Philip W. Hall

Characterization of human β2-microglobulin by isoelectric focusing☆

b2-Microglobulin (B2M) isolated from the urine of normal subjects and patients with cadaveric renal transplantation, showed 2 homologues by isoelectric focusing, one with a pI 5.3, the other with a pI 5.7. These proteins show identical molecular weights by dextran gel filtration and sodium dodecyl sulfate acrylamide gel electrophoresis. The immunogenic reactivity demonstrates partial identity using antiserum to human B2M from 2 different sources.

Effects of Anoxia on Postarteriolar Pulmonary Vascular Resistance

Studies on an isolated pulmonary lobe, perfused in situ from a carotid artery under regulated arterial pressure, showed that changes in its ventilation from room air to nitrogen promptly causes a slight but definite increase in pulmonary vascular resistance which, from the nature of the experimental arrangements, must lie beyond the pulmonary arterioles.

Endemic Balkan Nephropathy

Endemic Balkan nephropathy (EBN) is a unique form of chronic interstitial renal disease which is endemic to isolated rural populations of Bulgaria, Romania, and Yugoslavia. The area is confined within a 200-mile radius of Belgrade. The involved villages lie along river valleys in multiple areas of Romania and Yugoslavia where flooding periodically occurs (Wolstenholme and Knight, 1967). The disease is clinically characterized by the insidious onset of a normocytic, normochromic anemia, azotemia, and persistent proteinuria usually of <1 g/24 hr. There is no increase in the incidence of hypertension in the involved populations and the disease slowly progresses to end-stage renal failure over a period of 5–10 years following the onset of azotemia. While there is no uniform agreement concerning the early pathologic changes, it is generally accepted to be a chronic interstitial disease as it appears in the uremic patient. There is marked tubular atrophy with focal areas of tubular regeneration, interstitial fibrosis, and minimal round cell infiltration. The tissue loss is predominently cortical and most marked in the cortex opposite the hilum (Radonic et al., 1966).

Renal Handling of Beta-2-Microglobulin in Renal Disorders; with Special Reference to Hepatorenal Syndrome

A study of serum beta 2-microglobulin and urinary beta 2-microglobulin in patients with liver and/or kidney disease was done to determine if such information is of diagnostic help. Serum concentrations and beta 2M/Cr clearance ratios are higher in patients with primary tubular disorders than in those with glomerular diseases, a finding unaltered by hepatic disease. These data suggest either an increased production or decreased tubular degradation of beta 2M, independent of the glomerular filtration rate (GFR), in primary tubular disorders. The marked increase in urinary beta 2-microglobulin that followed insertion of the peritoneal-jugular shunt is evidence that this procedure resulted in improvement of the GFR, in previously underperfused nephrons.

Amniotic fluid beta-2 microglobulin concentration—an index of gestational age

Abstract Beta-2 microglobulin concentrations were measured in amniotic fluid obtained from 20 women at various stages of gestation. The concentrations averaged 6.3 μg per milliliter (range 5 to 10) between the tenth and thirty-sixth weeks and 0.87 μg per milliliter (range 0.2 to 1.3) after 36 weeks. This rapid third-trimester decrease in amniotic fluid concentration suggests that a major fetal pathway for metabolism of this protein becomes functional late in the course of gestation. From what is known of beta-2 microglobulin metabolism, this most likely relates to renal tubular function and suggests that this test may have significance in determining fetal age.

Renal Metabolism of β2-Microglobulin

Abstract. β2‐microglobulin (β2M) is a protein of 11,800 daltons which occurs in the plasma of normal individuals at concentrations of approximately 2 μg/ml. It is presumed to be relatively freely filterable. More than 99% of the filtered β2M is taken up by an active reabsorptive mechanism and catabolized by the renal tubule. The data presented here demonstrate that renal extraction is only slightly diminished by complete ureteral obstruction. The renal extraction of β2M is greater than can be accounted for by filtration alone. These data indicate that some uptake of β2M occurs from the peritubular capillary circulation. The loading of animals with β2M is associated with a marked tubular proteinuria suggesting that this protein may play a part in inducing tubular injury.

Demonstration of β2-Microglobulin in the Kidney by Direct Immunofluorescent Staining

Abstract. Direct immunofluorescent staining with fluorescein isothiocyanate conjugated goat anti‐human β2‐microglobulin (β2M) was used to determine the localization of β2M in kidney tissue, obtained by biopsies or nephrectomies for various renal diseases. β2M was found in the renal tubular epithelial cell cytoplasm and occasionally in the tubular basement membranes in 48 out of 79 pathologic specimens tested, but not in 3 normals. β2M was seen in the tubular cells in all cases of primary tubulointerstitial disease and in all cases with secondary tubular damage associated with glomerular disease or systemic disease. This supports the concept that β2M is metabolized in proximal tubular epithelial cells, and its deposition indicates impairment of tubular handling.

Fetal renal tubular function during late pregnancy and diabetes mellitus

The effect, if any, of diabetes mellitus on the fetal renal tubule has not been previously studied. The concentration of beta2 microglobulin in amniotic fluid is a marker of fetal renal tubular function and normally decreases with advancing gestation, implying increasing tubular function. This relationship was found to be disrupted in 12 diabetic pregnancies, suggesting that the fetal renal tubular cell may represent an example of altered fetal functional maturation occurring during diabetic pregnancy.

Renal Protein Metabolism in Obstructive Uropathy

Measurements of serum beta 2 microglobulin and creatinine concentrations were determined in 18 patients with lower urinary tract obstruction. Nine patients were azotemic on admission to the hospital. In 3 of these patients who had normal pre-treatment serum levels of beta 2 microglobulin, the correction of obstruction was followed by return of normal renal function. The remaining 6 patients with elevated serum beta 2 microglobulin concentrations on hospitalization, showed no significant improvement in renal function parameters in the post-obstructive period. These data suggest that determination of serum beta 2 microglobulin concentrations is helpful in predicting the return of renal function in azotemic patients with obstructive uropathy.