Chronic Renal Disorders Research Articles

Serum hepatocyte growth factor levels in patients with chronic renal disease - effect of GFR and pathogenesis

Hepatocyte growth factor (HGF) is a growth-promoting peptide that appears to act in a renotropic and nephroprotective manner during acute renal damage. Recent studies suggest that HGF is also of importance in chronic renal diseases. The serum HGF level is correlated with serum creatinine, and it has been suggested that glomerular and tubular diseases affect serum HGF differently. In the present study, levels of serum HGF were determined and correlated to glomerular filtration rate (GFR) in 118 patients with various chronic renal diseases. GFR was determined by 99m Tc-DTPA clearance, and the GFR values were evenly distributed in the interval 5-155 mL/min/1.73 m 2 . Serum HGF levels increased slightly with decreasing GFR; the Pearson correlation coefficient being 0.49 (p < 0.0001). In 21 additional patients with end-stage renal disease treated with continuous ambulatory peritoneal dialysis, there was a more marked increase in the serum levels of HGF. The effect of glomerular and tubular diseases on serum HGF was examined by comparing the HGF levels in two groups of patients with similar GFR values: 57 patients with mainly glomerular disorders (diabetic nephropathy with micro- or macroalbuminuria or glomerulonephritis) and 14 patients with mainly tubular disorders (polycystic kidney disease). There was no significant difference between the HGF levels of the two groups (p = 0.30). In conclusion: Serum HGF levels are correlated with GFR (for GFR U 5 mL/min/1.73 m 2 ) in patients with chronic renal diseases, and glomerular and tubular disorders seem to affect the HGF level similarly.

Emergency surgery in hematologic patients.

Patients at risk for clinically significant bleeding and who require urgent or emergent surgical procedures are encountered. Usually local causes are responsible, but a generalized hematologic defect may be uncovered. Quickly and effectively distinguishing the cause may be critical to rapid treatment and survival. A careful history, appropriate use of laboratory tests (e.g., partial thromboplastin time, prothrombin time, and platelet count), and knowledge of possible causes are key to prompt diagnosis and treatment. Bleeding from multiple sites, spontaneous bleeding, or unexpectedly severe bleeding suggests a systemic process. Immunocompromised or suppressed patients or systemically ill patients with chronic hepatic renal, lymphatic, and hematologic disorders are seen with urgent surgical problems. The key is rapid diagnosis and effective systemic and local therapy to counter the problem. The syndrome of diffuse "medical bleeding" frequently confronts the surgeon treating a patient who has received transfusions of more than 1.5 times blood volume. The coagulation defect is almost always associated with hypothermia and acidosis. Treatment consists in control of large-vessel bleeding by appropriate surgical techniques, blunt packing, and tamponade of diffuse bleeding, rapid rewarming of the patient, and adequate resuscitation for shock. Transfusion of platelets and fresh frozen plasma is empiric initially and subsequently guided by the clinical and laboratory coagulation profiles of the patient.

Carbohydrate metabolism in children receiving growth hormone for 5 years

Carbohydrate metabolism was evaluated by fasting and postprandial glucose, insulin, and hemoglobin (Hb)Alc levels in children with chronic renal insufficiency and various other growth disorders treated with growth hormone. Mean fasting and postprandial glucose remained unchanged throughout the 5-year study period in all four study groups. Median fasting insulin levels rose from low-normal levels into the normal range after 5 years of growth hormone. Average fasting insulin level after 5 years was 10 mU/l. Median postprandial insulin values also rose, yet remained within the normal range at the 5-year mark. Mean Hb Alc levels remained within low to middle end of the normal range in the patients with growth hormone deficiency, Turner syndrome, and idiopathic short stature. Mean Hb Alc levels at the 5 years were slightly elevated to 6.3% for the patients with chronic renal insufficiency.

Thrombocytosis. Etiologic analysis of 663 patients.

