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Absorption and disposition of moclobemide in patients with advanced age or reduced liver or kidney function.

Three different studies were conducted to assess the pharmacokinetics of moclobemide in subjects with conditions complicating dose determination. The first examined the absorption and disposition of moclobemide in an elderly population and compared these with results obtained in a group of normal young subjects. No significant differences were found between the groups in the intravenous (i.v.) parameters of disposition, and no differences with regard to disposition of the metabolite, Ro 12-8095. In addition, the minimum steady-state concentrations of moclobemide and the main plasma metabolite did not differ between the elderly and younger patients. In the second study, clearance tests in patients with cirrhosis of the liver confirmed that hepatic function is drastically reduced in this group of patients; it is therefore possible that moclobemide absorption and distribution might be influenced. In only 3 of the 12 patients investigated, slowly declining plasma concentrations after administration pointed to a severely limited elimination capacity for moclobemide. In the remaining 9 subjects, average values of several parameters changed significantly (t 1/2 beta, MRT and C1), whereas Vss and renal clearance were not significantly altered. In patients with kidney dysfunction, there were no differences in kinetics between patients undergoing hemodialysis and those who were not. Compared with normal healthy volunteers, no differences were found for renal patients, with the exception of the mean absorption time, which was significantly prolonged. From these studies it can be concluded that, pharmacokinetically, neither age nor renal impairment require adjusting the dosage of moclobemide. Patients with liver cirrhosis, however, need to have the usual dose reduced to one half or one third, or else the dosage intervals can be increased to prevent cumulation.

Administration, Oral↗

[Radiation thermometry used in the study of normal kidney functional activity].

In this paper, the results of use of active radiation heat flowmetry in the nephrological clinic are presented. Employment of rationalized loading tests permitted direct relationship to be established of radiation heat losses from the surface of the "open" kidney to the status of renal functions. Patterns of changes in the infrared radiation intensity have been ascertained in health and in the blockade of canalicular reabsorption. A hypothesis is documented about participation of autonomic system of regulation of renal bloodflow and glomerular filtration in thermostabilization of the kidney.

Aminophylline↗

[Effect of protein load on kidney functions in patients with chronic glomerulonephritis].

AIM: To study changes in renal function in response to protein loads in patients with chronic glomerulonephritis (CGN) who have normal renal function and initial uremia. MATERIAL AND METHODS: 63 CGN patients were divided into two groups: 40 patients of group 1 (17 males, 23 females, age 16-53 years, plasma creatinine-Pcr < 0.132 mmol/l); 23 patients of group 2 (10 males, 13 females, age 18-57 years, Pcr > 0.132 mmol/l). Renal functional reserve (RFR) was assessed with oral soa isolate SUPRO 760 test (protein Techn. Int., USA), 1.0 g of protein per 1 kg of ideal body mass. By three 2-h clearance periods measurements were made of RFR, absolute and fractional excretion, concentration indices and clearances of creatinine, urea, electrolytes, osmolality. All the parameters were referred to the standard body surface. RESULTS: RFR was intact in 14 patients of group 1 and 10 patients of group 2. In CGN without uremia with intact RFR, maximal Pcr corresponded to the highest values of minute diuresis and sharp increase of urea excretion, osmotically active substances. In CGN patients with uremia and intact RFR, development of hyperfiltration was accompanied with a significant rise in Pcr, minute diuresis, absolute excretion of urea and osmotically active substances. The rise in the latter two was much less active in CGN if RFR was absent. Multiple stepwise regression analysis showed that RFR intactness depends primarily on baseline values of absolute excretion of urea and osmotically active substances. CONCLUSION: A reverse relationship exists between absolute excretion of urea, osmotically active substances and the degree of SKF in response to protein load in CGN patients both in intact nitrogen-excreting function and uremia. It is suggested that urea may be involved in regulation of intraglomerular hemodynamics by means of effect on tubular-glomerular feedback mechanism.

Adolescent↗

[Kidney function in diabetic patients with diabetes of a duration less than 15 years].

All diabetics of a closed population were examined in respect to their renal function by means of their level of serum creatinine. 1,380 out of 1,490 diabetics (type I and type II) have their diabetes less than 15 years. The serum creatinine values are increased in 24.9% of these diabetics. The frequency of chronic renal insufficiency rose steply after a diabetes period of 15 and more years. A classification of the diabetics in groups with equal diabetes period showed that renal insufficient diabetics are significant older than those with normal renal function. The results of the investigation emphasize the demand to enclose the nephropathy in the diagnostic scale of diabetics with short disease period, too, to become therapeutic effectively very early.

Adolescent↗

[Kidney function after reconstructive operations on the renal arteries in renovascular hypertension].

