Intraperitoneal bladder rupture is a rare cause of acute abdomen with bloody ascites. We report herein the case of a patient who had alcoholic liver cirrhosis and multiple liver nodules, and experienced acute bloody ascites and oliguric acute renal failure in association with intraperitoneal bladder rupture. A 33-year-old male suffered from acute abdominal pain and oliguria following consumption of a large amount of alcohol and after blunt abdominal trauma. He was also found to have acute renal failure and newly onset bloody ascites that rapidly subsided following transurethral catheter drainage. Computed tomography cystography revealed intraperitoneal extravasation of contrast from the dome of the bladder, suggestive of intraperitoneal bladder rupture. The patient received surgical repair and was discharged with full recovery. This case shows that it is important for physicians to be aware of the possibility of intraperitoneal bladder rupture after alcohol consumption accompanied with abdominal blunt trauma. In particular, it has diagnostic complications for underlying liver tumors.

Aristolochic acid (AA) may reduce glomerular or proximal tubular function, or both. We report a married couple taking AA-containing herbal drugs. The man developed Fanconi's syndrome (FS) whereas his wife reached end-stage renal failure (ESRF). He was a 36-year-old alcoholic cirrhotic patient who had taken the Chinese herbal drugs for 6 years, presenting with muscle weakness and laboratory findings of FS; the renal pathological findings were compatible with the diagnosis of aristolochic acid nephropathy (AAN). His 38-year-old wife, who took a lower cumulative amount of the same herbal drug for a shorter duration, developed advanced renal failure and severe anemia with pathological findings of extensive tubular atrophy, interstitial fibrosis but spared glomeruli. AA-I was detected in one of the herbal drugs. The wife has been on hemodialysis for 7 years, but the husband is still at the stage of slowly progressive chronic renal failure and persistent FS. None of their 5 children ever took the herbal drug, and none had renal problems during follow-up. It is important to trace the history of herbal drug intake in all the family members because of the possibility of sharing of drugs within a family. In addition to the effect of cumulative doses of AAs and the potentially higher susceptibility of females to AAN, the roles of liver cirrhosis and related vasodilators in the protection of the renal interstitium from fibrosis are questions that warrant further study.

OBJECTIVE:Parathyroid cells synthesize and release endothelin-1 (ET-1). ET-1 displays an in vitro inhibitory effect on basal parathyroid hormone (PTH) secretion and also counteracts PTH hypersecretion stimulated by low calcium. Such effects are further demonstrated in vivo, independent of the changes in calcitonin. We propose that ET-1 may regulate the pathogenesis of uremic hyperparathyroidism. However, this was not directly demonstrated in human parathyroid glands.DESIGN:Hyperplastic parathyroid glands are obtained from the surgical operation for uremic hyperparathyroidism. Cells are isolated by enzyme digestion and treated with ET-1, and are assessed for PTH mRNA expression. PTH in the plasma and the medium is measured by a newly developed method to detect the whole PTH (1-84).PATIENTS:Uremic patients with severe secondary hyperparathyroidism and ultrasonography-proved hypertrophy of parathyroid glands received elective surgical approaches under general anesthesia. The resected glands were immediately taken to the laboratory for fresh isolation.MEASUREMENTS:Following ET-1 treatment, PTH mRNA expression is evaluated by RT-PCR method. ET-1 is detected with radioimmunoassay kit and PTH is measured by a new commercially available Duo PTH kit.RESULTS:ET-1 exhibited a dose-dependent inhibitory effect (from 10(-12) - 10(-7) M) on PTH mRNA expression of parathyroid cells, either in the basal or in the low-calcium-stimulated states. Release of PTH into the medium is also gradually inhibited by the increase in ET-1 concentrations.CONCLUSIONS:Our results demonstrate that ET-1 attenuates PTH mRNA expression in freshly isolated human parathyroid cells, and PTH release is also decreased. This result is consistent with our previously reported in vitro and in vivo experiments.

