Immunotherapy and metastic renal cell cancer.
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Biomedical subjects
Publications and source records attributed to C Buzio.
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In this study we investigated the short-term effects of calcium channel blockers and angiotensin-converting enzyme inhibitors on renal hemodynamics and the urinary excretion of proteins with different relative mass in subjects with mild to moderate essential hypertension and apparently normal glomerular filtration rate but reduced renal functional reserve. Sixteen subjects underwent the following four treatments: (1) low-protein meal (0.2 g protein/kg body wt), (2) high-protein meal (1.3 g protein/kg body wt), (3) high-protein meal plus oral nifedipine (20 mg), and (4) high-protein meal plus oral captopril (50 mg). Two urine samples were obtained after meals. Blood samples were drawn at the midpoint of each 120-minute urine collection period. Urine and serum were tested for total protein, immunoglobulin G, albumin, alpha 1-microglobulin, retinol binding protein, and beta 2-microglobulin. Glomerular filtration rate and renal plasma flow were assessed by iothalamate and p-aminohippuric clearance, respectively. Compared with the high-protein meal alone, nifedipine elicited a clear-cut increase in the urinary excretion of total protein (+60%, P < .01), immunoglobulin G (+58%, P < .01), albumin (+25%, P < .05), retinol binding protein (+47%, P < .05), and beta 2-microglobulin (+52%, P < .05); captopril decreased the urinary excretion rate of immunoglobulin G (-26%, P < .05), albumin (-22%, P < .05), and beta 2-microglobulin (-34%, P < .05). The ratio between the clearances of immunoglobulin G and albumin was higher after nifedipine (+21%, P < .01) and unchanged after captopril (-9%, P = NS) compared with the high-protein meal alone.(ABSTRACT TRUNCATED AT 250 WORDS)
The present study was aimed at assessing the diagnostic value of urinary albumin (uA) excretion rate in the long-term follow-up of patients suffering from acute post-streptococcal glomerulonephritis (APSGN). 26 patients, who had presented primarily with nephritic syndrome and showing increased uA without a concomitant rise in total proteinuria (uTP) were followed-up for 131 months on average (range 36-288). At the last check, 14 patients did not show urinary abnormalities, 9 had a persistent increase in uA, 1 increased uTP and 2 renal insufficiency. Urinary and clinical signs of the disease were not seen during observation periods prolonged for 79 months on average (range 20-156) after normalization of uA. No pathological findings were remarked in biopsy specimens obtained in 3 patients when uA was normalized; in contrast, when both uTP and uA (12 cases) or when isolated uA (14 cases) were increased a pattern of diffuse mesangial proliferative glomerulonephritis was constantly observed. These results indicate that the abnormal uA excretion rate during long-term follow-up of APSGN allows to identify a subset of patients with persistent renal disease; conversely, the occurrence of normal uA seems to point to a good diagnostic and prognostic significance.
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Glomerular hyperfiltration is thought to play a pivotal role in causing renal damage in essential hypertension. An increase in glomerular filtration rate can be experimentally induced by an acute oral protein load through still unclarified mechanisms, although hormonal factors have been postulated; in already hyperfiltering nephrons, the capacity to further increase glomerular filtration rate upon stimulation with an acute protein load (i.e. renal functional reserve) would conceivably be reduced, even in the presence of apparently normal renal function. The present study aimed at assessing whether renal functional reserve is preserved and/or is affected by different antihypertensive drugs in essential hypertensive patients without signs of renal function impairment; moreover, we tried to highlight changes in the plasma levels of natriuretic and antinatriuretic hormones potentially involved in the modulation of renal hemodynamics under the chosen experimental conditions. Renal hemodynamic parameters, plasma renin activity, aldosterone and atrial natriuretic factor were measured in fourteen essential hypertensives submitted to an acute oral protein load, alone or with a concomitant administration of either nifedipine or enalapril, as compared with a control carbohydrate meal. Glomerula filtration rate and renal plasma flow rose slightly but not significantly following an acute oral protein load as compared with a carbohydrate meal; no changes were noted in plasma atrial natriuretic factor levels, whereas plasma renin activity decreased. When nifedipine was administered together with the protein meal, both glomerular filtration rate and renal plasma flow increased significantly; there were also, parallel increases in plasma renin activity and atrial natriuretic factor. Administration of enalapril was associated with a decrease in both glomerular filtration rate and renal plasma flow; plasma renin activity showed an expected marked rise, whereas the plasma levels of atrial natriuretic factor were only slightly but not significantly reduced and plasma aldosterone fell. In conclusion, our data suggest that in our patients renal functional reserve was blunted. Clear-cut hyperfiltration was brought about by administration of nifedipine together with a protein meal, whereas enalapril completely abolished even the small increase in glomerular filtration rate seen after protein meal alone. The concomitant alterations in plasma renin activity, aldosterone and atrial natriuretic factor seemed to play no major role in the determinism of the observed renal hemodynamic changes.
