Hypomagnesemia is a risk factor for nonrecovery of renal function and mortality in AIDS patients with acute kidney injury

The objective of the present study was to determine the prevalence of electrolyte disturbances in AIDS patients developing acute kidney injury in the hospital setting, as well as to determine whether such disturbances constitute a risk factor for nephrotoxic and ischemic injury. A prospective, observational cohort study was carried out. Hospitalized AIDS patients were evaluated for age; gender; coinfection with hepatitis; diabetes mellitus; hypertension; time since HIV seroconversion; CD4 count; HIV viral load; proteinuria; serum levels of creatinine, urea, sodium, potassium and magnesium; antiretroviral use; nephrotoxic drug use; sepsis; intensive care unit (ICU) admission, and the need for dialysis. Each of these characteristics was correlated with the development of acute kidney injury, with recovery of renal function and with survival. Fifty-four patients developed acute kidney injury: 72 percent were males, 59 percent had been HIV-infected for >5 years, 72 percent had CD4 counts <200 cells/mm³, 87 percent developed electrolyte disturbances, 33 percent recovered renal function, and 56 percent survived. ICU admission, dialysis, sepsis and hypomagnesemia were all significantly associated with nonrecovery of renal function and with mortality. Nonrecovery of renal function was significantly associated with hypomagnesemia, as was mortality in the multivariate analysis. The risks for nonrecovery of renal function and for death were 6.94 and 6.92 times greater, respectively, for patients with hypomagnesemia. In hospitalized AIDS patients, hypomagnesemia is a risk factor for nonrecovery of renal function and for in-hospital mortality. To determine whether hypomagnesemia is a determinant or simply a marker of critical illness, further studies involving magnesium supplementation in AIDS patients are warranted.

Glomerular filtration is reduced by high tidal volume ventilation in an in vivo healthy rat model

Mechanical ventilation has been associated with organ failure in patients with acute respiratory distress syndrome. The present study examines the effects of tidal volume (V T) on renal function using two V T values (8 and 27 mL/kg) in anesthetized, paralyzed and mechanically ventilated male Wistar rats. Animals were randomized into two groups of 6 rats each: V T8 (V T, 8 mL/kg; 61.50 ± 0.92 breaths/min; positive end-expiratory pressure, 3.0 cmH2O; peak airway pressure (PAW), 11.8 ± 2.0 cmH2O), and V T27 (V T, 27 mL/kg; 33.60 ± 1.56 breaths/min; positive end-expiratory pressure, none, and PAW, 22.7 ± 4.0 cmH2O). Throughout the experiment, mean PAW remained comparable between the two groups (6.33 ± 0.21 vs 6.50 ± 0.22 cmH2O). For rats in the V T27 group, inulin clearance (mL·min-1·body weight-1) decreased acutely after 60 min of mechanical ventilation and even more significantly after 90 min, compared with baseline values (0.60 ± 0.05 and 0.45 ± 0.05 vs 0.95 ± 0.07; P < 0.001), although there were no differences between groups in mean arterial pressure or gasometric variables. In the V T8 group, inulin clearance at 120 min of mechanical ventilation remained unchanged in relation to baseline values (0.72 ± 0.03 vs 0.80 ± 0.05). The V T8 and V T27 groups did not differ in terms of serum thiobarbituric acid reactive substances (3.97 ± 0.27 vs 4.02 ± 0.45 nmol/mL) or endothelial nitric oxide synthase expression (94.25 ± 2.75 vs 96.25 ± 2.39 percent). Our results show that glomerular filtration is acutely affected by high tidal volume ventilation but do not provide information about the mechanism.

