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PubMed1977

Intrarenal dynamics in the pathogenesis and prevention of acute urate nephropathy.

Tubular fluid flow, urine osmolality, and pH were selectively altered to determine the relative protective roles of these factors in a rat model of acute urate nephrophathy. Various prehyper uricemic conditions were established in five groups of animals: (a) normopenic Wistar rats given no pretreatment (Group I); (b) Wistar rats given acetazolamide, 20 mg/kg, and isotonic NaHCO3 to produce urine alkalinization (Group II); (c) Wistar rats in which a moderate diuresis, similar to that observed in Group II but without urine alkalinization, was induced with furosemide, 2 mg/kg (Group III); (d) Wistar rats in which a high-flow solute diuresis was induced with furosemide, 15 mg/kg (Group IV); (e) Brattleboro rats, homozygous for pituitary diabetes insipidus, that had a spontaneous high-flow water diuresis (Group V). A comparable level of hyperuricemia (19.4+/-2.2 mg/100 ml) was achieved in all animals with intravenous urate infusion. Clearance and micropuncture studies were performed before and 1 h after induction of hyperuicemia. Group I rats had mean falls in renal plasma flow and glomerular filtration rate of 83 and 86%, respectively; nephron filtration rate decreased 66%, and tubular and microvascular pressures increased twofold. In Group II there were 45 and 47% declines in renal plasma flow and glomerular filtration rate, respectively, a 66% fall in nephron filtration rate, and a 30% increase in tubular and vascular pressures. Moderate amounts of urate were seen in the kidneys. Group III had changes in renal function identical to Group II suggesting that the moderate prehyperuricemic diuresis in the latter group and not urine alkalinization produced the partial protection observed. Groups IV and V were completely and comparably protected with renal function studies unchanged from controls. It is concluded that high tubular fluid flow, whether induced by a solute or water diuresis, is the primary mechanism of protection in acute urate nephropathy. At most, urine alkalinization plays a minor preventive role.

Animals↗
PubMed1999

[Fenofibrate increases blood creatinine, but does not change the glomerular filtration rate in patients with mild renal insufficiency].

Fenofibrate is a potent hypolipemic agent, widely used in patients with mild to severe renal failure in whom hyperlipoproteinemia is frequent. A moderate reversible increase in creatinine plasma levels has been reported with fenofibrate therapy; however, it is not known whether this increased creatininemia reflects a fenofibrate induced alteration of renal function or if fenofibrate interferes with creatinine tubular handling. We prospectively examined the effect of 2 weeks fenofibrate treatment (200 mg daily) on renal function in thirteen hyperlipidemic patients with normal renal function or mild to moderate renal failure (Creat Cl: 110 to 30 ml/min). This study confirms that fenofibrate therapy significantly increases creatininemia in patients with mild to moderate renal failure (147 +/- 12 versus 170 +/- 15 mmol/l; p = 0.014), but does not alter renal hemodynamic nor glomerular filtration rate as assessed by the stability of PAH (304 +/- 56 versus 311 +/- 49 ml/min; p = NS) and inulin clearances (51.7 +/- 6 versus 52.3 +/- 7 ml/min; p = NS). The increase in creatininemia is neither due to an inhibition of creatinine tubular excretion, since no change in creatinine clearance was observed (69 +/- 8 versus 68 +/- 8 ml/min; p = NS), but appears to be associated to a parallel increase in creatinine daily urinary excretion (13.7 +/- 5 versus 15.4 +/- 4 mmol; p = 0.03). In conclusion, fenofibrate therapy in renal patients does not worsen renal function, nor diminish the reliability of creatinine clearance for its follow-up in spite of a significant rise in creatininemia. The mechanism of the fenofibrate-induced increase in urinary creatinine excretion remains to be determined.

Aged↗
PubMed1978

[The uricosuric effect of benzbromaron and probenecid under fasting conditions (author's transl)].

As we could demonstrate in a group of 39 obese subjects submitted to a 15-days period of absolute fasting, the developing hyperuricemia coincides with a decrease of uric acid clearance following an increase of the reabsorbed amount of filtered uric acid. After daily application of 2 g probenecid a marked uricosuric effect was detectable only during the first 3 days, while in the following time this effect was perceptible only impaired. As a reason for the diminution of efficacy the fasting-dependent urinary acidosis is discussed, which leads to low tubular concentration of the pharmacon by non ionic diffusion. In a dosage of 100 and 300 mg/day benzbromaron proved to be a much more potent uricosuricum. Additionally, related to the increase of dose the unproportional strong fall of serum uric acid levels, which stood in contrast to higher rations of uric acid excretion under a lower dose and which exceeded the dose-depending increase of uric acid clearance, indicated an additional extrarenal site of action. The depression of PAH-excretion after application of 2 g/day probenecid, which comes about the competitive inhibition, did not occur under 100 mg/day benzbromaron. This difference signifies, that benzbromaron does not develop its uricosuric effect by influencing the tubular transport system, which is specific for PAH and probenecid.

Benzbromarone↗
PubMed1981

Stimulation of renal excretion of p-aminohippurate (PAH) after unilateral nephrectomy in adult and ageing rats.

Unilateral nephrectomy (UNX) is followed by a significant decrease of excreted amount of PAH in rats. In 105 and 240-day-old rats, we characterized the time course of restitution of the PAH transport process., Furthermore, we studied whether or not the regeneration of kidney function can be accelerated by repeated administration of cyclopenthiazide. After stimulation of tubular transport of PAH by repeated administration of cyclopenthiazide, the loss of one kidney after UNX can be compensated more rapidly as in nephrectomized rats without pretreatment. In 105-day-old rats the regeneration and the extent of stimulation are more marked than in 240-day-old rats.

Aging↗
PubMed1980

[Ultrastructure of rat proximal renal tubular epithelium during substrate stimulation of cardiotrast secretion].

An electron microscope study was made of the epithelium of rat kidney proximal tubule, following a 3 day (three times a day) injection of cardiotrast in dose of 500 mg/kg, aimed to detect some morphological equivalents of the substrate stimulation of kidney tubular secretion of organic substances. Changes have been revealed in the ultrastructure of endoplasmic reticulum, ribosomal apparatus, and microbodies.

Aminohippuric Acids↗
PubMed1977

[Changes of kidney function in obese subjects during absolute fasting (author's transl)].

In 28 obese subjects the influence of a 15-days fasting period on the kidney function was investigated by continuous measurement of the clearances for creatinine, urea and uric acid. In the course of fasting time the serum concentrations of creatinine in comparison to the initial value significantly increased, the creatinine clearance maximally decreased about 40%. The serum concentrations of urea were found lower, whilst the clearance of urea increased. Moreover a distinct increase of the serum levels in connection with a significant decrease of the uric acid clearance was to be observed. Under conditions of strict fasting changes of the kidney function are evident, whose intra- and extrarenal reasons are discussed.

Adult↗