phosphocreatine and Kidney-Failure--Chronic

Using the method of in vivo magnetic resonance spectroscopy we examined 17 patients with moderately advanced chronic renal insufficiency, 21 patients with chronic renal failure treated by haemodialysis, and 15 dialyzed patients with symptomatic renal osteopathy. The ratios of intracellular phosphocreatine and inorganic phosphate concentrations of these subjects measured at rest were compared with those found in healthy controls. While we noted significantly lower (p < 0.01) ratio values in all patients, subjects with osteopathy showed a lower value than dialyzed patients free of bone disease. Haemodialysis improved the result of examination in 7 patients. The results can be summarized as follows: (1) patients with altered renal function have significantly impaired energy metabolism of skeletal muscle, and (2) the disorder is more severe in patients with renal osteopathy than in those free of it.

Topics: Adenosine Triphosphate; Adult; Energy Metabolism; Humans; Kidney Failure, Chronic; Magnetic Resonance Spectroscopy; Middle Aged; Muscles; Phosphates; Phosphocreatine; Phosphorus; Uremia

The precise origin of phosphate that is removed during hemodialysis remains unclear; only a minority comes from the extracellular space. One possibility is that the remaining phosphate originates from the intracellular compartment, but there have been no available data from direct assessment of intracellular phosphate in patients undergoing hemodialysis.. We used phosphorus magnetic resonance spectroscopy to quantify intracellular inorganic phosphate (Pi), phosphocreatine (PCr), and. During the first hour of hemodialysis, mean phosphatemia decreased significantly (-41%;. Phosphorus magnetic resonance spectroscopy examination of patients with ESKD during hemodialysis treatment confirmed that depurated Pi originates from the intracellular compartment. This finding raises the possibility that excessive dialytic depuration of phosphate might adversely affect the intracellular availability of high-energy phosphates and ultimately, cellular metabolism. Further studies are needed to investigate the relationship between objective and subjective effects of hemodialysis and decreases of intracellular Pi and. Intracellular Phosphate Concentration Evolution During Hemodialysis by MR Spectroscopy (CIPHEMO), NCT03119818.

Topics: Acidosis; Adenosine Triphosphate; Adult; Aged; Calcium; Energy Metabolism; Female; Hemodynamics; Humans; Hydrogen-Ion Concentration; Kidney Failure, Chronic; Kinetics; Magnetic Resonance Spectroscopy; Male; Middle Aged; Phosphates; Phosphocreatine; Phosphorus; Phosphorus Isotopes; Pilot Projects; Prospective Studies; Renal Dialysis

Topics: Adenosine Triphosphate; Energy Metabolism; Exercise Therapy; Humans; Kidney Failure, Chronic; Lactic Acid; Leg; Muscular Atrophy; Oxygen; Phosphocreatine; Renal Dialysis; Self Care

We herein describe the case of a patient with chronic renal failure complicated by star fruit poisoning. T2-weighted and diffusion-weighted MR imaging showed hyperintense lesions at the thalami and right temporo-occipital cortex. Single voxel proton MR spectroscopy revealed elevation of lactate and (31)phosphorous MR spectroscopy revealed elevation of inorganic phosphate and decrease of phosphocreatine and nucleoside triphosphates. The imaging and metabolic changes indicated energy deprivation, with subsequent cortical necrosis proved at autopsy.

Topics: Aspartic Acid; Brain; Brain Chemistry; Diffusion Magnetic Resonance Imaging; Fruit; Humans; Kidney Failure, Chronic; Lactic Acid; Magnetic Resonance Spectroscopy; Male; Middle Aged; Nucleotides; Phosphates; Phosphocreatine; Renal Dialysis

