Sequential measurements of urinary albumin in recipients of renal allografts.
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Adult↗
Biomedical subjects
B Lacour
Publications and source records attributed to B Lacour.
Atherosclerosis and lipid disorders after renal transplantation.
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Arteriosclerosis↗
Calcium uptake kinetics into brush-border membrane vesicles: higher Vmax in the spontaneously hypertensive rat than in normotensive control.
Arterial hypertension in the spontaneously hypertensive rat (SHR) is associated with an abnormal Ca2+ homeostasis, compared with its normotensive control, the Wistar Kyoto rat (WKY). In particular, epithelial Ca2+ transport is perturbed, with intestinal absorption and renal tubular reabsorption being decreased in the adolescent and adult SHR. In the present study we examined Ca2+ uptake into isolated duodenal brush-border membrane vesicles (BBMV) in 12-14 week-old male rats. This uptake can be separated in a nonsaturable and a saturable component. The latter follows Michaelis-Menten kinetics. Vmax of this component was found to be significantly higher (p less than 0.05) in SHR than in WKY (0.58 +/- 0.19 versus 0.35 +/- 0.06 nmol/mg protein x 10 sec, mean +/- SD) whereas Km did not differ. Thus, the defect in the intestinal Ca2+ absorption previously identified in the SHR of this age is not due to a decrease in Ca uptake at the level of the duodenal brush-border membrane, but is most likely located in the baso-lateral membrane.
Animals↗
Simple and rapid method for the purification of human apolipoprotein C II by reversed-phase high-performance liquid chromatography.
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Apolipoprotein C-II↗
Ultrastructural and functional abnormalities of intestinal and renal epithelium in the SHR.
Intestinal calcium transport, renal tubular calcium reabsorption, and plasma 1.25 (OH)2 vitamin D3 (calcitriol) levels have all been reported to be diminished in the spontaneously hypertensive rat (SHR) compared with its genetic control the Wistar Kyoto rat (WKY). In the present study, absorptive duodenal and renal tubular epithelia of 12- to 14-week-old male SHR and WKY were examined by electron microscopy to determine whether such disturbances could be related to structural abnormalities. Patchy loss of microvilli in both duodenal and proximal tubular epithelia was observed in the SHR, whereas brush border membrane was entirely normal in the WKY. Irregular spaces were observed between the basal aspects of SHR intestinal epithelial cells and their basement membrane. In addition, the average height of duodenal and renal microvilli was reduced in the SHR. Two specific markers of the brush border membrane, alkaline phosphatase and villin, as well as the cytoplasmic vitamin-D dependent calcium-binding proteins, CaBP9K and CaBP28K were determined. Duodenal alkaline phosphatase activity was reduced in the SHR, compared with the WKY: 0.145 +/- 0.002 vs. 0.186 +/- 0.002 IE/min.microns 3 x 10(3) brush border, mean +/- SEM, N = 10 pairs, P less than 0.001. However, duodenal villin expression was not different from that of the WKY. Duodenal CaBP9K and renal CaBP28K content was diminished in the SHR: 21.0 +/- 0.80 vs. 29.9 +/- 2.19 micrograms/mg protein, N = 6 pairs, P less than 0.01 for duodenum, and 4.47 +/- 0.39 vs. 7.67 +/- 0.54 micrograms/mg protein, N = 6 pairs, P less than 0.001 for kidney. These data showing structural and functional abnormalities of intestinal and kidney cells in the SHR appear to reflect a disorder of transporting epithelia which may be either intrinsic or related to reduced circulating calcitriol.
Alkaline Phosphatase↗
Renal hemodynamics and segmental tubular reabsorption in early type 1 diabetes.
