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PubMed1966

The role of the microbial flora in uremia. II. Uremic colitis, cardiovascular lesions, and biochemical observations.

Uremic colitis of varying severity occurred in the majority of conventionalized rats dying after removal of both kidneys, but was not found in uremic conventionalized and germfree rats sacrificed preterminally, or in germfree and limited-flora rats dying from uremia, or in any of the controls. The lesions were restricted to the cecum and their incidence and severity paralleled a shorter duration of survival. Cardiovascular damage including focal myocardial necrosis and calcification and patchy aortic and coronary calcification were observed in uremic rats regardless of their microbial status. These lesions had a higher incidence, developed more rapidly, and were more severe in the germfree and limited-flora rats than in the conventionalized animals. The presence or severity of the lesions, however, did not correlate with survival time of rats dying from uremia or with total plasma calcium and inorganic phosphorus levels of individual animals. Generalized necrotizing arteritis was not observed. Wound healing was poor in all uremic rats regardless of microbial status. Focal infection was noted in a few conventionalized rats dying from uremia, did not correlate with survival time, and was absent in all other groups. Comparison of biochemical findings between uremic germfree and conventionalized rats show a higher blood urea nitrogen and elevated plasma indoxyl sulfate in the presence of a microbial flora and a greater amount of plasma inorganic phosphorus in its absence. Uremia resulted in a decrease in hematocrit and increase in plasma and muscle potassium that were similar for germfree and conventionalized rats. Plasma and muscle sodium, total plasma calcium, glucose, and total protein were essentially unchanged by microbial status or uremia. Because the foregoing differences in the metabolic and histopathologic changes of uremia are linked to the known difference in microbial status of the fasting bilaterally-nephrectomized rats that were studied, they are a tangible indication of ways by which the indigenous microbial flora and its composition may affect the course of acute uremia.

Animals↗
PubMed1997

Accelerated glycogenolysis in uremia and under sucrose feeding: role of phosphorylase alpha regulators.

To understand the mechanism of hepatic glycogen depletion found in uremia and under sucrose feeding, we examined net hepatic glycogenolysis-associated active enzymes and metabolites during fasting. Liver was taken 2, 7, and 18 h after food removal in uremic and pair-fed control rats fed either a sucrose or cornstarch diet for 21 days. Other uremic and control rats fasted for 18 h were refed a sucrose meal to measure glycogen increment. Glycogen storage in uremia was normal, suggesting effective glycogen synthesis. During a short fast, sucrose feeding and uremia enhanced net glycogenolysis through different but additive mechanisms. Under sucrose feeding, there were high phosphorylase alpha levels associated with hepatic insulin resistance. In uremia, phosphorylase alpha levels were low, but the enzyme was probably activated in vivo by a fall of inhibitors (ATP, alpha-glycerophosphate, fructose-1,6-diphosphate, and glucose) and a rise of Pi, as verified in vitro. Enhanced gluconeogenesis was also suggested, but excessive hepatic glucose production was unlikely in uremia. During fasting, hypoglycemia occurred in uremia due to reduced glycogenolysis, inefficient hepatic gluconeogenesis, and impaired renal gluconeogenesis. This may be relevant to poor fasting tolerance in uremia, which could be aggravated under excessive sucrose intake.

Animals↗
PubMed1987

Aspirin prolongs bleeding time in uremia by a mechanism distinct from platelet cyclooxygenase inhibition.

We reported that aspirin (ASA) abnormally prolongs bleeding time (BT) in uremia. The present study was designed to investigate whether the abnormally prolonged post-ASA BT in uremia is due to different ASA pharmacokinetics and bioavailability that might be a consequence of uremic condition, platelet cyclooxygenase is peculiarly sensitive to ASA in uremia, and ASA affects primary hemostasis in uremia by a mechanism independent of cyclooxygenase inhibition. Our results showed that in patients with uremia, but not in normal subjects, ASA markedly prolongs the BT. This effect is transient and depends on the presence of ASA in the blood. The observed differences in ASA kinetic parameters are not an explanation of the exaggerated effect of ASA on primary hemostasis in uremia. The sensitivity of platelet cyclooxygenase to ASA inhibition is comparable in uremics and in normal subjects. The temporal dissociation between ASA-induced prolongation of BT and the effect on platelet thromboxane A2 generation suggests that ASA inhibits platelet function in uremia by a mechanism distinct from cyclooxygenase blocking. This possibility is strengthened by the observation that ibuprofen at a dose that fully inhibits platelet cyclooxygenase activity does not significantly prolong BT.

