Jinn-Yuh Guh

Impact of Decreased Serum Transaminase Levels on the Evaluation of Viral Hepatitis in Hemodialysis Patients

The value of serum transaminases (ST) in evaluating hepatitis B (HBV) and C (HCV) infection was studied in 217 hemodialysis (HD) patients and 804 normal controls. Mean serum aspartate aminotransferase (AST) was 22.3 (22.0-22.7) and 22.6 (21.6-23.6) IU/l or 0.371 (0.366-0.378) and 0.376 (0.36-0.393) mu kat/l in controls and HD patients, respectively (nonsignificant), while mean serum alanine aminotransferase (ALT) was 20.3 (19.9-20.7) and 16.3 (15.3-17.3) IU/l or 0.338 (0.331-0.345) and 0.271 (0.255-0.288) mu kat/l in these two groups (p < 0.001). However, both AST and ALT became significantly depressed in HD patients after adjusting for age, gender, HBV surface antigen (HBsAg) and anti-HCV. The usual practice of regarding AST and ALT as being abnormal in evaluating viral hepatitis when they exceeded the upper reference range (40 and 46 IU/l or 0.666 and 0.766 mu kat/l in our laboratory) was then critically assessed by the receiver operating characteristic (ROC) curve. ROC analysis showed that ST was useless in detecting HBsAg, while the best cutoff point for detecting the presence of anti-HCV was 18 IU/l (0.3 mu kat/l) for AST and 16 IU/l (0.266 mu kat/l) for ALT in HD patients, respectively. These are considerably lower than the conventional criteria for an abnormal ST. We conclude that ST are decreased in HD patients and that the cutoff value of ST for detecting HCV should be set at lower levels to enhance their diagnostic yield.

Epidermal Growth Factor in Renal Hypertrophy in Streptozotocin-Diabetic Rats

Epidermal growth factor (EGF) concentrations in the plasma, kidneys and urine of 31 streptozotocin-diabetic rats and 21 insulin-treated diabetic rats were measured to study the role of EGF in initiating renal hypertrophy in the diabetic rats. Renal hypertrophy occurred from day 7 in the diabetic rats, but not in the insulin-treated rats. Renal EGF was not different between the diabetic and control rats, while that in the insulin-treated rats was significantly less than in the diabetic rats. There were no significant changes in plasma EGF in any of the rats. Urine EGF was 119 +/- 7.9 ng/day at day 7 in the control rats but it was significantly increased from day 2 in the diabetic rats (320 +/- 52.9 ng/day at day 2 and 298 +/- 18.4 ng/day at day 7), while in the insulin-treated rats it was significantly less than that in the diabetic rats (134 +/- 8.34 ng/day at day 2 and 220 +/- 15.2 ng/day at day 7). Since the kidney is the main source of urine EGF and EGF has been shown to induce renal growth both in vitro and in vivo, we conclude that EGF may have initiated renal hypertrophy in diabetic rats.

Differential Effects of Circulating IgA Isolated from Patients with IgA Nephropathy on Superoxide and Fibronectin Production of Mesangial Cells

Background: IgA nephropathy (IgAN) is characterized by predominant deposition of IgA in the glomerular mesangium. Serum IgA is often elevated in patients with IgAN, and it has been postulated that it is responsible for the mesangial lesions. However, the direct effect of circulating IgA on mesangial cells is not clear. Methods: We investigated the effects of sera and IgA which were isolated from patients with IgAN on thymidine uptake, superoxide and fibronectin production and fibronectin mRNA expression of cultured rat mesangial cells, and we compared the findings to the effects of IgA isolated from patients with non-IgA mesangial proliferative glomerulonephritis (MsPGN) and normal controls. IgA was isolated with affinity chromatography using cyanogen bromide activated Sepharose 4B coupled to sheep antihuman IgA antiserum. Results: Our results demonstrated that both sera and IgA from patients with IgAN dose-dependently increased mitogenesis of mesangial cells as measured by 3H-labeled thymidine uptake. The thymidine uptake by sera and IgA isolated from patients with IgAN was significantly higher than that of sera and IgA isolated from patients with MsPGN and normal controls. Sera and IgA from patients with IgAN significantly enhanced superoxide and fibronectin production and fibronectin mRNA expression of mesangial cells. The superoxide and fibronectin production was also significantly higher as compared with patients with MsPGN and normal controls. Conclusions: Our results indicate that circulating IgA isolated from patients with IgAN is different from that of patients with MsPGN and normal controls and may potentially induce oxidative injury and production of extracellular matrix of glomerular mesangial cells in IgAN.

