Creatinine Metabolism in Chronic Renal Failure

1980 ◽  
Vol 58 (4) ◽  
pp. 327-335 ◽  
Author(s):  
W. E. Mitch ◽  
V. U. Collier ◽  
M. Walser

1. Creatinine metabolism was studied in nine patients with severe chronic renal failure who were nevertheless in a nearly steady state with respect to their creatinine pool. Labelled creatinine was injected intravenously and the specific radioactivity of creatinine in urine was measured during the ensuing 5–7 days. 2. In each patient, the decline in specific radioactivity with time was a single exponential function after 12 h. The volume of distribution of creatinine averaged 49.1 ± 2.8% body weight. The average rate of creatinine production was 148 μmol day−1 kg−1, which is similar to predicted values for normal subjects of the same age, weight and sex. Creatinine metabolism rate/kg body weight, estimated as the difference between production rate/kg body weight, determined radioisotopically, and creatinine appearance rate (excretion plus accumulation), averaged 42 μmol day−1 kg−1. 3. Total creatinine metabolism rate/kg body weight was correlated with serum creatinine. Thus, as serum creatinine rises, an increasing fraction of the produced creatinine was metabolized rather than excreted. This relationship could account for the diminished creatinine excretion commonly seen in patients with chronic renal failure. 4. Extrarenal clearance (metabolism/serum creatinine) of this magnitude (approximately 31% of renal clearance in these patients) would be an undetectably small fraction of normal renal clearance. This could explain the absence of demonstrable creatinine metabolism in normal subjects. 5. Two pathways of metabolism were identified: a recycling of creatinine to creatine and an irreversible degradation of creatinine to products other than creatine.

1978 ◽  
Vol 54 (2) ◽  
pp. 133-140 ◽  
Author(s):  
S. Scherrer ◽  
B. Haldimann ◽  
A. Küpfer ◽  
F. Reubi ◽  
J. Bircher

1. To evaluate potential alterations in hepatic metabolism of drugs occurring in patients with renal insufficiency the fate of aminopyrine was studied in 17 patients with chronic renal failure and in 27 normal subjects. 2. Although patients with chronic renal failure exhibited large variations, their aminopyrine plasma disappearance times (mean 0·62 ± sd 0·24 h−1) were significantly higher than those found in normal subjects (0·30 ± 0·07 h−1, P < 0·002). 3. 14CO2 derived from [dimethylamine-14C]aminopyrine disappeared from breath more rapidly in patients with chronic renal failure and a history of analgesic abuse (0·40 ± 0·04 h−1) than in control subjects (0·22 ± 0·03 h−1, P < 0·01) and in other patients with chronic renal failure (0·24 ± 0·04 h−1). 4. Dialysis treatment and serum creatinine concentrations were not correlated with the rates of aminopyrine metabolism. Two additional patients, however, with combined renal and hepatic disease, exhibited markedly slowed rates of aminopyrine demethylation. 5. Although chronic renal failure by itself might not alter microsomal drug metabolism it is concluded that, in patients with a history of abuse of phenacetin-containing analgesics, marked acceleration in aminopyrine N-demethylation may be observed.


1980 ◽  
Vol 3 (1) ◽  
pp. 18-22
Author(s):  
F. Marumo ◽  
T. Sakai ◽  
M. Shirataka

The concentration of cyclic AMP which is known as an intracellular mediator of hormone action increased in the plasma of patients with chronic renal failure (CRF). In the present study, the plasma concentration of cyclic AMP significantly correlated not only with serum, creatinine, and urea levels, but also with plasma PTH and glucagon in patients with CRF. Furthermore, plasma concentrations of PTH and glucagon correlated with the serum creatinine concentration to a significant extent. To discuss the cause of the increased cyclic AMP concentration in plasma of patients with CRF, multivariate analyses were carried out on the obtained clinical data from patients and normal subjects. In the factor analysis on the clinical data from 61 subjects, cyclic AMP, creatinine and BUN correlated with the first factor and PTH correlated with the second factor. The cumulative contribution ratio by the second factor was 76%. The results of the cluster analysis indicated that cyclic AMP, creatinine, and BUN formed a cluster and PTH glucagon made another cluster. These results suggest that the elevated plasma concentration of cyclic AMP in patients with CRF was mainly introduced not by overproduction but by the retention of cyclic AMP due to the decreased renal function.


