Prevalence of Microalbuminuria and Overt Proteinuria in Diabetes Mellitus and their Association with Renal Function.

This cross sectional observational study was conducted in the Department of Nephrology, Mymensingh Medical College Hospital, Mymensingh, Bangladesh from April 2009 to March 2010. Samples were collectedfrom rural area of Khalishaur union of Purbadhala upazilla in Netrakona District, 30km away from Mymensingh Town. The main objective of the study was to find out the prevalence of microalbuminuria as well as overt proteinuria in diabetes mellitus in a rural population and to observe their association with renal function. In this study 1048 adult participants of 18 to 65 years in a rural area of Netrakona were included purposively as study subjects. Among them 54% were male and 46% were female. Mean age of study subjects was 42.4±13.4 years. Prevalence of microalbuminuria among diabetic participants was 29.72% where as in non diabetic non hypertensive participants it was 6.62%. Diabetic persons 9.45% and 3.9% of non diabetic participants showed overt proteinuria by dipstick test. Prevalence of hypertension in diabetic and non diabetic participants was 45.94% and 16.52% respectively. The mean eCCr of the diabetic patients and non-microalbuminuric healthy persons was 78.4±25.4 ml/min/1.73m² and 94.67±24.8 ml/min/l.73m² respectively according to Cock Croft-Gault equation. The mean eCCr of diabetic participants with overt proteinuria was 57.44±28.33 ml/min/l.73m² but diabetic patients with microalbuminuria had better mean eCCr 80.62±21.17 ml/min/1.73m² which justifies the importance of detection of microalbuminuria for early intervention. By regression analysis it was found that degree of microalbuminuria had linear relation with renal function and random blood sugar level. Neither BMI nor duration of diabetes showed any correlation with urine microalbumin. There was no effect of sex on the prevalence of microalbuminuria in diabetes mellitus. Microalbuminuria is the first sign of renal involvement in diabetic patients which is a risk factor for overt nephropathy. Monitoring of this condition is important because early treatment of microalbuminuria can prevent or postpone overt nephropathy.

Can latissimus dorsi muscle stimulation benefit heart during training period after vascular delay?

We hypothesized that a two-stage vascular delay procedure followed by 5 weeks of conditioning of the latissimus dorsi muscle (LDM) could benefit the heart during the training period and greatly increase cardiac assistance when examined with maximum potential. In mongrel dogs (n = 10), left ventricle (LV) dysfunction was induced by intracoronary injections of latex microspheres [90 +/- 2 micro diameter]. Vascular delay of the LDM was performed in one group (n = 6), whereas the other group (control, n = 4) did not undergo vascular delay. After 2 weeks, CMP was performed in all animals followed by LDM conditioning. After 5 weeks of muscle training, we examined left ventricular function at 20 Hz-4 volts, 33 Hz-4 volts, and 50 Hz-10 volts stimulation by assessing peak aortic pressure (AoP), left ventricular pressure (LVP), maximum LV +dP/dt, stroke volume (SV), stroke work (SW), stroke power (SP), and aortic flow. LDM assisted beats were compared with nonstimulated beats. LDM stimulation caused significant increases in pressure and flow in the vascular delay group. At 20 Hz-4 volts, absolute increases were LVP (10.2 +/- 0.6) mm Hg, AoP (9.8 +/- 1.7) mm Hg, SV (1.8 +/- 0.4) ml, SW (5.3 +/- 1.0) gm x m, SP (40.8 +/- 12.7) gm x m/sec, max LV dP/dt (104.8 +/- 53.2) mm Hg/sec, and peak aortic flow (0.9 +/- 0.3) L/min. At 33 Hz-4 volts, the absolute increases were LVP (13.6 +/- 1.3) mm Hg, AoP (12.1 +/- 2.4) mm Hg, SV (2.7 +/- 0.7) ml, SW (7.4 +/- 1.4) gm x m, SP (72.7 +/- 16.5) gm x m/sec, max LV dP/dt (294 +/- 19) mm Hg/sec, and peak aortic flow (1.8 +/- 0.5) L/min. At 50 Hz-10 volts, the absolute increases were LVP (17.7 +/- 0.7) mm Hg, AoP (21.1 +/- 1.9) mm Hg, SV (6.0 +/- 1.1) ml, SW (14.6 +/- 2.2) gm.m, SP (128.2 +/- 15.3) gm x m/sec, max LV dP/dt (352 +/- 62) mm Hg/sec, and peak aortic flow (3.3 +/- 0.4) l/min (p < 0.05). The percentage increases were significantly larger in the vascular delay group compared with controls at 50 Hz-10 volts LDM stimulation. By using a two-stage vascular delay procedure, LDM stimulation can provide meaningful cardiac assistance during training periods. Furthermore, brief periods of maximal potential benefit (demand cardiomyoplasty) can be achieved during the training period.