Six hundred sixty-three children aged 1 to 16 years with thrombocytosis (defined as a platelet count of more than 500 x 10(9)/L) seen in a university hospital over a 1-year period were studied prospectively for etiology. The causes of thrombocytosis were infection (30.6%), hemolytic anemia (19.3%), tissue damage (15.2%), rebound thrombocytosis (14.8%), chronic inflammation (4.1%), renal disorders (4.1%), and malignancy (2%). Thrombocytosis associated with multiple, simultaneous causative factors was seen in 3.3% of cases. Among all patients with infections, osteomyelitis and septic arthritis were associated with higher platelet counts than other infections (P < .0001). Thrombocytosis secondary to infections was significantly more common in children under 5 years of age, whereas chronic inflammation, malignancy, and renal disorders were more common causes of thrombocytosis in children over 5 years of age. Thrombocytosis of 1 million or more platelets was seen in 13 (2%) children. No thrombocytosis-related complications were seen in any children, and none required any specific treatment. Thrombocytosis is a frequent finding in children. It is due to a variety of etiologic factors and is of little clinical discriminatory value. It is often due to an acute-phase phenomenon in response to infection, tissue damage, blood loss, or anemia, and is rarely due to malignancy.

The diagnosis and steroid “pulse” therapy of systemic lupus erythematosus associated with mental disturbances at general hospital : Shun-Wei Li, Jian-Ming Wang Union Medical College Hospital, Beijing 100730, P.R. China

Twenty-eight patients suffering from systemic lupus erythematosus (SLE) associated with mental disturbances were analyzed clinically (1983-1990). Although no characteristic features of the mental disturbances of SLE were found, it should be differentiated from steroid- or chronic renal failure-induced mental disorders. One gram of methylprednisolone intravenously daily for 3 days was recommended as a pulse therapy to treat the mental disturbances of SLE. In this group, the mental disturbances of SLE showed improvement or disappearance in 18 of 25 patients (72%) after pulse therapy.

Beta 2-glycoprotein-1 (apolipoprotein H) excretion in chronic renal tubular disorders: comparison with other protein markers of tubular malfunction.

Urinary beta 2-glycoprotein-1 was measured in 60 patients with conditions recognised as causing renal tubular impairment and compared with established markers of early tubular malfunction. Increased beta 2-glycoprotein-1 excretion was found in 49 (82%) of the subjects; raised excretion of alpha 1-microglobulin, retinol-binding protein, and beta 2-microglobulin was found in 46 (77%), 45 (75%), and 31 (52%), respectively, and increased urinary N-acetyl-beta-D-glucosaminidase activity in 32 of 54 of the subjects (59%). The increase was particularly pronounced in those with proximal tubule malfunction, although considerable variation occurred. beta 2-glycoprotein-1 was shown to be stable in urine over the physiological pH range, and it is concluded that its measurement provides a means of detecting chronic malfunction of the renal tubules that is marginally more sensitive than assays of alpha 1-microglobulin or retinol-binding protein, and more reliable than assays of beta 2-microglobulin or N-acetyl-beta-D-glucosaminidase.

Absence of increased urinary excretion of adenosine-deaminase-binding protein by patients with chronic renal tubular malfunction

The urinary excretion of adenosine-deaminase-binding protein, a constituent of the brush border of proximal renal tubule cells, has been investigated in 39 patients with disorders associated with malfunction of the renal tubules, and its excretion has been compared with that of two low molecular mass plasma proteins and an enzyme derived from renal tubular cells. None of the 36 patients with disorders associated with chronic renal tubular malfunction were found to be excreting significantly increased quantities of adenosine-deaminase-binding protein but 30 had increased excretion of retinol-binding protein, α 1-microglobulin, or N-acetyl- β-D-glucosaminidase. Measurement of urinary adenosine-deaminase-binding protein may be useful in the assessment of acute renal tubular injuries but it is not of value in the detection of chronic renal tubular disorders.

Albuminuria vs urinary total protein for detecting chronic renal disorders

A literature review and our own data are presented to demonstrate that urinary albumin (UA) excretion increases in many renal disorders and that it offers a far more sensitive indicator than the commonly used urinary total protein (UTP) for the early detection of renal involvement in many chronic diseases such as diabetes mellitus, hypertension, and systemic lupus erythematosus. In many individuals with these disorders, UA increases severalfold, even while UTP remains within the reference interval. UA is also more suited than UTP for following therapeutic responses in these slowly progressive renal disorders. Increases in UA are associated with increased mortality. UTP measurements are plagued with many analytical problems, whereas UA is much easier to standardize. We recommend that both UA and UTP be measured when quantitative urine protein assays are ordered, especially when the UTP is less than 300 mg/g of creatinine.