Acetylation↗
PubMed1983

[Disorders of hormone metabolism in chronic uremia].

Uremia is accompanied by a variety of "true" and "laboratory" endocrine disorders, due in part to impaired degradation of hormones because of failing kidney function and in part to the interference of the uremic environment with extrarenal degradation or synthesis and secretion of certain hormones. "True" endocrine disorders, like hyperparathyroidism or hypogonadism, that are associated with renal insufficiency are in contrast with "laboratory" endocrine disorders in uremia, where pathological serum hormone levels lack clearcut clinical evidence for dysfunction of the respective endocrine organ (e.g. thyroid gland). This lack of a direct cause and effect relationship in uremia may be due to the fact that immunoassayable hormone levels may include cross reacting components without biological activity in uremia and to the fact that the uremic environment may alter hormonal effects on target organs. This review tries to give a survey of the big amount of available clinical and laboratory data for uremia induced changes in the following hormones: growth hormone and somatomedins, prolactin, cortisol and adrenocorticotrope hormone, the gonadal and thyroid function as well as parathyroid hormone action. The knowledge of these uremia-induced changes should facilitate the clinician the diagnosis of an additional primary endocrine ailment in a uremic patient and should, on the other hand, spare these patients unnecessary treatment for a suspected endocrine disorder.

Adrenocorticotropic Hormone↗
PubMed2003

[Determinants of uremia elevation in the first days of life in premature infants born before 30 weeks of gestation].

OBJECTIVE: To identify the determinants associated with uremia elevation in the first days of life in extremely premature infants. METHODS: We performed a prospective cohort study in a cohort of neonates born at less than 30 weeks of gestation. RESULTS: Forty-eight preterm infants were included, of which 10 died. The mean fluid administration was 55, 72, 88 and 124 mL/kg on the first, second, third and seventh days of life. Amino acid doses were low in the first two days of life and were unrelated to uremia elevation. Thirty-one percent of the infants presented hypernatremia. Uremia was measured in 31 infants between the fifth and tenth days of life and 12 infants (38.7 %) had uremia values of 100 mg/dL or higher, without creatinine elevation. All of these infants were born at less than 27 weeks of gestation, weighed less than 850 grams at birth, and showed greater weight loss (19.2 % vs. 13.8 %; p 5 0.037) and higher natremia (150.2 mEq/L vs. 146.6 mEq/L; p 5 0.023). The use of furosemide increased the risk of elevated uremia (relative risk: 2.54; 95 % confidence interval: 1.05 6.14). CONCLUSIONS: Total uremia of 100 mg/dL or higher was associated with dehydration, greater weight loss, higher natremia, furosemide use, lower gestational age, and lower birth weight.

Age Factors↗
PubMed1979

Effect of prolonged uremia on insulin metabolism by isolated liver and muscle.

As the prolonged metabolic clearance rate of insulin in chronic uremia cannot be entirely explained by impaired removal and degradation of insulin by the kidney, we set out to determine whether prolonged uremia depresses other major sites of insulin degradation. The study was conducted with livers and skeletal muscle obtained from normal control rats and uremic rats 4 weeks after 80% nephrectomy. Despite a significant difference between renal function in the control and uremic rats (BUN, 18 vs. 46 mg/dl), there was no significant difference in the clearance of insulin by isolated uremic or control livers perfused with a bloodless medium. Similarly, the 125I-insulin degrading activity of liver homogenates was not depressed by uremia. In contrast, binding and degradation by uremic liver cell membranes was significantly reduced to 58% and 85% of the controls, respectively. Degradation by homogenates of skeletal muscle and by intact epitrochlaris muscle was significantly less in uremics than in controls. These results indicate that chronic uremia depresses skeletal muscle insulin degradation but not hepatic insulin removal or degradation despite a decrease in insulin binding and degradation by liver plasma membranes. It thus appears that depression of insulin degradation by muscle may contribute to the prolonged insulin metabolic clearance rate seen in chronic uremia. Furthermore, it is possible that the impaired binding of insulin to liver membranes may play a role in the insulin resistance of uremia.