Vascular delay and intermittent stimulation: keys to successful latissimus dorsi muscle stimulation.

BACKGROUND: The goal of this study was to obtain physiologically significant increases in peak left ventricular (LV) systolic pressure and stroke volume with latissimus dorsi muscle (LDM) stimulation in cardiomyoplasty (CMP). We hypothesized that preserving LDM integrity by vascular delay and intermittent stimulation would significantly increase LDM cardiac assistance. METHODS: In 4 control dogs and 12 dogs that had undergone a vascular delay (VD) procedure, LV dysfunction was induced by intracoronary microsphere injections. Cardiomyoplasty surgery was performed 14 days later, followed by progressive LDM conditioning. In the control dogs and in 6 of the VD dogs, the LDM was stimulated 24 hours per day (VD plus constant stimulation [CS]). In the other 6 VD dogs, LDMs were stimulated on a daily schedule of 10 hours on and 14 hours off (VD plus interrupted stimulation [IS]). Latissimus dorsi muscle stimulated beats were compared with nonstimulated beats 9 weeks later. RESULTS: In the control dogs, LDM stimulation had minimal effects. In VD + CS and VD + IS, LDM stimulation increased peak LV pressure, stroke volume, stroke work, and stroke power (p < 0.05). However, these changes were greater in the VD + IS group, in which LDM stimulation increased peak aortic pressure by 17.6 +/- 1.7 mm Hg, peak LV pressure by 19.7 +/- 1.1 mm Hg, peak positive LV dp/dt by 398 +/- 144 mm Hg per second, stroke volume by 5.1 +/- 0.7 mL, stroke work by 10.9 +/- 0.9 gm.m, and stroke power by 122.7 +/- 11.6 gm.m per second (p < 0.05 compared with VD + CS). Quantitative morphometric analysis showed minimal LDM degeneration in the VD + IS group (7.5% +/- 1.1%), and VD + CS group (10.5% +/- 4.5%) compared with the control group (29.5% +/- 4.5%, p < 0.05). CONCLUSIONS: VD and IS considerably increased the LV assistance with LDM stimulation. Further studies of this combined approach to CMP should be planned.

Chemoreflexes: an experimental study.

HYPOTHESIS: Transmyocardial laser revascularization (TMLR) will not denervate the heart, because it does not destroy all of the afferents. This study was designed to determine if stimulation of cardiac sympathetic and vagal afferents from an area of the left ventricle treated with TMLR could evoke reflex effects, and thus whether TMLR would denervate the heart. METHODS: The effect of TMLR on reflexes evoked by chemically stimulating cardiac afferents was examined in 9 dogs. Bradykinin and capsaicin were applied topically or injected into the left anterior descending coronary artery before and after TMLR and after bilateral vagotomy and sympathectomy. Aortic (AoP) and left ventricular pressures (LVP) and electrocardiography were monitored. The first derivatives of LVP (dP/dt) were calculated. RESULTS: Topical bradykinin elicited variable hemodynamic responses. Topical capsaicin evoked pressor responses, increasing mean (+/- SEM) AoP (105+/-9 to 115+/-9 mm Hg; P<.001) and positive dP/dt (+dP/dt) (1032+/-81 to 1159+/-10 mm Hg/s; P<.01) before TMLR. Intracoronary capsaicin evoked a depressor response before TMLR. Pressor responses remained intact after TMLR with increases in mean AoP and +dP/dt (115+/-6 to 128+/-5 mm Hg and 1039+/-98 to 1136+/-100 mm Hg/s, respectively; P<.01). Depressor responses also remained intact after TMLR (91+/-10 vs 101+/-11 mm Hg [P<.02], and 865+/-104 vs 931+/-104 mm Hg/s [P<.05], respectively). Hemodynamic responses were diminished after bilateral vagotomy and abolished after bilateral sympathectomy. CONCLUSION: Since activation of cardiac afferent nerves and reflex responses remained intact after TMLR, but changed after vagotomy or sympathectomy, TMLR does not denervate the heart sufficiently to be the cause of improved angina after TMLR.

