The present survey of aminoglycoside nephro- and ototoxicity covers approximately 10,000 patients reported on in clinical trials published between 1975 and 1982. Included in the survey were clinical trials with at least 15 patients evaluable for nephro and/or ototoxicity provided relevant data were given on methodology, patient material and aminoglycoside dosage. Each publication was evaluated by both investigators and relevant data entered into a chart. One hundred and forty-four published trials were surveyed; 139, 63 and 34 for renal, cochlear and vestibular side effects, respectively. Frequencies were calculated as number of patients with side effect of total number of evaluated patients. In the average overall figures toxicity labelled by respective authors as 'definitely', 'probably' and 'possibly' related to study drug is included. When available, frequencies of toxicity 'definitely' and 'probably' related to study drug were analysed separately. The average daily dosages of gentamicin, tobramycin, netilmicin and amikacin were 3.9, 3.8, 5.2 and 15.4 mg/kg, respectively. The average frequencies of nephrotoxicity for gentamicin and tobramycin were 14.0 and 12.9%, respectively, and of netilmicin and amikacin 8.7 and 9.4%, respectively. The average frequency of cochlear toxicity was 13.9% for amikacin, 8.3 and 6.1% for gentamicin and tobramycin, respectively, and 2.4% for netilmicin. The material available for evaluation of vestibular toxicity was considerably smaller. The average frequencies for gentamicin, tobramycin and amikacin were similar (3.2 to 3.7%) while netilmicin again exhibited a somewhat lower figure (1.4%). The overall figures and the clinical ranking that they imply were basically substantiated when prospective comparative trials were analysed separately. However, some inconsistencies go unexplained: for example the frequency of gentamicin nephrotoxicity was markedly higher in trials where it was compared to tobramycin (20 trials) than when it was compared to netilmicin (16 trials).

Vascular resistance was determined in 40 rabbit kidneys after graded warm ischaemia up to 60 minutes and preservation in Collins' solution for 24 and 48 hours. Half of the animals were treated with chlorpromazine 3.5 mg/kg before induction of the ischaemia. Vascular function was determined during short-term perfusion with TIS-U-SOL at 4 degrees C. The experiments showed that warm ischaemia of 30 and 60 minutes duration gave an increase in vascular resistance. The increase was, however, smaller in kidneys pretreated with chlorpromazine. Preservation in Collins' solution for 24 and 48 hours did not change this correlation. Determination of the weights and thereby formation of oedema showed that all kidneys preserved had a small increase in weight. No difference was found between pretreated kidneys and untreated kidneys. It is concluded that pretreatment with chlorpromazine is capable of diminishing vascular contraction during the warm ischaemic period and that preservation in Collins' solution for up to 48 hours does not alter this beneficial effect.

125I-Hippuran renography was performed after temporary renal arterial clamping in contralateral nephrectomized rabbits. Mean renograms for the experimenttal groups were calculated for 0, 1, 1 1/2, 2, 2 1/2 and 3 h of warm ischaemia. The appearance phase, the 1 min uptake phase and excretion ratio were evaluated. The kidney function was monitored by serum-creatinine. Warm ischaemia of 1, 1 1/2 and 2 h resulted in a late maximum peak and delayed excretion, and for the last group in an accumulation curve. The uptake capacity was normal for these groups. Protracted ischaemia of 2 1/2 and 3 h affected also the appearance and uptake phase resulting in a slower and decreased Hippuran uptake of 50% and 34% respectively. Duration of warm ischaemia and changes in the renogram were well correlated. A normal uptake phase predicts restitution of the kidney function and 100% survival.

The effects of aminoglycoside antibiotics on 125I-hippurate (OIH) accumulation in rabbit renal cortical slices were assessed in vitro using incubation media with pH-values ranging from 6.4 to 8.4 and containing streptomycin, kanamycin, amikacin, gentamicin and tobramycin in concentrations ranging from 100 to 2,000 µg base/ml. The aminoglycoside-induced inhibition of OIH accumulation was clearly pH-dependent and most pronounced at alkaline pH-values. At pH 6.4 and 7.4 the aminoglycosides had either no or only moderate effects on OIH accumulation, while all drugs produced a distinct depression in accumulation at pH 7.9 and 8.4. The microbiologically inert N-acetyl gentamicin had no influence on accumulation.The influence of aminoglycosides on OIH accumulation is probably related to the pKa-values of these drugs and implies the presence of free amino groups.