Safety of Neoral conversion in maintenance renal transplant patients: A one-year, double-blind study. NOVARTIS OLN-353 Study Group.
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BACKGROUND: Despite the improved pharmacokinetic characteristics of Neoral, some centers have encountered difficulty with the conversion of some patients from Sandimmune to Neoral and have reported precipitation of toxicity and rejection. METHODS: We conducted a randomized, double-blind, parallel-group, multicenter prospective study of stable maintenance renal transplant patients to compare the safety and tolerability of converting from Sandimmune to Neoral (N = 132) versus continuing Sandimmune (N = 130). Patients were studied for one year. The cyclosporine (CsA) dose was adjusted as necessary to maintain site-specific trough whole blood levels. RESULTS: During the study, dose adjustments were frequent in both groups: 67% Neoral versus 65% Sandimmune patients. At study completion, the mean trough CsA levels were comparable; the dose change-from-baseline did not differ statistically between groups. Fewer Neoral (87.1%) than Sandimmune (95.4%) patients reported adverse events, and serious adverse events were comparable. Adverse events related to CsA were not more common in the Neoral group. Renal function measures also implied comparability of the two treatments. Three Neoral versus five Sandimmune patients experienced acute rejection; two Neoral versus five Sandimmune patients experienced chronic graft dysfunction. Two septic deaths occurred in the Neoral group. No grafts were lost. CONCLUSIONS: With careful monitoring, conversion of maintenance renal transplant patients to Neoral can be safely accomplished. (+info)
Glomerular filtration rate estimated from the uptake phase of 99mTc-DTPA renography in chronic renal failure.
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BACKGROUND: The purpose of the study was to compare the estimation of glomerular filtration rate (GFR) from 99mTc-DTPA renography with that estimated from the renal clearance of 51Cr-EDTA, creatinine and urea. METHODS: Fifty patients with reduced renal function (serum creatinine between 150 and 600 micromol/l) were enrolled in the study. GFR was estimated from the uptake phase of 99mTc-DTPA renography (GFR(DTPA)). The renal clearance of 51Cr-EDTA (GFR(EDTA)) was used as the reference method. Creatinine clearance (C(Cr)), urea clearance (C(Ur)) and the mean of urea and creatinine clearance (C(Cr+Ur)/2) were also calculated from urine collected during a period of 24 h. Limits of agreement were used for method comparison. RESULTS: The limit of agreement between GFR(DTPA) and GFR(EDTA) was 2 +/- 17 ml/min. The mean difference did not deviate significantly from zero. The other clearance techniques had larger limits of agreement and a mean difference significantly different from zero. Furthermore, C(Ur) and C(Cr+Ur)/2 had systematic deviations of the differences, indicating that C(Ur) and C(Cr+Ur)/2 are poor estimates of GFR. CONCLUSION: The limit of agreement between GFR(DTPA) and GFR(EDTA) are acceptable and, therefore, GFR estimated from 99mTc-DTPA renography is acceptable for clinical use in patients with reduced renal function. Furthermore, the method is simple and less time consuming compared with renal clearance techniques. (+info)
Effects of activation of renal adenosine A2 receptor on renal function and renin release in dogs.
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Direct effects of adenosine A2 receptor activation on renal function were examined in dogs. When renal perfusion pressure was maintained constant at 100 mmHg, renal administration of a selective A2 receptor agonist, CGS 21680C (sodium salt of CGS 21680, 2-[p-(2-carboxyethyl) phenethylamino]-5'-N-ethylcarboxamido adenosine) (1 microg x kg(-) x min (-1)), although it decreased blood pressure by 20 mmHg, increased renal blood flow and renin release, whereas glomerular filtration rate and urine flow were unaffected. These results suggest that stimulation of renal A2 receptor led to both afferent and efferent arteriolar dilatation, whereas renal A2 receptor plays a minor role in urine formation. CGS 21680C induced renin release and tachycardia that were blocked by propranolol, indicating these effects of A2 receptor stimulation appeared to be indirect. (+info)
Long-term evolution of renal function in patients with ovarian cancer after whole abdominal irradiation with or without preceding cisplatin.