Two step cardiomyoplasty with vascular delay: effect of stimulation of latissimus dorsi muscle on diastolic function.

A common concern in cardiomyoplasty is whether latissimus dorsi muscle (LDM) stimulation impairs diastolic function. This study determined the time course of left ventricular (LV) contraction and relaxation and their relationship to the diastolic function. Ten mongrel dogs underwent vascular delay of the left latissimus dorsi muscle 2 weeks before cardiomyoplasty. Fourteen to 18 days later, the effects of LDM stimulation were evaluated. Our study demonstrated that LDM stimulation significantly increased peak LV systolic pressure (131.3 +/- 7.5 to 152.0 +/- 7.5* mm Hg), +dP/dt (1585 +/- 151 to 2088 +/- 176 x mm Hg/s), stroke volume (10.8 +/- 1.5 to 13.8 +/- 1.9* ml), stroke work (17.2 +/- 2.7 to 25.6 +/- 3.8* gm x m), and peak aortic flow (4751 +/- 698 to 6712 +/- 926* ml/min), and significantly decreased the pre-ejection time (113.9 +/- 12.6 to 92.3 +/- 7.8* ms) and total systolic time (366.0 +/- 26.9 to 333.6 +/- 21.3* ms) (*p < 0.05). As for diastolic function, LDM stimulation decreased -dP/dt (-1462 +/- 116 to -1781 +/-116* mm Hg/s) and tau (64.0 +/- 6.1 to 52.1 +/- 2.9* ms). The diastolic filling time (Tdf) was significantly longer (177.9 +/- 17.6 to 213.7 +/- 18.7* ms) during the beat immediately after LDM stimulation. These changes reflected an overall stronger contraction and faster relaxation. Our results imply that with vascular delay, stimulation of LDM not only assists systolic function but also improves diastolic function in cardiomyoplasty.

The effect of dialysate glucose on phagocyte superoxide generation in CAPD patients.

OBJECTIVE: In the present study, we investigated the influence of dialysate glucose on superoxide (O2-) generation by peripheral and peritoneal phagocytes in continuous ambulatory peritoneal dialysis (CAPD) patients. DESIGN: Peripheral polymorphonuclear leukocytes (PMNL) and mononuclear leukocytes (MNL), and peritoneal cells were isolated from peripheral blood and peritoneal effluents, respectively, and their oxidative metabolism was assessed by measuring O2- generation after stimulation with a soluble stimulant [phorbol myristate acetate (PMA), 1 mg/mL, Sigma Chemical, St. Louis, MO, U.S.A.] using the chemiluminescence method. Dialysate glucose effect on O2- generation was also studied in vitro by exposing peripheral PMNL and MNL from healthy controls to peritoneal dialysis fluid (PDF) containing glucose or amino acids at a neutral pH for different time periods. RESULTS: The amount of O2- generation by both peripheral and peritoneal phagocytes in CAPD patients was significantly higher than that in the control, and the response was greater in patients who were dialyzed with high glucose dialysate than those using low glucose dialysate. In an in vitro study, all incubated cells, except the control, showed suppression of O2- generation in the early dwell time (2 hr), and subsequently showed increased responses (peaking at 6 hr), although lower in degree than those observed in vivo. In contrast, amino acid-based PDF exhibited no such effect on O2- generation at identical pH with similar or lower osmolality. Furthermore, the respective increased or decreased oxidative responses with the increased or decreased PDF glucose concentrations in the same patient confirmed the positive effect of PDF glucose on phagocyte O2- generation. CONCLUSION: It is suggested that increased O2- generation by peritoneal and circulating phagocytes in CAPD patients is at least partly due to the enhancement of hexose monophosphate shunt activity by increasing glucose metabolism in phagocytes, and the increased O2- generation might be involved in long-term complications of CAPD. Therefore, a suitable alternative osmotic agent is needed to provide a more physiological environment to minimize the adverse effects of glucose on cell functions.

Glomerular Fc alphaR expression and disease activity in IgA nephropathy.

