In situ hybridization of interleukin 6 in diabetic nephropathy.

Increased mesangial expansion is one of the most characteristic histological changes in diabetic nephropathy (DN). Although the pathogenesis of DN remains unclear, recent studies associate interleukin (IL) 6 with mesangial proliferative glomerulonephritis. To elucidate the expression and localization of IL-6 mRNA in renal tissues of patients with DN, a high-resolution in situ hybridization using digoxigenin-labeled oligonucleotide was performed. Patients were divided into three groups based on light microscopy findings: mild (group 1), moderate (group 2), and severe (group 3) mesangial expansion. The relationship between the expression of IL-6 mRNA and the degree of glomerular mesangial expansion in DN was examined. Individual cells positive for IL-6 mRNA were observed in glomeruli. These cells were mesangial cells, glomerular epithelial cells, and Bowman's capsule. The signal intensity was strongest in tissues from group 2 but was weak in those from groups 1 and 3. Most cells in the area of mesangial proliferation were strongly stained for IL-6 mRNA, and few positive cells were found in the Kimmelstiel-Wilson nodular lesion. In the interstitium, some tubules, particularly atrophic tubules, and some infiltrating cells were positively stained for IL-6 mRNA. The interstitial expression of IL-6 mRNA correlated significantly with the degree of interstitial injury and was remarkable in tissues from groups 2 and 3. We conclude that IL-6 mRNA is expressed by glomerular resident cells and interstitial cells in the renal tissue of patients with DN and that its expression may be associated with mesangial proliferation and may be involved in the tissue injury of DN.

Scleritis and IgA nephropathy.

Follow-up studies on 113 patients with various types of primary glomerular diseases were performed for one to 33 months to determine the clinical spectrum of primary glomerulonephritis. Of those studied, six patients exhibited scleritis. All of these six patients with scleritis were identified as having "IgA nephropathy." None of the patients other than those with IgA nephropathy showed scleritis during the study period. It is suggested that some autoimmune mechanisms similar to the manifestation of IgA nephropathy may be involved in the development of scleritis.

Abnormal glucose tolerance in patients with chronic glomerulonephritis without renal failure.

An oral glucose tolerance test and an assay of insulin receptor activity were performed in patients with chronic glomerulonephritis (CGN) to elucidate the aberration of glucose metabolism in such patients. Ninety of 123 patients with CGN without renal failure showed abnormal glucose tolerance, including 72.6% with IgA nephropathy, 81% with benign recurrent hematuria, 87% with chronic proliferative glomerulonephritis, 100% with membranoproliferative glomerulonephritis, and 80.0% with membranous nephropathy. Insulin responses in CGN patients during oral glucose tolerance tests showed lower levels of basal insulin and significantly higher levels after 90, 120, and 180 min compared with those of normal controls. The binding of radiolabeled insulin to blood mononuclear cells in 22 CGN patients with abnormal glucose tolerance was significantly (P = 0.0023) decreased in comparison with 5 normal controls. However, plasma obtained from such patients showed no significant (P = 0.4761) inhibition of the binding of insulin to normal mononuclear cells. It was concluded that glucose tolerance capacity was impaired in 80.4% of patients with CGN without renal failure. Such impairment of glucose metabolism might be due to decreased activity of insulin receptors on cells in CGN patients.

Studies of cardiotonic agents. 8. Synthesis and biological activities of optically active 6-(4-(benzylamino)-7-quinazolinyl)-4,5-dihydro-5-methyl-3(2H)- pyridazinone (KF15232).

We previously reported that (+/-)-6-(4-(benzylamino)-7-quinazolinyl)-4,5- dihydro-5-methyl-3(2H)-pyridazinone (+/-)-1, KF15232) showed potent cardiotonic activity with a strong myofibrillar Ca(2+)-sensitizing effect. As an extension of our work, we attempted to synthesize optically active 1. (+/-)-4-(4-(Benzylamino)-7-quinazolinyl)-3-methyl-4-oxobutyric acid (-)-menthyl ester (6) was separated into both diastereoisomers, and each was converted to optically pure 1 (> 99% ee) in an enantioselective manner. In order to determine the absolute configuration of the isomers, an alternative synthesis of optically active 1 was employed. The precursor of (-)-1 ((+)-9) was obtained by enantioselective synthesis from (R)-D-alanine. Consequently, we concluded that the absolute configuration of (-)-1 at the 5-position of the pyridazinone ring was R. The cardiotonic effects and inhibitory activities to PDE III and V of racemic 1 and (-)-1 were more potent than those of (+)-1. These compounds also demonstrated greater vasorelaxant effects in guinea pig aorta. In contrast, (+)-1 showed only weak cardiotonic and vasodilating effects, although the compound displayed potent Ca(2+)-sensitizing activity. Racemic and (-)-1 attracted our interest for the treatment of congestive heart failure.