AIMSWe previously reported 2 hemodialysis (HD) patients with recurrent infections and selective immunoglobulin A deficiency (IgAD). We further demonstrated that serum IgA levels were lower and the prevalence of IgAD was higher in uremic patients. The exact mechanisms of IgAD in uremic patients largely remained unclear. In some patients, it was caused by anti-IgA antibody neutralization and subsequent destruction. We performed the present study to survey if there is any defect in IgA production.MATERIALS AND METHODS288 patients were initially included for examination of serum immunoglobulins. 16 normal persons, 16 dialysis patients without IgAD, and 12 dialysis patients with IgAD were enrolled after the initial examination. Blood was drawn into heparinized tubes. WBC counts and lymphocyte percentage were examined by a CBC counter. Lymphocytes were separated by the Ficoll-Paque method. Flow cytometry was utilized to isolate the B cell and IgA-secreting B cell after staining with CD 19 phycoerythrin and FITC-conjugated rabbit anti-human IgA antibody.RESULTSThere is no significant difference between WBC counts or total lymphocyte counts of these 3 groups. However, we found a lower percentage of total lymphocyte counts in dialysis patients, either with or without IgAD. The total B cell numbers were lower in dialysis patients with IgAD. In addition, there were fewer IgA-secreting B cells in dialysis patients with IgAD.CONCLUSIONDecreased B cell and IgA-secreting B cell counts are seen in uremic patients with IgAD. This, in turn, indicates that there might be a defect of IgA production in some patients, rather than IgA destruction by anti-IgA antibodies as seen in some other patients. Further study is needed to investigate the mechanisms of decreased B cells and IgA-secreting B cells.

Integrins attach cells to extracellular matrix (ECM) and mediate signals from ECM to cells or from cells to ECM. They regulate cell functions, including adhesion, migration, cell cycle regulation, and differentiation. Podocytes may detach from the glomerular basement membrane (GBM) and be excreted in the urine, and proteinuria is found in patients with primary focal segmental glomerulosclerosis (FSGS); both may be associated with loss of alpha 3 beta 1 integrins. In this study, we have examined the podocyte number in patients with primary FSGS and normal controls, and the alpha 3- and beta 1-integrin subunits expression of podocytes in patients with primary FSGS and chronic puromycin aminonucleoside (PAN)-treated rats by the morphometric, immunoperoxidase histochemical, and immunoelectron microscopic examination. We also measured their expression serially in rats that received repeated PAN injection. The results showed that the podocyte number was significantly decreased in patients with primary FSGS than in normal control (P < 0.05). The immunostaining score showed that both alpha 3- and beta 1 integrin subunits on podocytes in patients with primary FSGS were significantly lower than in normal controls (both P < 0.01). The number of immuno-gold particles of alpha 3- and beta 1-integrins at the effaced foot process area of patients with primary FSGS were also significantly decreased than that of normal controls (both P < 0.05). The immunostaining score of both alpha 3- and beta 1-integrin subunits was negatively correlated with the degree of glomerular sclerosing score and the amount of daily protein loss, and they were positively correlated with the number of podocytes. Chronic 12-week PAN-treated rats showed similar findings with decreased immunostaining expression and immuno-gold particles of alpha 3-integrin on podocytes than in normal control (both P < 0.05). The chronic PAN-treated rats also showed a trend toward gradually decreased immunostaining expression of a3-integrin subunit on podocyte during the progress from normal to FSGS state. These studies indicate that podocyte expression of alpha 3- and beta 1-integrin subunits is significantly reduced in humans with primary FSGS and chronic PAN-treated rats, before the morphological changes of FSGS are observed. The decreased podocyte expression of alpha 3 beta 1 integrins is closely related with podocyte depletion, glomerular sclerosis, and daily protein loss in patients with primary FSGS.

Results from animal experiments have suggested that reactive oxygen species (ROS) play an important role in tissue damage associated with diabetes. To determine whether ROS are involved in patients with diabetic nephropathy, we measured the plasma and urinary levels of malondialdehyde (MDA), an important marker of lipid peroxidation, and assessed the immunoreactivity of MDA and superoxide dismutase (SOD) in glomeruli of patients and experimental rats with diabetic nephropathy. Both plasma and urinary MDA levels were significantly higher in patients with diabetic glomerulosclerosis (DGS) than those of diabetic patients without proteinuria, proteinuric patients without diabetes, and normal controls. In DGS patients, the plasma MDA was significantly correlated with urinary MDA (p<0.05). The urinary MDA, but not plasma MDA, was significantly correlated with the degree of glomerulosclerosis and the index of mesangial expansion (both p<0.01) in DGS patients. The immunostaining score of glomerular MDA and SOD were also significantly higher in DGS patients than in control kidneys. In rats with diabetes for more than one month, the glomerular immunostaining for both MDA and SOD were also significantly higher than in controls rats, and both were increased with the progression of diabetes. Our results suggest that oxidative stress is involved in the pathogenesis and the progression of DGS.

