Urinary Beta 2-microglobulin Research Articles

Assessment of urinary protein 1 and transferrin as early markers of cadmium nephrotoxicity.

Transferrin and protein 1, a sex linked alpha 2-microprotein, were assayed in urine from 58 workers exposed to cadmium (Cd) in a non-ferrous smelter and from 58 age matched referents. These two new markers of nephrotoxicity were compared with urinary beta 2-microglobulin (beta 2-m), retinol binding protein (RBP), albumin, and beta-N-acetyl-glucosaminidase (NAG). The response of protein 1 to Cd tubulotoxicity was similar to that of beta 2-m, RBP, and NAG. In Cd workers, protein 1 had a correlation with urinary Cd (r = 0.56) similar to beta 2-m (r = 0.48), RBP (r = 0.58), and NAG (r = 0.49). Values of these three low molecular weight proteins and of NAG were increased only in workers with urinary Cd higher than 10 micrograms/g creatinine. Urinary transferrin and albumin were similarly affected by exposure to Cd. Their response, however, was clearly more sensitive than that of low molecular weight proteins. Prevalences of positive values of these two high molecular weight proteins were not only higher but also tended to rise at lower concentrations of Cd in urine or blood. This finding suggests that in some subjects subtle defects in glomerular barrier function may precede the onset of proximal tubular impairment after chronic exposure to Cd. It remains to be assessed whether these subjects are more at risk of developing renal insufficiency.

Urinary excretion of kappa light chains in patients with diabetes mellitus

The urinary excretion of kappa light chains, beta 2-microglobulin and albumin was examined in patients with newly diagnosed and long-standing insulin-dependent (IDDM) and non-insulin-dependent (NIDDM) diabetes mellitus, and compared to age-matched control subjects. Patients with IDDM diagnosed within two months, presented with normal albumin excretion, whereas the concentrations of beta 2-microglobulin and kappa light chain in urine were higher than in control subjects. The initiation of insulin therapy reduced, but did not completely normalize, the elevated rate of kappa light chain excretion. Patients with IDDM of long duration showed increased urine excretion of kappa light chains and albumin. In keeping with the findings in IDDM, patients with newly diagnosed NIDDM (within one year) showed increased urinary excretion of kappa light chains compared with control subjects. There was, however, no further increase in light chain excretion with longer duration of NIDDM. To study the effect of short-term hyperglycemia on urinary protein excretion, 12 normal subjects participated in a three-step hyperglycemic clamp study, during which their plasma glucose concentration was raised by +50, +125 and +300 mg/dl. The urine excretion of albumin and beta 2-microglobulin rose progressively with each hyperglycemic clamp step, whereas that of kappa light chain excretion was unaffected by hyperglycemia. We conclude that increased urinary excretion of kappa light chain is a consistent finding in all types of diabetes mellitus, and can be observed even when the albumin excretion is normal. Since the serum concentration of kappa light chain is normal in diabetes, the increased urinary excretion of kappa light chains must be of renal origin.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical Usefulness of Urinary Growth Hormone Measurement in Short Children

Growth hormone (GH) levels in nocturnal urine were measured in 96 short children and 73 children of normal height in order to investigate whether urinary GH levels reflect spontaneous GH secretion and whether they might be used to screen short children for GH treatment. GH levels in 24-hour urine samples were significantly correlated with urinary albumin and beta 2-microglobulin levels in normal children, demonstrating an influence of renal function on urinary GH measurements. Nocturnal urinary GH levels showed significant positive correlations with mean serum GH levels during 3 hours of sleep (r = 0.26, p less than 0.05) and plasma insulin-like growth factor I (IGF-I) levels, reflecting physiological GH secretion. Urinary GH levels were significantly lower in the eight children with complete GH deficiency (3.1 +/- 2.3 ng/g creatinine) than in the normal children (13.8 +/- 11.2 ng/g creatinine). Urinary GH levels in three other groups of short children, partial GH deficiency (11.1 +/- 16.9 ng/g creatinine), impaired GH secretion during sleep (10.4 +/- 12.6 ng/g creatinine) and non-endocrine short stature (18.8 +/- 19.5 ng/g creatinine), were not significantly different from those in the normal children. However, when the cut-off point for defining GH insufficiency was set at 5 ng/g creatinine, 87.5% (21 out of 24) of the short children with low urinary GH levels were suitable subjects for GH treatment (i.e. had complete GH deficiency, partial GH deficiency or impaired GH secretion during sleep).(ABSTRACT TRUNCATED AT 250 WORDS)