In this study, we examined the receptors for the Fc portion of immunoglobulin A (IgA) (Fc alphaR) in the glomeruli as well as circulating polymorphonuclear leukocytes and monocytes at the mRNA level by reverse transcription-polymerase chain reaction (RT-PCR) assay and at the protein level by an immunohistochemistry/flow cytometry technique using a specific anti-Fc alphaR monoclonal antibody (My 43). Glomeruli were isolated from biopsy specimens of renal tissues from IgA nephropathy (IgAN; 20 cases) and non-IgA mesangial proliferative glomerulonephritis (PGN; 13 cases) patients, and from normal renal tissue specimens obtained from kidneys removed because of malignancies (five cases) applying the microdissection method. There was a relative increase in Fc alphaR in the circulating phagocytes from IgAN patients compared with those from PGN and healthy controls. Fc alphaR expression was present in approximately 40% of glomeruli samples from IgAN patients at the message levels. Fc alphaR-positive specimens were also strongly positive for expression of tumor necrosis factor-alpha, interleukin-1, and interleukin-6 mRNA. Specimens from PGN patients and healthy controls did not show any detectable Fc alphaR message. Serum IgA levels and severity of hematuria were significantly higher in patients with positive Fc alphaR expression. A message for Fc alphaR was detected in the tissues that were more damaged histologically. Our data suggest that there is some in vivo induction of glomerular Fc alphaR expression, possibly mediated by a synergistic stimulus from IgA and inflammatory cytokines, and the expressed receptor is likely to be involved in the disease process of IgAN.

Expression of thromboxane synthase in kidney tissues from patients with IgA nephropathy.

Thromboxane A2 (TXA2) is a potent vasoconstrictor which is known to be involved in the pathogenesis of experimental glomerulonephritis, although its exact pathogenic significance is not clear in human glomerulonephritis. We have investigated the expression of thromboxane synthase (TXS) in kidney tissues from patients with IgA nephropathy (IgAN), using RT-PCR and immunohistochemical methods. Biopsied renal tissues from thirty-four patients with IgAN (24 whole tissues and 10 isolated glomeruli) and normal renal tissues from 11 nephrectomized kidneys (control, eight whole tissues and three isolated glomeruli) were included in this study. TXS mRNA expression was observed in 10 out of 24 (42%) whole tissue specimens from IgAN, but no such message was disclosed in the control tissue. There was no detectable TXS mRNA expression in the isolated glomeruli either from IgAN patients or controls, although constant mRNA expressions for GAPDH and VPF/VEGF were observed. IgAN patients with positive TXS mRNA had significantly reduced GFR with elevated serum creatinine and serum beta 2-microglobulin levels. Immunostaining, using a monoclonal anti-TXS antibody, identified the localization of the TXS protein in the interstitial areas where monocyte/macrophage infiltration was abundant, as well as in the arterioles of the kidney tissues with advanced tissue damage. It was concluded that TXA2 produced by the interstitial infiltrating cells during the inflammatory process might be involved in the progression of IgA nephropathy.

Expression of inducible-NOS in human glomerulonephritis: the possible source is infiltrating monocytes/macrophages.

Nitric oxide (NO) is a biological mediator which is synthesized from L-arginine by a family of nitric oxide synthases (NOS). In this paper, we have studied the expression of the inducible NO synthase (iNOS) in the tissues of the human kidney at the mRNA level by RT-PCR assay and at the protein level by an immunohistochemistry technique using a specific anti-macrophage NOS monoclonal antibody. Biopsied renal tissues from patients with IgA nephropathy (IgAN; 28 cases) and with non-IgA mesangial proliferative glomerulonephritis (PGN;12 cases), and normal renal tissues obtained from kidneys removed for malignancies (11 cases) were included in this experiment. iNOS message was present in about 73% tissues from IgAN and PGN patients, which was supported by histochemical findings and the iNOS positive cells were predominantly in the tubulointerstitial areas where infiltration of monocytes/macrophages was abundant. The iNOS positive tissues were also strongly positive for CD14, INF-gamma and TNF-alpha mRNA expression. In our in vitro study, iNOS expression was found only in cytokines (INF-gamma and TNF-alpha) stimulated monocytes/macrophages but not in lymphocytes and neutrophils. Normal renal tissues did not show any iNOS expression either at the mRNA level or at the protein level in this study. Clinical and histological data showed that decreased renal function and tubulointerstitial damage were greater in the iNOS expressing patients. This study demonstrates that there is some in vivo induction for iNOS expression, likely to be mediated by cytokines, for local NO production that might be involved in the initiation and/or progression of mesangial proliferative glomerulonephritis.

Superoxide dismutase activity in human glomerulonephritis.