Increase of IgA-bearing peripheral blood lymphocytes in children with Henoch-Schoenlein purpura.

Aberration of IgA-bearing peripheral blood lymphocytes in children with Henoch-Schoenlein purpura has been investigated. Eighteen children with Henoch-Schoenlein purpura demonstrated a marked increase of IgA-bearing lymphocytes in peripheral blood during the acute phase of the disease. The levels of IgA-bearing lymphocytes returned to the normal levels after the acute symptoms of Henoch-Schoenlein purpura had subsided. However, in patients who developed purpura nephritis, the increased levels of IgA-bearing lymphocytes in peripheral blood were retained after the disappearance of purpura, and lasted for more than 12 months. It is concluded that the monitoring of IgA-bearing peripheral blood lymphocytes is useful for the screening of patients with Henoch-Schoenlein purpura and purpura nephritis.

Increase of HLA-DR-positive natural killer cells in peripheral blood from patients with IgA nephropathy.

Previous in vivo and in vitro studies have presented various abnormalities of cellular immunity in patients with IgA nephropathy (IgAN). In the present study, we described increased expression of HLA-DR antigens on peripheral natural killer cells (NK cells) in relation to altered cytokine interactions. The numbers of HLA-DR expressing NK cells were enumerated by two-color flow cytometry and found to be significantly increased in patients with IgAN. Peripheral blood mononuclear cells were then fractionated into pure NK cells by a magnetic cell-sorting system and analyzed concerning expression of messages of interleukin (IL)-2, IL-4, tumor necrosis factor (TNF)-alpha, and interferon (IFN)-gamma by semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR). Among the four cytokines, only the IFN-gamma message was significantly increased in patients' NK cells. Furthermore, intensity of the IFN-gamma message in NK cells showed positive correlation with the percentage of HLA-DR-positive NK cells from the same patient. Then we assayed serum levels of IL-2, IL-12, and IFN-gamma by enzyme-linked immunosorbent assay (ELISA) and the levels of IL-12 and IFN-gamma showed positive correlations with HLA-DR expression on NK cells. Creatinine clearance of the patients was reevaluated 36 months later, and patients with high HLA-DR on NK cells tended to show faster deterioration of renal function than patients with lower HLA-Dr expression. On the basis of these findings, we suggested that HLA-DR-positive NK cells in patients with IgAN form an "activated" population that produces IFN-gamma, and this unique cell population may be maintained by multiple factors and be involved in the development and progression of IgAN.

High dose rate endobronchial brachytherapy using a new applicator.

BACKGROUND AND PURPOSE: To obtain adequate spatial dose distribution for endobronchial brachytherapy, we applied reference dose points according to the bronchial diameter. For this purpose, we devised a new applicator of which the source transfer tube is contained in the center of the lumen for high dose rate (HDR) brachytherapy. MATERIALS AND METHODS: Thirty-nine patients with endobronchial cancer underwent endobronchial brachytherapy using an HDR afterloading machine with an Ir-192 source. In the nine patients treated with curative intent, treatment consisted of external beam radiotherapy with 40-60 Gy for 4-6 weeks and endobronchial brachytherapy with three fractions of 6 Gy. The 30 patients treated with palliative intent received one fraction of 10 Gy with or without external beam irradiation. The reference dose points were prescribed according to bronchial diameter, which was measured by the applicator's radiopaque wing expansion reflecting the bronchial caliber. RESULTS: The new applicator could be placed at the intended site in 37 lesions. Of 12 lesions which were treated with curative intent, eight (67%) disappeared after brachytherapy. The overall survival at 3 years of all patients and of the patients treated with curative intent was 22 and 64%, respectively. CONCLUSIONS: The source should be positioned in the center of the lumen; this technique is helpful in reducing side-effects caused by inhomogeneous dose distribution of endobronchial brachytherapy.

Clinical efficacy of brachytherapy combined with external-beam radiotherapy and repeated arterial infusion chemotherapy in patients with unresectable extrahepatic bile duct cancer.

