Variability of kidney tubular interstitial distortions in glomerulonephritis as measured by 1H-NMR urinalysis.

1H-NMR urinalysis is used for reliable non-invasive diagnostics of tubular and papillary distortions in glomerulonephritis. The study of urine from 52 patients with various clinical forms of the disease shows that these dysfunctions can manifest and develop independently of the degree of glomerular lesions at any stage of the glomerulonephritis. Tubular and papillary changes can be negligible even in terminal uremia and drastic in cases of clinically preserved kidney function. In addition, the results indicate that not only tubular interstitial changes, but also isolated tubular or papillary distortions can develop at any stage of the disease. Thus 1H-NMR urinalysis is suitable for diagnosing latent tubular interstitial changes which are not readily detected by traditional techniques. This is important since early tubular intervention worsens the prognosis of the glomerulonephritis progression. Thus an approach enables identification of a group at risk of rapid deterioration of the disease among patients whose serum has normal creatinine levels. This additional information is valuable for the proper treatment of patients, and makes 1H-NMR urinalysis a prospective method for screening urine in glomerulonephritis. Further studies are required to decide whether the technique can be recommended for clinical practice.

1H NMR urinalysis in glomerulonephritis: a new prognostic criterion.

The applicability of 1H NMR urinalysis to glomerulonephritis was investigated: storage of urine at -18 degrees C and its subsequent lyophilization were shown to cause no loss of available biochemical information. Proteinuria was demonstrated not to interfere with the breadth and intensities of 1H NMR signals of low-molecular-weight metabolites in urine. The urine content of patients with glomerulonephritis was shown to be independent of exogenous factors, whereas these factors did affect the content of the urine of healthy volunteers. Statistical analysis of 1H NMR data for 52 patients with glomerulonephritis and 8 healthy volunteers on a pseudo-nephrological diet allowed the confirmation of the obligatory tubular interstitial changes that accompany the disease progression. It was established that severe tubular interstitial distortions can be revealed in patients with clinically preserved kidney function who display early stages of the glomerulonephritis, whereas these distortions can be practically negligible even at the terminal phase of uremia. Among patients with clinically preserved kidney function, especially those with nephrotic variant of the disease, isolated tubular and papilla distortions, as well as simultaneous tubular interstitial changes, were discovered, and this complicated the prognosis of glomerulonephritis progression. Thus, a new criterion to unmask a group at risk of rapid progression to uremia can be proposed, justifying an early prescription of immune suppressive drugs or other adequate treatment to these patients.

[Free radical oxidation and tubular dysfunctions in patients with chronic kidney failure]. / Sobodnoradikal'noe okislenie i kanal'tsevye disfunktsii u bol'nykh s khronicheskoi pochechnoi nedostatochnost'iu.

Sixty patients with chronic renal failure (CRF) were studied for the rates of lipid peroxidation (LPO), the state of the antioxidative system (AOS) as well as for the morphofunctional state of biomembranes in renal tubules measured by excretion of low-molecular compounds tested in urine x by means of proton nuclear magnetic resonance spectroscopy. The control group numbered 35 patients with glomerulonephritis free of functional disturbances in the kidneys. The increased values of malonic dialdehyde levels in red blood cells and blood serum and those of diene conjugates in red blood cell membranes provide evidence for a significant increase of the LPO levels. Furthermore, depression of the AOS was revealed, manifested by the decreased levels of blood serum alpha-tocopherol as well as by unstable levels of superoxide dismutase in red blood cells. In the presence of the high LPO levels significant tubular dysfunctions were progressing, parallel with aggravation of renal function. Disturbances detected in excretion and reabsorption of amino acids (leucine, alanine, glycine, valine, histidine), thin organic acids and ketone bodies in CRF patients point to the existence of disturbances in tubular membranes. Tubular dysfunction appears to be caused by the disturbances of the biomembrane morphofunctional states induced by the high levels of free radical oxidation as well as by the AOS function failure.