Superoxide dismutase (SOD) in renal tissue biopsy specimens obtained from patients with immunoglobulin A nephropathy (13 cases) and non-immunoglobulin A mesangial proliferative glomerulonephritis (nine cases) was studied at the protein level by an enzyme-linked immunosorbent assay method and at the mRNA level by the reverse transcriptase-polymerase chain reaction (RT-PCR) assay. Total SOD activity in the tissue supernatant was measured by applying an electron paramagnetic resonance/spin trapping method. Normal renal tissues obtained from kidneys removed for malignancies (six cases) were included as healthy controls. The copper and zinc form of SOD (Cu,Zn-SOD) activity at both the protein and mRNA levels was lower in the moderately or severely damaged tissues compared with that in the normal or mildly damaged tissues. On the other hand, manganese SOD (Mn-SOD) values at either the protein level or the mRNA level did not differ significantly between control and patient samples. In the histochemical study using a polyclonal rabbit anti-Cu,Zn-SOD antibody, the staining intensity for Cu,Zn-SOD antigen was lower in the areas with advanced histologic damage than in the intact tissues. A follow-up study showed that renal function deterioration was proportionately slower in patients whose SOD activity was within the range of healthy tissue levels at the time of biopsy. Our data suggest that a lower level of SOD activity, whether as a cause or a consequence of the disease process, might induce a decrease in the scavenger reaction of superoxide (O2-) thus causing the tissue to become more vulnerable to oxidative stress.

Involvement of interleukin-4 and soluble CD23 in hypersynthesis of immunoglobulins A and E in patients with IgA nephropathy.

To determine the cytokines responsible for the increase in production of IgA in patients with IgA nephropathy (IgAN), the roles of interleukin-4 (IL-4) and soluble CD23 (sCD23) were examined. Peripheral blood mononuclear cells (PBMCs) and serum were obtained from 24 patients with IgAN and 14 patients with non-IgA proliferative glomerulonephritis. Twenty healthy adults served as controls. Concentrations of IgA and IgE in 10-day culture supernatants of PBMCs were measured by the sandwich ELISA method. Levels of sCD23 and activities of IL-4 in 4-day (96-hour) culture supernatants and serum were measured by ELISA and bioassay, respectively. Activities of IL-4 both in culture supernatants and serum were significantly elevated in patients with IgAN compared with controls (1.26 +/- 0.53 vs. 0.68 +/- 0.37 U/ml in culture supernatants, p < 0.05; 1.35 +/- 1.34 vs. 0.89 +/- 0.82 U/ml in serum, p < 0.05). Levels of sCD23 in IgAN patients' serum were also significantly elevated (521.7 +/- 514.9 vs. 173.0 +/- 166.2 U/ml, p < 0.01). In vitro IgA and IgE synthesis were suppressed by anti-IL-4 monoclonal antibody (mAb) only when the antibody was added on the day when the culture was started (day 0). No suppression of IgA or IgE synthesis was observed when the antibody was added on day 4. IgE but not IgA synthesis was suppressed by anti-CD23 mAb when added on both days 0 and 4. Serum levels of IgE showed positive correlations with serum activities of IL-4 and with levels of serum sCD23. It is concluded that IL-4 and sCD23 might play decisive roles in in vitro and in vivo hyperproduction of IgA and IgE in patients with IgAN, and that sCD23 seemed to control IgE but not IgA synthesis through a unique pathway.

Monocyte superoxide generation and its IgA-receptor in IgA nephropathy.

Recent studies indicated that polymorphonuclear leukocytes (PMNL) were primed to produce superoxide (O2-) in various types of glomerulonephritis with a particular importance in IgA nephropathy (IgAN). In this study, we have examined O2- production and receptor expression for the Fc portion of IgA (Fc alpha R) in monocytes to evaluate their incorporation in IgAN, since infiltration of these cells in the glomeruli are more commonly observed than that of PMNL. Similar to PMNL, monocytes obtained from IgA nephropathy (IgAN) seemed to be primed both non-specifically and specifically, as increased O2- generation was observed to N-formyl methionyl leucyl phenylalanine (FMLP) and phorbol myristate acetate (PMA), as well as IgA aggregates stimulants, respectively. Monocytes O2- generation to IgA aggregates was comparatively higher in amount than in PMNL, and showed a correlation with the severity of proteinuria in IgAN patients. Flow cytometric assessment showed an increased expression of Fc alpha R on circulating monocytes in IgAN patients which showed a linear correlation with the amount of IgA-induced O2- generation. Comparing with the previous literature on PMNL, inflammation-related substances such as cytokines/immune complexes, particularly IgA immune complexes which present in the circulation of IgAN, can prime the phagocytic cells in the circulation for a burst of O2- generation to a second stimulus. The increased expression of Fc alpha R appears to be associated with the increase in priming and the degree of priming can be reflected in the severity of proteinuria/hematuria, although it can not be defined as a cause or consequence of this disease.