Adrenomedullin (AM) immunostaining and gene expression have seldom been measured in human kidneys. Because previous studies have shown that AM exerts antiproliferative effects on rat mesangial cells in vitro and that urine AM levels are decreased in patients with chronic glomerulonephritis, we measured glomerular AM and its gene expression in patients with primary IgA nephropathy (IgAN). Glomerular AM was measured by immunohistochemical staining, and glomerular AM mRNA was measured by in situ hybridization. Plasma and urine AM were measured by radioimmunoassay. The results showed that both the intensity of immunostaining for glomerular AM and the glomerular expression of AM mRNA were significantly decreased in IgAN patients compared with normal controls (both P < .05). Similar results were not observed in patients with non-IgA MsPGN. Glomerular AM immunostaining and glomerular AM mRNA expression were significantly correlated ( P < .001), and both were negatively correlated with the number of glomerular cells ( P < .05 and < .01, respectively). Both glomerular AM immunostaining and glomerular AM mRNA expression were correlated with urine AM levels (both P < .001), but not with plasma AM levels. The urine AM level was significantly lower in IgAN patients than in normal controls ( P < .01), whereas the plasma level was not different between the 2 groups. Our findings indicate that glomerular production of AM was decreased in patients with IgA nephropathy and that this lack of glomerular AM may be related to the pathogenesis of this mesangial disease.

BACKGROUND:Evidence suggests an increase in oxidative stress in patients with chronic kidney disease, as glomerulosclerosis is the prerequisite for chronic kidney disease; whether the oxidative stress already exists early on is not known.MATERIALS AND METHODS:In this study we measured the plasma and urinary levels of malondialdehyde (MDA), the end product of lipid peroxidation, and assessed the immunoreactivity of MDA and superoxide dismutase (SOD) in glomeruli of patients and rats with primary focal segmental glomerulosclerosis (FSGS), and compared our findings with those of minimal change disease (MCD) and normal controls (NC).RESULTS:Our results showed that plasma MDA level was significantly increased in patients with FSGS compared with both patients with MCD and normal controls. The urinary MDA level was also significantly increased and was significantly correlated with plasma MDA level in patients with FSGS. The immunostaining for glomerular MDA and SOD was significantly higher in the patients with FSGS than in either the patients with MCD or NC, and was also significantly higher in rats with puromycin aminonucleoside (PAN)-induced FSGS than in rats with MCD. Glomerular MDA level was significantly correlated with the degree of glomerulosclerosis in the patients with FSGS.CONCLUSIONS:Our data suggest that oxidative stress occurs early on before the onset of renal failure, and may play an important role in the pathogenesis of glomerulosclerosis.

Patients with diabetic nephropathy are known to be associated with many lipoprotein abnormalities, including higher plasma levels of very low-density lipoprotein, low-density lipoprotein and triglycerides, and lower levels of high-density lipoprotein. Many studies have reported that lipids may induce both glomerular and tubulointerstitial injury through mediators such as cytokines, reactive oxygen species, chemokines, and through hemodynamic changes. Clinical studies in patients with diabetic nephropathy showed that lipid control can be associated with an additional effect of reduction in proteinuria. Experimental studies demonstrated that lipid-lowering agents exerted a certain degree of renoprotection, through both indirect effects from lipid lowering and a direct effect on cell protection. Therefore, lipid control appears to be important in the prevention and treatment of diabetic nephropathy. Diabetic nephropathy has become the leading cause of end-stage renal failure in many countries, including Taiwan. One of the major risk factors for the development and progression of diabetic nephropathy is dyslipidemia. In this paper we will review the role of lipid in mediating renal injury and the beneficial effects of lipid control in diabetic nephropathy.