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Two separate experiments were carried out to study the effects of the same acute protein load given at different hours of the day and to assess the ability of proteins from different sources to induce hyperfiltration. In the first experiment, 9 healthy volunteers were kept at strict bedrest for 48 h, during which both a meat high-protein meal (protein load, PL) and a vegetable low-protein meal (control load, CL) were given either at lunch or at suppertime. As compared to a CL, PL determined a significant increase in GFR, total proteinuria (uTP), albuminuria (uA), and urinary retinol-binding protein (uRBP). These effects were much more significant after lunch PL than after supper PL, thus indicating an interaction between the PL and the time of the day. The existence of a circadian rhythm for GFR, uTP, uA, and uRBP was corroborated by spontaneous changes over baseline levels, which also were prominent after lunch CL as compared to those following supper CL. In the second experiment, 7 healthy volunteers ingested at lunch three protein-rich meals at 1-week intervals. The three protein loads consisted of about 80 g protein in the form of cooked red meat, cheese, and soya, respectively. The only significant differences between groups were urea appearance and urea clearance, lower and higher, respectively after soya load. These findings suggest that when evaluating the renal functional reserve after acute protein load both the spontaneous changes and the time-dependent sensitivity of kidney functions to acute challenges should be considered. Finally, the amount rather than quality of dietary proteins seems to be the determinant factor for protein-induced glomerular hyperfiltration.
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Ten healthy volunteers were studied to test the effect of a meat meal on the circadian rhythm of urinary proteins. All subjects were kept at bed-rest during the whole 24-h evaluation period. An oral protein load (0.6 g/kg bodyweight) was given at supper-time (19.00 hours). Urinary and serum samples were collected every 3 h and examined for total protein, albumin, retinol-binding protein, and creatinine. All these variables and glomerular filtration rate (GFR), as measured by creatinine clearance, showed circadian rhythms. Acrophases were located at 14.21 hours (range 11.11-16.25) for urinary total protein, at 17.27 hours (13.14-22.31) for serum total protein, at 15.13 hours (13.01-18.04) for urinary albumin, at 14.18 hours (11.13-19.20) for serum albumin, at 21.22 hours (18.42-02.41) for urinary retinol-binding protein, at 14.51 hours (08.52-19.57) for serum retinol-binding protein, and at 16.17 hours (13.38-19.25) for creatinine clearance. Thus, the acrophases of urinary total protein and urinary albumin excretion rates occurred before the supper protein load, in a time span common to the acrophases of their serum levels and maximal GFR, whereas the acrophase of urinary retinol-binding protein occurred after the supper meat meal, concomitantly with the lowest value of serum retinol-binding protein. These findings suggest that circadian rhythms of urinary total protein and urinary albumin are influenced by changes in GFR, which occur also independently from an oral protein load. In fact, the latter did not modify creatinine clearance when administered at supper time.(ABSTRACT TRUNCATED AT 250 WORDS)
Seven healthy male volunteers were studied to test the effect of timing of an oral protein load on renal function. Creatinine clearance (Ccr) was measured during the 4-h period after administration of 72 g of protein in the form of cooked red meat at 1200 hours (lunch protein load, PL) and at 2000 hours (supper PL) the next evening. A low-protein meal in the form of vegetables was given as a control load at 2000 hours on the first day (supper control load, CL) and at 1200 hours on the second day (lunch CL). The 12-h night-time Ccr at fasting was used as the baseline reference value. After the lunch PL, Ccr (mean 127 +/- 6.8 ml/min) was 45% (p less than 0.001) higher than the baseline value (mean 87.9 +/- 5.3 ml/min) and 33% (p less than 0.001) higher than lunch CL (mean 95.8 +/- 5.6 ml/min). After the supper PL, Ccr (mean 106.2 +/- 8.7 ml/min) was 20% (p less than 0.01) higher than the baseline value and 15% (p less than 0.01) higher than the supper CL (mean 93.0 +/- 9.3 ml/min). The differences between baseline and control load values were not statistically significant. In all seven patients, the protein load induced a maximum Ccr value at lunchtime, and Ccr after the lunch PL was 22% higher than Ccr after the supper PL (p less than 0.01). We conclude that in healthy individuals, the Ccr after an oral protein load is correlated to the hour of the day when the study is performed.(ABSTRACT TRUNCATED AT 250 WORDS)
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The existence of circadian variations in the urinary excretion of total protein, albumin and creatinine was investigated in subjects with normal and impaired renal function. All individuals were kept at bedrest for 24 hours. Eight consecutive urine specimens were collected every 3 hours and examined. In normal subjects the urinary total protein, albumin and creatinine excretion showed a significant increase during the 12 daytime hours compared with the night-time. The diurnal variations with peak occurrence at 13.26 h (range 09.58-16.43 h) for total protein, at 12.37 h (range 10.33-15.18 h) for albumin, at 16.33 h (range 13.22-19.24 h) for creatinine are temporally related to the ingestion of meat. In patients, by contrast, total protein, albumin and creatinine excretion in the urine were not modified significantly throughout the 24 hours period. Thus, impaired renal function is associated with the loss of the physiological circadian rhythm.
Urines of 6 normal subjects, collected during three consecutive 12-hour periods, were examined for proteinuria and albuminuria. During the first period, subjects were kept in the upright position, and during the next two periods in the recumbent position. Both position (upright and recumbent) and the urine collection period (day or night) significantly modify protein and albumin excretion. Proteinuria is more sensitive to different posture and albuminuria to different times of urine collection.
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Filtration through membranes with different nominal cut-off was used for isolation of middle molecule fractions from uremic serum. Comparison was made with test substances which in gel filtration did not show a regular relationship between molecular weight and partition coefficient. The XM50 membrane (cut-off 50,000 D) showed the highest permeability to middle molecules (greater than 84%) whereas CF50 (same cut-off) retained middle molecules to some extent if filtration was carried out only once. The UM05 membrane (cut-off 500 D) was highly permeable for small molecules less than 300 D, intermediary permeable for molecules between 300 and 1000 D and retained molecules between 1,100 and 1,350 D more efficiently. It is concluded that filtration through membranes is a suitable method for identification of middle molecules.