To investigate mechanisms underlying GFR control in diabetes mellitus, renal hemodynamics and segmental tubular handling of sodium, using lithium clearance, were assessed in 41 insulin-dependent diabetics (IDD) treated by insulin for 11 +/- 8 days, and in 19 normal controls. Average GFR and effective renal plasma flow (ERPF) were slightly but not significantly higher (136 +/- 22 vs. 123 +/- 16 ml/min.1.73 m2) in IDD than in normal subjects. GFR and ERPF were positively and strongly correlated in controls (r = 0.61, P less than 0.001) and in diabetics (r = 0.72, P less than 0.0001) indicating the marked flow dependency of GFR in both populations. After adjustment for ERPF, GFR was significantly higher in diabetics, suggesting a role of increased glomerular capillary pressure and ultrafiltration coefficient in the subset of "hyperfiltering" patients. Both fractional (FPRNa) and absolute (APRNa) proximal sodium reabsorption were significantly higher in IDD and significantly correlated with GFR. The ensuing decrease in sodium distal delivery could deactivate the tubuloglomerular feedback response and thus favor sustained vasodilation and high GFR in some diabetics. The renal effects of acute administration of drugs acting predominantly at either the pre- or the postglomerular resistance using nicardipine (N = 16) or captopril (N = 25) were further evaluated in IDD. The renal response to captopril or nicardipine was different in IDD. Whereas both drugs induced a marked decrease in renal vascular resistance, GFR was slightly decreased by captopril and was unchanged after nicardipine; these results are similar to those observed in normotensive non-diabetic subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Epithelial abnormalities in intestine and kidney of the spontaneously hypertensive rat.
A variety of perturbations of calcium metabolism are reported to occur in the spontaneously hypertensive rat (SHR) compared to its genetic control the Wistar-Kyoto rat (WKY), including significant dysfunction of calcium handling by the proximal renal tubule of the SHR, resulting in impaired active calcium transport in the gut and an apparent renal calcium leak. We explored the intestinal and renal epithelia of 12- to 14-week-old SHR and WKY using electron microscopy. Biochemical comparisons of these transport epithelia included measurements of three vitamin D dependent cellular proteins and one structural protein: alkaline phosphatase, intestinal CaBP9K, renal CaBP28K, and villin expression. Electron microscopy demonstrated a patchy loss in microvilli in the SHR, accounting for approximately 10 to 15% of the total microvillar surface. In the kidney, morphological abnormalities were observed only in the proximal renal tubule. Again, there was patchy loss of microvilli from the brush border membrane. In SHR duodenal alkaline phosphatase activity was significantly reduced compared to the WKY (0.145 +/- 0.002 v 0.186 +/- 0.002 integrated extinction/min/micron 3 X 10(3) brush border (P less than .001). Duodenal CaBP9K and renal CaBP28K were significantly reduced in SHR compared to WKY. There were no differences in villin expression. These data are consistent with the previously characterized disturbances of active calcium transport in the intestine and inappropriate renal calcium leak in the SHR. While a possible link between these disturbances and hypertension remains to be determined, this study provides supportive evidence for a primary disturbance in cell calcium handling and transporting epithelia in this form of genetic hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)
Alkaline Phosphatase↗
Adverse effects of sucrose-rich diets on uraemic rats.
The nature of carbohydrate may affect the tolerance and progression of uraemia. The effects of three diets differing only in their carbohydrate source: namely corn starch (C), glucose (G) or sucrose (S) were examined. Study 1 examined the effects of the three carbohydrate diets on unilaterally nephrectomised control rats and severely uraemic rats. The three carbohydrates produced similar nutritional effects in uninephrectomised rats, whereas sucrose rapidly induced anorexia, stunting and slightly accelerated renal damage in uraemia. Study 2 examined the long-term effects of the three carbohydrates in moderate uraemia under conditions of high and identical carbohydrate intakes. Hyperphagic Zucker uraemic rats (F rats) received a daily allotment of each diet plus pure carbohydrate. Lean uraemic rats (L rats) received the same dietary allotment without the carbohydrate supplement. The F rats fed sucrose showed greater morbidity and mortality but little renal deterioration. Their plasma triglycerides increased dramatically. The L rats fed sucrose had the greatest urinary protein, the least creatinine clearance and the most severe renal damage. Thus, sucrose-rich but not glucose-rich diets have two adverse effects in uraemia: a deterioration in nutritional status, perhaps related to abnormal fructose utilisation, and a long-term effect on the kidney, resulting in accelerated renal deterioration.
Animals↗
Does lithium affect renal sodium handling and renal haemodynamics in normal man?