Assessment of left ventricular metabolism and function is important in patients on maintenance dialysis because congestive heart failure occurs quite frequently and has a poor prognosis. The purpose of this study was to evaluate the changes of myocardial high energy metabolism in dialysis patients by using phosphorus-31 (31P) magnetic resonance (MR) spectroscopy.. Phosphorus-31 spectra were obtained from anteroseptal wall of the heart in six normal subjects (mean age, 24 +/- 1 years) and 14 dialysis patients (mean age, 52 +/- 11 years), using a 1.5-tesla clinical MR system. Four patients had previous history of heart failure. Echocardiography was performed in all patients to evaluate left ventricular (LV) hypertrophy and LV function.. The averaged ratio of phosphocreatine (PCr)/beta-adenosine triphosphate (beta-ATP) in dialysis patients (1.15 +/- 0.25 mean +/- standard deviation), was significantly lower than that in healthy subjects (1.63 +/- 0.21; P < 0.01). There was no significant difference in PCr/beta-ATP ratios between the non-LV hypertrophy group (1.21 +/- 0.24; n = 7) and the LV hypertrophy group (1.09 +/- 0.24; n = 7). The averaged PCr/beta-ATP ratio in four patients with history of heart failure (0.96 +/- 0.18) was significantly lower than that of the 10 patients without history of heart failure (1.22 +/- 0.23; P < 0.05).. These results indicate that patients on maintenance dialysis have decreased PCr/beta-ATP ratio and 31P MR spectroscopy can provide noninvasive assessment of altered high energy phosphate metabolism.

Topics: Adenosine Triphosphate; Adult; Aged; Female; Heart Failure; Heart Ventricles; Humans; Kidney Failure, Chronic; Magnetic Resonance Spectroscopy; Male; Middle Aged; Myocardium; Phosphocreatine; Phosphorus; Phosphorus Radioisotopes; Renal Dialysis

The effect of propionyl L-carnitine on skeletal muscle metabolism in chronic renal failure. Carnitine deficiency, resulting in defective oxidative ATP synthesis, has been implicated in the myopathy of chronic renal failure. Using 31P magnetic resonance spectroscopy we examined calf muscle metabolism in 10 dialysed patients before and after 8 weeks of propionyl L-carnitine (PLC) 2 g.p.o. daily. Resting phosphocreatine/ATP (4.41 +/- 0.20 [SEM]) decreased to normal control levels on PLC (3.98 +/- 0.14; controls 4.00 +/- 0.06). In contrast, there was no effect of PLC on aerobic and anaerobic metabolism of muscle during or following 2-10 min exercise. The maximal calculated oxidative capacity (Qmax) remained below normal (28 +/- 3 mM/min before and 24 +/- 3 mM/min after PLC; controls 49 +/- 3 mM/min). Qmax correlated positively with hemoglobin concentration ([Hb]) after PLC (p < 0.03). Oxidative capacity assessed by phosphocreatine recovery T significantly improved with PLC administration (0.93 +/- 0.1 to 0.74 +/- 0.08 min) in those patients (n = 6) with [Hb] > 10 g/dl. [Hb] was rate limiting to oxidative metabolism in recovery from exercise but only following treatment with PLC. Patients with anemia or those subjects who use relatively more non-oxidatively synthesized ATP during exercise, do not respond to PLC. Oxidative metabolism did not normalize on PLC suggesting that anemia and carnitine deficiency are not the only causes of mitochondrial dysfunction in renal failure.

Topics: Adenosine Triphosphate; Anemia; Carnitine; Exercise; Female; Hemoglobins; Humans; Kidney Failure, Chronic; Magnetic Resonance Spectroscopy; Male; Middle Aged; Mitochondria, Muscle; Muscle, Skeletal; Oxygen Consumption; Peritoneal Dialysis, Continuous Ambulatory; Phosphocreatine; Renal Dialysis

Skeletal muscle biopsies were performed on 12 healthy sedentary subjects and on 22 non-dyalized chronic renal failure patients (CRF) on a free diet and after overnight fasting. Parathormone, glucagon and insulin were determined at the same time of biopsies. CRF patients showed significantly low ATP and creatine phosphate levels. Regarding enzyme activities, a high hexokinase Vmax was found, while the pyruvate kinase activity was lower than in the control group. For the tricarboxylic acid cycle, citrate synthase, succinate dehydrogenase and malate dehydrogenase activities were higher; total NADH cytochrome c reductase activity was also high, while cytochrome oxidase activity was slightly lower. Both alanine aminotransferase and aspartate aminotransferase activities were considerably high in comparison with the control group. In conclusion, our study revealed a hypermetabolic TCA cycle, but impaired oxidative phosphorylation, which partly explained the reduced ATP concentration. Excessive protein intake and hormonal derangements may play a role in these metabolic changes.