The association between renal dysfunction and osteopenia in environmental cadmium-exposed subjects

Two hundred and three cadmium (Cd)-exposed subjects with renal dysfunction and 80 non-exposed subjects were examined to reveal the relationship between Cd-induced renal dysfunction and osteopenia. As biological indicators of renal function, urinary beta 2-microglobulin (beta 2-mg), and serum creatinine, calcium, and phosphorus were selected. Cd in the urine and blood was also measured. The results indicated that significant differences exist between both sexes in Cd-exposed as well as nonexposed subjects. To evaluate the degree of osteopenia, a microdensitometrical (MD) method was used. The relationships between biological parameters and each index of the MD method were analyzed using multivariate analysis. Age, urinary beta 2-mg, and serum creatinine were significantly associated with indices of osteopenia in Cd-exposed men. In contrast, age showed the most significant association with MD indices in women of both groups. However, urinary beta 2-mg was significantly associated with MD indices only in Cd-exposed women. In Cd-exposed subjects, after the number of predictor variables was increased, urinary beta 2-mg was also strongly associated with osteopenia. These results suggest a causal relationship between renal dysfunction and osteopenia in Cd-exposed subjects.

No adverse effects of lead on renal function in lead-exposed workers.

A cross-sectional study was performed on 165 male lead-exposed workers to clarify the quantitative relationships between less severe exposure to lead and its effects on renal function in 1985. Mean and range of blood lead concentration (Pb-B) were 36.5 micrograms/dl and 6-73 micrograms/dl, respectively. Duration of lead exposure was 0.1 to 26.3 years. No lead-related changes were detected in serum creatinine concentration, beta-2 microglobulin in urine, creatinine clearance, beta-2 microglobulin clearance, and uric acid clearance. Twenty of the 165 workers had been exposed to lead for more than 10 years with mean duration of 21.0 years. Average concentrations of Pb-B in each individual during 1972 to 1984 were 26.1-66.6 micrograms/dl. Renal function indices of these 20 workers were not different from those of remaining lead-exposed workers whose lead exposure duration were 10 years or less. These results suggest that long-term less severe exposure to lead up to 70 micrograms/dl of Pb-B may not cause adverse effects on renal glomerular function and proximal tubular function.

Significance of the excretion of urinary indicator proteins for a low level of occupational exposure to cadmium

Urinary cadmium (Cd), N-acetyl-beta-D-glucosaminidase (NAG), metallothionein (MT), beta 2-microglobulin (BMG), and blood cadmium were determined in 79 workers who had been employed at a Cd pigment factory in Japan. The workers who had been dealing with Cd pigment manufacturing processes were estimated to be exposed to cadmium pigment dust at a maximum concentration of 3.0 micrograms/m3/8 h for about 20 years. The urinary Cd level ranged from 0.2 to 9.7 micrograms/g creatinine with a geometric mean of 1.02 micrograms/g creatinine. Pearson's correlation coefficients between logarithm of urinary Cd and that of NAG, MT, and BMG in urine were 0.45, 0.62, and 0.05, respectively. The correlation coefficients between blood Cd and urinary NAG, MT, and BMG were 0.21, 0.40, and -0.074, respectively. When partial correlation coefficients were calculated to exclude the contribution of age factor, urinary Cd turned out to be significantly correlated with urinary MT (r = 0.55) and NAG (r = 0.52). The present results indicate that urinary Cd is more closely associated with urinary MT and NAG than with BMG, and suggest that MT and NAG could be good indicators of Cd absorption in a Cd-exposed population whose mean urinary Cd level is relatively low, or less than 10 micrograms/g creatinine.