The objective of this study was to evaluate the clinical efficacy of brachytherapy combined with external-beam radiotherapy and repeated arterial infusion chemotherapy in improving stent patency and prognosis in patients with unresectable bile duct cancer as compared with brachytherapy alone. Seventeen patients were treated. Five patients received brachytherapy alone before stent placement. Twelve patients received brachytherapy combined with external-beam radiotherapy (n=5), repeated hepatic arterial infusion chemotherapy using an implanted catheter and port (n=1), or both (n=6). Mean survival was significantly improved in the group that received combined therapy as compared with the group that received brachytherapy alone (16.2 months vs. 4.6 months, p<0.01). Although stent occlusion rates were similar in the two groups (42% vs. 40%), there was a trend towards longer stent patency in the combined therapy group than in the brachytherapy group (22 months vs. 3.6 months, p<0.2). Radiation gastritis necessitating gastrectomy developed in 1 patient who received external-beam radiotherapy at more than 50 Gy. Brachytherapy combined with external-beam radiotherapy and repeated hepatic arterial infusion chemotherapy increases survival compared with brachytherapy alone in patients with unresectable bile duct cancer.

Diagnostic value of perfusion MRI in classifying stroke.

Our study was designed to determine whether supplementary information obtained with perfusion MRI can enhance accuracy. We used delayed perfusion, as represented by time to peak map on perfusion MRI, to classify strokes in 39 patients. Strokes were classified as hemodynamic if delayed perfusion extended to a whole territory of the occluded arterial trunk; as embolic if delayed perfusion was absent or restricted to infarcts; as arteriosclerotic if infarcts were small, multiple, and located mainly in the basal ganglias; or as unclassified if the pathophysiology was unclear. We compared these findings with vascular lesions on cerebral angiography, neurological signs, infarction on MRI, ischemia on xenon-enhanced CT (Xe/CT) and collateral pathway development. Delayed perfusion clearly indicated the area of arterial occlusion. Strokes were classified as hemodynamic in 13 patients, embolic in 14 patients, arteriosclerotic in 6 patients and unclassified in 6 patients. Hemodynamic infarcts were seen only in deep white-matter areas such as the centrum semiovale or corona radiata, whereas embolic infarcts were in the cortex, cortex and subjacent white matter, and lenticulo-striatum. Embolic and arteriosclerotic infarcts occurred even in hemo-dynamically compromised hemispheres. Our findings indicate that perfusion MRI, in association with a detailed analysis of T2-weighted MRI of cerebral infarcts in the axial and coronal planes, can accurately classify stroke as hemodynamic, embolic or arteriosclerotic.

Activation of fronto-limbic system in the human brain by cigarette smoking: evaluated by a CBF measurement.

Nicotine produces profound behavioral effects in humans, but little is known about the sites of its action. There is a hypothesis that frontal lobe and limbic/cingulate cortical structures might be the sites. In this study, we examined the effects of cigarette smoking on feeling and cerebral blood flow (CBF) in human subjects. Young and healthy 9 cigarette smokers (all males, 24-33 years, average, 26.4) were included. After prohibiting them from smoking for 15 hours, CBF was measured using a Xenon CT-CBF system. Fifteen minutes later after allowing them to smoke two pieces of cigarette, the second CBF measurement was performed. Subtraction CBF map was created to display the changes after smoking. CT images were taken at three levels so as to include the cerebral lobes, basal ganglia, limbic system, brainstem and cerebellum. Arterial nicotine increased up to the levels 8 times higher than before smoking. The increases of blood pressure and pulse rate were minimal. Arterial carbon dioxide level and hematocrit did not change. Feeling after smoking was variable in individual subject. In 8 subjects with a relatively high feeling, CBF increased mainly in the frontal lobe, hippocampus, uncus, thalamus and caudate nucleus. CBF did not change in the parietal, temporal and occipital lobes, and in the putamen, insula, brainstem and cerebellum. In two subjects with uncomfortable feeling, CBF did reduce in the whole brain. The CBF increase in frontal lobe and limbic structures seems to be secondary to nicotine-induced neuronal activation in each structure. Mesocorticolimbic dopamine system, which is believed to influence learning, memory or emotional performance, appears to be a target for nicotine. The CBF reduction in the whole brain might be due to cerebral vasoconstriction or be secondary to a systemic hypotension.

