected dose corrected by the absorption material. To decide upon the appropriate correction method and time interval, RURs were compared with standard ERPF. Among the three correction methods, procedure 2 showed the highest correlation between RUR and standard ERPF, but the correlation coefficient was low (r=0.75). No significant difference was observed among the RURs of each time interval. Individual kidney function measured from early renal uptake may be inaccurate even when appropriate correction is made for attenuation, background activity or time lag between injection and data acquisition. Gamma camera-based measurement of renal function using 123I-OIH is limited with regard to accuracy and reproducibility, though it is convenient and non-invasive.

Adult↗
PubMed2005

Influence of occupational exposure to organic solvents on kidney function.

Exposure to nephrotoxic substances may cause renal tubular and glomerular dysfunction. The aim of the paper was to evaluate, based on literature reports, whether occupational exposure to organic solvents entails a risk of renal dysfunction. The results of the studies performed over the last twenty years are contradictory. In workers occupationally exposed to organic solvents, tubular, glomerular, or no effects were found. The lack of association between the renal effects and the intensity or duration of exposure was reported in most of the studies. It has been suggested that this can be attributed to an individual susceptibility. Available information points to a possibility of mild renal effects, but not to a serious influence on the kidney function at the current levels of occupational exposure to organic solvents. Biological monitoring of early effects can help identify individuals susceptible to nephrotoxicity of this group of chemicals.

Environmental Monitoring↗
PubMed1978

Validity of 99mTc dimercaptosuccinic acid renal uptake for an assessment for individual kidney function.

99mTc dimercaptosuccinic acid is a new renal scanning agent that provides a good quality of renal image as a result of preferential cortical accumulation and also makes feasible a quantitative assessment of separate kidney function, correlating well with renal plasma flow obtained from a 131I hippuran renogram of each kidney. By measuring the dimercaptosuccinic acid uptake, the cortical functioning nephrons can be determined independent of the activity from the urinary outflow tract. Such evaluations may replace the conventional split renal function study in which traumatic procedures, such as cystoscopy and ureteral catheterizations, are required. 99mTc dimercaptosuccinic acid scintigraphy causes less discomfort to the patient and can be performed repeatedly and routinely even in children and debilitated geriatric patients.

Humans↗
PubMed1978

Effects of polybrominated biphenyls on kidney function and activity of renal microsomal enzymes.

Polybrominated biphenyls (PBBs) cause hepatic microsomal enzyme stimulation and histopathological alterations in several organs, including kidney. Concern about effects of PBBs on the health of newborns has increased after the discovery of PBBs in milk of nursing mothers. Therefore, it was of interest to investigate the effects of PBBs on kidney function and the activity of renal microsomal enzymes in adult and immature animals. Seven and eleven day old pups were treated with a single IP injection of either peanut oil or 150 mg/kg PBBs (FireMaster BP-6) in peanut oil. Adult virgin rats were fed diet containing 0 or 100 ppm PBBs for 30 or 90 days. Treatment with PBBs only retarded weight gain after 90 days exposure. Kidney-to-body weight ratio was not altered by PBBs. Arylhydrocarbon hydroxylase activity was increased while epoxide hydratase activity was decreased (adults) or not affected (immature rats) in kidney following treatment with PBBs. Administration of PBBs had no effect on blood urea nitrogen, the clearance of inulin, p-aminohippurate (PAH), or fractional sodium excretion. Similarly, the in vitro accumulation of PAH and N-methylnicotinamide (NMN) by thin renal cortical slices and ammoniagenesis and gluconeogenesis in renal cortical slices were not affected by PBBs. In conclusion, treatment with PBBs resulted in modification of the activity of renal microsomal enzyme activities but had no detectable effect on renal function.

Animals↗
PubMed1994

[Diagnostic and pathophysiological aspects of the determination of kidney function in animals].

Early diagnosis of loss in renal function (< 60-70%) is not possible either by resorting to the parameters of plasma urea and creatinine concentrations (responsive to functional loss by > 75% or by reference to urine concentration capacity (urine density: sensitive to concentrations > 60%). However, clearance techniques for determination of the glomerular filtration rate (GFR) have proved suitable for quantitative assessment of renal function. Endogenous creatinine clearance is one of the most common clinical approaches in GFR determination. Criticism of results obtainable from endogenous creatinine clearance appears to be justified by pharmacokinetic aspects of creatinine as an indicator, as well as by some of its analytical peculiarities. The tediousness of the procedure is another counterproductive aspect pertaining to large-scale use of endogenous creatinine clearance in veterinary medicine. Total blood-plasma clearance of exogenous creatinine (T-Clexo.Creatinine) would provide vets with an accurate (diagnostic validity) and practical method for carrying out clinical kidney-function diagnostics. However, more research on a number of related issues will be required before the general introduction of the procedure.

Animals↗
PubMed1987

Converting enzyme inhibition and kidney function in normotensive diabetic patients with persistent microalbuminuria.

The effects of a long term reduction in blood pressure on the kidney function of normotensive diabetic patients who had persistent microalbuminuria (30-300 mg albumin/24 hours) were studied in two groups of 10 such patients before and during six months of treatment with either 20 mg enalapril or placebo daily. Treatments were assigned randomly in a double blind fashion. Before treatment both groups had similar clinical characteristics, weight, diet, total glycosylated haemoglobin, median albumin excretion rate (enalapril group 124 mg/24 h, placebo group 81 mg/24 h), and mean arterial pressure (enalapril group 100 (SD 8) mm Hg, placebo group 99 (6) mm Hg). During treatment weight, urinary urea excretion, and total glycosylated haemoglobin remained unchanged. The mean arterial pressure decreased in the enalapril group but not in the placebo group (enalapril group 90 (10) mm Hg, placebo group 98 (8) mm Hg). The median albumin excretion rate also fell in the enalapril group but not in the placebo group (enalapril group 37 mg/24 h, placebo group 183 mg/24 h.) The glomerular filtration rate rose in the enalapril group from 130 (23) ml/min/1.73 m2 to 141 (24) ml/min/1.73 m2, and total renal resistances and fractional albumin clearance decreased while fractional albumin clearance increased in the placebo group. These results show that in patients who have diabetes but not hypertension a reduction in blood pressure by inhibition of converting enzyme for six months can reduce persistent microalbuminuria, perhaps by decreasing the intraglomerular pressure.

Adult↗
PubMed1980

1 alpha-hydroxy vitamin D3 treatment of non-dialyzed patients with chronic renal failure. Effects on bone, mineral metabolism and kidney function.

Nine non-dialyzed patients with creatinine clearance below 20 ml/min and histological and biochemical signs of renal osteodystrophy received 1 alpha-hydroxy vitamin D3 for 6 months in a mean daily dosage of 0.9 microgram. The serum concentrations of calcium and phosphate increased, and the serum concentrations of alkaline phosphatase and parathyroid hormone decreased during treatment. Quantitative histological examination of iliac crest bone biopsies showed a marked improvement of uremic bone changes, including normalization of the initial low mineralization rates evaluated by tetracycline uptake in bone. No significant change was seen in bone mineral content in the forearm measured by photon absorptiometry. An accelerated loss of kidney function was observed during the treatment period with 1 alpha-OH-vitamin D3 as compared with control periods before and after the treatment.

Adult↗