2005 ◽  
Vol 33 (03) ◽  
pp. 491-500 ◽  
Author(s):  
Heidi H. Y. Ngai ◽  
Wai-Hung Sit ◽  
Jennifer M. F. Wan

In this study, we evaluated the renal protective effects of a Chinese herbal preparation WH30+in male Wistar rats with glycerol-induced acute renal failure and adenine-induced chronic renal failure. WH30+is a Chinese herb preparation composed of Rheum Palmatum, Salvia Miltiorrhiza, Cordyceps Sinensis, Leonurus Sibiricus, Epihedium Macranthum, Radix Astragali, and Radix Codonopsis Pilosulae, which has been used to treat kidney deficiency in human. An acute renal failure and chronic renal failure rat model were introduced by glycerol injection (i.m.) and fed with adenine-excessive diet, respectively. WH30+was administered to rats at the dose of 50 mg/kg/day from 10 days before the diseases were induced until the rats were sacrificed. A reduction in body weight ( p < 0.01) was observed in rats with chronic renal failure, but there was no difference between treatment groups. However, the body weight of rats with acute renal failure without treatment was significantly lower than those treated with WH30+( p < 0.05). Overall, serum creatinine and urea nitrogen were elevated significantly ( p < 0.01) in renal failure rats compared to control. Treatment with WH30+improved both serum creatinine and urea nitrogen slightly in both models. The WH30+-treated rats with acute renal failure had significantly ( p < 0.05) greater creatinine clearance than those without treatment. The results of the study show that WH30+is more effective in the prevention of acute renal failure than chronic renal failure.


1980 ◽  
Vol 58 (5) ◽  
pp. 427-430 ◽  
Author(s):  
D. E. L. Wilcken ◽  
Vatsala J. Gupta ◽  
S. G. Reddy

1. Plasma sulphur-containing amino acids were measured in 19 patients with renal failure on chronic haemodialysis and in 22 normal subjects, to determine the rate of accumulation of these amino acids in chronic azotaemia. 2. Cysteine-homocysteine mixed disulphide was significantly increased in patients before dialysis and homocystine was detected in low concentration in 10 patients. Cystine and taurine were also increased. Changes in other neutral and acidic amino acids were similar to those reported in chronic renal insufficiency. 3. In 3–4 h of dialysis serum creatinine was decreased by a mean of 55%, cysteine-homocysteine by 41%and cystine by 58.5%(P<0.001 for each). Methionine concentrations were normal throughout. 4. We conclude that sulphur-containing amino acids, except methionine, accumulate in chronic renal failure as rapidly as creatinine.


1988 ◽  
Vol 60 (02) ◽  
pp. 205-208 ◽  
Author(s):  
Paul A Kyrle ◽  
Felix Stockenhuber ◽  
Brigitte Brenner ◽  
Heinz Gössinger ◽  
Christian Korninger ◽  
...  

SummaryThe formation of prostacyclin (PGI2) and thromboxane A2 and the release of beta-thromboglobulin (beta-TG) at the site of platelet-vessel wall interaction, i.e. in blood emerging from a standardized injury of the micro vasculature made to determine bleeding time, was studied in patients with end-stage chronic renal failure undergoing regular haemodialysis and in normal subjects. In the uraemic patients, levels of 6-keto-prostaglandin F1α (6-keto-PGF1α) were 1.3-fold to 6.3-fold higher than the corresponding values in the control subjects indicating an increased PGI2 formation in chronic uraemia. Formation of thromboxane B2 (TxB2) at the site of plug formation in vivo and during whole blood clotting in vitro was similar in the uraemic subjects and in the normals excluding a major defect in platelet prostaglandin metabolism in chronic renal failure. Significantly smaller amounts of beta-TG were found in blood obtained from the site of vascular injury as well as after in vitro blood clotting in patients with chronic renal failure indicating an impairment of the a-granule release in chronic uraemia. We therefore conclude that the haemorrhagic diathesis commonly seen in patients with chronic renal failure is - at least partially - due to an acquired defect of the platelet a-granule release and an increased generation of PGI2 in the micro vasculature.


1995 ◽  
Vol 6 (5) ◽  
pp. 1379-1385
Author(s):  
J Coresh ◽  
M Walser ◽  
S Hill

Concerns have been raised about the possibility of protein restriction resulting in malnutrition and poor subsequent survival on dialysis. However, no studies have examined patients treated with protein restriction to determine their subsequent survival on dialysis. This study prospectively monitored 67 patients with established chronic renal failure (mean initial serum creatinine of 4.3 mg/dL) who were treated with a very low-protein diet (0.3 g/kg per day) supplemented with either essential amino acids or a ketoacid-amino acid mixture and observed closely for clinical complications. Forty-four patients required dialysis. Once dialysis was started, dietary treatment was no longer prescribed. The cumulative mortality rate during the first 2 yr after starting dialysis was 7% (95% confidence interval, 0 to 16%). During this period, only two deaths occurred compared with 11.5 deaths expected on the basis of national mortality rates adjusted for age, sex, race, and cause of renal disease (P = 0.002). However, the protective effect was limited to the first 2 yr on dialysis. Thereafter, mortality rates increased, resulting in a total of 10 deaths during 96.4 person-years of follow-up, which was not significantly lower than the 14.9 deaths expected (P = 0.25). Extrapolation of sequential serum creatinine measurements made before dietary treatment suggests that the improved survival cannot be due to the early initiation of dialysis. Although the lack of an internal control group and data on dialysis lends uncertainty, the large difference in mortality rate between these patients and the nationwide experience indicates that protein restriction and close clinical monitoring predialysis does not worsen and may substantially improve survival during the first 2 yr on dialysis. These findings point out the importance of studying predialysis treatments as a means for lowering mortality on dialysis.


