Altered organic anion and osmolyte content and excretion in rat polycystic kidney disease: an NMR study.

Polycystic kidney disease (PKD) is the fourth most common cause of end-stage renal disease and the most common potentially lethal inherited disease in humans. Early identification of carriers of dominant PKD in the absence of genetic markers is problematic in both humans and the Han:SPRD-cy/+ rat, a model of PKD that shares many features of human disease. We undertook a proton magnetic resonance imaging (MRI) study of young Han:SPRD-cy/+ and unaffected Han:SPRD(-)+/+ animals to determine whether carrier status could be identified based upon image appearance or signal characteristics. Affected animals demonstrated significant prolongation of longitudinal relaxation time (T1) and transverse relaxation time (T2) in both cystic renal cortex and noncystic renal medulla. Both of these measurements correlated significantly with whole kidney section tubular luminal space measurements, a correlate of water space, in the renal cortex, but only T1 in renal medulla showed a relationship to tubular luminal volume measured throughout the kidney. Urine and perchloric acid kidney extracts were studied using proton nuclear magnetic resonance (1H-NMR) spectroscopy to test the hypothesis that imaging differences implied specific urinary and tissue biochemical differences between affected and normal animals. 1H-NMR spectra of urine from cy/+ animals showed significantly increased excretion of alanine, citrate, succinate, and, 2-oxoglutarate but not methylamine compounds compared with +/+ animals. 1H-NMR spectra of aqueous perchloric acid kidney extracts confirmed reduced concentrations of the above ions and others involved in the citric acid cycle, as well the osmolytes betaine, taurine, and glycerophosphocholine PKD in the Han:SPRD-cy/+ rat is associated with distinct early MRI changes and alterations in urinary and tissue levels of organic anions and osmolytes.

Biochemical changes in denervated muscle identified by magnetic resonance spectroscopy.

OBJECTIVE: Magnetic resonance spectroscopy (MRS) has the potential to noninvasively delineate early biochemical changes in denervated muscle. In this study, we examine metabolic changes in denervated rat facial muscles using quantitative invitro 1H and 31P MRS. METHODS: Forty male Wistar rats were subjected to transection of the facial nerve trunk on the left and sham exposure on the right, and allowed to recover. The animals were then reoperated at 1, 2, 4, or 8 weeks after the initial procedure. EMG of the facial muscles and facial nerve conduction studies were performed at both time points, and facial muscles were harvested from normal and control sides at the second procedure. Perchloric acid extracts of facial muscles were then prepared for analysis using MRS. RESULTS: The results showed a progressive time-dependent decrease in Cr, PCr, Pi, ATP, and ADP all on the transected side. CONCLUSION: This study is an important step in the development of clinically relevant noninvasive methods of assessing and quantifying degeneration in nerve-muscle systems.