Significance of salivary epidermal growth factor in peptic ulcer disease in hemodialysis patients.

Background/Aims: Hemodialysis (HD) patients are prone to developing peptic ulcers. However, of all the risk factors associated with peptic ulcers, none have been shown to be more prevalent in HD patients than in the general population. However, salivary epidermal growth factor (EGF) may play a role in peptic ulcer diseases. Methods: Salivary EGF levels and bioactivities were assayed in 47 maintenance HD patients and 30 normal controls, and the molecular weights of EGF were assessed using high-performance liquid chromatography (HPLC). Results: Salivary EGF levels were not different between both groups of subjects (4.2 ± 0.34 vs. 5 ± 0.54 ng/mg protein, NS), and HPLC revealed that salivary EGF in both groups had similar molecular weights. However, salivary EGF bioactivity was significantly depressed in the HD patients as compared to the normal controls (0.59 ± 0.08 vs. 1.55 ± 0.15 ng/mg protein, p < 0.01). Stepwise multiple regression showed that the low salivary EGF levels were associated with female gender (p < 0.05), while low salivary EGF bioactivity was associated with HD per se (p < 0.05). In the 22 HD patients who underwent gastric endoscopy, salivary EGF bioactivity was significantly lower in those with peptic ulcers than in those without (0.38 ± 0.08 vs. 0.69 ± 0.08 ng/mg protein, p < 0.05). Conclusion: Decreased salivary EGF bioactivity may contribute to peptic ulcer disease among maintenance HD patients.

Differential Effects of FMLP-Activated Neutrophils from Patients with IgA Nephropathy Enhanced Endothelin 1 Production of Glomerular Mesangial Cells

Background: Neutrophil infiltration in the glomeruli is common in patients with IgA nephropathy (IgAN). The pathogenetic roles of the infiltrated neutrophils and their relationship with glomerular mesangial cells, however, are not clear. Methods: We examined the effects of coculture with N-formyl-methionyl-leucyl-phenylalanine (FMLP) activated neutrophils on the viability, endothelin 1 (ET-1) production, and ET-1 mRNA expression of rat glomerular mesangial cells. Neutrophils were isolated from 15 IgAN patients, from 13 patients with non-IgA mesangial proliferative glomerulonephritis (MsPGN), and from 10 normal controls. Results: The ET-1 production by mesangial cells was significantly higher after stimulation with FMLP-activated neutrophils from IgAN patients than that of MsPGN patients and normal controls, and this effect was significantly abolished by pretreating mesangial cells with superoxide dismutase and partly abolished by catalase. The ET-I mRNA expression of mesangial cells showed a parallel increase with ET-1 protein. The trypan blue exclusion test showed significant mesangial cell death after stimulation with FMLP-activated neutrophils as compared with quiescent neutrophils, and the cell death was also prevented by superoxide dismutase but not catalase. The FMLP-activated neutrophils from IgAN patients produced more superoxide than those of MsPGN patients and normal controls. Conclusion: The FMLP-activated neutrophils from patients with IgAN have differential effects in enhancing the cell death and the ET-1 production of glomerular mesangial cells through the release of superoxide.

