Malnutrition as an additional risk factor to gentamicin nephrotoxicity / Desnutrição como um fator de risco adicional na nefrotoxidade à gentamicina

A relação entre a desnutrição e as doenças infecciosas tem sido descrita há algum tempo. A gentamicina é um antibiótico aminoglicosídeo muito utilizado no tratamento de infecções graves por gram-negativos, apesar de sua nefrotoxidade. Estudos experimentais e clínicos também mostraram alterações importantes na função renal durante a desnutrição. Assim sendo, o objetivo do presente estudo foi verificar se o uso da gentamicina (G) em ratos submetidos à restrição alimentar (R) pode interferir no desenvolvimento da nefrotoxidade à gentamicina. Ratos Wistar machos com dois meses de idade foram submetidos à restrição alimentar (50 porcento) durante 30 dias. Nos 10 últimos dias, eles foram tratados com soro fisiológico ou gentamicina (40mg/kg/dia intraperitoneal). Os grupos estudados foram: C)- ratos com alimentação ad libitum + soro fisiológico, G)- alimentação ad libitum + gentamicina, R)- restrição alimentar + soro fisiológico, RG)- restrição alimentar + gentamicina. Uma queda significativa na taxa de filtração glomerular (TFG) foi observada nos grupos R (5,69 ± 0,22) e G (5,31 ± 0,27) se comparados ao grupo C (7,17 ± 0,42 ml.min kg). No grupo RG, a diminuição a TFG foi mais evidente do que nos grupos G ou R, (4,42 ± 0,24 ml.min-1.kg-1). Em todos os grupos experimentais, a diminuição da TFG ocorreu paralelamente à diminuição do fluxo plasmático renal (FPR), de modo que a fração de filtração (FF porcento) foi mantida. Um declínio na proporção inulina urina/plasma foi observado em ambos os grupos tratados com gentamicina e também no grupo com restrição alimentar. Apesar de G e R "per se" causarem um aumento na excreção de Na elevado a +, os valores mais altos foram obtidos no grupo RG. Apesar do nosso estudo ter sido realizado num modelo experimental, se extrapolado a protocolos humanos pode-se sugerir que o uso de antibióticos aminoglicosídeos nos pacientes desnutridos deve ser feito com cautela, especialmente devido a função renal e considerando o risco aumentado potencial exibido por estes pacientes.

Effect of D-glucose and L-glutamate on the kinetics of bicarbonate reabsorption in rat proximal tubules

The effect of D-glucose or L-glutamate on the kinetics of bicarbonate reabsorption in the early (EPT) and middle proximal tubule (MPT) was studied in vivo in Munich-Wistar rats by microperfusion techniques. The presence of 20 mM D-glucose in the lumen increased acidification half-time (t/2) (from 2.54 + or - 0.09s to 3.11 + or - 0.17 s in EPT and from 4.75 + or - 0.20 s to 6.04 + or - 0.49 s in MPT). Bicarbonate reabsorption 9JHCO-3) decreased as a consequence of this change (from 3.80 + or - 0.17 to 2.46 + or - 0.20 nmol cm-2s-1 in EPT and from 2.30 + or - 0.10 to 1.64 + or - 0.10 nmol cm-2s-1 in MPT). In this situation the basolateral membrane potential difference (BLMPD) in the MPT decereased from -41.6 + or - 2.47 to -29.7 + or - 2.45 mV and returned to control values after perfusion with D-glucose. The addition of 20 mM L-glutamate to the luminal perfusion caused an opposite effect, i.e., a decrease in t/2 (1.54 + or - 0.21 s in EPT and 3.25 + or - 0.26 s in MPT) and a consequent increase in JHCO-3 in both segments (5.09 + or - 0.58 nmol cm-2s-1 in EPT and 3.92 + or - 0.30 nmol cm-2s-1 in MPT). The BLMPD of MPT increased during L-glutamate perfusion (-39 + or - 2.48 mV in control and -52.0 + or - 2.72 mV with L-glutamate) and returned to control values after perfusion. The results observed may be the consequence of coupled Na+ - substrate transport altering the BLMPD with modifies the electrical driving force for coupled Na+ -HCO-3 efflux across the basolateral membrane. The alteration of this process may in turn affect intracellular pH, which is an important modulator of luminal Na+./H+ enchange. This possibility is supported by the observed depolarization of BLMPD by D-glucose (electroneutral molecule), and hyperpolarization by glutamate anion

Atrial natriuretic peptide modulates the effect of angiotensin II on the concentration of free calcium in the cytosol of Mandin-Darby canine kidney cells

The effect of angiotensin II (ANG II) and atrial natriuretic peptide (ANP) on intracellular free calcium concentration [ Ca²+]i was investigated in Mandin-Darby canine kidney (MDCK) cells in culture. Changes in [Ca²+]i were monitored fluorometrically with the Ca²+ -sensitive probel fura -2/AM at 37ºC using Perkin-Elmer LS-5 spectrofluorimeter (excitation 340/380 nm,slite 3 nm; emission 520 nm, slit 10 nm). MDCK cells exhibited a mean baseline [Ca²+]i of 98 ñ 10 nM. the addition of increasing concentrations of SNG II (1 pM to 1 µM) to the cell suspension led to a progressive increase in [Ca²+]i to 2-3 times basal levels. In contrast, addition of 1 µM ANP to the cell suspension led to a very rapid 60 percent decrease in [Ca²+]i. The addition of 1 pM to 1 µM ANG II immediately after 1 µM ANP caused an increase in [Ca²+]i which never exceded the basal level in the absence of ANP. The data indicate that ANG II increases cell [Ca²+]i as expected, and provide the new observation that ANP reduces [Ca²+]i in these cells. Further more, ANP reduces the increase in [Ca²+]i elicited by ANG II, thus modulating the effect of ANG II on [Ca²+]i

Effect of glucose on the kinetics of bicarbonate reabsorption in the early and middle proximal tubule

The kinetics of bicarbonate reabsorption in the early (EPT) and middle proximal tubule (MPT) was studied in Munich Wistar rats by means of microperfusion techniques. The early proximal tubule (EPT) had a higher capacity of reabsorbing bicarbonate than the middle segment. The calculated bicarbonate flow (JHCO3) was 4.47 nmol s**-1 cm**-2 int the EPT and 2.30 nmol s**-1 cm**-2 in the MPT and the half time of injected bicarbonate (t/2) was less in the EPT (2.24 s) than in the MPT (5.20 s). The presence of 20 mM glucose in the lumen led to a reduction in the velocity of tubular acidification in the EPT (3.11 s) and caused a decrease in JHCO3 in both segments (2.46 nmol s**-1 cm**-2 in the EPT and 1.64 nmols s**-1 cm**-2 in the MPT). These alterations may be the result either of lumen-to-cell sodium gradient dissipation or electrical changes induced by sodium-glucose cotransport that may depolarize the basolateral membrane leading to intracellular alkalinization. This effect may then impair the Na +/H+ exchanger, thus decreasing bicarbonate reabsorption