Renal haemodynamics, sodium excretion, and free-water clearance were evaluated at baseline and after acute frusemide administration in nine moderately volume-expanded healthy volunteers receiving a single administration of either 750 mg lithium carbonate or placebo. Lithium plasma concentration under 0.29 mmol/l exerted no significant effect on renal haemodynamics, on absolute, fractional, or cumulative sodium excretion, or on free-water and chloride clearances at baseline or after frusemide administration. Despite previous volume expansion and presumably depressed proximal reabsorption, frusemide decreased the fractional reabsorption of lithium significantly, suggesting that a small but significant part of lithium may be reabsorbed in the thick ascending limb of Henle's loop. By contrast, frusemide did not change renal haemodynamics or plasma renin activity. Using combined free-water and lithium clearances at baseline and after frusemide administration, fractional reabsorption of sodium in the (FRTAL) was calculated as delta CH2O/CLi, where delta CH2O, the difference in free water clearance before minus after frusemide, is taken as an index of sodium reabsorption in the thick ascending limb, and lithium clearance as an estimation of sodium delivery to the thick ascending limb. FRTAL was calculated in these volume-expanded subjects to lie from 11% to 20% depending on whether some lithium is assumed to be in the thick ascending limb.
Adult↗
Renal haemodynamic effects of short term cyclosporin A administration in patients with insulin-dependent diabetes mellitus.
To investigate the time relationships involved in cyclosporin-induced nephrotoxicity we studied changes in blood pressure, renal haemodynamics and sodium excretion in 22 adult patients with insulin-dependent diabetes mellitus treated with cyclosporin (CsA) for 4 +/- 2 days, compared to 22 insulin-dependent diabetic patients receiving conventional insulin therapy, who were matched for age and duration of diabetes. To further clarify the pathogenic role of the renin-angiotensin system, insulin-dependent diabetic patients receiving CsA were studied before and after sublingual administration of 75 mg captopril. An average of 4 days CsA treatment markedly increased blood pressure and renal vascular resistance, but did not alter glomerular filtration rate, renal plasma flow, sodium urinary excretion, or body-weight. The marked renal vasoconstriction without early changes in GFR suggests that the late decrease in GFR may involve other factors in addition to renal hypoperfusion. Acute inhibition of angiotension II formation was still able to decrease blood pressure and renal vascular resistance, although not to normal control values. These results indicate that a physiological concentration of angiotensin II may potentialise but may not be the sole factor involved in the vasopressor effect of CsA.
Adult↗
Developmental changes of Ca2+, PO4, and calcitriol metabolism in spontaneously hypertensive rats.
We have measured Ca and P balance, serum calcitriol, and vitamin D-dependent intestinal calcium-binding protein (CaBP9k) in the spontaneously hypertensive rat (SHR) and its normotensive control, the Wistar-Kyoto rat (WKY) at 4-5 and again at 13-14 wk of age. In rats on a 1% Ca diet, P balance was significantly more positive in the 5-wk-old SHR than WKY (P less than 0.01); Ca balance tended to be greater in the 5-wk-old SHR. In contrast, in the 14-wk-old SHR, P and Ca balance were less positive than in the WKY (P was 5.8 +/- 1.3 vs. 13 +/- 1.7 mg/day, P less than 0.01, and Ca was 53 +/- 4.6 vs. 67 +/- 2.7 mg/day, P less than 0.05). On the 1% Ca diet, plasma calcitriol levels of the 5-wk-old SHR were higher than those of the WKY (58 +/- 3.2 vs. 40 +/- 2.1 pg/ml, P less than 0.002), whereas at 12 wk there was no difference. On Ca-deficient (0.1%) diets, plasma calcitriol was increased in 5-wk-old and 12-wk-old SHR and WKY, compared with the 1% Ca diet (P less than 0.001). Calcitriol metabolic clearance rate was the same in the 13-wk-old SHR and WKY on either Ca diet. Intestinal CaBP9k content of the 5-wk-old (38 +/- 2.6 vs. 40 +/- 3.9 micrograms/mg) and the 12-wk-old (11 +/- 1.6 vs. 14 +/- 1.4 micrograms/mg) SHR and WKY were similar on the 1% Ca diet.(ABSTRACT TRUNCATED AT 250 WORDS)
Aging↗
Proteinuria in multiple myeloma and related diseases.
Proteinuria is frequently found in multiple myeloma and related disorders. Immunofixation electrophoresis is very helpful for the identification and characterization of the monoclonal component. In multiple myeloma, the presence of Bence-Jones (BJ) proteinuria is significantly associated with renal failure. The coexistence of BJ proteinuria and the nephrotic syndrome in myeloma patients should suggest AL amyloidosis or light chain deposition disease. In the latter, BJ proteinuria is absent in 30% of the cases and diagnosis is based on the demonstration of the monoclonal light chain deposits in tissues, predominantly in kidneys.
