We evaluated the renal handling of beta2-microglobulin (β2-M) and creatinine in healthy outpatients (n = 6), normal children hospitalized for infections treated with antibiotics (not including an aminoglycoside) (n = 4); outpatients with cystic fibrosis (CF; n = 12), and hospitalized patients with CF (n = 6) who received a 10- to 14-day course of antibiotic treatment that included an aminoglycoside. The serum β2-M concentrations in the normal outpatients (2020.1 ± 276.6 μg/L) were significantly lower (p <0.05) than those observed for outpatients (2833.3 ± 202.6 μg/L) or patients with CF (2861.8 ± 340.5 μg/L. There were no significant differences found for creatinine clearance or fractional excretion of β2-M when subjects without CF were compared with those with the disease. Furthermore, no significant differences were observed in hospitalized patients with CF when creatinine clearance and fractional excretion of β2-M were compared between the initiation and conclusion of aminoglycoside treatment. Glomerular filtration and proximal tubular reabsorption of β2-M were not altered in patients with CF. These findings do not support a global defect in proximal renal tubular reabsorption as the underlying cause for altered aminoglycoside clearance in patients with CF.
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References
1.
PECHEREJC, DUGALRClinical pharmacokinetics of aminoglycoside antibiotics. Clin Pharmacokinet1979; 4: 170–99.
2.
KEARNSGL, HILMANBC, WILSONJTDosing implications of altered gentamicin disposition in patients with cystic fibrosis. J Pediatr1982; 100: 312–8.
3.
LEVYJ, SMITHAL, KOUPJR, WILLIAMS-WARRENJ, RAMSEYBDis-position of tobramycin in patients with cystic fibrosis: a prospective controlled study. J Pediatr1984; 105: 117–24.
4.
MACDONALDNE, ANASNG, PETERSONRG, SCHWARTZRH, BROOKSJG, POWELLKRRenal clearance of gentamicin in cystic fibrosis. J Pediatr1983; 103: 985–90.
5.
KELLYHW, LOVATOCAntibiotic use in cystic fibrosis. Drug lntell Clin Pharm1984; 18: 772–83.
6.
DI SANT'AGNESEPA, DAVISPBResearch in cystic fibrosis. N Engl J Med1976; 295: 481–5.
7.
QUINTONPMSuggestion of abnormal anion exchange mechanism in sweat glands of cystic fibrosis patients. Pediatr Res1982; 16: 533–7.
8.
YAFFESJ, GERBRACHTLM, MOSOVICHLL, MATTARME, DANISHJ, JUSKOWJPharmacokinetics of methicillin in patients with cystic fibrosis. J Infect Dis1977; 135: 828–31.
9.
ARVIDSSONA, ALVANG, STRANDVIKBDifferences in renal handling of cefsulodin between patients with cystic fibrosis and normal subjects. Acta Pediatr Scand1983; 72: 293–4.
10.
SPINOM, CHAIRP, ISLESAFAssessment of glomerular filtration rate and effective renal plasma flow in cystic fibrosis. J Pediatr1985; 107: 64–70.
11.
HILLM, HENDELESL, SCHNAPFB, MERWING, SCHENTAGJ, STILLWELLPVestibulo-acoustic and renal affects of individualized doses of tobramycin in patients with cystic fibrosis (abstract). Drug lntell Clin Pharm1984; 18: 504.
BRARENV, GODDARDJ, BRILLAB, TOUYAJJBeta-2-microglobulin as a renal diagnostic agent. Urology1979; 13: 624–8.
14.
APERIAA, BROBERGERUBeta-2-microglobulin, an indicator of renal tubular maturation and dysfunction in the newborn. Acta Pediatr Scand1979; 68: 669–76.
15.
COLEJW, PORTMANRJ, LIMY, PERLMANJM, ROBSONAMUrinary (β2-microglobulin in full-term newborns: evidence for proximal tubular dysfunction in infants with meconium-stained amniotic fluid. Pediatrics1985; 76: 958–64.
16.
ROXEDM, SANTHANAMSS, DEL GRECOF, WOLFJRationale and application of beta-2-microglobulin measurements to detect acute transplant rejection. Nephron1981; 27: 260–4.
LANDERSS, BERRYPL, KEARNSGL, KAPLANSL, RUDOLPHAJGentamicin disposition and effect on development of renal function in the very low birth weight infant. Dev Pharmacol Ther1984; 7: 285–302.
19.
WHELTONATherapeutic initiatives for the avoidance of aminoglycoside toxicity. J Clin Pharmacol1985; 25: 67–75.
20.
RADIGANLR, ROBINSONSEffects of environmental heat stress and exercise on renal blood flow and filtration rate. J Appl Physiol1949; 2: 185–91.
21.
VREETB, GUELENPJM, JONGMAN-NIXB, WALENKAMPGHIMThe relationship between the renal clearance of creatinine and the apparent renal clearance of beta-2-microglobulin in patients with normal and impaired kidney function. Clin Chim Acta1981; 114: 93–9.
22.
HALLPW, RICANATIESRenal handling of beta-2-microglobulin in renal disorders; with special reference to hepatorenal syndrome. Nephron1981; 27: 62–6.
23.
PAPADOPOULOUZL, TINALU, SANDLERP, JOSEPA, CALCOGNOPLSize and function of the kidneys. In: JohnsonTR, MooreWM, JeffriesJE ed. Children are different: developmental physiology, 2nd ed.Columbus, OH: Ross Laboratories, 1978: 97–104.
24.
VINCENTC, REVILLARDJPBeta-2-microglobulin and HLA-related glycoproteins in human urine and serum. Contr Nephrol1981; 26: 66–89.
25.
AMODIOP, GATTAA, RUOLAβ2-microglobulin concentration in plasma and production in liver cirrhosis. J Chem Clin Biochem1984; 22: 147–51.
26.
GREICOMH, REDDYMM, KOTHARIHB, LANGM, BUIMOVICI-KLEINE, WILLIAMDElevated β2-microglobulin and lysozyme levels in patients with acquired immune deficiency syndrome. Clin Immunol Immunopath1984; 32: 174–84.
SCHOFIELDDH, MANGIONERA, KAYBG, GORVOYJDLack of aminoglycoside-induced nephrotoxicity in cystic fibrosis. Drug Intell Clin Pharm1984; 18: 153–5.
29.
ABRAMOWSKYCR, SWINEHARTGLThe nephropathy of cystic fibrosis: a human model of chronic nephrotoxicity. Hum Pathol1982; 73: 934–9.
30.
ROBSONAM, TATEISHIS, INGLEFINGERJR, STROMINGERDB, KLAHRSRenal function in patients with cystic fibrosis. J Pediatr1971; 79: 42–50.
31.
SPINOM, CHAIRP, ISLESAFCloxacillin absorption and disposition in cystic fibrosis. J Pediatr1984; 105: 829–35.
32.
LEEDERJS, SPINOM, ISLESAF, TESOROA, GOLDR, MACLEODSMCeftazidime disposition in acute and stable cystic fibrosis. Clin Pharmacol Ther1984; 36: 355–62.
33.
JUSTM, HABERMANNEThe renal handling of polybasic drugs. Parts 1 and 2. Arch Pharmacol1977; 300: 57–76.
34.
MOGENSENCE, SOLLINGKStudies on renal tubular protein reabsorption: partial and near complete inhibition by certain amino acids. Scand J Clin Lab Invest1977; 37: 477–86.
35.
WHELTONA, SOLEZKAminoglycoside nephrotoxicity—a tale of two transports. J Lab Clin Med1982; 99: 148–55.