Detection of group C adenovirus DNA in small-cell lung cancer with the nested polymerase chain reaction.

Group C adenovirus is latent in human tissues and can malignantly transform cells. The purpose of this study was to investigate the association between this virus and lung cancer. We investigated latent adenoviral infection using the nested polymerase chain reaction and in situ hybridization in transbronchial biopsy specimens from patients with small-cell lung cancer and non-small-cell lung cancer. The polymerase chain reaction was performed on DNA extracts with two sets of primers directed at a 261-base-pair target sequence of the E1A region of the adenoviral genome. In situ hybridization was performed on histological sections using DNA representing the entire adenovirus type 5 genome. E1A target DNA was present in 11 (31%) of 35 cases of small-cell lung cancer but in none of the 40 cases of non-small-cell lung cancer (P < 0.01). Of the 11 cases found positive by PCR, 8 were positive for adenovirus DNA by in situ hybridization. Adenovirus was prominent in tumor cells in 5 of the 8 cases, and in normal epithelial cells in the 3 remaining cases. Adenovirus DNA was not detected by in situ hybridization in specimens in which E1A DNA was not detected by the polymerase chain reaction. Small-cell lung cancer has mutations or deletions in the p53 and retinoblastoma genes more frequently than are found in non-small-cell lung cancer. Therefore, we speculate that adenovirus infection might participate in the pathogenesis of SCLC by producing mutation in these genes, rather than by inhibiting the function of these proteins.

Increase of IgA-bearing lymphocytes in peripheral blood from patients with IgA nephropathy.

Aberration of IgA-bearing B lymphocytes in patients with IgA nephropathy has been investigated. Twelve patients with IgA nephropathy demonstrated a marked increase of IgA-bearing lymphocytes in peripheral blood, while ten patients with chronic proliferative glomerulonephritis without mesangial deposition of IgA showed normal amounts of IgA-bearing lymphocytes. The increase of IgA-bearing lymphocytes reflected that of IgA-producing lymphocytes, since lymphocytes obtained from patients with IgA nephropathy restored a high percentage of IgA-bearing cells in vitro after treatment with trypsin. Quantitation of IgA-bearing lymphocytes in peripheral blood is a useful method for screening of patients with IgA nephropathy.

Increase of IgA-bearing peripheral blood lymphocytes in families of patients with IgA nephropathy.

IgA-bearing peripheral blood lymphocytes, serum IgA, urinary sediments and HLA types of patients with IgA nephropathy and members of their families were examined to elucidate whether some familial factors might be related to the development of IgA nephropathy. Ten patients with IgA nephropathy, 31 family members and 36 age-matched healthy persons were examined. All families included certain members with increased amounts of IgA-bearing peripheral blood lymphocytes. The pattern of the emergence of family members with increased IgA-bearing lymphocytes was vertical. Some family members who had increased IgA-bearing lymphocytes showed microhematuria at the time of the study. There was no significant correlation between the amounts of IgA-bearing peripheral blood lymphocytes and levels of serum IgA. HLA types of the ten patients did not show significant deviation from those in the general population. It is suggested that the measurement of IgA-bearing peripheral blood lymphocytes among family members is useful for the screening of patients with IgA nephropathy.

Activation of complement by renal tissues from patients with IgA nephropathy.

In a study of complement activation by renal tissues, renal biopsy specimens were obtained from patients with IgA nephropathy and other glomerular diseases. These specimens were incubated with freshly frozen guinea-pig serum, and the activation of guinea-pig complement systems was evaluated by immunofluorescent staining with FITC-conjugated anti-guinea-pig complement antisera. It was shown that the alternative pathway of the complement was activated in situ in renal tissues from patients with IgA nephropathy. it is suggested that analysis of in situ activation of complement in such patients is useful for elucidating the mechanism of complement activation in various glomerular diseases.

KF31327, a new potent and selective inhibitor of cyclic nucleotide phosphodiesterase 5.