Preanalytical handling of stored urine samples, and measurement of β2-microglobulin, orosomucoid, albumin, transferrin and immunoglobulin G in urine by enzyme-linked immunosorbent assays (ELISA)

Urinary beta 2-microglobulin, orosomucoid, albumin, transferrin and IgG were measured by enzyme-linked immunosorbent assays (ELISA). In urine samples stored at -20 degrees C three of these proteins decreased during the period of freezing. After 1 week at -20 degrees C urinary transferrin decreased by 81%, IgG by 39% and albumin by 26% of the pre-freezing values; however, addition of Tween-20 restored these values. In previously stored urine samples with bovine albumin, the decreased value after freezing at -20 degrees C could be increased by changing the thawing procedure and including addition of Tween-20. Urine samples thawed at room temperature just before analysis decreased by 80% for transferrin, 57% for IgG, 30% for albumin and 26% for beta 2-microglobulin compared with samples thawed at 37 degrees C, had Tween-20 added and then were kept for a few days at room temperature before analysis. Furthermore, previously frozen urine samples that were thawed at 37 degrees C, had Tween-20 added and then were stored at room temperature did not show significant changes in any of the protein results measured the day after thawing and 35 days later. Orosomucoid seemed to be less variable as regards the effect of freezing and thawing procedure.

糖尿病における尿中酵素測定の臨床的意義

The aim of this study was to clarify the clinical significance of urinary enzyme activity in patients with diabetes mellitus. Patients were divided into two groups: group A - 102 outpatients, group B-23 inpatients. Spot urine samples before breakfast from group A and aliquots of 24-hours urine collections at 4 degrees C from group B were used. Urinary enzyme activities (N-acetyl- beta-D-glucosaminidase: NAG, alkaline phosphatase: ALP, leucine aminopeptidase: LAP, gamma-glutamyl transpeptidase: gamma-GTP) were determined by spectrophotometric assay, rate assay, Tuppy method and Orlowski method, respectively. 1) In group A, the percentage of the cases which showed higher than the normal range (NAG: 1.3-8.7, ALP: 4.2-17.7, LAP: 0-22.9 U/g. cer.) was 42.2% in NAG, 21.6% in ALP, and 8.8% in LAP. In a multiple regression analysis, the predictor variables which contributed to NAG were HbA1c, age, urinary protein and the one that contributed to ALP, LAP, gamma-GTP was urinary beta 2-microglobulin. 2) In group B, 87% of NAG was above the normal range (Mean +/- 2 SD; 4.8 +/- 3.9 U/day). There was no difference in the NAG activity between patients with and without nephropathy. The percent of high activities of ALP, LAP and gamma-GTP were 17%, 17%, 4%, respectively. Most of them were patients with nephropathy. There were correlations among ALP, LAP and gamma-GTP, though no correlation existed between NAG and the other three enzymes. These results suggested: 1) NAG reflects lysosomal dysfunction of both glomerular and proximal tubular epithelial cells which may be caused by poor glycemic control.(ABSTRACT TRUNCATED AT 250 WORDS)

幼少児膀胱尿管逆流症例における腎機能評価

The function of 99 refluxing kidneys of 61 children up to two years old at the time of diagnosis was evaluated by 99mTc-DMSA renoscintigraphy, urinary beta 2-microglobulin (beta 2-MG), alpha 1-microglobulin (alpha 1-MG) and N-acetyl-beta-D-glucosamidase (NAG). High grade reflex (grade IV, V) was found in 45% of the cases. 76%, 51% and 92% of the cases showed abnormally high value of urinary beta 2-MG, alpha 1-MG and NAG, respectively. These results indicate that they have already had tubular dysfunction at the time of diagnosis. DMSA renoscintigraphy of 82 refluxing kidneys of 49 children was performed. Of these, 48% had renal scar and 28% had serious renal dysfunction [DMSA uptake rate less than 18%]. 10-20% of low grade VUR had less than 18% DMSA uptake rate. Two patterns were noticed in the group in which urinary beta 2-MG ranged 0.33-1.0. One was characterized by good bilateral renal function with slight tubular damage and the other serious renal dysfunction with fixed tubular damage. No remarkable recovery of the renal function was noticed after antireflux operation in the second pattern cases. In many cases, in which urinary beta 2-MG was more than 1.0, improvement of DMSA uptake rate was noticed after antireflux operation.

