Excretion Rate Of Beta 2-microglobulin Research Articles

Urinary excretion of ceruloplasmin is elevated in the subjects with "borderline glucose tolerance test".

To examine whether or not there are any renal alterations in subjects with borderline glucose tolerance and in patients with non-insulin dependent diabetes mellitus (NIDDM) classified by the criteria of Japan Diabetic Association, urinary excretions of plasma proteins including albumin, ceruloplasmin (Cerulo) and IgG were measured in timed overnight urine samples. Eighty middle-aged, non-obese, normotensive, untreated men with urinary albumin excretion rates below 20 microg/minutes, beta2-microglobulin excretion rates below 140 microg/minutes and creatinine clearance values exceeding 80 ml x min(-1) x (1.73 m2)(-1) were included in this study. Three groups were defined according to the results of 75 g oral glucose tolerance test (OGTT) as follows: D group, 10 subjects with NIDDM; B group, 40 subjects with "borderline glucose tolerance test" and N group, 30 subjects with normal glucose tolerance. The fractional clearance (theta) of Cerulo, but not albumin and IgG, was elevated in 37. 5% of the B group compared with the upper limit of that of the N group. Furthermore, theta-Cerulo and theta-IgG increased in the D group compared with those of the N and the B groups. Recently, we found that theta-Cerulo and theta-IgG increased in healthy volunteers when GFR was elevated by acute protein loading and that increase in theta-Cerulo is remarkable than increase in theta-IgG. The present result, taken together with our recent finding mentioned above, suggests that increases in theta-Cerulo and theta-IgG may not be due to an impairment of charge selectivity in the glomerular basement membrane, but due to an increase of intraglomerular hydraulic pressure.

No effect of dietary fish oil on renal hemodynamics, tubular function, and renal functional reserve in long-term renal transplant recipients.

Dietary supplementation with fish oil rich in n-3 polyunsaturated fatty acids has been suggested to protect the kidney against cyclosporin A (CsA) toxicity. This study investigated the effects of a 10-wk dietary supplementation with fish oil on renal function and renal functional reserve in healthy volunteers (N = 9) and two groups of stable long-term kidney-transplanted patients treated with maintenance low-dose CsA (3.0 +/- 0.6 mg/kg; N = 9) or without CsA (N = 9). After an overnight fast, the subjects were water loaded, and clearance studies were performed, postponing morning medication. GFR and effective RPF were measured as the renal clearances of (99mTc)DTPA and (131I)hippuran, respectively. Renal tubular function was evaluated by use of the renal clearance of lithium and the urinary excretion of beta 2-microglobulin. Fish oil did not change baseline values of effective RPF, GFR, lithium clearance, and urinary excretion of beta 2-microglobulin in any of the groups. The infusion of amino acids induced a comparable increase in GFR, lithium clearance, and the urinary excretion rate of beta 2-microglobulin in all three groups with no additional effect of fish oil. Thus, long-term renal transplant recipients treated with a low maintenance dose of CsA had a well-preserved renal functional reserve, and dietary supplementation with fish oil in these patients did not improve renal function.

Does increased glomerular filtration rate or disturbed tubular function early in the course of childhood type 1 diabetes predict the development of nephropathy?

To clarify whether glomerular hyperfiltration or disturbances in renal tubular function may be early markers of the later development of nephropathy a follow-up study was performed in 34 young Type 1 diabetic patients, who had originally been investigated 12 years previously. The initial median age was 14 (range 7-18) years and median diabetes duration 7 (2-14) years. At initial examination only one of the 34 diabetic patients exhibited increased urinary albumin excretion rate. The median glomerular filtration rate was increased (136 vs 107 ml min-1 1.73 m-2; p less than 0.0001) and median threshold concentration of phosphate per litre of glomerular filtrate was decreased (1.27 vs 1.76 mmol l-1; p less than 0.0001) in the diabetic group as compared to that of 28 healthy children. At follow-up 17 patients showed increased urinary albumin excretion rate and the median glomerular filtration rate in this group was significantly lower than that of 17 patients with normal urinary albumin excretion rate (108 vs 125 ml min-1 1.73 m-2; p less than 0.05). However, no relationships were found between the increased urinary albumin excretion (incipient and/or overt diabetic nephropathy) at follow-up to either the initial glomerular filtration rate (134 vs 137 ml min-1 1.73 m-2; p greater than 0.05) or to renal tubular function assessed from urinary excretion rate of beta 2-microglobulin (0.059 vs 0.069 microgram min-1; p greater than 0.05) and the renal threshold concentration of phosphate per litre of glomerular filtrate (1.29 vs 1.22 mmol l-1; p greater than 0.05).

