Steady state pharmacokinetics and dose equivalents of oral clodronate in renal failure

2011 ◽  
Vol 49 (02) ◽  
pp. 128-136 ◽  
Author(s):  
S. Mäkelä ◽  
H. Saha ◽  
I. Ala-Houhala ◽  
S. Liukko-Sipi ◽  
P. Ylitalo
1989 ◽  
Vol 37 (2) ◽  
pp. 185-189 ◽  
Author(s):  
L. v. Bortel ◽  
R. Böhm ◽  
J. Mooij ◽  
P. Schiffers ◽  
K. H. Rahn

1989 ◽  
Vol 13 ◽  
pp. S52-S54 ◽  
Author(s):  
H. Schunkert ◽  
J. Kindler ◽  
M. Gassmann ◽  
W. Lahn ◽  
R. Irmisch ◽  
...  

1998 ◽  
Vol 54 (1) ◽  
pp. 59-61 ◽  
Author(s):  
J. F. W. Hoogkamer ◽  
C. H. Kleinbloesem ◽  
A. Nokhodian ◽  
M. J. A. Ouwerkerk ◽  
G. Lankhaar ◽  
...  

1993 ◽  
Vol 264 (6) ◽  
pp. F963-F967 ◽  
Author(s):  
S. A. Rogers ◽  
S. B. Miller ◽  
M. R. Hammerman

Renal insulin-like growth factor (IGF)-I expression is enhanced in tissue that remains following removal of kidney mass. To characterize the expression of renal IGF-I after reduction of kidney mass by partial unilateral infarction, we measured levels of IGF-I extracted from noninfarcted (remnant) renal tissue that remained after one-half unilateral kidney infarction that was performed without (1/2NX) or with (1 1/2NX) contralateral nephrectomy. Levels of IGF-I extracted from remnant renal tissue after 1/2NX increased significantly, peaking on day 3 after renal mass reduction, and then returned toward baseline. Steady-state levels of IGF-I mRNA were also elevated on day 3, suggesting that the increase in IGF-I results from enhanced synthesis. A similar pattern of increased extracted IGF-I and elevated IGF-I mRNA occurred after 1 1/2NX. Levels of IGF-I extracted from remnant renal tissue 3 days after 1 1/2NX were not higher than levels extracted from remnant tissue 3 days after 1/2NX, and both were higher than levels of IGF-I extracted from contralateral kidneys 3 days after unilateral nephrectomy. Therefore, levels of IGF-I did not correlate with the extent of reduction of renal mass per se. We conclude that partial renal infarction provides a stimulus to enhance IGF-I expression. Increased renal IGF-I must be considered in the interpretation of findings originating from use of remnant kidney models of chronic renal failure.


1997 ◽  
Vol 8 (5) ◽  
pp. 804-812
Author(s):  
W R Clark ◽  
B A Mueller ◽  
M A Kraus ◽  
W L Macias

Renal replacement therapy (RRT) requirements for critically ill patients with acute renal failure (ARF) depend on numerous factors, including the degree of hypercatabolism, patient size, and desired level of metabolic control. However, the current practice at many institutions is to prescribe generally similar amounts of RRT to ARF patients essentially without regard for the above factors. In this study, a computer-based model designed to permit individualized RRT prescription to ARF patients was developed. The critical input parameter is the desired level of metabolic control, which is the time-averaged BUN (BUNa) or steady-state BUN (BUNs) for intermittent hemodialysis (IHD) or continuous RRT (CRRT), respectively. The basis for the model was a group of 20 patients who received uninterrupted CRRT for at least 5 days. In these patients, the normalized protein catabolic rate (nPCR) increased linearly (r = 0.974) from 1.55 +/- 0.14 g/kg per day (mean +/- SEM) on day 1 to 1.95 +/- 0.15 g/kg per day on day 6. The daily urea generation rate (G), determined from the above linear relationship, was utilized to produce BUN versus time curves by the direct quantification method for simulated patients of varying dry weights (50 to 100 kg) who received variable CRRT urea clearances (500 to 2000 ml/h). Steady-state BUN versus time profiles for the same simulated patient population treated with IHD regimens (K = 180 ml/min, T = 4 h) of variable frequency were generated by use of a variable-volume, single-pool kinetic model. From these profiles, regression lines of required IHD frequency (per week) versus patient weight for desired BUNa values of 60, 80, and 100 mg/dl were obtained. Regression lines of required CRRT urea K (ml/h) versus patient weight for desired BUNs values of 60, 80, and 100 mg/dl were also generated. For the attainment of intensive IHD metabolic control (BUNa = 60 mg/dl) at steady state, a required treatment frequency of 4.4 dialyses per week is predicted for a 50-kg patient. However, the model predicts that the same degree of metabolic control cannot be achieved even with daily IHD therapy in patients > or = 90 kg. On the other hand, for the attainment of intensive CRRT metabolic control (BUNs = 60 mg/dl), required urea clearance rates of approximately 900 ml/h and 1900 ml/h are predicted for 50- and 100-kg patients, respectively. This model suggests that, for many patients, rigorous azotemia control equivalent to that readily attainable with most CRRT can only be achieved with intensive IHD regimens. Following prospective clinical validation, this methodology may be a useful RRT prescription tool for critically ill ARF patients.