A total of 117 patients with renovascular hypertension operated upon by employing reconstructive surgery upon renal arteries for producing hypotensive effect and restoration of renal functions were examined. Examination was made before surgery, in the near (up to 6 months) and remote post-operative periods (after a lapse of up to 10 years time). Soon after the operation persistent normalization of the arterial pressure was recorded in 78 (67 per cent) of 117 patients, improvement supervened in 12 per cent of the cases, and a positive hypotensive effect could be achieved in 92 or 79 per cent of the patients. The immediate normalization and improvement in the evolution of arterial hypertension continue, as a rule, also late after surgery. Following reconstructive operations on the renal arteries with normalized arterial pressure or its improvement the great majority of the patients demonstrated re-establishment or a significant improvement of both the summary (filtration, concentration and even nitrogen-excretory) and individual renal functions (as shown by the results of radioisotope renography with I131 hippuranium and excretory urography. In patients with malignant course of arterial hypertension successful reconstructive surgery was followed by a tendency toward retrograde development of the arterial hypertension malignancy.

Arteries↗

[Effect of gamma-hydroxybutyric acid and pentoxifylline on kidney function parameters in coronary surgery interventions].

After cardiac surgery, transient renal dysfunction often occurs. The main reasons for impairment of renal function are intraoperative hypotension, ischemia/reperfusion injury and inflammatory response to cardiopulmonary bypass (CPB). Pentoxifylline is known to have anti-inflammatory properties. Gamma-hydroxybutyrate (GHB), an endogenous regulator of energy metabolism, showed beneficial effects on experimental intestinal ischemia/reperfusion injury and liver graft function. Both drugs may be of practical interest in diminishing renal damage during and after cardiac surgery. After approval by the ethics committee and informed consent, 45 patients for elective coronary artery bypass grafting with no clinical and laboratory impairment of renal function were randomized into 3 groups (15 patients each): group 1 received saline as control, group 2 received pentoxifylline intraoperatively (1 mg/kg/h after a priming dose of 1 mg/kg) and group 3 received GHB intraoperatively (25 mg/kg/h after a priming dose of 25 mg/kg) in a double-blinded fashion. During 3 periods (before CPB, from the beginning of CPB until the end of surgery, 24 hours postoperatively), glomerular (creatinine clearance, CCr) and tubular markers of renal function (beta-NAG, alpha 1-microglobulin) were detected in addition to clinical routine standards (creatinine, urea, fractional excretion of sodium). Changes in glomerular and in tubular function were comparable in all groups without characteristic effects of either GHB or pentoxifylline. With CPB, CCr decreased significantly until the end of operation, but showed a rise to preoperative levels on the first day after operation. Tubular function markers (beta-NAG, alpha 1-microglobulin, related to simultaneous excretion of creatinine) showed a remarkable rise after the beginning of CPB up to the postoperative period. The results of the present pilot study suggest the detection of tubular proteins and enzymes a useful addition to present routine clinical standards for recognizing early intraoperative changes in renal function. In the patients studied, there were no clinical signs of renal dysfunction. Neither GHB nor pentoxifylline--in the doses applied--was able to show a therapeutic benefit despite the theoretical advantages.

Aged↗

[Water-electrolyte balance and kidney function for 3 weeks following severe trauma].

A study on water-electrolyte metabolism and renal function was performed in 32 patients (mainly young to middle-aged males) over three weeks after severe accidental trauma (mainly brain trauma), who did not suffer from acute renal failure. With a mean water input of 4 l/day the difference of water input and urine volume was positive over the whole observation time. Patients had a mean osmolar excretion of 1800 mosm/day which was twice normal and was mainly caused by a high urea excretion. They were almost invariably in the state of antidiuresis and achieved unusually high values for negative free-water clearance around 2 ml/min. This, however, was adequate in terms of normotonicity of body water. Cumulated sodium balance over 21 days was negative and, on the average, amounted to minus 440 mmol. The median value for creatinine clearance was in the range of predicted normal (156 ml/min.) between day 5 and 10 and a little less before and thereafter. We frequently observed an elevation of creatinine clearance to 120-150% of normal. Renal clearance of urea was around 100 ml/min. during the phase of maximal protein catabolism. Therefore the reasonable increases in urea production up to a mean of 60 g/day resulted only in moderately elevated levels of plasma urea (40-50 mg/100 ml). In 14 patients we performed a total of 83 measurements of plasma volume (Evans-Blue). In patients with intact renal function mean plasma volume amounted to 110% normal. This, in combination with a reduced red all volume on the average, resulted in mild hypovolaemia (blood volume about 90% of predicted normal).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗

[Improvement in nuclear medicine diagnosis of kidney function using 99m technetium mercaptoacetyltriglycine (MAG3)].