The proteinuria of industrial lead intoxication

Studies of protein excretion were undertaken in seven males, aged 35-42 years, who had more than 5 years exposure to industrial lead and had clinically established Pb intoxication. Heavy metal intoxication with Cd and Hg causes proximal tubular abnormalities, i.e., aminoaciduria, glycosuria, phosphaturia. Similar abnormalities occur in Pb intoxication except that the nature of the proteinuria remains controversial. Studies of urinary proteins included 24-hr urine protein excretion, dextran gel separations, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and beta 2 microglobulin (B2M) measurements. Creatinine clearances, and serum B2M concentrations were normal. Urine total protein distribution by SDS-PAGE and the B2M excretion rate were also normal. These data imply that the nephrotoxicity of Cd and Hg are different than that of Pb. We speculate on what might account for this difference. This study suggests that when examining a population exposed to Pb, the finding of tubular proteinuria should alert investigators to search for the presence of other toxic agents.

The influence of intravenous furosemide on the renal excretion pattern of protein and protein degradation products.

To assist the attending physician who may have difficulties in deciding whether observed deviations from normal renal physiology are disease-induced or diuresis-induced we studied urinary excretion rate of proteins and protein degradation products in eight healthy male volunteers between 60 and 70 years. After a 24 hr control period in the ward the subjects received 80 mg furosemide intravenously. The 24 hr creatinine clearance was reduced from 95 +/- 9 to 83 +/- 6 ml/min. (P less than 0.05). The reduction in the 24 hr carbamide clearance from 35.8 +/- 9.4 to 33.1 +/- 6.2 ml/min. was not significant. The urinary pH was significantly increased during the first hour but after the pH showed a fall which was significant during 2-8 hours after the injection. Initially the urate excretion showed an apparent increase but from 1-8 hours after the injection significantly less urate was excreted. The 24 hr urate clearance was reduced by furosemide from 5.3 +/- 1.6 to 3.4 +/- 1.1 ml/min. (P less than 0.05) and the amount of urate excreted was reduced from 2.6 to 1.6 mmol per 24 hrs (p = 0.05). The excretion rate of beta 2-microglobulin was reduced (P less than 0.01) whereas the excretion rate of albumin was increased (P less than 0.05).

Rapidly Reversible Albumin and ??2-microglobulin Hyperexcretion in Recent Severe Essential Hypertension

Seven young patients with newly diagnosed severe hypertension were studied for one week. The mean age was 34.9 years (range 28-44). The mean initial values +/- s.d. for systolic and diastolic pressures were 223 +/- 27 and 141 +/- 8 mmHg, respectively. Secondary hypertension was excluded by conventional methods and serum creatinine was normal. A pronounced but quite variably elevated albumin excretion 440 +/- 448 micrograms/min (mean +/- s.d.) and a moderately increased beta 2-microglobulin excretion 3.06 +/- 3.29 micrograms/min was noted before treatment. The abnormal albumin excretion with ensuing fall in blood pressure was rapidly and almost completely reversible in all but one patient during conventional treatment and the increased beta 2-microglobulin excretion was totally reversible in all but one patient. Both albumin and beta 2-microglobulin excretion rate were positively correlated to arterial pressures in all patients. Thus glomerular and to some extent tubular protein handling were both affected in untreated patients, but rapidly reversible during initial antihypertensive treatment. The data indicate that the beta 2-microglobulin hyperexcretion is secondary to enhanced filtration of plasma protein saturating the tubular reabsorption capacity, while the hyperexcretion of albumin is mainly due to the increased filtration pressure per se, though other factors may be partly responsible.

Exercise-induced proteinuria in children and adolescents with type 1 (insulin dependent) diabetes.

The urinary excretion excretion of albumin and Beta2-microglobulin was measured by radioimmunoassay in 64 children and adolescents with Type 1 (insulin dependent) diabetes and in 68 non-diabetic subjects aged from 9 to 19 years. At rest the albumin excretion of te diabetic subjects did not differ from that of te non-diabetic children and adolescents but during exercise the albumin excretion was significantly higher in children and adolescents with Type 1 diabetes (p less than 0.02). the excretion rate of Beta2-microglobulin in diabetic subjects did not differ from that of the healthy subjects. Both at rest and during exercise the albumin excretion rate was highest in those diabetics with poorest metabolic control of their disease.

The influence of glucose-induced hyperinsulinaemia on renal glomerular function and circulating catecholamines in normal man.