Lack of Influence of Recombinant Human Erythropoietin on Parathyroid Function in Hemodialysis Patients with Secondary Hyperparathyroidism

The effects of recombinant human erythropoietin (rHuEPO) treatment on parathyroid function in patients on maintenance hemodialysis (HD) with secondary hyperparathyroidism (HPT) is poorly understood. We compared the levels of serum intact parathyroid hormone (PTH) and the suppressibility of PTH by intravenous calcium infusion before and after 12 weeks of rHuEPO treatment in 8 HD patients with secondary HPT. The suppressibility of PTH by calcium infusion in HD patients was also compared with that of normal subjects. After rHuEPO treatment, in HD patients hematocrit and hemoglobin levels increased significantly from 20.1 +/- 1.3% and 6.65 +/- 0.46 g/dl to 28.7 +/- 1.0% and 9.68 +/- 0.39 g/dl, respectively. The serum intact PTH levels did not change significantly (541.9 +/- 65.3 pg/ml before versus 572.9 +/- 75.3 pg/ml after rHuEPO treatment), nor did serum ionized calcium, phosphate, magnesium, aluminum, alkaline phosphatase, and 1.25(OH)2D levels. Calcium infusion significantly increased serum ionized calcium and suppressed serum PTH levels. However, the increment in serum calcium levels and the percent decrement of serum PTH showed no significant differences before and after rHuEPO treatment in HD patients. Elevations in serum calcium levels during calcium infusions were not significantly different between normal subjects and HD patients. However, the percent maximal decrement in serum PTH level was less in HD patients both before and after rHuEPO treatment than in normal subjects (-75.4 +/- 3.9 and -76.4 +/- 4.1% versus -91.4 +/- 1.4%). We conclude that rHuEPO treatment has no influence on parathyroid function in maintenance HD patients with secondary HPT. In addition, PTH secretion is less suppressed by calcium infusion in the same group of patients.

Urinary Epidermal Growth Factor Excretion in Glomerulonephritic Patients

Jinn-Yuh Guh, MD, Department of Internal Medicine, Kaohsiung Medical College, 100 Shi-Chuan 1st Rd., Kaohsiung (Taiwan) Dear Sir, Epidermal growth factor (EGF) is likely synthesized by the thick ascending Henle’s loop and distal tubules in the mouse kidneys [1], whereas EGF immunoreactivity was found in proximal tubules [2] and renal pre-pro-EGF mRNA expression was the most abundant among many tissues in humans [3]. The source of human urinary EGF was shown to be the kidneys per se rather than glomerular filtration [4]. Urinary EGF excretion decreased in patients with end-stage renal disease [5], acute renal failure [6] and diabetic nephropathy [7] which had been proposed to be an early marker of tubular dysfunction [7]. Recently, Mat-tilla et al. [8] showed that urinary EGF excretion decreased in patients with glomerulone-phritis (GN) who had impaired renal function. But they had only 11 patients whose renal pathology was not described. Furthermore, urinary EGF excretion in GN patients with normal renal function was not shown. Since EGF is mitogenic for many renal cells in vitro [9] and also induces renal growth in vivo [10], it may have a role in proliferative GN. In this regard, EGF immunoreactivity was recently found in human glomerulus, although there was no difference between normal and GN kidneys [11]. In contrast, Goodyer et al. [12] found that urinary EGF-like material increased in pediatric patients with acute He-noch-Schönlein purpura nephritis, although this material was shown to be more like transforming growth factor-α. Thus, urinary EGF excretion was measured in 25 adult GN patients (aged 38 ± 2.6 SEM years, 15 male, 10 female) who received renal biopsy for various reasons. Twenty healthy adults (aged 44 ± 3.7 years, 11 male, 9 female) served as the normal controls. A random morning urine was collected for the measurements of urinary EGF (by a human EGF reagent pack for radioimmu-noassay, Amersham, UK) and creatinine which was kept at -20 °C until assay. The renal biopsy showed: membranous nephropathy (n = 3), membranoproliferative GN (n = l), minimal change disease (n = 3), IgA nephropathy (n = 5), diffuse proliferative lupus nephritis (n = 2), focal glomeruloscle-rosis (n = 5), mesangial proliferative GN (n = 2), crescentic GN (n = 2) and chronic sclerosing GN (n = 2). Urinary EGF was 41.9 ± 5.9 ng/mg creatinine in the controls. It was marginally decreased to 29 ± 5.4 ng/mg creatinine in the patients with normal renal function (n = 19, NS) and