Animals↗
PubMed1975

Endocrinology and metabolism in uremia and dialysis: a clinical review.

The salient information regarding the effects of uremia and dialysis on each of the metabolic fuels and hormones presented in the preceding sections is summarized in three tables. Tables 1 and 2 provide data on plasma levels, metabolism, dialysance, and literature references for each substance. Table 3 organizes the data according to the general mechanisms by which uremia and chronic dialysis may affect biological substances. Together these tables provide a reasonably complete summary of the information presently available. The pathophysiology of the uremic syndrome is still incompletely understood. The numerous metabolic and endocrine alterations associated with uremia and chronic dialytic therapy underscore the complexity of the problem and identify several specific areas for future research. One which deserves emphasis is the poolic and endocrine abnormalities found in uremia. A recent review by Chantler and Holliday (63) stressed in the importance of protein-calorie deficiency in the pathogensis of growth retardation and disturbed hormonal metabolism in children with chronic renal failure. The importance of this factor in adult patients with chronic uremia has been less well appreciated. However, striking similarities exist between the metabolic and endocrine abnormalities found in protein-calorie malnutrition and those found in uremia. These include, for example, altered albumin and amino acid metabolism, decreased levels of serum transferrin, peripheral insulin resistance and carbohydrate intolerance, elevated levels of glucagon, cortisol and growth hormone, and possibly diminished secretion of thyrotropin and thyroxine. Although not absolutely identical, the similarities between these two clinical syndromes suggest intriguing possible approaches to a better understanding of the pathophysiology of the uremic syndrome and its treatment.

Adult↗
PubMed1974

Calcium metabolism of brain in acute renal failure. Effects of uremia, hemodialysis, and parathyroid hormone.

Studies were carried out to evaluate the changes in content of calcium and magnesium in brain during acute uremia in dogs. Ca content in gray and white matter of brain increased significantly after 3 days of acute uremia and this increment was prevented by thyroparathyroidectomy (TPTX). The administration of parathyroid extract (PTE) to normal dogs and TPTX uremic animals produced a significant rise in brain Ca. These changes were not related to alteration in the concentration of Ca in plasma or cerebrospinal fluid, to changes in calcium-phosphorus product, or to changes in blood pH. Furthermore, the infusion of large amounts of phosphate to vitamin D2-treated animals with suppressed parathyroid gland activity produced marked elevation in calcium-phosphorus product but no significant change in brain Ca. Also, uremia in vitamin D2-treated TPTX dogs failed to increase calcium content in brain despite marked elevation in calcium-phosphorus product. Hemodialysis significantly reduced Ca content of brain but the values were still significantly higher than normal. Mg content increased modestly only in the white matter of uremic dogs with intact parathyroid glands and in normal dogs and TPTX uremic dogs receiving PTE. The results indicate that (a) acute uremia of 3 days is associated with a marked rise of Ca content of brain and modest increment of Mg in certain parts of the brain, and (b) these alterations are not related to uremia, per se, but are dependent on the presence of excess parathyroid hormone. It is suggested that the neurological abnormalities noted in acute uremia may be related in part to the rise in the Ca content of brain.

Acute Disease↗
PubMed1978

Effect of parathyroid hormone and uremia on peripheral nerve calcium and motor nerve conduction velocity.

