Hiromichi Kumagai

Erythropoietin production in patients with chronic renal failure

Studies were performed to reexamine the response of erythropoietin (Epo) production to acute hypoxic stimuli in patients with end-stage renal disease (ESRD). In the absence of acute bleeding or hypoxia, the serum Epo level in ESRD was similar to that of normal subjects despite severe anemia. In 11 dialysis patients with acute bleeding, the decrease in the Hb level from 8.9 to 5.8 g/dL provoked a significant increase in serum Epo up to 52.2 times the normal value. The increase in serum Epo was associated with a significant increase in corrected reticulocyte. Systemic hypoxemia (PaO2 < 65 mm Hg) in 8 dialysis patients provoked a significant elevation in the serum Epo level up to 24.6 times the normal level. There was an inverse relationship between serum Epo and arterial PaO2 (r = -0.715). The serum Epo level in these patients declined to or near the normal value after recovery from acute hypoxic stress. These data suggest that the ability of the Epo production is well preserved in ESRD, indicating that acute hypoxic stimuli provoke a significant increase in serum Epo.

Blood Monocyte Count Is a Predictor of Total and Cardiovascular Mortality in Hemodialysis Patients

An increase in white blood cell (WBC) count is an independent predictor of mortality in hemodialysis (HD) patients. However, few studies have assessed the association of specific WBC subtypes with mortality. We prospectively studied the predictive value of WBC subtypes for total and cardiovascular death in 333 HD patients (age 63 ± 12 years; HD duration 129 ± 109 months) during a 40-month of follow-up. There was a significant and positive correlation between highly sensitive C-reactive protein and neutrophil (r = 0.28, p < 0.01) and monocyte (r = 0.20, p < 0.01) counts by a non-parametric Spearman rank analysis. Blood monocyte counts were significantly correlated inversely with ankle-brachial pressure index (r = –0.24, p < 0.01). Kaplan-Meier analysis revealed that basal neutrophil (>4,060/μl) and monocyte (>270/μl) counts in the highest tertile had a significantly lower survival rate compared to the middle and the lowest tertiles, respectively (p < 0.03). Cox hazards analysis after adjustment for other conventional risk factors revealed that monocyte counts of >270/μl became a determinant of total death compared with those of <180/μl (hazards ratio 1.98 [1.10–3.57], p = 0.02). In contrast, neutrophil and lymphocyte counts were not associated with mortality. Our findings suggest that an increased blood monocyte count is an independent predictor of long-term mortality in chronic HD patients.

Suppression of Proteinuria by Dipyridamole in Rats with Aminonucleoside Nephropathy

Nephrosis was induced by single injections of puromycin of aminonucleoside to rats which were divided into two groups; the experimental group receiving dipyridamole in addition to aminonucleoside and the control group receiving aminonucleoside alone. 24-hour urinary albumin increased in rats of both groups after aminonucleoside injections. However, the experimental rats excreted significantly less albumin than controls. On the contrary, there was no significant difference in urinary IgG between the two groups. The stainings of anionic sites of glomerular basement membrane using ruthenium red revealed the reduction of anionic charge in the glomerular basement membrane of both groups, but the decrease of anionic charge was suppressed in lamina rara interna of the experimental rats. Considering the role of charge barrier in the glomerular basement membrane, it is concluded that the maintenance of anionic charge in experimental rats is causally related to the suppressed excretion of albumin.