A study of nephrotoxin-induced acute tubular necrosis with31P magnetic resonance spectroscopy
ABSTRACT Phosphorus magnetic resonance spectroscopy (31P MRS) was used to obtain in vivo spectra from rat kidneys undergoing acute tubular necrosis induced by a nephrotoxic dose of cephaloridine (CLD). Spectra were obtained 0, 24, and 48 h after injection of CLD (experimental group, n = 6) or saline vehicle (control group, n = 6). The nephrotoxicity of CLD was demonstrated by severely increased serum creatinine levels and the development of extensive proximal tubular necrosis in the CLD-injected rats, and the lack of such changes in the controls. 31P MRS showed an increase in the inorganic phosphate region signal (Pi, p = 0.004) and a decrease in the phosphodiester region signal (PDE, p = 0.01) in the experimental group by 48 h, whereas these parameters did not vary significantly in the control group during the experiment. Significant correlations were found between serum creatinine and the same two 31P MRS parameters. In summary, rat kidneys which have developed severe CLD-induced proximal tubular necrosis exhibit changes in the 31P spectrum 48 h after administration of the drug. The causes of these changes were not determined.
The Journal of Infectious Diseases 07/1970; 122(1):33-44. DOI:10.1093/infdis/122.1-2.33 · 5.78 Impact Factor
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ABSTRACT: To evaluate the role of magnetic resonance spectroscopy (MRS) and to develop surface coils for assessing cadaveric renal viability during hypothermic storage, we used the monophosphate/inorganic phosphate ratio (MP/Pi) to monitor phosphorous metabolites in intact kidneys during various renal preservation maneuvers. Eighteen canine kidneys and 16 cadaveric kidneys were studied as follows: Group 1 (N = 4) in situ kidneys were monitored by implanted MRS coils; Group 1 (N = 4) ex vivo kidneys were immediately attached to vascular cannulas and monitored by MRS surface coils during normothermic perfusion; Group 3 (N = 4) kidneys were removed, cold-flushed and, after 24 hours of 4C storage, monitored by MRS surface coils before and during four hours of reperfusion via vascular cannulas; Group 4 (N = 6) kidneys were removed, cold-flushed and monitored by surface coils during cold storage up to 72 hours. In addition, 16 cadaveric kidneys were studied while in sterile cold-storage containers. Postoperative renal function was followed in recipient patients. The MP/Pi ratios in Group 1 kidneys correlated with the ability to regenerate adenosine triphosphate (ATP). Groups 2 and 3 showed similar regeneration of ATP and MP/Pi after postischemic reperfusion, and the signal-to-noise ratios of the surface coils were better than those in the implanted coils in Group 1. Surface-coil monitoring in Group 4 kidneys showed predictable decay rates of MP/Pi during one to 72 hours of cold storage; in contrast, simultaneous cortical medullary microcirculation studies with 99mTc-macroaggregated albumin were inconclusive. Human cadaveric kidneys with high MP levels were associated with excellent renal function after transplantation, while those with low MP (less than or equal to 0.50) were associated with nonviability. We conclude that MRS is a practical and safe diagnostic modality for clinical transplantation.The Journal of Urology 02/1987; 137(1):146-50. · 3.75 Impact Factor
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ABSTRACT: Titration curves plotting chemical shift vs. pH for inorganic phosphate and glucose 6-phosphate in solutions of various composition are presented. Physiological concentrations of K+ (0.1 M) and Mg2+ (5 mM) are shown to significantly shift the titration curve. The Mg2+ effect can be partly or completely reversed by addition of sufficient quantities of adenosine triphosphate or organic acids. The acidic protein bovine serum albumin and soluble maize root tip protein have no noticeable effect on the titration curves, whereas the basic protein protamine exerts a profound effect. The results clearly indicate that knowledge of intracellular ionic strength and free Mg2+ concentrations in the sample are required if the determination of intracellular pH by 31P NMR is to be considered accurate within +/- 0.05-01 pH unit.Biochemistry 10/1981; 20(19):5389-94. · 3.19 Impact Factor