AIMSRecent progress in PTH assay has revealed that the intact PTH assay kit in current use does not differentiate between the truncated 7-84 PTH molecule and the 1-84 PTH molecule. In our series, we examined the effectiveness of a new PTH assay as a noninvasive method of evaluating severity of uremic hyperparathyroidism.METHODS AND MATERIALSTwo hundred and seventy hemodialysis (HD) patients recruited from three HD centers were included and divided into subgroups according to the conventional iPTH assay results. Pre-dialysis blood samples were collected and subjected to two different PTH assays: "intact" PTH assay (iPTH) and "whole" PTH (wPTH) assay. Two biochemical markers of bone remodeling were also examined.RESULTSIn all cases, PTH levels determined by the wPTH assay were in the average 32.3% lower than those determined by the iPTH assay. The difference of the results of the two PTH assay methods, which indicated the portion of 7-84 PTH fragments of the total PTH molecules measured with the iPTH assay, was gradually increased while the severity of uremic hyperparathyroidism increased. Biochemical markers of bone formation/resorption showed a similar change.CONCLUSIONThe portion of the 7-84 PTH fragments and markers of increased bone turnover increased in proportion to the severity of uremic hyperparathyroidism. This finding disproves the hypothetical role of 7-84 PTH fragments alone as the noninvasive marker of low-turnover bone disease in HD patients.

Elevated plasma homocysteine, arterial stiffness, and increased pulse pressure (PP) are independently associated with higher cardiovascular risk in patients with end-stage renal disease. The aim of this study is to investigate the influence of plasma homocysteine on arterial stiffness and PP in hemodialysis (HD) patients. One hundred and nine HD patients were stratified into three groups by plasma homocysteine levels: low (11.2-20.8 micromol/L), middle (21.2-25.1 micromol/L), and high tertiles of plasma homocysteine (Hcy) group (25.2-43.9 micromol/L). Using a computerized oscillometry, we measured the arterial stiffness index (ASI) and blood pressure (BP) hemodynamic parameters in the brachial artery. The high Hcy group exhibited a higher ASI (110.4+/-129.5 versus 46.2+/-17.5, mean+/-S.E., P<0.01), PP (59.7+/-23.1 versus 43.3+/-16.3 mmHg, P<0.01), and age (57.8+/-14.1 versus 49.9+/-12.7 years, P<0.05) compared with the low Hcy group. Plasma homocysteine was significantly correlated with ASI (r=0.25, P<0.001), PP (r=0.33, P<0.001), systolic BP (r=0.31, P<0.001), and age (r=0.24, P<0.05). Serum ferritin was significantly correlated with ASI (r=0.24, P<0.05) and PP (r=0.23, P<0.05). ASI was also correlated with PP (r=0.64, P<0.001). Multiple regression analyses showed that both plasma homocysteine and serum ferritin had significant associations with ASI (beta=4.246, P=0.007 and beta=0.024, P=0.006, respectively), and with PP (beta=1.089, P=0.002 and beta=0.005, P=0.005, respectively) independent of other classic risk factors for atherosclerosis. In conclusion, plasma homocysteine, along with serum ferritin, may act as an important predictor for arterial stiffness and PP in HD patients.

The expression of inducible nitric oxide synthase (iNOS) expression and release of nitric oxide (NO) from macrophages are markedly increased in granulomatous infections. Activation of macrophages 1α-hydroxylase results in an increase of 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3]. However, the significance of this increased production is not completely understood. In this study, we analyzed 1,25(OH)2D3 and NO production in patients with tuberculosis infection and hypercalcemia and used lipopolysaccharide (LPS) to stimulate RAW 264.7 cells in an attempt to assess iNOS expression and gaseous NO production regulated by 1,25(OH)2D3. Peroxynitrite (OONO−) production and lactate dehydrogenase activity were also examined. Without additional stimulation, peripheral-blood mononuclear cells (PBMCs) from patients with tuberculosis converted more 25-hydroxyvitamin D3 to 1,25(OH)2D3 than did those from normal controls. These PBMCs released less NO than did those from control subjects, at baseline and in the stimulated state. We found that 1,25(OH)2D3 dose-dependently inhibited iNOS messenger RNA expression of the LPS-stimulated RAW 264.7 cells and also significantly reduced the gaseous NO release and OONO− production. Paralleling the 1,25(OH)2D3-induced inhibition of NO release were reductions in OONO− and LDH production. In conclusion, 1,25(OH)2D3 inhibited iNOS expression and reduced NO production by LPS-stimulated macrophages in the range of physiological doses. Inhibition of the NO surge was coupled with a reduction in OONO− and LDH production. Increased 1,25(OH)2D3 production and decreased release of NO from the PBMCs of patients with tuberculosis and hypercalcemia were also noted. We propose that 1,25(OH)2D3 production by macrophages may protect themselves against oxidative injuries caused by the NO burst. In the case of tuberculosis infection, increased 1,25(OH)2D3 synthesis may further contribute to the development of an unwanted phenomenon—hypercalcemia.