Fc alpha R expression on polymorphonuclear leukocyte and superoxide generation in IgA nephropathy.

Superoxide (O2-) production and Fc alpha R antigen expression of circulating polymorphonuclear leukocytes (PMNL) isolated from patients with IgA nephropathy (IgAN) and non-IgA mesangial proliferative glomerulonephritis (PGN) and healthy volunteers were investigated to establish their biological importance in the immunopathogenesis of mesangial proliferative glomerulonephritis. PMNL from both patient groups showed increased O2- production when stimulated with N-formyl methionyl leucyl phenylalanine (FMLP) and phorbol myristate acetate (PMA). The increased O2- generation demonstrated a positive correlation with the degree of proteinuria. Aggregated IgA caused enhanced O2- production only in patients with IgAN who also showed a significant correlation with proteinuria. Increased expression of Fc alpha R on circulating PMNL was observed in IgAN patients as determined by flow cytometric analysis. The amount of Fc alpha R on PMNL was positively correlated with O2- generation triggered with IgA aggregates. These results suggest that: 1. Circulating PMNL may potentially be participating in the pathogenesis of glomerular injury in mesangial proliferative glomerulonephritis, and 2. IgA aggregates/immune complexes may contribute to the immunopathogenesis of IgAN through augmenting the Fc alpha receptor-mediated generation of superoxide anion.

CD4 subsets in IgA nephropathy.

CD45RA+ (2H4+) and CD45RA-(CD29, 4B4+) antigenic expressions, recognized as a suppressor inducer and a helper inducer, respectively, on CD4+ and T alpha 4+ cells (Fc alpha receptor bearing CD4 T cells) were measured by three color flow cytometry in patients with IgA nephropathy (IgAN). The 4B4+ subsets of CD4 and T alpha 4 T cells were increased significantly in the patient group compared with the control group. The level of the 2H4+ subset did not differ between the two groups. No significant correlation was observed between the increase in the 4B4+ subset and disease severity, as estimated by measuring the proteinuria, levels of serum creatinine and immunoglobulins (Igs) or renal tissue damage. It was concluded that 4B4+ CD4+ and 4B4+ T alpha 4+ subsets might be involved in the mechanism of immunopathogenesis of IgA nephropathy.

Increased frequency of the heterozygous switch region of IgA2 in Japanese patients with IgA nephropathy.

The relation between IgA hyperproduction and restriction fragment length polymorphism (RFLP) of the immunoglobulin heavy chain switch (S) region was examined in Japanese patients with IgA nephropathy (IgAN) using Southern blot hybridization. Polymorphism in the S regions of IgM, IgA1 and IgA2 (SA2) was detected. A significant increase in the frequency of heterozygous phenotype of SA2 was shown in the patients. These patients showed a significant increase in the amount of serum IgA, IgA bearing cells and levels of proteinuria. Although two reports on RFLP of the S region have been published in Europe, the results differed. A comparison of the three reports showed different frequencies in the phenotype of the S region between Caucasian and Japanese patients. These results suggested that there is heterogeneity at the S region in IgAN patients in various countries and that this polymorphism might be associated with IgA hyperproduction and the development of proteinuria in Japanese patients.

In vivo antibody response to mucosal (NASAL) and subcutaneous stimulation of influenza virus in patients with IgA nephropathy.

Anomalies in the production of antibodies have been postulated in the development of IgA nephropathy. In order to study the aberrant immune response in patients with IgA nephropathy (IgAN), an influenza virus vaccine was administered to healthy adults and patients with IgAN to demonstrate if there was any in vivo alteration in the antibody production to mucosal and non-mucosal antigenic stimulation in these groups. The vaccine was administered subcutaneously (s.c) or intranasally at a dose of 350 CCA or 1,050 CCA at an interval of 4 weeks, respectively. IgG, IgA, IgM class antibodies to influenza virus were determined using the enzyme linked immunosorbent assay (ELISA). Subcutaneous stimulation induced IgM antibody response in both groups. However, positive response to nasal stimulation was observed only in the patient group. Serum IgA and IgM responses in the patient group were significantly higher than those in the control group. These data suggested that patients with IgA nephropathy showed higher antibody response to mucosal stimulation than healthy controls.