Renal scintigraphy and clearance measurement are indispensable in nephro-urologic disorders. A continuous series of 103 sequential scintigraphies and clearance measurements were performed with the new technetium-labelled agent MAG3 (Gamma-kamera, Phillips Tomo Diagnost) and 131I-orthohippuric acid (OIH) using the Oberhausen method (Nucleopan, Siemens). The time-activity curves obtained with the two radionuclides agreed exactly. Reaching a tubular excretion rate of nearly 90%, the clearance of MAG3 differed by no more than 6% from the OIH clearance in 95% of the cases. The factor between clearances of the two radionuclides was determined by means of a commercially available software according to the Oberhausen method and amounted to 0.59 +/- 0.09. The favorable physical properties and high activity of MAG3 permit exact examination of tubular function and better assessment of renal morphology than hippuran-labelled radionuclides. The low radiation dose combined with a better spatial resolution, especially, the constant availability in a nuclear medicine department should give the preference to MAG3.

Adult↗

[Long-term evaluation of kidney function in Schoenlein-Henoch syndrome].

The Authors studied 104 children (58 males and 46 female) with Schoenlein-Henoch syndrome, admitted to the Department of Pediatrics, Ospedale Civile di Pescara, in the period 1961-1985. Clinical and laboratory aspects were evaluated. Fifty-one subjects (25 males and 26 females) were re-evaluated, after a period of 17.0 +/- 4.2 years after first hospital admission: in particular, the mean blood laboratory parameters and renal function were assessed. None of these 51 subjects showed important abnormalities, especially evidence of renal impairment. This study suggests that the Schoenlein-Henoch syndrome can have a good long-term prognosis, without important renal abnormalities.

Adolescent↗

[Effect of a synthetic prostacyclin analog on kidney function and the system of regulation of blood coagulation in experimental acute renal failure].

The influence of a stable analogue of prostacyclin on the renal function and parameters of hemostasis was investigated in experiments on animals with the nephrotic form of acute renal insufficiency. Diuresis, glomerular filtration, water and sodium reabsorption in the presence of diminished intravascular coagulation were recovered after two injections of the compound in a dose of 115 micrograms/kg.

Acute Kidney Injury↗

[The clinical significance of kidney function tests].

Clearance studies have lost much of their importance in clinical nephrology during the last two decades, having been replaced by percutaneous renal biopsy for diagnostic purposes. Serum creatinine, if increased, is a rather reliable index for glomerular filtration rate (GFR) provided nonrenal factors influencing creatinine values are taken into account. Thus, the necessity of performing endogenous creatinine clearance to assess GFR is confined to the clearance range between 50-120 ml/min. For long-term observation of progressive renal failure the reciprocal of serum creatinine with time has become popular, the relationship usually being linear if obstruction or infection do not disturb the course. Kinking of the straight line towards the baseline means acceleration of progression, while kinking away from the abscissa expresses retardation of the process. Physiologic aging of the kidneys includes a decrease in glomerular filtration rate starting after the age of 20. In a healthy population of 80-years-olds mean GFR is about 50 ml/min.

Aging↗

Verapamil sustained-release in renal parenchymal hypertension: effect on blood pressure, kidney function, angiotensin II, aldosterone, arginine vasopressin, atrial natriuretic peptide, and lipoproteins.

In 14 patients with arterial hypertension secondary to chronic renal parenchymal disease and impaired renal function, 24-h ambulatory blood pressure, casual blood pressure, plasma concentrations of angiotensin II, aldosterone, arginine vasopressin and atrial natriuretic peptide, serum creatinine, plasma lipids and lipoproteins, and body weight were determined at the end of two consecutive 3-week periods; placebo was administered in the first period and verapamil sustained-release 240 mg was given in the second period. Verapamil reduced mean 24-h ambulatory blood pressure from 152/104 mm Hg (means) to 142/97 mm Hg. Blood pressure was reduced significantly during the daytime, in the evening, and in the early morning, but not at night. Casual blood pressure was also significantly reduced from 176/106 mm Hg to 154/96 mm Hg. No significant changes were determined in the hormones, serum creatinine, plasma lipids and lipoproteins, heart rate, or body weight. Atrial natriuretic peptide was correlated significantly with serum creatinine (p = 0.733, n = 14, p less than 0.01). We conclude that verapamil sustained-release 240 mg in one daily dose has a moderate blood-pressure-lowering effect in patients with chronic renal disease and hypertension without inducing tachycardia, activation of the renin-angiotensin-aldosterone system, or increase in body weight, and without altering renal function and plasma lipids and lipoproteins. The positive correlation between atrial natriuretic peptide and serum creatinine may support the hypothesis that extracellular volume increases during progression of renal disease.

Adult↗

[Tienilic acid, hyperuricemia and kidney function].

Tienilic acid (Diflurex) was given to 10 patients with secondary hyperuricemia following hydrochlorothiazide or furosemide administration. Eight of these 10 patients suffered acute worsening of renal function reflected in a significant increase in plasma creatinine. Plasma urates fell in all patients. Plasma creatinine returned to pretreatment levels in all patients within 4 to 15 days. Extreme caution should be exercised in prescribing tienilic acid to hyperuricemic patients, in view of the significant risk of reversible renal impairment.

Aged↗