Urinary NO3 excretion and renal failure in indinavir-treated patients

Treatment with indinavir (IDV), a protease inhibitor, is frequently associated with renal abnormalities. We determined the incidence of renal failure (creatinine clearance <80 mL min-1 1.73 (m²)-1) in HIV patients treated with highly active antiretroviral therapy, including IDV, and investigated the possible mechanisms and risk factors of IDV nephrotoxicity. Thirty-six patients receiving IDV were followed for 3 years. All were assessed for age, body weight, duration of infection, duration of IDV treatment, sulfur-derivative use, total cholesterol, triglycerides, magnesium, sodium, potassium, creatinine, and urinalysis. We also determined renal function in terms of creatinine clearance, urine osmolality and fractional excretion of sodium, potassium, and water. Urinary nitrate (NO3) excretion was measured in 18 IDV-treated patients and compared with that of 8 patients treated with efavirenz, a drug without renal side effects. Sterile leukocyturia occurred in 80.5 percent of the IDV-treated patients. Creatinine clearance <80 mL min-1 1.73 (m²)-1 was observed in 22 patients (61 percent) and was associated with low body weight and the use of sulfur-derivatives. These patients also had lower osmolality, lower urine volume and a higher fractional excretion of water compared to the normal renal function group. Urinary NO3 excretion was significantly lower in IDV-treated patients (809 ± 181 æM NO3-/mg creatinine) than in efavirenz-treated patients (2247 ± 648 æM NO3-/mg creatinine, P < 0.01). The lower NO3 excretion suggests that IDV decreases nitric oxide production.

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.

Regulacao renal da excrecao de sodio na insuficiencia cardiaca experimental: estudo da hemodinamica e da funcao tubular renal / Renal regulation of sodium excretion in experimental heart failure: study of hemodynamics and renal tubular function

O objetivo do presente trabalho foi estudar o papel desempenhado pelo rim na retencao de sodio e agua na insuficiencia cardiaca em caes com fistulas arterio-venosas femorais atraves de medidas de clearance e hemodinamica. Vinte e sete caes foram estudados em hidropenia e em diurese aquosa, 96 horas apos a realizacao de fistulas arterio-venosas femorais bilaterais, em 3 periodos: 1) fistulas abertas; 2) fistulas fechadas e 3) fistulas reabertas. Os animais retinham sal e agua e desenvolveram edema no periodo em que as fistulas estavam abertas. Quando as mesmas foram fechadas ocorreu uma maior diurese, natriurese, com aumento da excrecao urinaria de fosfato e do aporte distal de solutos, sugerindo uma diminuicao da reabsorcao proximal de sodio e agua. Apos a reabertura das fistulas, observou-se um aumento da reabsorcao de sodio pelos segmentos distais do nefron, sugerido pela elevacao da excrecao de agua livre por unidade de aporte de solutos. Estes achados nao foram acompanhados por alteracoes da distribuicao do fluxo sanguineo renal cortical. Em conclusao, a retencao de sodio e agua na insuficiencia cardiaca congestiva produzida por fistulas arterio-venosas se deve a um aumento da reabsorcao de sodio pelos segmentos distais do nefron e nao e devida a uma redistribuicao do fluxo sanguineo renal cortical.

Efeito do furosemide e aminofilina na insuficiencia renal aguda pos-isquemica experimental. / Effects of furosemide and aminophylline in experimental post-ischemic acute renal failure

O efeito do furosemide e da aminofilina sobre a recuperacao da insuficiencia renal aguda foi estudado em ratos submetidos a isquemia renal por clampeamento da aorta,abaixo e acima da arteria renal esquerda, permanecendo o rim direito como controle. A administracao de altas doses de furosemide (100 mg/kg peso), antes de se proceder a isquemia renal,nao impediu a queda de filtracao glomerular e o efeito oligurico. O furosemide injetado em outros oito animais, apos a inducao da isquemia renal, nao alterou a taxa de filtracao glomerular (0,24 +/- 0,04 ml/min para 0,23 +/- 0,04 ml/min), produzindo apenas aumento da diurese e natriurese em seis dos animais estudados. A administracao de aminofilina, inibidor da adenosina, substancia vasoconstritora renal, cuja producao aumenta durante a isquemia renal, tambem nao aumentou a taxa de filtracao glomerular do rim pos-isquemico (0,09 +/- 0,04 ml/min para 0,10 +/- 0,02 ml/ min) e nem alterou a excrecao de agua e soluto. Estes dados permitem concluir que nem o furosemide e nem a aminofilina produzem uma recuperacao mais rapida da filtracao glomerular na insuficiencia renal aguda experimental e que apenas o furosemide pode transformar uma insuficiencia renal aguda oligurica em poliurica