Objective We examined whether amino acid–based peritoneal dialysate that contains 85 mg/dL L-methionine affects homocysteine (Hcy) metabolism. Design The study enrolled 17 adult CAPD patients (11 men, 6 women) who had been receiving CAPD for at least 6 months and who had low serum albumin levels (<3.7 g/dL). Diet was not specifically changed. All of the study patients received daily 4-exchange CAPD treatment, and they used Nutrineal (Baxter Healthcare, Deerfield, IL, U.S.A.) as one of their daily exchanges (first or second exchange). Blood samples were collected every 2 weeks, and Hcy was measured. Results After use of Nutrineal, serum albumin was unchanged, but blood urea nitrogen (BUN) and total protein were increased. Before the study began, 1 patient had a very high Hcy level (256 μmol/L); his data were excluded from the analysis. In the remaining 16 patients, baseline Hcy was 24.4 ± 7.0 μmol/L. Levels of Hcy progressively increased with the use of Nutrineal: 28.1 ± 6.2 μmol/L in week 2, 28.4 ± 7.1 μmol/L in week 4, 29.1 ± 7.6 μmol/L in week 6, 29.3 ± 9.0 μmol/L in week 8, 27.5±9.7 μmol/L in week 10, and 30.3 ± 8.2 μmol/L in week 12. Conclusions Nutrineal might help to replenish daily protein loss, but it also increased formation of Hcy and, therefore, the potential risk of cardiovascular illness. Further studies will be needed to examine the effect of folic acid and vitamin B12 supplementation in the rescue of that Hcy increase, and also a possible correlation with methylenetetrahydrofolate reductase gene polymorphism.

Both reactive oxygen species (ROS) and endothelin-1 (ET-1) have been implicated in the pathophysiology of minimal change disease (MCD). The interrelationship between them, however, has not been documented in this disease. To determine whether ROS regulates ET-1 production in MCD, we examined the in vitro and in vivo effects of ROS donors and scavengers on the glomerular production of ET-1 by MCD rats that were induced by puromycin aminonucleoside. For in vitro study, the glomeruli were isolated from MCD and normal rats using a sieving method. The ET-1 was measured by radioimmunoassay and ET-1 mRNA expression was measured by Northern blot analysis. The results demonstrated that the basal production of ET-1 and superoxide were higher in MCD glomeruli than in normal glomeruli in vitro. There was a positive correlation between the production of ET-1 and superoxide in MCD but not in control glomeruli. The basal ET-1 production were markedly attenuate dby ROS scavengers including superoxide dismutase, catalase, dimethylsulfoxide and deferroxamine in MCD glomeruli, and the golmerular ET-1 mRNA expression was equally supperessed. Exogenous ROS generated by xanthine/xanthine oxidase significantly enhanced ET-1 generation by both MCD and normal glomeruli. The in vivo study demonstrated that when MCD rats were injected daily with superoxide dismutase or catalase after PAN injection, the basal production of ET-1 was markedly attenuated. These results indicate that endogenously or exogenously derived ROS can enhance ET-1 production by MCD rat glomeruli, and that ROS scavengers suppress ET-1 production both in vitro and in vivio, indicating the ROS mediate the glomerular production of ET-1 in MCD.