Topics: Adenosine Triphosphate; Adult; Aged; Biopsy; Citric Acid Cycle; Energy Metabolism; Enzymes; Fasting; Fatigue; Female; Humans; Intestinal Absorption; Kidney Failure, Chronic; Male; Middle Aged; Muscle, Skeletal; Phosphocreatine; Uremia

Cardiac function and energetics in experimental renal failure in the rat (5/6 nephrectomy) have been investigated by means of an isolated perfused working heart preparation and an isometric Langendorff preparation using 31P nuclear magnetic resonance (31P NMR). 4 wk after nephrectomy cardiac output of isolated hearts perfused with Krebs-Henseleit buffer was significantly lower (P < 0.0001) at all levels of preload and afterload in the renal failure groups than in the pair-fed sham operated control group. In control hearts, cardiac output increased with increases in perfusate calcium from 0.73 to 5.61 mmol/liter whereas uremic hearts failed in high calcium perfusate. Collection of 31P NMR spectra from hearts of renal failure and control animals during 30 min normoxic Langendorff perfusion showed that basal phosphocreatine was reduced by 32% to 4.7 mumol/g wet wt (P < 0.01) and the phosphocreatine to ATP ratio was reduced by 32% (P < 0.01) in uremic hearts. During low flow ischemia, there was a substantial decrease in phosphocreatine in the uremic hearts and an accompanying marked increase in release of inosine into the coronary effluent (14.9 vs 6.1 microM, P < 0.01). We conclude that cardiac function is impaired in experimental renal failure, in association with abnormal cardiac energetics and increased susceptibility to ischemic damage. Disordered myocardial calcium utilization may contribute to these derangements.

Topics: Adenosine Diphosphate; Adenosine Triphosphate; Animals; Blood Pressure; Cardiac Output; Coronary Circulation; Creatinine; Disease Models, Animal; Heart; Heart Rate; Hydrogen-Ion Concentration; In Vitro Techniques; Kidney Failure, Chronic; Magnetic Resonance Spectroscopy; Male; Multivariate Analysis; Myocardium; Nephrectomy; Phosphates; Phosphocreatine; Rats; Rats, Wistar; Reference Values; Urea

Fatigue and lethargy, common symptoms in uraemia, have been attributed to many factors. To assess possible bioenergetic contributions to this, we examined the forearm muscle of five patients in end-stage renal failure using 31P-magnetic resonance spectroscopy. There was a small increase in the ratio of intracellular inorganic phosphate to ATP in resting muscle, suggesting an increased cytosolic phosphate concentration. During exercise, increased phosphocreatine breakdown was accompanied by rapid intracellular acidification and an increase in calculated lactic acid accumulation in the muscle of the uraemic subjects, suggesting glycolysis dominating over oxidative phosphorylation as a source of ATP. After exercise, the half-time of phosphocreatine (PCr) recovery was longer in the uraemic subjects, suggesting diminished mitochondrial function. The initial rate of PCr resynthesis was not significantly decreased, but when account was taken of the high cytosolic ADP concentration (which drives mitochondrial oxidative ATP synthesis) the calculated maximum oxidative capacity was significantly reduced in the uraemic subjects. Thus there was evidence of mitochondrial dysfunction in uraemia due either to limitation of oxygen supply, reduced mitochondrial content, or an intrinsic mitochondrial defect. This resulted in increased phosphocreatine depletion and increased glycolytic ATP production during exercise and there was partial compensation of the mitochondrial abnormality by increased ADP concentration. In three of these patients studied after elevation of haemoglobin with erythropoeitin (from 8 to 12 g/dl), initial phosphocreatine breakdown and lactic acid accumulation during exercise were normalized, while exercise duration and calculated maximum oxidative capacity remained significantly abnormal. This suggests that anaemia contributes to these metabolic abnormalities but does not fully explain them.

