The excretion of carbonic anhydrase isozymes CAI and CAII in the urine of apparently healthy subjects and in patients with kidney disease

Abstract

Carbonic anhydrase isozymes CA I and CA II were assayed by a radio-immunosorbent technique in the plasma and urine of apparently healthy subjects and of patients with renal disease. The concentrations (mean +/- SD, n = 8) of CA I and CA II in the plasma of healthy subjects were 2.3 +/- 2.3 and 0.8 +/- 0.5 mg/l, respectively. The urinary excretion values were 3.8 +/- 2.0 and 3.5 +/- 1.9 micrograms/24 h, and the apparent renal clearances were 21 +/- 17 and 52 +/- 44 microliters/min, respectively, values that are similar to those of other low molecular weight proteins. CA I and CA II have mol. wt of 28,850 and 29,300, respectively, they are globular in shape and have a Stoke-Einstein radius of 25 A. They could, therefore, be expected to be filtered at the glomeruli and thereafter reabsorbed by the proximal tubules. CA II is also present in the cytoplasm of renal proximal and distal tubular cells. A study of the pattern of urinary excretion of CA I and CA II could permit detection of damage to renal tubular cells in two ways--either from defective reabsorption of filtered CA I and CA II by the proximal tubular cells, or from leakage of CA II from the proximal or distal tubules into the urine. Some patients with hypercalcuria and renal tubular acidosis showed increased excretion of these enzyme proteins and of beta 2-microglobulin (BMG) into the urine, but the prevalence was rather low (27%). Further studies of patients with more severely damaged kidneys are required.

Expression and immunolocalization of metallothioneins MT1, MT2 and MT3 in rat nephron

“…As suggested previously [16], the liberated MT1/2 in the tubule lumen may have a protective role by neutralizing ROS and RNS, and by binding toxic metals that may reach the tubule fluid by glomerular filtration or be released from the tubule cells. Also, these vesicles may be the source of various molecules for cell-to-cell communication (reviewed in [64]), CA II and other proteins (previously attributed to the glomerular filtration and "leakage" of the protein from the proximal and distal tubules [65]), and microvesicles and other membranous material in the urine of healthy people and of patients with kidney diseses [66].…”

Renal handling and plasma elimination kinetics of carbonic anhydrase isoenzymes I, II and III in the rat

“…An increased urinary excretion of CA I1 has been reported in patients exposed to cadmium and in patients with renal acidification defects. CA I1 in the urine can therefore be used as a marker for damage to proximal and distal tubules (Backman et al 1990).…”

“…The amounts of CA I, CA I1 and CA I11 that appear in the circulation are very small compared with the amounts of these isoenzymes in the tissues. It has been calculated that, at steady state, the rate of efflux of CA I and CA I1 into the circulation, expressed as a percentage of the total amounts released from the senescent red cells, could not be higher than 0.001% h-' (Backman et al 1990). Similarly the amount of CA 111 that leaks out into the circulation is only O.Olyo of the total amounts in the skeletal muscle, and thus considerably slower than the turnover rate, O.l-l.O% h-', for most muscle proteins (Schapira et al 1960, Askmark & Wistrand 1992.…”

Carbonic anhydrase II was detected in urine of a patient with osteosarcoma during high-dose methotrexate and leucovorin rescue therapy

“…The presence of CAI and CAII in human plasma has been known, and their excretions into the urine are higher in patients with kidney disease than apparently healthy subjects 8) . This, taken together with the two reports above, motivated us to study urinary proteins before and during high-dose MTX and leucovorin rescue therapy.…”