Peripheral neuropathy is not an uncommon complication of chronic uremia. Because parathyroid hormone, by raising brain calcium, is partly responsible for central nervous system aberrations in uremia, we studied the relative role of uremia, per se, and(or) parathyroid hormone on peripheral nerve calcium and motor nerve conduction velocity (MNCV). Studies were made in six groups of six dogs each, as follows: (a) normal dogs, (b) thyroparathyroidectomized (T-PTX) animals, (c) dogs with 3 days of uremia produced by bilateral nephrectomy, (d) T-PTX before the induction of acute renal failure, (e) normal dogs receiving 100 U/day of parathyroid extract (PTE) for 3 days, and (f) normal animals receiving 3 days of PTE followed by 5 days without PTE. Calcium content in peripheral nerve (expressed as milligram per kilogram of dry weight) was 252+/-5 (SE) in normal animals and 262+/-4 in T-PTX dogs. It was significantly (P < 0.01) higher in dogs with acute renal failure and intact parathyroid glands (410+/-12) and in normal animals receiving PTE (362+/-7). T-PTX, before acute renal failure, prevented the rise in peripheral nerve calcium (262+/-4) and PTE withdrawal was followed by the return of peripheral nerve calcium to normal (261+/-3). The increments in peripheral nerve calcium were associated with slowing of MNCV. It decreased significantly from 70+/-4 to 43+/-1 m/s after 3 days of acute uremia in dogs with intact parathyroid glands and T-PTX before acute renal failure prevented the fall in MNCV. Administration of PTE to normal animals reduced MNCV from 63+/-3 to 35+/-3 m/s and the withdrawal of PTE restored MNCV to normal (73+/-2 m/s). The results show that (a) excess parathyroid hormone increases peripheral nerve calcium and slows MNCV, (b) T-PTX, previously performed, prevents these changes in acute uremia, and (c) the withdrawal of PTE administration is followed by a reversal of the abnormalities.

Animals↗
PubMed1993

A model of reversible uremia employing isogenic kidney transplantation in the rat. Reversibility of secondary hyperparathyroidism.

Kidney transplanted patients with normalized kidney function may still exhibit a variety of problems such as bone problems, vascularly problems, and hormonal dysfunctions. A part of the symptoms may be persisting uremic symptoms, secondary to the pretransplanted period of chronic uremia. An experimental rat model, designed to the study of the reversibility of the chronic uremic implications is therefore described. A stable, severe chronic uremia was induced by 5/6 nephrectomy to inbred Lewis rats. Ten weeks later uremia was reverted by a successful isogenic rat kidney transplantation. During the period of chronic uremia the p-urea was elevated to an average of 21.8 +/- 0.9 mmol/l and p-creatinine to 105.7 +/- 5.7 microM/l. The isogenic kidney transplantation resulted in reestablishment of normal kidney function with an average level of p-urea of 7.6 +/- 0.2 mmol/l and p-creatinine 42.5 +/- 1.9 microM/l perfectly corresponding to the sham-operated rats, i.e. one-kidney rats. Reversibility of the secondary hyperparathyroidism due to chronic uremia was investigated in the model. In rats with chronic renal failure PTH increased from 52 +/- 4.9 pg/ml to 152 +/- 12.2 pg/ml and was normalized after transplantation. It is therefore concluded that the present described technique of introducing long term uremia followed up by a successful kidney transplantation in the rat may be a useful model to study the reversibility of different uremic manifestations.

Animals↗
PubMed2001

Gastric emptying and intestinal transit of liquid and solid markers in rats with chronic uremia.

Gastrointestinal motor abnormalities may account for dyspeptic symptoms of chronic uremia patients. However, the data on gastric emptying are conflicting in human studies. We, therefore, assessed gastric emptying and gastrointestinal transit in a rat uremia model. Chronic uremia was induced by five-sixths nephrectomy in the rats. After 20-hour fasting, the rats were loaded with 70 glass beads as solid markers through a gastric catheter. Two hours later, the stomach was exposed and the small intestine was equally divided into 10 segments. The glass beads in the stomach and in each intestinal segment were counted. The gastric emptying was expressed as the ratio of the number of glass beads in the small intestine to that counted from the entire gastrointestinal tract. The intestinal transit was assessed by analyzing the geometric center of the distribution of glass beads in the intestinal segments. Two conventional nonabsorbable markers, radioactive chromate and charcoal, were also used to evaluate gastric emptying and intestinal transit in the fasted state. Additionally, similar experiments of glass beads were performed in the fed state. It was found that, in the fasted state, the gastric emptying and the intestinal transit of liquid or solid markers were little affected by uremia. In the fed state, however, chronic uremia significantly decreased the intestinal transit but hardly affected the gastric emptying. We conclude that the postprandial intestinal transit, but not the gastric emptying, of solid markers may be decreased in the fed state by chronic uremia in a severity-dependent manner of a rat model, which resembles the findings in uremic patients.