Amyloidosis↗
[Hypertension induced by cyclosporin A in insulin-dependent diabetic patients. A one-year follow-up].
UNLABELLED: Forty-five recent insulin-dependent diabetics (IDD) were treated with cyclosporine A (CsA) 7.5 mg/kg b.i.d. as single immunosuppressive therapy to achieve remission of diabetes. Measurements of mean arterial pressure (MAP), glomerular filtration rate (GFR:inulin clearance), renal vascular resistance (RVR: MAP x [1-haematocrit] divided by PAH clearance), absolute (UNa.V) and fractional (FENa) urinary sodium excretion, were performed initially (M0) and after 3 (M3) and 12 (M12) months of treatment. Results were (mean +/- SD): [table: see text] Prevalence of hypertension defined as MAP greater than or equal to 107 mmHg was 12% at M3 and 24% at M12. Whereas the maximal changes in GFR and RVR occurred at M3, MAP increased further and sodium excretion decreased at M12. IN CONCLUSION: 1) CyA-induced increase in blood pressure paralleled that in RVR at M3 and decreased sodium excretion at M12. 2) There was a dissociation between MAP and GFR changes after 12 months of treatment with CyA.
Adult↗
Disturbances of calcium metabolism in experimental hypertension.
The metabolism of Ca2+ is profoundly disturbed in the spontaneously hypertensive rat (SHR), compared with its normotensive control, the Wistar-Kyoto rat. This is true for the whole animal as well as at the cellular and the subcellular level. Many apparently discrepant results of the literature could be due to differences in age, gender, strain, and type of diet. It is possible that the SHR has initially an epithelial (and a nonepithelial) Ca2+ transport defect. This could in turn lead to a more or less efficient stimulation of calcitriol synthesis and a compensatory increase in calcium absorption during early life. With the maturation of the animal, however, a state of calcium and vitamin D deficiency would prevail. In this scheme, the observed defect of epithelial Ca2+ transport in the SHR is primary in nature, reflecting some perturbation of Ca2+ handling by the cell, and the changes of vitamin D metabolism and hyperparathyroidism are secondary. Altered cellular Ca2+ permeability and a compromised ability of the cell to remove or sequester Ca2+ may be relevant to the pathogenesis and maintenance of hypertension. Parathyroid gland overfunction and vitamin D deficiency may also be involved in the elevation of arterial pressure. Our knowledge of such interactions is however still incomplete. Much more has to be learnt about the probable link between alterations of Ca2+ metabolism and elevated blood pressure.
Animals↗
Blood pressure changes induced by ciclosporin A in type I diabetes.
The determinants of ciclosporin A-induced blood pressure changes were analyzed initially and after 3 months in 30 recent type I diabetics submitted to chronic treatment with ciclosporin as single immunosuppressive drug. Prevalence of hypertension was 17% and relatively low as compared to those reported in organ transplantation. Ciclosporin induced a slight decrease in glomerular filtration rate and renal plasma flow, with unchanged filtration fraction, a mild average increase in blood pressure and a more pronounced increase in renal vascular resistance. There was a trend toward decrease in absolute urinary sodium excretion whereas fractional excretion of sodium was unchanged. Presence of familial history of essential hypertension was characterized by a slightly insignificantly lower renal plasma flow and did not affect the renal effect of ciclosporin except that the renal plasma flow was significantly lower in the groups of patients genetically predisposed.
Adult↗
Rapid stimulation of calcium uptake by isolated rat enterocytes by 1,25(OH)2D3.