High sensitive photometric assay of pancreatic lipase and clinical investigation of urinary lipase in patients with various histopathological types of primary glomerulonephritis

We measured the activity of urinary lipase by high sensitive photometric method using 1,2-dirinoleoilglycerol as a substrate. Also, we investigated the clinical significance of the activity of urinary lipase in patients with chronic glomerulonephritis (GN) with special reference to the relation between the levels of the enzyme and histopathological changes of the kidney. Urinary activity of N-acetyl-beta-D-glucosaminidase (NAG) and urinary beta 2-microglobulin (BMG) were also measured to compare the difference of renal handling of these 3 substances. We could obtain the following results; 1) Good coefficient of correlation was observed between the activity of urinary lipase and the excretion of urinary BMG. 2) No correlation was observed between the activity of urinary lipase and the amount of urinary NAG in patients with chronic GN. 3) In some of the cases with secondary tubulointerstitial edema and inflammatory infiltration, the values of the activity of urinary lipase were markedly elevated. These results suggested that lipase was removed from the serum mainly by glomerular filtration and reabsorbed almost completely by tubular epithelial cells like the renal handling of BMG. In contrast, NAG secreted through the different renal metabolism in proximal tubule. The activity of urinary lipase might be a diagnostic marker for the secondary acute tubulointerstitial lesions in patients with chronic GN.

Islet Transplantation to the Renal Subcapsular Space Improves Late Complications in Streptozotocin-Diabetic Rats

Transplantation of isolated islets is a promising approach in the treatment of diabetes. We have examined the long-term effects on the late complications of islet transplantation in an experimental diabetes model in the rat. Diabetes was induced by streptozotocin (70 mg/kg i.v.) and the rats were treated with either insulin (daily injection of 40 U) or transplantation of 1,000 freshly isolated, hand-picked, islets into the left renal subcapsular space. Both islet transplantation and insulin treatment completely normalized the increased levels of blood glucose, urine volume and water intake that were observed in the diabetic rats. The decreased growth rate of the diabetic rats was almost normalized by both treatment protocols. As for late complications, after 3 months, all untreated diabetic rats had cataract. They also had swelling and vacuolation of renal tubular cells, and, consistent with this, very high levels of urinary beta 2-microglobulin excretion. Both islet transplantation and insulin treatment completely prevented these late complications. Thus, islet transplantation to the renal subcapsular space is in this experimental model as good as insulin treatment in treating the clinical signs of diabetes and in preventing diabetic complications in the eye and kidney.

Assessment of tubular function in neonates using urinary ?2-microglobulin

Renal proximal tubular function was assessed in neonates by measuring urinary beta 2-microglobulin (beta 2M) concentrations on days 1, 4, 7, 14 and 28. Values were elevated in stable preterm low-birthweight (LBW) neonates but not in stable term LBW neonates, suggesting that proximal tubular maturation is related to gestational age rather than birthweight. The urinary beta 2M was significantly increased on day 1 in neonates with the meconium aspiration syndrome but was not significantly different from normal subsequently. This indicated that although the proximal tubular cells may be susceptible to perinatal hypoxia, they maintain a remarkable capacity to recover in a relatively short period. Neonates with transient tachypnoea of the newborn had normal urinary levels of beta 2M indicating their renal tubular function was not impaired.

Metabolic and renal changes in two athletes during a world 24 hour relay record performance.

Metabolic parameters and renal function were studied in two subjects before, during and after they established a world two-man 24 hour relay record. During the race, the athletes expended an estimated 37.747 and 42.880 kJ running at 54 and 61 per cent of maximum oxygen consumption (VO2max). Rectal temperatures reached maxima of 38.6 and 39.2 degrees C respectively during the race. Serum free fatty acid levels peaked at 2108 and 1875 mumol ml-1 after 24 hours; blood glucose levels varied from 4.3-6.5 and 4.9-8.5 mmol.l-1 respectively. Plasma insulin levels fell from 42.9 and 22.7 microU.ml-1 to 11.5 microU.ml-1. Plasma urea, creatinine, beta 2-microglobulin and C-reactive protein concentrations were elevated at the end of the race (to 9.0 and 8.0 mmol.l-1, 119 and 102 mumol.l-1, 3.508 and 3203 micrograms.l-1 and 2.7 and 3.9 mg per cent respectively). Plasma osmolality was altered from 293 and 304 to 302 and 280 mosmol.Kg-1 during the race but increased to 312 and 318 mosmol.Kg-1 the following day probably due to intercompartmental fluid shifts. Plasma creatinine concentration was increased by 38 and 26 per cent due to reduced urinary excretion. Urine flow rate increased 40 and 123 per cent respectively during the race, but creatinine clearance decreased by 38 and 40 per cent. Urine osmolality decreased by 38 and 65 per cent and osmolal clearance decreased by 15 and 16 per cent respectively. Urine sodium excretion was greatly reduced (85 and 90 per cent) on the post-race days (by 88 and 92 per cent on day 2). Both urine total protein and beta2-microglobulin excretion increased during the race (by 89 and 35 per cent and by 334 and 136 per cent respectively), but owing to the increased beta2-microglobulin production renal clearance was unaltered. The changes in renal function were temporary and some aspects of renal tubular function were enhanced during the post-race days. We conclude that, although C-reactive protein concentrations increased sooner and were higher than other shorter events and although creatinine, urine excretion and urine osmolality decreased markedly, the intermittent nature of the event, the mild environmental conditions, the moderate percentage of VO2 max maintained by the well conditioned subjects and a high fluid intake enabled a rapid return to normality and indeed to enhanced renal tubular function. The only moderate increases in body temperature would be due to the same factors.