Animals↗
PubMed1975

[Influence of uremia on the proliferation kinetics of a solid transplantable carcinoma (author's transl)].

UNLABELLED: Previous autoradiographic investigations revealed an impaired regeneration of epithelial tissues in acute experimental uremia. It was the aim of the present study to get information about the effect of uremia on the growth and the proliferation kinetics of a solid tumor (mammary carcinoma HB). MATERIAL AND METHODS: The partly differentiated mammary carcinoma HB (Dr. C. W. Friis/Ry/Denmark) was examined in adult female mice (C3H/Tif). Acute renal failure was induced by ligation of the right ureter and by infarction of two thirds of the left kidney. A group of animals served for urea estimation during the first 7 postoperative days. A sham operation was performed in a control group. A starvation effect was avoided by additional tube feeding. Hemoglobin levels and reticulocytes were estimated in tumour bearing uremic mice and in a control group to get information about anemia in acute uremia. Calculating the tumour volume as a sphere with the geometrical mean of two diameters the tumour doubling time was derived from the growth curve. The autoradiographic experiments started on the 21th day after transplantation of the tumour (= 7th day after experimental uremia and sham operation respectively). The cell cycle was determined by the method of percentage of labeled mitoses. The growth fraction was estimated by continuous labeling method. For details of autoradiographic techniques see Fíaux de Lacroix et al. (1973. RESULTS AND DISCUSSION: During the first 48 hours the blood urea increased to more than 230 mg% and then decreased to a level of about 133 mg% at the 7th postoperative day. The blood urea of control animals was in the range of 50 mg%. Tumor bearing mice revealed an anemia (Hb: 8.1 +/- 1.2 g%, reticulocytes 60.1 +/- 36.5%) but no significant differences in hemoglobin levels and reticulocytes counts could be detected in uremic animals (Hb 9.7 +/- 1.7 g%; reticulocytes 31.4 +/- 11.6%). The growth of the tumour was impaired by uremia. The tumour doubling time was prolonged from 7.5 days in untreated and sham operated animals to 15 days in uremic mice. This was mainly due to a lowered growth fraction (from about 50% to 20%), and on the other hand to a prolongation of the generation time (from 15.5 to 19 hours) mainly caused by a prolonged Tg1-phase. The cell loss factor remained constant (about 81% in every group). Our findings in the transplantable solid tumour of uremic mice were similar to the results observed in the epithelium of the stomach, the intestine and of the skin as well as in erythroblasts especially in regard of the changes of the cell cycle. These observations in various tissues suggest a generally impaired cell proliferation in uremia.

Anemia↗
PubMed2006

Erythropoiesis activity, iron availability and reticulocyte hemoglobinization during treatment with hemodialysis and in subjects with uremia.

In hemodialysis subjects correction of anemia is facilitated by combined supplementation of intravenous iron and recombinant human erythropoietin. Reticulocyte hemoglobin content (RET-He) is considered to be an actual indicator reflecting functional iron availability for erythropoiesis. In the present study, interdependence between biochemical analytes reflecting iron status and hemocytometric parameters indicating the degree of hemoglobinization of reticulocytes and red blood cells, respectively, is established. Participants of the study were reference subjects (n=75), subjects with iron deficiency anemia (n=52), subjects with uremia (n=19) and subjects undergoing hemodialysis treatment (n=43). If compared with the reference subjects the results for RBC counts and MCHC are statistically significantly decreased in case of subjects with hemodialysis and uremia, whereas increased results are established with regard to RDW-sd values. Significantly increased results for absolute reticulocyte counts and immature reticulocyte fractions (IRF) are also observed in case of subjects with hemodialysis and uremia. Slightly increased values for the ZPP/heme ratio in combination with elevated reticulocyte count reflect increased activity of erythropoiesis. At a definite MCV value, decreased levels for the hemoglobin content of reticulocytes (RET-He) and hemoglobin content of red blood cells (RBC-He) are observed in case of subjects treated with hemodialysis and in subjects with uremia if compared with identical MCV values of the group of reference subjects. For the ratio of RET-He and RBC-He obviously decreased results are demonstrated in case of subjects with iron deficiency anemia (1.02 +/- 0.08, mean +/- SD), hemodialysis (1.05 +/- 0.05) and uremia (1.02 +/- 0.10) if compared with the group of reference subjects (1.11 +/- 0.02). From the combined interpretation of the MCV values within the reference range and decreased values for RET-He and RET-He/RBC-He ratios, respectively, a decreased degree of hemoglobinization is concluded in the case of subjects with hemodialysis or uremia. The conclusion implicating the presumption of reduced functional availability of iron for hemoglobin synthesis is supported by the detection of increased results for sTfR concentrations and ZPP/heme ratios.