[Evaluation of maximal Na K ATPase activity in the erythrocytes of patients with various types of arterial hypertension using the Na-23-NMR method]. / Otsenka maksimal'noi aktivnosti Na+, K+ ATFazy v éritrotsitakh u bol'nykh s razlichnymi formami arterial'noi gipertenzii metodom 23Na-IaMR.

The paper provides measurements of maximal Na+, K(+)-ATPase activity in 20 patients with hypertensive disease, 20 patients with secondary hypertension and 20 healthy donors. The investigation was made by high-resolution nuclear magnetic resonance using sodium nuclei. A significant decrease was found in Na+, K(+)-ATPase activity in the patients with hypertensive disease (9.0 +/- 0.3 mg-equiv. per lites cells an hour) as compared with those with secondary hypertension (10.3 +/- 0.3 mg-equiv. per liter cells an hour) and the controls (10.5 +/- 0.3 mg-equiv. per liter cells an hour), which supports the findings of impaired membrane morphology in hypertensive disease.

[Possibilities of using proton nuclear magnetic resonance spectroscopy in multicomponent analysis of the urine in glomerulonephritis]. / Vozmozhnost' ispol'zovaniia spektroskopii iadernogo magnitnogo rezonansa na protonakh dlia mnogokomponentnogo analiza mochi pri glomerulonefrite.

Methodological approaches to investigation of low-molecular urine metabolites in health and glomerulonephritis (GN) by means of proton nuclear magnetic resonance spectroscopy (1H NMR) have been analysed. The ways to preserve and concentrate the urine samples by freezing and lyophilization for further storage and spectra quality improvement are substantiated. The method of the spectra treatment with calculation of relative levels of urine substances is detailed. The differences in the ratios of excreted low-molecular metabolites revealed in healthy subjects and GN patients in relation to the severity of chronic renal insufficiency confirm the feasibility of using the 1H NMR data of urine as diagnostic and predictive criteria in GN.

23Na NMR measurement of the maximal rate of active sodium efflux from human red blood cells.

The method for 23Na NMR measurement of the maximal rate of active Na+ efflux from human red blood cells (RBC) is proposed. The nonpenetrating paramagnetic shift reagent (SR) bis(tripolyphosphate)dysprosium(III) complex is used to distinguish extracellular Na+ ions from intracellular. RBC are proved to retain their physiological activity in the presence of SR. Intracellular Na+ is shown to be 100% NMR visible. The levels of intracellular and extracellular Na+ and K+ ions are changed to decrease their concentration gradients across the erythrocyte membrane to make active Na+ efflux the only 23Na NMR measurable process; so the integrated areas of intra- and extracellular Na+ peaks remain invariant throughout the incubation period in the presence of 0.25 mM ouabain, a specific inhibitor of Na+, K+-ATPase. The accuracy of the proposed technique is evaluated to be 10%. The maximal Na+ efflux is determined to be 10.1 +/- 1.0 mM/h/liter of cells.

[Levels of labile phosphorus-containing metabolites]. / Soderzhanie labil'nykh fosforsoderzhashchikh metabolitov.

The work deals with the investigation of possible use of 31P-NMR for revealing metabolism changes in the mouse liver during the development of leukemia. This method was shown to permit observation of the extreme pattern of relative concentrations of sugar phosphate and bioorganic phosphate in the latent period. This observed increase in the metabolic activity of hepatocytes correlates with biophysical shifts found by other methods.

[Possibility of the evaluation of the functional activity of human erythrocytes using the 31P-NMR method]. / O vozmozhnosti otsenki funktsional'noi aktivnosti éritrotsitov cheloveka metodom 31P-IaMR.

Intact human erythrocytes from venous blood were investigated. It has been found that the width and form of signals of 2.3 DFG vary strongly, but for the given person these characteristics of the signals are stable parameters. These variations were shown to correspond to the degree of inhomogeneity of erythrocytes population in venous blood as regards their relative concentrations of Hb and HbO2. The width of the signals of 2.3 DFG, so far reflects functional activity of the human red blood cells in oxygen transport.