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BACKGROUND: The upper limit of the natural decline in creatinine clearance is 1 ml/min/year. To define the loss of renal function, we started a long-term assessment of patients with ovarian cancer treated by whole abdominal irradiation (WAI) with preceding cisplatin chemotherapy (CDDP) and second-look laparotomy (SLL). PATIENTS AND METHODS: We analyzed the creatinine clearance over time of 56 patients treated from 1982 to 1988 for ovarian cancer. Thirty-one of 56 patients had received WAI after their initial surgery, and 25 of 56 patients had undergone CDDP therapy followed by SLL, and then WAI after their initial surgery. Median follow-up was 99 months (7-156). Twenty of 56 patients accepted our invitation for additional assessment of tubular function, nine of the 31 patients without CDDP therapy and SLL, and 11 of the 25 patients with CDDP followed by SLL and WAI. Ten of twenty patients had received four to six cycles CDDP, 80 mg/m2/cycle, and one patient nine cycles. The median total dose for each kidney was 1450 cGy (480-1690). RESULTS: The mean creatinine clearance decreased from 84 ml/min to 66 ml/min. Seventy-six percent of the 25 patients who had undergone CDDP therapy, SLL and WAI had declines of more than 1 ml/min/year, 64% of these patients of more than 2 ml/min/year. For the 31 patients who had received WAI after their initial surgery, the corresponding numbers were 71% and 55%, respectively. The tubular function of the 20 patients who had undergone the additional investigations was not impaired. CONCLUSION: The decline in renal function after WAI is more pronounced than in healthy subjects. The treatment with cisplatin and SLL prior to WAI does not seem to contribute to this loss of kidney function. (+info)
Functional significance of the pattern of renal sympathetic nerve activation.
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To assess the renal functional significance of the pattern of renal sympathetic nerve activation, computer-generated stimulus patterns (delivered at constant integrated voltage) were applied to the decentralized renal sympathetic nerve bundle and renal hemodynamic and excretory responses determined in anesthetized rats. When delivered at the same integrated voltage, stimulus patterns resembling those observed in in vivo multifiber recordings of renal sympathetic nerve activity (diamond-wave patterns) produced greater renal vasoconstrictor responses than conventional square-wave patterns. Within diamond-wave patterns, increasing integrated voltage by increasing amplitude produced twofold greater renal vasoconstrictor responses than by increasing duration. With similar integrated voltages that were subthreshold for renal vasoconstriction, neither diamond- nor square-wave pattern altered glomerular filtration rate, whereas diamond- but not square-wave pattern reversibly decreased urinary sodium excretion by 25 +/- 3%. At the same number of pulses per second, intermittent stimulation produced faster and greater renal vasoconstriction than continuous stimulation. At the same number of pulses per second, increases in rest period during intermittent stimulation proportionally augmented the renal vasoconstrictor response compared with that observed with continuous stimulation; the maximum augmentation of 55% occurred at a rest period of 500 ms. These results indicate that the pattern of renal sympathetic nerve stimulation (activity) significantly influences the rapidity, magnitude, and selectivity of the renal vascular and tubular responses. (+info)
Impact of hyperglycemia on the renin angiotensin system in early human type 1 diabetes mellitus.