URINARY EXCRETION OF BETA-2-MICROGLOBULIN IN CHILDREN WITH URINARY TRACT INFECTIONS

The aim of this study was to evaluate, if urinary Beta-2-Microglobulin (B2M) excretion is useful in the level diagnosis of urinary tract infections (UTI). 161 children with significant bacteriuria were studied. B2M was measured in 24-hrs urine collection (ph>6) by solid-phase-radioimmunoassay (B2M-monoclonal RIA KIT Prague). The samples were studied at the onset of the disease and after antibacterial treatment. The excretion of B2M was significantly higher in patiens with upper UTI than in those with lower UTI or asymptomatic bacteriuria. Especially high values were observed among children with upper UTI and with accompanying radiological changes. After antibacterial treatment the excretion of B2M decreased significantly in all patients with UTI. The sensitivity of urinary B2M as a predictor of parenchymal involvment was 89.4% with a specifity of 96.5%. Conclusions: 1) B2M excretion helps to distinguish between upper and lower UTI in children. 2) High values of B2M excretion in children with UTI are highly suggestive of parenchymal involvment, particularly in cases with radiological changes.

Renal function after autotransplantation with direct pyelocystostomy. Long-term follow-up.

The function of 20 human autologous kidney grafts was studied for 4 to 8 years (mean 5 1/2) after autotransplantation with a direct pyelocystostomy. The indications for the operation were low-grade, low-stage tumour of the renal pelvis and/or ureter, frequently recurrent renal stones and remaining outflow obstruction after pyeloplasty for hydronephrosis. The wide pyelocystostomy implies reflux of urine from the urinary bladder to the renal pelvis but no significant changes were found in glomerular or tubular function, studied with 51Cr-EDTA clearance, 131I-Hippuran renography, analysis of beta 2-microglobulin and total protein excretion in urine, and determination of concentration ability after administration of desmopressin. No increase in the severity or frequency of urinary tract infections was observed.

Beta-2-microglobulin for differentiation between ciclosporin A nephrotoxicity and graft rejection in renal transplant recipients.

The clinical relevance of daily measurement of beta 2-microglobulin in serum and urine was evaluated in 49 patients undergoing renal transplantation. The changes in beta 2-microglobulin levels were compared to standard parameters for assessment of renal function. One hundred episodes of acute deterioration of renal function, clinically diagnosed as rejection, were analyzed retrospectively: (1) In 18 episodes renal malfunction did not respond to methylprednisone but improved immediately upon dose reduction of ciclosporin A, thus indicating a nephrotoxic effect of the drug. In these cases a mean increase of beta 2-microglobulin in urine as high as 7.9 mg/l was observed while serum values decreased. (2) Fifty episodes of apparent rejection (responsive to steroids) were preceded by a 3-day lasting continuous rise of beta 2-microglobulin in serum of up to 3.6 mg/l as a mean with only a moderate elevation in urine. (3) In 13 episodes antirejection treatment could have been avoided as continuously declining laboratory parameters indicated spontaneous improvement of renal function. We conclude that parallel determination of beta 2-microglobulin in serum and urine allows to differentiate between ciclosporin A nephrotoxicity and rejection in 91% of the cases.

Cadmium, NAG activity, and beta 2-microglobulin in the urine of cadmium pigment workers.