The effects of KF31327 (3-ethyl-8-[2-(4-hydroxymethylpiperidino)benzylamino]-2,3-dihydro-1H-imidazo[4,5-g]quinazoline-2-thione dihydrochloride) on phosphodiesterase 5 (cyclic GMP-specific phosphodiesterase) activity and platelet aggregation were investigated and compared with those of sildenafil, a well-known phosphodiesterase 5 inhibitor. KF31327 inhibited phosphodiesterase 5 from canine trachea (K(i)=0.16 nM) more potently than sildenafil (K(i)=7.2 nM). The kinetic analysis revealed that KF31327 was a non-competitive inhibitor. In the presence of nitroglycerin (nitric oxide generator), both compounds inhibited the collagen-induced aggregation of rabbit platelets at less than 0.1 microM, augmenting intracellular cyclic GMP level without affecting cyclic AMP. In contrast, in the absence of nitroglycerin, a higher concentration (10 microM) of KF31327 was required to inhibit platelet aggregation and increased both cyclic nucleotide levels. However, 10 microM sildenafil did not affect aggregation despite elevation of cyclic GMP comparable to that in the presence of nitroglycerin. These results indicate that in the presence of nitroglycerin, the inhibition of platelet aggregation by KF31327 is due to the elevation of cyclic GMP, whereas the mechanism underlying the inhibition without nitroglycerin might be related to a rise in intracellular cyclic AMP.

Expression of nuclear factor kappaB and tumor necrosis factor alpha in the mouse brain after experimental thermal ablation injury.

OBJECTIVE: Nuclear factor kappa B (NFkappaB) participates in the regulation of a diverse range of genes involved in inflammation and acute phase responses. We investigated the expression of the activated form of NFkappaB and tumor necrosis factor alpha (TNFalpha), an inflammatory cytokine, in experimental brain injury. METHODS: We generated focal brain injury in mice using radiofrequency thermal ablation at the caudate putamen in mice. Intracerebral expression of TNFalpha and the p50 and p65 subunits of NFkappaB were studied using immunohistochemistry at 1, 4, and 8 hours and at 1, 2, 4, 8, 14, and 28 days postinjury. RESULTS: Coagulative necrosis approximately 2 mm in diameter was produced at the site of injury. No immunoreactivity for TNFalpha, NFkappaB p50, or NFkappaB p65 was detected in the injured area in the early phase postinjury. On posttrauma Day 2, however, weak expression of TNFalpha, NFkappaB p50, and NFkappaB p65 was detected in mononuclear cells that infiltrated edematous tissue surrounding the lesion. On posttrauma Days 4 to 8, the expression of TNFalpha, NFkappaB p50, and NFkappaB p65 was prominently increased in infiltrating and proliferating mononuclear cells (macrophages and microglia) and in proliferating reactive astrocytes surrounding the lesion. Nuclear subcellular localization of the expression of NFkappaB p50 and p65 was observed, which indicated that these subunits might be activated in these cells. On posttrauma Day 14, the expression of TNFalpha, NFkappaB p50, and NFkappaB p65 decreased and was limited to mononuclear cells, and it finally disappeared on Day 28. The temporal profiles of TNFalpha, NFkappaB p50, and NFkappaB p65 were closely associated with the occurrence of secondary insults and the tissue-remodeling process in wound healing. CONCLUSION: These results suggest that TNFalpha, NFkappaB p50, and NFkappaB p65 may play a central role in the injury-induced immune response that leads to secondary insults or wound healing after brain injury. Inappropriate and deregulated activation of NFkappaB in injured brain tissue may be implicated in the development of secondary brain damage.

Cytomorphologic features characteristic of tumor stages of thymomas.

The cytologic findings of the tumor cells characteristic of the stages of thymomas were investigated to assess the invasiveness of the tumors. Forty-six patients with thymoma who underwent extensive thymectomy without pre-operative corticosteroid therapy were included in this study. The histologic subtypes included 18 round/oval, 20 mixed, and 8 spindle type. The stages of thymoma classified according to Masaoka's clinicopathological classification included 16 stage I, 20 stage II, 6 stage III, 2 stage IVa, and 2 stage IVb, and myasthenia gravis was recognized in 5 patients. Cytologic findings were retrospectively analyzed in the Papanicolaou-stained stamp smears obtained from the cut surfaces of thymoma specimens. Morphometry of the epithelial tumor cells using Cosmozone-1A was performed to evaluate the validity of our cytologic categories. Compared with the cytologic findings of stage I or II thymomas, those of epithelial tumor cells in stage III or IV more frequently showed necrotic background (50.0%-stage III or IV vs 11.1%-stage I or II, p=0.006), large clusters of epithelial tumor cells (70.0% vs 36.1%, p=0.055), marked nuclear enlargement (90.0% vs 52.7%, p=0.033), marked anisokaryosis (100% vs 52.7%, p=0.006), marked nuclear polymorphism (40.0% vs 5.5%, p=0.004), hyperchromasia (50.0% vs 11.4%, p=0.007) and prominent nucleoli (50.0% vs 16.6%, p=0.028) whereas no significant correlation was observed between cytologic findings and tumor volume. Morphometric studies of thymoma tumor cells revealed that the nuclear size (mean values, 78.8 microm(3)-stage III or IV vs 58.2 microm(3)-stage I or II), the coefficient of variation of the nuclear size (0.326 vs 0.282), and the nuclear rotundity (0.849 vs 0.858) differed significantly between the two categories (p<0.05). Our findings demonstrated that there were significant differences between the cytologic findings of epithelial tumor cells of stage I or II thymomas and those of stage III or IV thymomas, and that the cytologic findings of thymoma tumor cells appear to be useful for distinguishing between non-invasive and invasive thymomas.