Adult↗
PubMed1992

Expression of hepatic microsomal cytochrome P450s as altered by uremia.

The proportions of different hepatic microsomal cytochrome P450s expressed in uremic rats were studied with specific antibodies and with a steroid hydroxylase assay. In male uremic rats, the hepatic levels of P450 2C11, a male-specific form, and 3A2, a male-dominant form, were decreased to about 30% at 5 weeks after the induction of uremia. These changes were paralleled by decreases in the activities of testosterone 2 alpha-, 16 alpha-, and 6 beta-hydroxylation. The level of P450 2A1, abundant in immature rats, was increased 2-fold by uremia and accompanied by an increase in testosterone 7 alpha-hydroxylation activity. The levels of P450 2C6 and 2E1 were not changed by uremia. The levels of male-specific and male-dominant forms such as P450 2C11 and 3A2 are affected by the serum level of testosterone, which was decreased in the male rats with uremia. Therefore, castrated rats were prepared to compare the effects of testosterone on hepatic cytochrome P450s in uremic rats with those in castrated rats. When testosterone was administered to the castrated rats, the decreased levels of both P450 2C11 and 3A2 returned to normal. However, the administration of testosterone to the uremic rats did not prevent the decrease in the levels of these P450s. In female rats, changes in the levels of cytochrome P450s were not as great during uremia as those in male uremic rats. The level of P450 2C12, a female-specific form, was not changed; the level of P450 2A1 was increased by 50%, that of 3A2 which is barely detected in female rats was increased by 60%, and that of 2E1 was increased by 25%. These results suggested that the changes in the hepatic levels of cytochrome P450s were affected by factors other than testosterone in uremic rats.

Animals↗
PubMed1989

Protein C assays in uremia.

Protein C was determined in 42 patients with terminal uremia and 20 healthy controls in three different ways 1) anticoagulant activity 2) amidolytic activity 3) antigen level. Protein C anticoagulant activity was markedly decreased in uremia, but was partly normalized during hemodialysis treatment, whereas the amidolytic activity and antigen level of protein C were normal and without changes during dialysis. The activities and antigen levels of factor II and X were normal before and after hemodialysis. In anticoagulated patients we found a good correlation between prothrombin levels and protein C levels determined with three different assays. We did not find any evidence for a defect carboxylation of protein C as the cause for the defective protein C in uremia. The BaCl2 precipitation in the Protein C anticoagulant assay was incomplete both in uremia and in controls but without differences between the two groups. In vitro addition of urea and creatinine did not decrease protein C activity. The cause of the defective protein C in uremia is still not known but it might contribute to thromboembolic complications.

Adult↗
PubMed1988

Myocardial interstitial fibrosis in experimental uremia--implications for cardiac compliance.