Evidence is accumulating that 1,25(OH)2D3 may stimulate calcium transport from the intestinal lumen extremely rapidly by a mechanism which appears independent of de novo protein synthesis. To investigate this rapid action of 1,25(OH)2D3, the rate of calcium uptake by isolated enterocytes from duodena of young rats was determined in vitro as the uptake of 45Ca from 1-15 min. Prior in vitro exposure of cells to 1,25(OH)2D3 (100 pM) for 20 min significantly increased the rate of calcium uptake (p less than 0.001), an effect unaltered by 50 microM cycloheximide. Incubation with 100 pM 1-alpha-hydroxyvitamin D3 produced the same effect (p less than 0.01). In contrast, exposure to 10 pM 1,25(OH)2D3, as well as to 100 pM or to 1,000 pM 25-hydroxyvitamin D3 induced no significant change. Because both 1,25(OH)2D3 and starvation may stimulate key enzymes in polyamine metabolism, we investigated the effects of (i) difluoromethyl-ornithine (CHF2-Orn), a specific irreversible inhibitor of ornithine decarboxylase and (ii) varying the timing of feeding prior to sacrifice. Both in vitro CHF2-Orn and feeding prior to sacrifice significantly decreased the baseline rate of calcium uptake (p less than 0.05) and reduced the effect of 1,25(OH)2D3. Increased duration of starvation significantly increased the baseline rate of calcium uptake (p less than 0.02) without changing the increment in rate of calcium uptake induced by 1,25(OH)2D3. The study suggests (i) that the early action of 1,25(OH)2D3 on the influx process of intestinal calcium transport may involve a different molecular specificity from that involved in the genomic action of 1,25(OH)2D3 and (ii) that changes in polyamine metabolism may play a part in this process.
Animals↗
Short-term effects of parathyroidectomy on plasma biochemistry in chronic uremia.
Parathyroidectomy (PTx) is indicated in hemodialysis (HD) patients who have severe osteitis fibrosa unresponsive to vitamin D therapy or in whom the latter treatment is contraindicated. Immediately after PTx, plasma immunoreactive parathyroid hormone, calcium and phosphorus concentrations decline abruptly. However, little is known in such patients about the short-term effects of PTx on plasma alkaline phosphatase (AP) activity and plasma aluminum (Al) levels. The present, preliminary study was performed to determine such parameters in 37 HD patients, and to correlate them with data of bone histology. Mean plasma AP activity started to increase after PTx from day 4 onwards. Thus, AP values significantly higher than pre-PTx values were observed at day 7 and 14 (415 +/- 54 vs. 619 +/- 77 and 749 +/- 83 IU/liter, means +/- SEM; N = 37; P less than 0.05 and 0.001, respectively). This increase, in the absence of changes in liver function, was mainly due to the bone-specific iso-AP. Moreover, the degree of increase in plasma AP activity was higher in the subgroup with negative (group I, 21 patients) than in that with positive bone Al staining (group II, 16 patients). However, plasma osteocalcin (BGP) did not change after PTx (N = 8). Basal plasma Al levels were significantly higher in group II both before and two weeks after surgery.(ABSTRACT TRUNCATED AT 250 WORDS)
Alkaline Phosphatase↗
Decreased duodenal enterocyte calcium flux rates in the spontaneously hypertensive rat.
We have previously reported serum 1,25(OH)2 vitamin D3 (calcitriol) and active transduodenal calcium absorption measured in the Ussing chamber to be reduced in 12- to 14-week-old male Okamoto-Aoki spontaneously hypertensive rats (SHR). In the present study, we compared rates of calcium influx and efflux in isolated duodenal enterocytes in SHR and corresponding controls, Wistar-Kyoto rats (WKY). The early (0 to 1 minute) and the late (1 to 15 minute) phase of calcium influx rates at 1.0 mmol Ca2+ in the incubation medium were lower in the SHR than in the WKY (mean +/- SEM): 1.93 +/- 0.22 v 2.85 +/- 0.41 nmol/mg protein/min, n = 8 and n = 7 experiments, respectively, P less than .05; and 0.334 +/- 0.025 v 0.488 +/- 0.059 nmol/mg protein/min, n = 14 pairs, P less than .01. The calcium efflux rate constant of the SHR was reduced: 34.3 +/- 1.4 v 51.9 +/- 1.4% per hour, n = 11 pairs, P less than .01. However, in the absence of sodium or the presence of ouabain (4.0 mmol) in the incubation medium, a decrease in this constant was observed in the WKY but not in the SHR. These data, at the cellular level, support our previous observation in intact tissue of reduced active transduodenal calcium transport in the 12- to 14-week-old SHR. Whether the primary defect in calcium transport involves the luminal or the basolateral membrane of the enterocyte, or whether both disturbances are due to a common primary perturbation cannot be deduced from the present experiments.
Animals↗