Urinary Red Cell Size: Diagnostic Value and Determinants

Abstract

Urinary red blood cells (RBC) are usually small and morphologically abnormal in glomerular (GN) hematuria, and slightly enlarged and morphologically normal in nonglomerular (NG) hematuria. This study was performed to evaluate the diagnostic value of urinary red cell size and morphology and to investigate the mechanism of the alteration in cell size. In 34 consecutive patients with hematuria we examined the urinary RBC size distribution and mean corpuscular volume (MCV) by electronic sizing of suspensions of RBC in an isotonic medium and, in 28 cases, compared it with the presence of 50% or greater dysmorphia. In 15 consecutive cases, we correlated MCV values with urine chemistries. In two GN cases we recorded the urine MCV serially during a furosemide-induced diuresis. In vitro incubations of peripheral or urinary RBC in various electrolyte solutions prior to sizing were also performed. The MCVs were significantly lower in GN (p < 10∼⁶) and probable GN (p < 10–⁴) than NG hematuria. A cutoff of 72 fl completely separated GN and probable GN from NG cases. Fifty percent or more ‘dysmorphic’ RBC were seen in 12 of 13 GN, 3 of 4 probable GN but in no NG sediments. In patients with NG hematuria, the ratio of urinary to peripheral MCV tended to be greater than unity and correlated strongly with pH (r = -0.97; p < 0.002). The effect of pH was confirmed in vitro. Furosemide diuresis induced a partial correction of the microcytosis of GN RBC, which correlated with the changes in urine composition. Furosemide had no effect on GN cells in vitro. Incubation of venous RBC in saline ranging from 0.5 to 6% did not alter MCV. Saline of 0.45% or less caused partial to total hemolysis and the appearance of RBC fragments with extremely low ‘MCV values. We conclude that electronic RBC sizing is a highly accurate and objective method for differentiating GN from NG hematuria. Urinary pH is an important determinant of MCV for NG RBC. A hypothesis is proposed to explain the microcytosis of GN RBC.

Effect of Urine Chemistry on Red Cells

“…The model was more effective when the stresses were applied simultaneously than when applied sequentially, although the latter more closely simulates in vivo conditions. Their conclusion is in accord with our recent conclusion, based on studying urinary MCV dur ing a furosemide-induced diuresis, that both glomerular and tubular injuries to red cells are necessary to explain the full degree of microcytosis of glomerular hematuria [10].…”

“…We also believe that hemolysis of a subset of nonglom erular red cells, due to a combination of hypotonicity and acidity, probably accounts for the 'mixed' red cell size histogram patern that has been observed by us and others in nonglomerular hematuria [10][11][12][13]. It would be interest ing to reanalyze the hemolysis data of Turitzen et al [1] in light of the interaction between tonicity and pH.…”

“…The explanation is probably that red cells swell in acidic media [9]. We have found that urine pH is the most important determinant of the MCV of nonglomerular hematuria and it exerts a modest effect on the MCV of glomerular hematuria [10].…”

Dysmorphic erythrocytes and G1 cells as markers of glomerular hematuria

“…Studies using this criteria have reported sensitivities and specificities ranging from 52% to 100% and 98% to 100%, respectively [3,4,8,20,26].…”

“…These might not be identical in all patients with glomerulonephritis. Recent research on the mechanisms of erythrocyte dysmorphism suggests that mechanical damage caused by passage through the glomerular membrane [14,26,29], osmotic stress during the passage through the hypotonic renal tubular segment [26,30], urine pH [30,31], and ion concentration [32] might be important in determining the shape of the urinary red cell. Kohler et al [3] and Tomita et al [4] were unable to confirm the effect of urine pH and osmolality on red cell morphology.…”