Reduction of Albuminuria after Angiotensin Converting Enzyme Inhibition in Various Renal Disorders

The urinary albumin excretion measured by the albumin creatinine clearance ratio (Calb/Ccreat) and the mean supine arterial blood pressure (MAP) were studied before the start of ACE inhibition, at the start and during up to 1 year of ACE inhibition with Captopril or Enalapril in 35 patients with various chronic proteinuric renal disorders with or without renal failure, arterial hypertension and nephrotic syndrome. Before the start of ACE inhibition mean Calb/Ccreat, MAP, s-albumin and s-creatinine did not change. During ACE inhibition the Calb/Ccreat was reduced from 75% (p less than 0.05) in patients with minimal albuminuria to 41% (p less than 0.005) in patients with extensive albuminuria. Average reduction of albuminuria was 44% at one year's observation time. Serum albumin increased 9% (p less than 0.05), serum creatinine did not change significantly and MAP showed a slight, not uniformly significant decrease. The reduction of Calb/Ccreat was of the same order in the different renal disorders studied and was independent of the renal function, presence or absence of nephrotic syndrome and treatment with antihypertensive or immunosuppressive drugs. The decrease in Calb/Ccreat during ACE inhibition was related to the reduction in MAP at most time intervals, but Calb/Ccreat decreased also when MAP was unchanged or increased. Thus the decrease in Calb/Ccreat during ACE inhibition does not only seem to be a consequence of a decrease in the systemic arterial blood pressure but reasonably also due to changes in the intra-renal hemodynamics and most probably a decrease in the glomerular capillary pressure.

High-performance liquid chromatographic methods with fluorescence detection for the determination of branched-chain amino acids and their alpha-keto analogues in plasma samples of healthy subjects and uraemic patients

High-performance liquid chromatographic (HPLC) methods have been developed for the quantification of branched-chain amino acids (BCAA) and their keto analogues (BCKA). Amino acids and their keto analogues were derivatized with o-phthalaldehyde, 2-mercaptoethanol and o-phenylenediamine sulphate prior to HPLC. Both separations were performed on a reversed-phase column, using a mul-ti-step gradient system with two solvents and a fluorescence detector. These methods are simple and sensitive and give highly reproducible results. By using an automatic system, the instability problem is avoided and the reaction kinetics are controlled. The use of a simple clean-up procedure with preparative cation-exchange chromato-graphy before BCKA analysis concentrates the dilute plasma sample. The methods were applied to the determination of BCAA and BCKA in plasma samples of healthy volunteers and patients with chronic renal disorders. The relationship between the concentrations of BCAA and BCKA in plasma for these two groups is shown.

Plasma levels of proinsulin, insulin and C-peptide in chronic renal, hepatic and muscular disorders.

Proinsulin, insulin and C-peptide levels were investigated in chronic renal, hepatic and muscular disorders. The proinsulin levels in human plasma were determined by radioimmunoassay using insulin-degrading enzyme (IDE). The fasting levels of proinsulin in 29 patients with chronic renal failure (0.95 +/- 0.05) were significantly higher than those in 10 patients with liver cirrhosis (0.46 +/- 0.04), six with muscular dystrophy (0.37 +/- 0.02) and 52 normal subjects (0.24 +/- 0.02 ng/ml, mean +/- S.E.). The fasting levels of insulin and C-peptide in chronic renal failure were also the highest among these groups. The insulin levels in liver cirrhosis and muscular dystrophy were significantly greater than those in normal subjects and increased molar ratios of proinsulin to total insulin immunoreactivity in chronic renal failure were observed. These results suggest that the kidney, liver and muscle are related to circulating insulin levels and that the kidney plays a particularly important role in circulating proinsulin levels. It can be concluded that increases in these peptides are due to a hypersecretion of B-cells, a decreased degradation or excretion.

Plasma lipid alterations in patients with chronic renal disease.