Significance of high levels of serum IgA and IgA-class circulating immune complexes (IgA-CIC) in patients with non-insulin-dependent diabetes mellitus.

Significance of serum IgA and IgA-class circulating immune complexes (IgA-CIC) elevation in patients with non-insulin-dependent diabetes mellitus (NIDDM) was described. Seventeen patients with NIDDM and 17 patients with diffuse mesangial proliferative glomerulonephritis without deposition of IgA (DPGN) as controls were examined. The levels of serum IgA in patients with NIDDM were significantly higher than those in patients with DPGN (p < or = 0.01). The levels of IgA-CIC in patients with NIDDM were also significantly higher than those in patients with DPGN (p < or = 0.01). Production of IgA derived from B cells and the proportion of IgA bearing B cells in patients with NIDDM were not significantly higher than those in patients with DPGN. Furthermore, the levels of IgA in pharyngeal washings from diabetic patients were not significantly higher than those for DPGN patients. Duration of diabetes, the level of HbA1c, and the presence of hypertension, microalbuminuria, or retinopathy showed no significant correlations with the levels of serum IgA or IgA-CIC in patients with NIDDM. It was postulated that the elevations of serum IgA and IgA-CIC were based on subclinical infection of the mucosa and/or deterioration of IgA clearance in patients with NIDDM.

Immunofluorescence staining of renal biopsy samples in patients with diabetic nephropathy in non-insulin-dependent diabetes mellitus using monoclonal antibody to reduced glycated lysine.

This is the first report on immunofluorescence staining of renal biopsy samples in human diabetic nephropathy (DN) using monoclonal antibodies to reduced glycated lysine. In order to detect the localization of glycated lysine in the mesangial matrix and/or the glomerular basement membrane (GBM), we examined immunofluorescence staining using antibodies against reduced glycated lysine in the glomeruli of 16 patients with DN and ten age-matched patients with diffuse mesangial proliferative glomerulonephritis without IgA deposition (DPGN) as controls. In the early stage of DN, immunofluorescence microscopy revealed the presence of intense staining for reduced glycated lysine in the GBM as well as in part of the tubular basement membrane, but not in the mesangial area. In contrast, immunofluorescence microscopy revealed less staining for glycated lysine in the GBM in the advanced stage of DN, and no reaction with any part of the renal tissue in patients with DPGN. It was concluded that detection of reduced glycated lysine in GBM in the early stage of DN might be associated with the initial pathogenesis of this disease.

Evidence of enhanced uric acid clearance in macrohematuric patients with IgA nephropathy: prognostic significance of macrohematuria.

Renal handling of uric acid and clinical prognosis following episodes of macroscopic hematuria (EMH) were examined in 113 patients with IgA nephropathy (IgAN). EMH was observed in 34 out of 113 patients (30.1%). The levels of blood urea nitrogen, proteinuria, serum uric acid, beta 2-microglobulin in sera and the degrees of glomerular sclerosis in renal tissues in macrohematuric patients were significantly decreased than those in patients without EMH. The levels of uric acid clearance (Cua) and fractional excretion of uric acid (FEua) was significantly enhanced in macrohematuric patients (p less than 0.01, p less than 0.05, respectively). There was a significant correlation between the tubular atrophy and the levels of Cua in macrohematuric patients (p less than 0.005). The levels of serum creatinine in macrohematuric patients before and after three years were significantly decreased when compared with microhematuric patients (p less than 0.005). It is concluded that enhanced Cua was related to renal tubular atrophy, and EMH did not clinically influence the glomerular deterioration in patients with IgAN.