[Adult idiopathic extramembranous glomerulonephritis (EMG): results of treatment with corticoids and chlorambucil].
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Biomedical subjects
Publications and source records attributed to M Dhib.
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A decrease in bone density of the spine has been reported in individuals with hypercalciuria and the finding of the latter in osteoporosis patients is not uncommon. We studied 21 men and 8 women (mean age 47 +/- 13) with idiopathic hypercalciuria (IHCU) defined by an urinary calcium of more than 7.5 mmol/24 h in men and 6.25 mmol/24 h in women. The duration of IHCU was 10 (+/-) 8 years. Among the 29 patients, 24 had one or more renal calculi. Twenty one had been treated, by low calcium diet only (and diuresis), combined with a thiazide diuretic, or sodium phytate, or phosphorus. Bone mineral content (BMC) was measured in the lumbar spine and the upper end of the femur using an ORIS ODC 200 densitometer and compared with 29 control subjects paired for age and sex. No difference was found between the two groups concerning BMC values in either the spine or the 3 femoral sites (neck, Ward, trochanter). BMC was not correlated with urinary calcium. Thus individuals with IHCU showed no decrease in their bone mass, among this group seen in a department of nephrology. The influence of the treatment of IHCU remains to be defined.
Between November 1985 and November 1989, percutaneous renal biopsy was performed in 32 patients aged 75 or more (mean age 78). The major clinical presentations were nephrotic syndrome in 22 patients, variable amounts of proteinuria in 6 patients and unexplained severe renal insufficiency in 4 patients. In 27 cases the histological study revealed a glomerular disease. Minimal change disease (7 cases), membranous nephropathy (6 cases), amyloidosis (5 cases) and crescentic glomerulonephritis were the most frequent types. The rate of complications after biopsy was low (3 percent) with only one retroperitoneal hematoma. Owing to the atypical renal presentation of some glomerulopathies in the elderly, renal biopsy was useful to differentiate between minimal change disease, membranous nephropathy and amyloidosis. In 4 patients with minimal change disease, remission of nephrotic syndrome was obtained with corticosteroids. Moreover renal biopsy allowed to detect underlying diseases and gave indications to initiate specific therapy particularly in crescentic glomerulonephritis the outcome of which remained unfavourable. It is concluded that, even in elderly, renal biopsy is a valuable and safe diagnostic tool to obtain a rapid diagnosis, particularly in glomerular diseases, leading to a biopsy-guided therapy. It must therefore have the same indications as in younger adults with glomerular syndrome or rapidly progressive renal insufficiency.
The pharmacokinetics of cefixime following a single oral dose of 200 mg have been investigated in 6 normal subjects and in 22 patients with various degrees of renal insufficiency. Serum and urine samples were collected between 0 and 72 h and were subjected to two methods of analysis: bioassay and HPLC. There was a linear relationship between the two sets of results from 228 samples. This result suggests that none of the metabolites, which may accumulate in uraemic patients, has antibacterial activity. In normal subjects, the peak serum level (Cmax) was 2.50 micrograms.ml-1 at 2.83 h (tmax); the apparent elimination half-life (t1/2) was 3.73 h; the apparent total body clearance (CL.f-1) was 154 ml.min-1, the mean renal clearance (CLR) was 39.1 ml.min-1 and the apparent fraction of the dose recovered in 24 h urine was 0.22. In uraemic patients, Cmax and tmax were slightly increased and t1/2 was increased to 12-14 h in patients with an endogenous creatinine clearance below 20 ml.min-1. The apparent volume of distribution was decreased. Apparent total and renal clearances were lower in proportion to the degree of renal insufficiency. Linear relationships were found between CL/f, CLR and creatinine clearance (CLCR). The findings suggest that the dose of cefixime needs to be reduced only in patients with severe renal failure.
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During a 30 months period, 70 patients (60-84 years old) underwent a renal artery angiographic investigation, either by combined intravenous angiography and pyelography, either by intravenous or intra-arterial digital angiography. Thirty-nine were males, 31 were females. All patients were hypertensive. Thirty-three had a normal renal function and 37 had a renal insufficiency arbitrarily definite as creatinine clearance lower than 60 ml/min (m = 33 +/- 15 ml/min). Eight aortic anevrysms were discovered. Thirteen patients (18.6%) had atherosclerotic renovascular disease. Criteria which led to undertake these investigations and results are listed in the following table. [table; see text] Transluminal percutaneous angioplasty and surgical treatment were performed 7 and 3 times respectively. In one case, nephrectomy was done. In all these patients but one, improvement of hypertension and/or renal function occurred. In patients with renal impairment, difference in size between the two kidneys detected by echography or plain abdominal X-rays were noted in 8 among the 9 patients with renovascular disease; six among them had proteinuria less than 0.5 g/day. In conclusion, in hypertensive patients older than 60, criteria for detection of renovascular disease are the same as in younger patients. When renal function is decreased, difference in size between the two kidneys requires an angiographic evaluation. Proteinuria does not exclude renovascular pathology.