The circulatory, renal, and hormonal responses to physiological elevation of plasma insulin induced with oral glucose have been studied in seven healthy subjects. glomerular filtration rate, urinary excretion rates of albumin and Beta2-microglobulin, haematocrit, pulse rate, blood pressure and plasma catecholamine concentrations have been measured. Physiological hyperinsulinaemia following glucose ingestion was associated with an increase in noradrenaline levels and brief tachycardia. No effect was noted on haematocrit, creatinine clearance, urinary albumin excretion, plasma adrenaline concentrations and arterial blood pressure. Urinary Beta2-microglobulin excretion rates fell shortly after the elevation of plasma insulin, probably indicating enhanced tubular reabsorption. Thus, glucose-induced physiological hyperinsulinaemia does not reduce glomerular filtration rate nor does it increase transglomerular passage of albumin, effects seen after the intravenous bolus injection of 6-8 U of insulin in diabetics.

Exercise-induced proteinuria in children and adolescents.

Urinary albumin and beta 2-microglobulin excretion rates were measured by radioimmunological methods in 60 children and adolescents at rest and during physical exercise. The geometric mean of the albumin excretion rate was 4.4 (microgram/min)/m2 at rest and rose to 7.9 (micrograms/min)/m2 during exercise (P less than 0.001), while the geometric mean of beta 2-microglobulin was 31.9 (ng/min)/m2 at rest and 26.2 (ng/min)/m2 during exercise. These results indicate that exercise-induced proteinuria is of a glomerular leaking type. The albumin excretion rate was not dependent on the age or sex of the subjects. The exercise-induced albuminuria correlated weakly but significantly with the maximal blood pressure (r = 0.27; P less than 0.05) and with the physical fitness of the subjects (r = 0.28; P less than 0.05).

The effect of glucagon infusion on kidney function in short-term insulin-dependent juvenile diabetics.

Kidney function was studied in nine, metabolically well controlled, short-term insulin-dependent male diabetics before and during glucagon infusion of 4 to 5 and 8 to 10 ng/kg/min. Glomerular filtration rate, effective renal plasma flow (steady-state infusion technique, with urinary collections, using 125I-iothalamate and 131I-iodohippurate), and urinary albumin and beta 2-microglobulin excretion rates were measured. The mean plasma glucagon concentration increased during infusion from 254 +/- 19 pg/ml to 440 +/- 31 pg/ml (low dose) and 730 +/- 52 pg/ml (high dose). Glomerular filtration rate increased in all subjects from 133 +/- 5 before the glucagon infusion to 141 +/- 4 with the low dose, and 148 +/- 7 ml/min/1.73 m2 with the high dose (p < 0.01). The increase in glomerular filtration rate correlated with the rise in plasma glucagon concentration (r = 0.67; p < 0.01). Renal plasma flow increased from 530 +/- 21 before the glucagon infusion to 555 +/- 20 with the low dose and 572 +/- 29 ml/min/1.73 m2 with the high dose (p < 0.01). Urinary beta 2-microglobulin excretion rate rose from 5.8 +/- 1.0 before infusion to 8.7 +/- 1.7 with the low dose, and 17.9 +/- 5.7 micrograms X 10(-2)/min with the high dose (p < 0.01). Urinary albumin excretion remained unchanged during the glucagon infusion. These results suggest that glucagon may contribute to the reversible elevation of glomerular filtration rate typically found in poorly regulated insulin-dependent diabetics, but not to the moderate elevation found in well controlled diabetics.

Kidney Function in Acromegaly

Creatinine clearance and daily urinary albumin and beta2-microglobulin excretion rates (radio-immunoassays) were measured several times in 14 patients with acromegaly. Eleven patients were treated with bromocriptine, 5 to 55 mg/day. The activity of the disease was assessed by measuring urinary growth hormone excretion (radio-immunoassay). In agreement with previous investigations we found the creatinine clearance elevated. However, no correlation was found between this variable and urinary growth hormone excretion. Urinary albumin and beta 2-microglobulin excretion rates were not significantly different from our previous results in 27 adults control subjects. There was no correlation between urinary growth hormone excretion and urinary albumin or beta 2-microglobulin excretion rates. Bromocriptine treatment reduced urinary growth hormone excretion from 220 to 91 ng/24 hours, p less than 0.01, but no significant alterations were induced in the above mentioned kidney function variables.

The effect of short-term glucagon infusion on kidney function in normal man

Kidney function was studied in six normal males before and during a 2 h glucagon (10 ng/kg/min) infusion. The following variables were determined during each 20 min clearance period; glomerular filtration rate (GFR), renal plasma-flow (RPF) , filtration fraction (FF), urinary albumin and beta2-microglobulin-excretion rates. Glucagon infusion resulted in a fourfold increase in plasma glucagon concentration. The infusion induced a significant increase in GFR (+9%), FF (+9%) and urinary beta2-microglobulin excretion rate (+32%), (p less than 0.01). RPF and urinary albumin excretion rates were not significantly changed. We suggest that glucagon may contribute to the reversible kidney function alterations typically found in poorly regulated juvenile diabetes, a state with relative or absolute hyperglucagonaemia.