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It has been demonstrated previously that moderate hyperglycemia without glucosuria can increase plasma renin activity and mean arterial pressure in young healthy males with early uncomplicated type 1 diabetes mellitus. This study was conducted to extend these observations by testing the hypothesis that mild to moderate hyperglycemia can affect renal function by increasing renin angiotensin system (RAS) activity in diabetic humans. The study included 10 men and women with early, uncomplicated type 1 diabetes (duration <5 yr), all ingesting a controlled sodium and protein diet. They were studied on four separate occasions, during a subdepressor dose of the angiotensin II (AngII) receptor blocker losartan, and during graded AngII infusion, 1.5 and 2.5 ng/kg per min, while euglycemic (blood glucose 4 to 6 mmol/L) and again while hyperglycemic without glucosuria (blood glucose 9 to 11 mmol/L), according to a randomized crossover design. Outcome measures included mean arterial pressure (MAP), GFR, effective renal plasma flow (ERPF), renal vascular resistance (RVR), filtration fraction (FF), and urine sodium excretion (UNaV) at baseline and in response to the above maneuvers. During hyperglycemic conditions, MAP was significantly higher compared with euglycemia, as were RVR and FF. After the administration of losartan, a significant renal and peripheral depressor effect was noted, with decreases in MAP, RVR, and FF, whereas during euglycemia the responses to losartan were minimal. AngII infusion resulted in elevations in MAP, RVR, and FF and a decline in UNaV during both glycemic phases, but the responses during hyperglycemia, most significantly at the 1.5 ng/kg per min infusion rate, were blunted. These data support the hypothesis that hyperglycemia affects renal function by activating the RAS. The mechanism remains obscure, but these contrasting responses may provide a link between the observations that maintenance of euglycemia and blockade of the RAS prevent or delay diabetic kidney disease, and furthermore, may clarify the mechanism whereby high glucose promotes renal disease progression in diabetes. (+info)
Renal processing of glucose in well and sick neonates.
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AIMS: To determine the extent of renal processing of glucose in sick and well neonates. METHODS: Glomerular filtration rate (GFR) and the renal processing of glucose, sodium, and water were measured using prolonged inulin infusion in 47 infants of 26-40 weeks of gestation, aged 1-13 days. RESULTS: GFR rose by 15% after ventilatory support was withdrawn, and was unaffected by clinical instability. Fractional glucose excretion was low in the stable unventilated babies except at very high filtered loads, but rose in one unstable, unventilated baby. It was higher in ventilated babies, and remained high for at least six days after ventilation. For water and sodium, net differences between intake and urine excretion were not affected by ventilation, clinical stability, or glycosuria. CONCLUSIONS: A combination of a low GFR and a high fluid intake, urine flow, and urine concentrating capacity, makes neonates very unlikely to develop an osmotic diuresis due to glycosuria while they have a blood glucose below 12 mmol/l, despite assertions to the contrary. (+info)
Long-term follow-up of the tubular secretion of creatinine in renal graft recipients.
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The differences in glomerular filtration rate (GFR) based on creatinine clearance (Ccr) or obtained by the more exact methods are caused mainly by tubular creatinine secretion. In this study, we monitored creatinine clearance (Ccr), GFR on the basis of polyfructosan renal clearance (C(PF)) and parameters characterizing tubular creatinine secretion (Ccr/C(PF), Ccr - C(PF), Tcr/C(PF) x 100) in 12 individuals with renal grafts (Group A), 12 kidney graft donors for related transplantation (Group B), and in 27 individuals undergoing nephrectomy for a pathological process in one kidney (Group C). In the monitored groups, C(PF) and Ccr values were within the limits consistent with the normal function of a single kidney in a healthy individual. The values characterizing tubular creatinine secretion in Group A did not differ significantly from those obtained in Groups B and C. However, the parameters showed a wide range in all groups. In seven individuals with a renal graft, all the above functional parameters were monitored at three-month intervals for a period of 24 months. Significant differences in the time courses of Ccr and C(PF) due to marked intra-individual fluctuations were found in tubular creatinine secretion. The findings suggest that the rate of tubular creatinine secretion in the renal graft does not differ significantly from that in individuals with a single native (normally functioning) kidney. However, there are large inter-individual differences. The large intra-individual fluctuations in tubular creatinine secretion in the kidney graft result in significant differences in the time courses of Ccr and C(PF) and a possibility of erroneous evaluation of graft function if based exclusively on Ccr. (+info)