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The pharmacokinetics of the new fluoroquinolone derivatives have been extensively studied in patients with various degrees of chronic renal insufficiency during the last few years. Their kinetic profiles depend on the elimination pathways and on the degree of metabolic transformation. Renal insufficiency does not significantly modify pefloxacin kinetics. For the other new quinolones, a decrease in glomerular filtration rate below 20-30 ml/min induces an increase in terminal half-life and a decrease in plasma and renal clearance, related to the degree of renal impairment. These drugs are poorly removed by haemodialysis. Dosage adjustments are required, particularly in severe renal failure and for the drugs almost exclusively excreted, in unchanged form, via the renal route.
The pharmacokinetics of fleroxacin and its metabolites following a single oral dose of fleroxacin 400mg were examined in 6 healthy subjects and 24 patients with various degrees of renal insufficiency. Plasma and urine samples, collected at various times after administration, were assayed by high performance liquid chromatography (HPLC). In healthy subjects, Cmax was 6.8 +/- 0.7 mg/L; tmax = about 1h, t1/2 = 14 +/- 2h, total clearance = 4.86 +/- 0.72 L/h and the percentage of unchanged fleroxacin excreted in urine in 48 hours was 48 +/- 4% (HPLC). Plasma concentrations of metabolites were very low and accounted for no more than 5% of the levels of unchanged fleroxacin. In uraemic patients Cmax did not change, whatever the degree of renal failure; tmax was increased in patients with a glomerular filtration rate below 0.6 L/h, and Vd/f was independent of the severity of renal failure. These data suggest that bioavailability of the drug is unchanged. In uraemic patients t1/2 was prolonged and AUC multiplied by a factor of 2 to 3. A linear relationship was found between total and renal clearances of fleroxacin and creatinine clearance. Accumulation of N-demethyl-fleroxacin and N-oxide-fleroxacin was very high in uraemic patients, due to slow formation of these metabolites and decreased urinary elimination. Dialysance of fleroxacin and of its metabolites was approximately 3.6 to 4.8 L/h. These findings suggest that fleroxacin dosage may need to be reduced in patients with severe renal disease; in haemodialysed patients, treated every 2 days, a single dose of fleroxacin 400mg is recommended at the end of each dialysis session.
Visceral insufficiencies appeared or might be more important with age, thus it is not surprising to note pharmacokinetic alterations in elderly subjects. There are several age related changes in gastrointestinal function that might alter absorption of drugs. Gastric acid secretion and motility both decline with age. Intestinal surface and blood flow also diminished. But the effect of these changes is far eclipsed by other factors. The plasma-binding proteins diminish. The intracorporeal distribution of drugs is modified in elderly subjects. Total body weight and especially lean body mass is reduced: thus higher plasma levels of drug result. Hepatic clearance is in relation to liver mass and hepatic blood flow, both of which diminish with age. Hepatic enzymatic function, particularly oxidative process, is also decreased. The most important modification is a reduced excretion of drugs. Renal blood flow, glomerular filtration rate are decreased and these alterations may induce an accumulation of drugs or metabolites. Thus, it is necessary to be cautious when we prescribe drugs to elderly patients. We recommended to give small dosage and to increase dosage progressively. It is also necessary to pay attention to clinical or biological signs of intolerance in these subjects.
A high protein meal acutely stimulates the glomerular filtration rate. In order to assess the possible role of atrial natriuretic peptide (ANP) as a mediator of this renal response, the ANP plasma concentrations were measured with a sensitive radioimmunoassay method before and after a large protein load (1.5 g/kg body weight given as a meat meal). Creatinine clearance increased significantly while fractional excretion of sodium remained constant. ANP plasma concentrations did not change after the protein load and the intra-individual variations of creatinine clearance were not correlated with the intra-individual changes in ANP plasma concentrations. It was concluded that ANP was probably not involved in the renal haemodynamic changes observed after a large protein load.
The list of nephrotoxic drugs is long. The kidney is particularly susceptible to the nephrotoxic action of drugs, because of its functional properties, including: a) the high volume of renal blood flow, which brings large amounts of toxin; b) the large area in contact with the drug, either in the glomerulus or the tubule epithelium, which enables toxin interaction or uptake; c) the kidney's ability to transfer active substances, which provides specific transfer mechanisms that mediate cellular uptake; d) drug breakdown, which may occur in renal tubules and lead to the formation of toxic metabolites from non-toxic parent substances; e) the kidney's concentrating mechanisms, which can increase urinary and interstitial concentrations of non-absorbed products; f) the high metabolic rate of tubule cells required for normal function, which is subject to perturbation. Indeed, nephrotoxins affect every aspect of renal pathology, from acute renal failure due to functional alterations to that resulting from tubule cell necrosis. These anomalies may occur suddenly or after a long period of exposure to the toxic agent. They may be localized in the cortex or the medulla and affect all parts of the nephron: the glomeruli, the tubules, the interstitium or the vessels. How then is the topic of a brief expose to be chosen? It was made based upon the results of a questionnaire addressed to French nephrologists.
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