In the differential diagnosis, protein-losing enteropathy (PLE) is a rarely considered explanation of edema. Three such cases are reported in this article. Clinical presentations varied from severe generalized anasarca and respiratory distress to mild pitting edema on the pretibial surface. Hypoalbuminemia (< 35 g/l) was another common finding in addition to edema. The patients were carefully examined to exclude other causes of hypoalbuminemia. Two patients experienced diarrhea. Endoscopic studies (plus biopsies) for any mucosal lesion in the stomach and colon were also performed. PLE was confirmed by the positive radionuclide scanning results after infusing intravenous 99mTc human serum albumin (USA). Investigation for the etiologies showed intestinal lymphangiectasia in 1 patient, Menetrier's disease in another, and no recognizable cause in the third. The severe anasarca of the patient with intestinal lymphangiectasia didn't respond to corticosteroids and albumin supplement plus large doses of furosemide. She died of overwhelming pulmonary infection despite the use of powerful antibiotics (ceftriaxone and amikacin). We planned to treat the Menetrier's disease patient with somatostatin to decrease the exocrine activities of the intestinal tract. The patient with presumable idiopathic PLE had the least severe edema and was not treated with any medication. In addition to the above patients, another 3 patients with hypoalbuminemia and edema were also noted to have positive HSA scan results. However, 2 of these patients had systemic lupus erythromatosus and the third pulmonary tuberculosis and biopsy-proven membranous nephropathy. Treatment of their underlying diseases showed satisfactory remission of edema.

Clinical presentation of unilateral renal cystic disease (URCD) is characterized by multiple simple cysts in only 1 kidney. Involvement of other intra-abdominal organs is not found. Renal function is usually preserved despite the existence of multiple cysts. No genetic background can be delineated up to the present. We present 1 patient with URCD, who was evaluated for his right flank pain. Urinalysis and biochemical tests showed normal renal function (BUN 5.03 mmol/l, creatinine 110.5 micromol/l). Ultrasonographic examination was done and it revealed 2 right renal stones. Furthermore, multiple renal cysts over the juxta-medullary area were noted. His left kidney was intact. Computed tomography (CT) of both kidneys confirmed this finding. 99mTc-DTPA renal scan showed that the glomerular filtration rate of both kidneys was not significantly different. There was no family history of renal diseases. His parents, grandparents and siblings were examined for possible kidney lesions, but none of them had any renal cystic lesion. This patient was followed for only a relatively short period of time (3 years) and his renal function did not deteriorate. Follow-up image studies with sonography and CT were not different from the previous ones.

SUMMARY: Acyclovir is an effective antiviral agent in the treatment of herpes simplex and varicella‐zoster viral infections. the best known side‐effects of this drug are significant nephrotoxicity and neurotoxicity. We report on a diabetic patient with acute retinal necrosis who developed non‐oliguric acute renal failure during the administration of high doses of intravenous acyclovir (500 mg/m 2 intravenous infusion every 8h). No obvious uremic symptoms or signs were noted. No obvious haematuria, proteinuria or crystalluria were noted in the urine. After discontinuing the acyclovir administration, renal function partially recovered. In this paper, we also review the mechanism of acyclovir‐induced acute renal failure, and the precipitating factor of acyclovir‐induced acute renal failure. Finally, we must once again emphasize the importance of hydration and routine check ups for renal function in preventing acyclovir‐induced acute renal failure.

The kidney is an important site of endothelin-1 (ET-1) production and is particularly susceptible to ET-1 action. Infusion of ET-1 in rats induces both functional and morphological alterations in the kidneys. Increased plasma level of ET-1 has been reported in patients with chronic renal failure. However, there are still no reports on the plasma and urinary ET-1 levels in patients with focal segmental glomerulosclerosis (FSGS). In the present study, we have measured the plasma concentration and urinary excretion rate of ET-1 in 15 patients with nephrotic syndrome due to FSGS, and observed the serial changes of plasma and urinary ET-1 in nephrotic rats with FSGS, induced by repeated injection with puromycin aminonucleoside (PAN). ET-1 was measured with radioimmunoassay. The results showed that plasma ET-1 concentration in FSGS patients was significantly higher than in normal controls (P < 0.05), and that urinary ET-1 excretion rate was also significantly higher in FSGS patients than in normal controls (P < 0.01). In FSGS patients, the plasma and urinary ET-1 was significantly correlated (P < 0.05), and the urinary ET-1 excretion rate was significantly correlated with the amount of proteinuria (P < 0.05) and the glomerular sclerosing score (P < 0.01). In the ten rats with PAN-induced FSGS, serial examination showed a significant increase in plasma ET-1 after 8 weeks of injections, while the urinary ET-1 excretion rate showed a biphasic increase that showed a peak after 4 to 6 weeks. The same changes in plasma and urinary ET-1 levels were not observed in control rats injected with normal saline at the same frequency. Our results suggest that ET-1 may be involved in the pathogenesis of FSGS in both humans and rats.

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.