Experimental uremia is known to cause cardiac hypertrophy. In the present study we examined the effect of uremia with or without concomitant treatment of hypertension by the converting enzyme Ramipril (125 micrograms/day) on micromorphometric indices of cardiac interstitium at the light microscopical and ultrastructural level. In male SD rats, 21 days of uremia caused an increase of total heart weight (1040 +/- 73 mg wet wt vs. 871 +/- 81 in controls, P less than 0.05) with an increase of both right and left ventricular weight. This was accompanied by reduction of capillary cross-sectional area despite unchanged capillary length. The volume density (cm3/cm3) of cardiomyocytes was unchanged (0.881 +/- 0.01 vs. 0.871 +/- 0.016 in controls), but volume density of interstitial tissue (excluding capillary lumen) was significantly increased (0.042 +/- 0.011 cm3 interstitial tissue/cm3 total heart tissue vs. 0.019 +/- 0.007 in controls). This was associated with signs of activation of interstitial cells, that is, increased volume of interstitial cell nuclei and interstitial cell cytoplasm. Concomitantly, a significant increase of volume density of non-cellular interstitial ground substance was found which was not normalized by antihypertensive treatment using Ramipril. After three months of uremia, electron microscopy showed collagen fiber deposition in the interstitium. Comparable interstitial fibrosis was not observed in hearts of rats with renovascular (one clip-two kidney) hypertension. It is concluded that uremia increases myocardial interstitial ground substance by mechanisms independent of hypertension. The data may be relevant for recent findings of diastolic heart malfunction secondary to impaired compliance in uremic patients.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1990

Effects of acute and chronic uremia on active cation transport in rat myocardium.

As abnormalities of active cation transport could contribute to the genesis of uremic cardiomyopathy, we investigated myocardial sodium pump function in rats with acute renal failure (ARF) and with a model of experimental chronic renal failure (CRF) that has metabolic similarities to advanced chronic uremia in humans. CRF rats were hypertensive and had left ventricular hypertrophy (33% higher heart:body weight ratio; P less than 0.01) at four weeks compared to pair-fed sham-operated rats. Importantly, both ouabain- and furosemide-sensitive 86Rb uptake rates were unchanged in left ventricular myocardial slices from CRF, and the intracellular sodium concentration was not different from that of control rats even though skeletal muscle sodium was increased, as we found previously (J Clin Invest 81:1197, 1988). Insulin-stimulated, ouabain-sensitive 86Rb influx was also preserved. There also were no abnormalities in myocardium cation transport in rats with ARF. However, [3H]ouabain binding was decreased 45% in CRF rats (P less than 0.01); it was unchanged in acute uremia. Decreased ouabain binding in chronic uremia was due entirely to fewer low affinity [3H]ouabain binding sites (the binding affinity for ouabain was unaffected). We conclude that in chronic, (but not acute) renal failure, sodium pump number is reduced in myocardium but intracellular sodium is unchanged and active cation flux rates are maintained. These results emphasize that in rats with chronic uremia, intracellular sodium homeostasis is preserved in myocardium, despite the presence of marked abnormalities of active cation transport in skeletal muscle that are characteristic of chronic uremia.

Acute Kidney Injury↗
PubMed1994

Reduced hepatic growth hormone (GH) receptor gene expression and increased plasma GH binding protein in experimental uremia.

In uremia, reduced longitudinal growth and decreased hepatic insulin-like growth factor-I (IGF-I) secretion despite elevated GH serum levels point to an insensitivity to the action of GH. The molecular basis that accounts for this insensitivity could comprise decreased GH receptor expression in the target organs for GH or binding of GH in the circulation to substances that compete with the receptor. To address this hypothesis, the abundance of hepatic GH receptor mRNA was measured by solution hybridization RNase protection assay in uremic female Sprague-Dawley rats, following two-stage 5/6 nephrectomy, and in pair-fed and in ad libitum-fed sham-operated controls; rat GH binding protein (GHBP) plasma concentration was measured by a sensitive direct RIA. Uremia was associated with a 50% decrease of hepatic GH receptor expression compared to pair-fed controls, which themselves showed a 25% reduction of hepatic GH receptor mRNA abundance when compared to ad libitum-fed controls. Plasma GHBP levels in uremia were markedly higher than in both control groups. Treatment with recombinant human GH (rhGH) (10 IU/kg body wt per day s.c. for 10 days) led to a comparable induction of IGF-I plasma levels and weight gain in uremia and pair-fed controls, indicating that the insensitivity to GH in uremia can be overcome by large rhGH doses. Subcutaneous rhGH injections did not significantly alter the hepatic GH receptor transcript abundance or plasma GHBP levels in any of the groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