1992 ◽  
Vol 83 (5) ◽  
pp. 583-587 ◽  
Author(s):  
Nicholas B. Argent ◽  
Robert Wilkinson ◽  
Peter H. Baylis

1. The metabolic clearance rate of arginine vasopressin was determined using a constant infusion technique in normal subjects and patients with chronic renal failure immediately before commencing dialysis. Endogenous arginine vasopressin was suppressed in all subjects before the infusion with a water load. 2. Plasma arginine vasopressin concentrations were determined using a sensitive and specific radioimmunoassay after Florisil extraction. The detection limit of the assay was 0.3 pmol/l, and intra- and inter-assay coefficients of variation at 2 pmol/l were 9.7% and 15.3%, respectively. 3. In normal subjects, the metabolic clearance rate was determined at two infusion rates producing steady-state concentrations of arginine vasopressin of 1.3 and 4.4 pmol/l. In the patients with renal failure, a single infusion rate was used, producing a steady-state concentration of 1.5 pmol/l. 4. At comparable plasma arginine vasopressin concentrations, metabolic clearance rate was significantly reduced in patients with renal failure (normal 1168 ± 235 ml/min versus renal failure 584 ± 169 ml/min; means ± sd; P<0.001). 5. Free water clearance was significantly reduced in normal subjects during the arginine vasopressin infusion from 8.19 ± 2.61 to −1.41 ± 0.51 ml/min (P<0.001), but was unchanged in the patients with renal failure after attaining comparable plasma arginine vasopressin concentrations. 6. In normal subjects there was a small but significant fall in metabolic clearance rate at the higher steady-state arginine vasopressin concentration (1168 ± 235 ml/min at 1.3 pmol/l versus 1059 ± 269 ml/min at 4.4 pmol/l; P = 0.016). 7. Our results show that the metabolic clearance rate of arginine vasopressin is reduced by approximately 50% in severe chronic renal failure. This alone may account for the raised plasma concentrations of the hormone seen in this condition.


1994 ◽  
Vol 5 (1) ◽  
pp. 27-35
Author(s):  
J C da Silva ◽  
X J Shi ◽  
C A Johns ◽  
D M Jefferson ◽  
S A Grubman ◽  
...  

The decreased abundance and enzymatic activity of myocardial Na,K-ATPase have been recognized previously to occur in chronic uremia. However, the activity of the cardiac sodium pump as defined by the uptake of 86Rb is normal. The discrepancies between these findings may have resulted from the inability to distinguish between the different Na,K-ATPase isoforms now known to exist in cardiac muscle. To investigate this question, steady-state levels of Na,K-ATPase alpha and beta mRNA isoforms, alpha 1, alpha 2, and beta 1 protein, and specific high-affinity binding of [3H]ouabain were quantitated in cardiac muscle from uremic and pair-fed, sham-operated control rats. Steady-state levels of alpha 2 and beta 2 mRNA were significantly decreased (percentage of control levels: alpha 2, 48 +/- 10; beta 2, 74 +/- 9; N = 10; P < 0.025) in chronic renal failure without any change in alpha 1, alpha 3, or beta 1 expression. The number of high-affinity [3H]ouabain-binding sites and Na,K-ATPase alpha 1, alpha 2, and beta 1 subunits was not different from control. In acute renal failure, alpha 2 and beta 2 mRNA levels also were significantly decreased (percentage of control levels: alpha 2, 24 +/- 5; beta 2, 44 +/- 8; N = 6; P < 0.001), but there was no change in the level of alpha 3 or beta 1 mRNA, the number of high-affinity [3H]ouabain-binding sites, or the level of Na,K-ATPase alpha 2 and beta 1 subunits.(ABSTRACT TRUNCATED AT 250 WORDS)


Pain ◽  
1991 ◽  
Vol 47 (1) ◽  
pp. 13-19 ◽  
Author(s):  
Russell K. Portenoy ◽  
Kathleen M. Foley ◽  
James Stulman ◽  
Elizabeth Khan ◽  
Jean Adelhardt ◽  
...  

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