Topics: Adenosine Triphosphate; Aged; Anemia; Chronic Disease; Energy Metabolism; Exercise; Humans; Hydrogen-Ion Concentration; Kidney Failure, Chronic; Lactates; Lactic Acid; Male; Middle Aged; Muscles; Phosphocreatine; Uremia

Topics: Calcitriol; Calcium; Humans; Kidney Failure, Chronic; Muscular Diseases; Myosins; Phosphocreatine; Renal Dialysis; Troponin; Uremia

Topics: Adult; Aged; Aspartic Acid; Brain Chemistry; Choline; Female; Humans; Kidney Failure, Chronic; Magnetic Resonance Spectroscopy; Male; Middle Aged; Phosphocreatine

A normal reference interval for serum amyloid P component (SAP) concentration in the serum was established in 500 healthy adult individuals (274 women, 226 men), by electroimmunoassay calibrated with standards of highly purified, isolated SAP. The mass of SAP in these was determined from the extinction coefficient of SAP at 280 nm measured here precisely for the first time by spectrophotometry and cryogenic drying. The mean (SD, range) SAP concentration was significantly lower in women: 24 mg/l (8, 8-55), compared to 32 mg/l (7, 12-50) in men (P less than 0.001). In renal insufficiency patients, 38 with chronic renal failure, 79 on hemodialysis and 66 on continuous ambulatory peritoneal dialysis, the mean values for SAP concentration were all significantly higher than normal (range of means, 39-59 mg/l in men and 35-42 mg/l in women), but did not correlate with serum creatinine, duration of dialysis or the presence of an acute phase response. The metabolism of SAP is thus altered in renal failure and is not normalized by dialysis, but it is not clear whether this is relevant to the pathogenesis of dialysis related arthropathy and amyloidosis.

Topics: Adult; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Peritoneal Dialysis; Phosphocreatine; Reference Values; Renal Dialysis; Serum Amyloid P-Component; Sex Characteristics; Spectrophotometry

Previous reports have suggested that creatine kinase isoenzymes are elevated in patients with chronic renal failure and thus are less useful in the evaluation of chest pain in such patients. Our data in 88 patients with chronic renal failure receiving maintenance dialysis confirm this observation for total plasma creatine kinase. However, elevations in MB and BB creatine kinase, although statistically significant, were biologically unimpressive (5.9 +/- 0.05 [SEM] IU/L compared with 4.8 +/- 0.04 IU/L for MB creatine kinase [p less than 0.02], and 5.5 +/- 0.08 ng/ml compared with 3.2 +/- 0.05 ng/ml for BB creatine kinase [p less than 0.0002] ), and were unlikely to cause diagnostic confusion. In 92% of patients with chronic renal failure, plasma MB creatine kinase activity was within the normal range (less than 13 IU/L). Eight percent of patients manifested abnormal MB creatine kinase values; the highest was 20 IU/L. The glass bead method for measuring MB creatine kinase was used to avoid the potential confusion induced by non-creatine kinase-mediated fluorescence, which occurs in the region of MB and BB creatine kinase on electrophoresis. The infrequent and modest increases in plasma MB creatine kinase observed in patients with chronic renal failure should be appreciated, but it should not cause diagnostic confusion, because acute myocardial infarction usually results in more substantial elevations of MB creatine kinase.

Topics: Clinical Enzyme Tests; Creatine Kinase; Electrophoresis, Cellulose Acetate; False Positive Reactions; Humans; Isoenzymes; Kidney Failure, Chronic; Myocardial Infarction; Peritoneal Dialysis; Phosphocreatine; Radioimmunoassay; Renal Dialysis; Spectrophotometry

Topics: Alcoholism; Collagen Diseases; Creatine Kinase; Humans; Kidney Failure, Chronic; Lung Neoplasms; Muscular Dystrophies; Phosphocreatine