Cadmium (Cd), N-acetyl-beta-D-glucosaminidase (NAG) activity, beta 2-microglobulin (BMG), and creatinine (cr) in urine were measured during April and September 1986 in workers exposed to cadmium pigment dust (maximum exposure 3.0 micrograms/m3/8 h for respirable dust). In April and September urinary Cd ranged from 0.2 to 9.5 and from 0.5 to 7.0 micrograms/g cr with a geometric mean of 0.7 and 1.2 micrograms/g cr, respectively. The correlation coefficient between Cd and NAG was 0.261 (n = 61) in April and 0.389 (n = 50) in September. The correlation coefficient between Cd and BMG was 0.241 (n = 63) in April and 0.115 (n = 50) in September. It appears that urinary Cd concentrations have a closer relation with urinary NAG than urinary BMG, even when urinary Cd concentrations are less than 10 micrograms/g cr. It is concluded that NAG is a more sensitive indicator of Cd absorption than BMG even at urinary Cd concentrations of less than 10 micrograms/g cr.

Stability of alpha 1-microglobulin, beta 2-microglobulin and retinol binding protein in urine

The stability of alpha 1-microglobulin ( α 1M), beta 2-microglobulin ( β 2M) and retinol binding protein (RBP) in urine was determined in 135 random samples from children with renal disease, febrile illness, malignancy, and from controls. Immediately after voiding, samples were divided into two portions, one of which was alkalinised. After identical transit times and laboratory handling the pH and concentrations of the individual proteins in each pair were measured. β 2 M was unstable in urine of pH < 7 and grossly so below pH 6. In some instances β 2M was low or undetectable even in the alkalinised samples when α 1M and RBP levels were raised, suggesting that degradation of β 2M may have occurred prior to voiding. Concentrations of α 1M and RBP were significantly lower in the non-alkalinised fractions at pH < 7, although to lesser degree than for β 2M. Contrary to previous reports, we conclude that the stability of all 3 proteins is affected by urinary pH and recommend that this be measured and alkalinisation performed at the time of voiding.

Amyloid Urinary-Tract Calculi in Patients on Chronic Dialysis

Urinary calculi found in 4 patients on chronic hemodialysis or continuous ambulatory peritoneal dialysis (CAPD) were identified as protein calculi by infrared spectroscopic analysis. Positive Congo red staining and immunological assessment revealed that the calculi were composed of amyloid protein derived from beta 2-microglobulin. A comparison of the patients who excreted calculi with 10 patients on chronic dialysis without urinary calculi showed no significant differences in the urinary and serum levels of beta 2-microglobulin. The mechanism of amyloid calculus formation may involve factors independent of the concentration of beta 2-microglobulin in urine or serum. Urinary calculi found in patients on chronic hemodialysis or CAPD were composed of amyloid protein derived from beta 2-microglobulin.

Safety of aerosol tobramycin administration for 3 months to patients with cystic fibrosis

To determine the potential toxicity of prolonged aerosol tobramycin administration, 22 patients with cystic fibrosis were monitored while receiving inhaled tobramycin three times a day for 12 weeks. Prior to, four times during administration and approximately 6 weeks after discontinuation of treatment, we assessed pulmonary function, weight, height, body temperature, eighth cranial nerve function, serum creatinine, blood urea nitrogen, urinary creatinine clearance, plasma iothalamate clearance, urinary beta-2 microglobulin concentration, and Pseudomonas aeruginosa density in sputum. There was no detectable laboratory evidence of nephrotoxicity. Neither a decrease in auditory acuity (range 250-20,000 Hz) nor vestibular dysfunction was detected. Pulmonary function tests significantly improved during the first month in all subjects (P less than 0.05) but returned to enrollment values by the end of the 12th week of administration of tobramycin aerosol. Sputum P. aeruginosa density initially decreased from a mean of 10(7) cfu/gm to a mean of 10(4) cfu/gm after 2 weeks of aerosol tobramycin administration and remained significantly below the enrollment value throughout. Coincident with the reduced bacterial density, a reduction in cough frequency and sputum production, as well as a weight gain was observed. Seventy-three percent of the patients with sputum P. aeruginosa isolates susceptible to tobramycin on enrollment yielded resistant organisms during aerosol administration. However, 1 year later all sputum P. aeruginosa isolates obtained from patients were susceptible to tobramycin. We conclude that thrice daily aerosol tobramycin administration for 3 months is not associated with detectable eighth cranial nerve or renal toxicity. Transient emergence of tobramycin resistant P. aeruginosa may occur.