1985 ◽  
Vol 31 (12) ◽  
pp. 1988-1992 ◽  
Author(s):  
M Shaykh ◽  
N Bazilinski ◽  
D S McCaul ◽  
S Ahmed ◽  
A Dubin ◽  
...  

Abstract We measured the fluorescence, at various excitation (Ex) and emission (Em) wavelengths, of serum ultrafiltrates and fractions of serum resolved by chromatography on Sephadex G15, studying both normal subjects and patients in chronic renal failure requiring hemodialysis. We found hitherto undescribed fluorescence at Ex 380 nm/Em 440 nm and Ex 400 nm/Em 460 nm, the intensity being greatly increased in patients with chronic renal failure in comparison with normal subjects (p less than 0.005). This fluorescence persisted unaltered when serum was filtered through membranes having cutoffs ranging from 10 000 to 500 Da. Each serum fraction resolved by gel chromatography demonstrated a characteristic fluorescence, which was generally much more intense in uremics. The most intense fluorescence (Ex 380 nm/Em 440 nm and Ex 400 nm/Em 460 nm) was emitted in the higher-Mr fractions.


1978 ◽  
Vol 24 (3) ◽  
pp. 451-454 ◽  
Author(s):  
F P Di Bella ◽  
J M Kehrwald ◽  
K Laakso ◽  
L Zitzner

Abstract Antisera directed toward the carboxyl-terminal region of human parathyrin (parathyroid hormone), for use in daignostically applicable radioimmunoassays of the hormone in serum, are scarce, largely because of the lack of suitable immunogens of human origin. We produced four antisera in goats and guinea pigs by immunization with recently discovered carboxyl-terminal fragments of human parathyrin extracted from parathyroid tumors. Here, we report results of radioimmunoassays of nearly 200 normal and pathological sera with one of these antisera; we observed almost complete differentiation between concentrations of parathyrin in serum of healthy normal subjects and patients with primary, secondary (due to chronic renal failure), or "ectopic" hyperparathyroidism (due to nonparathyroid cancer). The availability of a new immunogen should now make possible the deliberate production of large quantities of diagnostically applicable parathyrin antisera directed toward the carboxyl-terminal region of human parathyrin. This should, in turn, lead to more widespread availability of this useful radioimmunoassay.


1981 ◽  
Author(s):  
Y Endo ◽  
M Mamiya ◽  
K Takahashi ◽  

We have reported that jS-thromboglobulin (β-TG) and platelet factor 4 (PF4) increased in chronic renal failure. The purpose of the current study is to reveal a correlation between plasma β-TG (Amersham Corp. England) and renal function, a correlation between plasma β-TG and PF. (Abbott Lab., USA) and the effect of hemodialysis on patients with chronic renal failure.Significantly increased levels of plasma β-TG (76.8±25.5 ng/ml, p<0.01) were observed in 24 patients with chronic renal failure (BUN>20mg/dl), compared to normal subjects (13.2±5.6ng/ml). The increase in β-TG was highly correlated with BUN (r=0.651, p<0.01), creatinine (r=0.778, p<0.01) and creatinine clearance (r=-0.723, p<0.01). Although plasma PF4 (normal 5.0±2.0ng/ml) increased also, no statistical significance could be found. Statistical correlation between β-TG and PF4 was not found in these patients. This reason is thought to Be due to the difference of molecular weight (PF. 8000MW, β-TG 36000MW) and half-life (PF4 30min,β-TG 100min) The high levels of β-TG (89.4±3.4ng/ml) showed a further increase (109.4±5.8ng/dl, p<0.01) after dialysis. This is thought to be due to hemoconcentration, because of no adhesion of platelet to cellulose membrane but about 20% elevation in mean of other blood factors such as RBC, WBC, platelet, fibrinogen etc. The PF4 levels (before, 7.7±1.3ng/ml) which increased at 15min (55.2±19.6ng/ml, p<0.01) and 1 hr (23.7±8.4ng/ml, p< 0.01) are thought to be due to the influence of heparin infusion. The change in PF4. was not accompanied by the change in β-TG. During hemodialysis the decrease of other platelet functions such as adhesiveness, aggregation induced by ADP, collagen and PF3remained unchanged.


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