Hyperlipidemia is common in patients with renal disease. This fact may be of great clinical relevance in view of the overwhelming evidence associating disturbed lipid metabolism and atherogenesis. Thus, hyperlipidemia may predispose to vascular disease in patients with chronic renal disorders and premature atherosclerosis could be an important risk in renal disease and a major factor limiting survival of patients on long-term maintenance hemodialysis. The aim of the present review is to present a brief but clinically relevant description of lipoprotein physiology and then to survey the now considerable literature concerned with lipoprotein and thus lipid abnormalities in patients with renal disease. A particular emphasis is placed on the role of the plasma lipoproteins in forming an integrated and controlled pathway for lipid metabolism, and how altered regulatory control within the pathway may be associated with pathogenic mechanisms. Finally, the evidence for accelerated development of vascular disease associated with these lipid abnormalities is briefly considered.

Human plasma C-peptide immunoreactivity: Its correlation with immunoreactive insulin in diabetes, and chronic liver and renal diseases.

The correlation between plasma C-peptide immunoreactivity (CPR) and immunoreactive insulin (IRI) was investigated during the oral glucose tolerance test in 20 normals, 127 diabetics, and 39 non-diabetics with chronic liver or renal disorders. When all subjects were included, the increment of CPR 30 minutes after glucose load (deltaCPR) correlated well with that of IRI (deltaIRI) (r = 0.66, p less than 0.001), but the return of CPR towards the basal level was delayed as compared with IRI. The positive correlation was also observed between the sum of 6 IRI and that of 6 CPR values during the glucose tolerance test in diabetics and controls (r = 0.53, p less than 0.001). deltaCPR/deltaBS (30 min.) was also well correlated with deltaIRI/deltaBS (30 min.), and was specifically low in diabetics. Insulin-treated maturity-onset diabetics showed low but considerable CPR responses while no CPR responses were observed in insulin-treated juvenile diabetics. In each plasma sample, CPR always exceeded IRI on the molar basis. At fasting CPR/IRI ratio was 15.6 +/- 1.7 (mean +/- SE) in normals and 14.9 +/- 1.3 approximately 16.9 +/- 1.0 in diabetics. In chronic liver diseases IRI response was augmented while CPR response was not different from that of controls, and the molar ratio of CPR/IRI was significantly low (9.5 +/- 1.1). On the contrary, it exceeded that of normals in chronic renal diseases (35.7 +/- 14.9). It is concluded that, first, the plasma CPR response appears to be a valuable indicator of pancreatic B-cell function, and second, it is, nevertheless, modified in chronic liver or renal disorders.

Influence of renal function on the kinetics of pancreatic hormones in chronic renal disorders

Influence of renal function on the kinetics of pancreatic hormones in chronic renal disorders

Primary Hypophosphatemic Rickets in an Elderly Woman

The appearance of nonfamilial rickets in adults is most frequently due to generalized gastrointestinal malabsorption. Recent studies suggest that rickets secondary to a specific gastrointestinal malabsorption of vitamin D and of calcium is now more common in adults and especially in elderly individuals, possibly because of concomitant dietary deficiencies, inadequate exposure to sunlight, and previous gastric surgery. 1 Other conditions which commonly cause rickets are chronic renal glomerular insufficiency and renal tubular disorders such as renal tubular acidosis and the Fanconi syndrome. 2 On rare occasions, rickets may complicate hypoparathyroidism, hyperthyroidism, ureterosigmoidostomy, the prolonged ingestion of magnesiumaluminum gel antacids, and hypophosphatasia. 2,3 Primary hypophosphatemic rickets (phosphate diabetes) unrelated to the conditions enumerated above may be either familial or sporadic. 2 The familial variety is transmitted by sex-linked or autosomal inheritance and usually begins in infancy or childhood, whereas the sporadic variety may occur at any age. The biochemical characteristics of

Clinical characteristics of hypertension associated with unilateral renal disease.

A comparison has been made of 20 patients with unilateral renal disease, apparently cured of their hypertension by nephrectomy, and of another group of 20 who showed persistence of elevated blood pressure readings after surgery. Evidence is presented that unilateral renal disease, when it is responsible for hypertension, produces an acute, severe and accelerated process different in many respects from the usual picture of essential hypertension or of chronic bilateral renal disorders. The diagnostic value and the possible bearing of this observation on the mechanisms of renal hypertension are discussed.