Effect of cyclooxygenase inhibitors on gentamicin-induced nephrotoxicity in rats

The frequent use of nonsteroidal anti-inflammatory drugs (NSAID) in combination with gentamicin poses the additional risk of nephrotoxic renal failure. Cyclooxygenase-1 (COX-1) is the main enzyme responsible for the synthesis of renal vasodilator prostaglandins, while COX-2 participates predominantly in the inflammatory process. Both are inhibited by non-selective NSAID such as indomethacin. Selective COX-2 inhibitors such as rofecoxib seem to have fewer renal side effects than non-selective inhibitors. The objective of the present study was to determine whether the combined use of rofecoxib and gentamicin can prevent the increased renal injury caused by gentamicin and indomethacin. Male Wistar rats (250-300 g) were treated with gentamicin (100 mg/kg body weight, ip, N = 7), indomethacin (5 mg/kg, orally, N = 7), rofecoxib (1.4 mg/kg, orally, N = 7), gentamicin + rofecoxib (100 and 1.4 mg/kg, respectively) or gentamicin + indomethacin (100 and 5 mg/kg, respectively, N = 8) for 5 days. Creatinine clearance and alpha-glutathione-S-transferase concentrations were used as markers of renal injury. Animals were anesthetized with ether and sacrificed for blood collection. The use of gentamicin plus indomethacin led to worsened renal function (0.199 ± 0.019 ml/min), as opposed to the absence of a nephrotoxic effect of rofecoxib when gentamicin plus rofexicob was used (0.242 ± 0.011 ml/min). These results indicate that COX-2-selective inhibitors can be used as an alternative treatment to conventional NSAID, especially in situations in which risk factors for nephrotoxicity are present.

Métodos dialíticos utilizados nos cardiopatas graves / Dialysis modalities for the treatment of patients with severe cardiac disease

Nas últimas três décadas, os avanços tecnológicos permitiram a disponibilização de diversas modalidades dialíticas, as quais oferecem vantagens e desvantagens, que devem ser levadas em conta quando da prescrição e escolha da modalidade para determinado paciente. Isso é particularmente importante nos pacientes que apresentam instabilidade hemodinâmica. Na sepse, discute-se hoje a dose de diálise e o uso de terapias contínuas de reposição da função renal. Grandes progressos têm sido feitos nessa área nos últimos anos. Dados recentes sugerem que a diálise peritoneal e a ultrafiltração lenta podem beneficiar pacientes com insuficiência cardíaca terminal. Nesta revisão, abordaremos os aspectos básicos e técnicos, e a aplicação clínica dos métodos dialíticos no paciente criticamente enfermo, particularmente na sepse e na insuficiência cardíaca.

Effect of cisplatin on glomerular hemodynamics

The effects of cisplatin on renal microcirculation were evaluated in euvolemic Munich-Wistar rats submitted to micropuncture. Nine rats received a single dose of cisplatin (6 mg/kg,ip), and 6 control rats received the same volume (0.3 ml) of 15 mM NaCl 4 days before the measurements. Cisplatin administration induced non-oliguric acute renal failure by decreasing glomerular filtration rate (GFR) from 0.96 + or- 0.5 to 0.33 + or - 0.04 ml/min (P<0.05) and by increasing urinary volume from 3.3 + or - 0.3 to 12.4 + or - 2.2 micronl/min (P<0.05). Cisplatin administration decreased single nephron GFR from 34.2 + or - 2.1 to 20.1 + or - 2.3 nl/min (P<0.05) due to a reduction in both glomerular plasma flow from 106 + or - 9 to 61 + or - 6 nl/min (P<0.05) and transcapillary hydraulic pressure difference from 31 + or - 1 to 27 + or - 1 mmHg (P<0.05). An increase in arteriolar resistances, mainly afferent arteriolar resistance from 2.5 + or - 0.2 to 4.7 + or - 0.5 x 10**10 dyn.s.cm**-5 (P<0.05), was observed. The glomerular ultrafiltration coefficient was unchanged