Serum uric acid and renal prognosis in patients with IgA nephropathy

BACKGROUND/AIMS: This study was designed to elucidate the clinical significance of serum uric acid (SUA) and the relationship between hyperuricemia and renal prognosis in IgA nephropathy. METHODS: The correlation between SUA and other clinical parameters were examined in 748 IgA nephropathy patients (432 males and 316 females). Among these patients, 226 (144 males and 82 females) who were followed for more than 5 years were examined for the relationship between hyperuricemia and renal prognosis. RESULTS: In IgA nephropathy, SUA correlated negatively with creatinine clearance (Ccr), and positively with urinary protein and tubulointerstitial damage. SUA was higher in patients with hypertension or diffuse proliferative glomerulonephritis. Hyperuricemia was a risk factor for renal prognosis, both in terms of serum creatinine (p = 0.0025) and Ccr (p = 0.0057). In 56 patients with normal Ccr at renal biopsy, the change of Ccr after more than 8 years was -22.3 +/- 20.8% in 13 patients with hyperuricemia, compared with +2.6 +/- 39.4% in 43 patients without hyperuricemia (p = 0.0238). Hyperuricemia was related independently to deterioration of Ccr (p = 0.0461). CONCLUSION: Hyperuricemia in IgA nephropathy is derived from both glomerular and tubulointerstitial damage, and correlated with hypertension. Hyperuricemia is a risk factor for renal prognosis in IgA nephropathy.     

Superimposition of poststreptococcal acute glomerulonephritis on the course of IgA nephropathy

A 17-year-old male with poststreptococcal acute glomerulonephritis (PSAGN) superimposed on the course of IgA nephropathy is presented. The histological findings of the first renal biopsy showed mild IgA nephropathy with a mesangial deposition of IgA and C3. Eighteen months later, acute nephritic syndrome with hypocomplementemia and rising antihyaluronidase titer occurred 10 days following the onset of an upper respiratory infection. The second renal biopsy revealed severe diffuse endocapillary proliferative and exudative glomerulonephritis with cellular crescents in 70% of the glomeruli. Immunofluorescence showed granular staining of C3 alone along the capillary walls. The pre-existing IgA deposits had disappeared. Typical 'humps' were observed by electron microscopy. The symptoms were gradually resolved by intensive steroid and anticoagulant therapy. Five months after the episode of acute nephritic syndrome, the patient was clear of symptoms except for mild proteinuria and hematuria. The third renal biopsy at that time showed morphologic changes similar to those of the first renal biopsy with mild mesangial IgA deposits.     

Influences of pregnancy on the natural course of chronic glomerulonephritis with impaired renal function]

In an attempt to clarify the influence of pregnancy on the natural course of the chronic glomerulonephritis with impaired renal function (glomerular filtration rate: GFR less than or equal to 70 ml/min), the courses of 14 pregnancies occurring in 10 patients (seven with IgA nephropathy, one with membranoproliferative glomerulonephritis, one with membranous nephropathy and one with hereditary nephropathy) were studied. In 8 patients GFR measured before pregnancies ranged from 46 to 70 ml/min and in the other two creatinine clearance estimated in the first trimester of pregnancies was 62 and 49 ml/min, respectively. The pregnancies resulted in 10 live births, one spontaneous abortion, one artificial abortion and 2 neonatal deaths. In 2 out of 10 live births fetal weight was less than 2500 g. In 3 of 11 pregnancies there was neither increase in urinary protein nor elevation of blood pressure during pregnancies, while seven (64%) had increased proteinuria during the third trimester, and 4 of them were also complicated with hypertension. In 6 of 10 patients, there was no decrease in GFR during pregnancies. In three patients GFR was decreased from 70 to 36 ml/min, 70 to 58 ml/min and 62 to 48 ml/min, respectively. However, these reductions were considered to go with the natural course of respective patients because the reduction slopes were almost the same or rather mild in comparison with those estimated before or after pregnancies. The other patient also had a transient increase in serum creatinine level during two pregnancies, but the reciprocals of serum creatinine concentration before and after the pregnanciesdeclined linearly with time. These data suggest that pregnancy might have little influence on the natural course of the chronic glomerulonephritis even if complicated with renal functional impairment defined as GFR of 70 ml/min or less.     

Steroid and cyclophosphamide therapy for IgA nephropathy associated with crescenteric change: an effective treatment

BACKGROUND: IgA nephropathy is the most common form of idiopathic glomerulonephritis. There is no current consensus on treatment for this condition. We report on the effect of immunosuppression with corticosteroids and cyclophosphamide for the treatment of IgA nephropathy associated with crescenteric change. METHODS: The effect of oral prednisolone (0.8 mg/kg initially, reducing to 0.4 mg/kg after 4 weeks) and cyclophosphamide (1.5 mg/kg) given until a plateau of response was obtained was studied in 9 patients with IgA nephropathy associated with severe inflammatory change and crescents. The initial diagnostic renal biopsies of these patients revealed 25-70% of the glomeruli effected with active cellular crescents. When response to therapy, plateaued cyclophosphamide was discontinued and prednisolone reduced from 0.4 mg/kg. Follow-up renal biopsy was performed in 8 of the 9 patients. Patients were maintained on prednisolone (5- 7.5 mg) and azathioprine (1 mg/kg) for further 2 years. RESULTS: The mean time until discontinuation of cyclophosphamide was 17.8 weeks (+/-1.23, range 12-25 weeks). There were no serious complications of therapy. There was an improvement in renal function in all patients with serum creatinine falling from a mean of 149.6+/-16.5, range 81-227 micromol/l to 116.4+/-8.6, range 80-158 micromol/l, p=0.01. Creatinine clearance improved from a mean of 57.1+/-9.9, range 21-104 ml/min to 87.2+/-10.1, range 39-125 ml/min, p=0.004. 24-hour urinary total protein fell over the same time m period from a mean of 4.54+/-1.1, range 1.0-11.27 g to 1.2+/-0.27, range 0.01-2.65 g, p=0.004. There were no significant differences in blood pressure during this time. Repeat renal biopsies showed significant degrees of histological improvement with healing of crescents and a reduction in acute inflammatory change in all except one patient. The mean period of follow-up after cessation of cyclophosphamide was 17.4+/-2.8 months, range 10-36 months. There was no significant change over this period in serum creatinine, creatinine clearance or urinary protein losses. CONCLUSION: These data suggest that IgA nephropathy associated with severe inflammatory and crescenteric change can be effectively and safely treated with a low-cost regime based on oral corticosteroids and cyclophosphamide tailored to a plateau of treatment response in individual patients.     

IgA nephropathy: prognostic significance of proteinuria and histological alterations

A retrospective study of 166 patients with IgA nephropathy was undertaken to clarify possible correlations between clinical and histological features, and the severity and prognosis of the disease. At the time of biopsy, impaired renal function, with creatinine clearance (Ccr) below 90 ml/min was found in 61 cases. At the final examination, after a mean follow-up period of 34 months, 82 patients had impaired renal function, 12 of these patients went into terminal renal failure requiring hemodialysis treatment. The presence of proteinuria of more than 1.0 g/day was closely correlated with impairment of renal function both at the time of biopsy and at the final observation. An unfavorable outcome was also anticipated in the presence of hypertension. In contrast, microhematuria, macrohematuria or high serum IgA levels did not appear to be related to the outcome. Histologically, sclerotic lesions such as mesangial or global sclerosis, interstitial fibrosis and tubular atrophy, and some active changes such as mesangial hypercellularity and tuft adhesion were more frequent and severe in patients with impaired renal function. Impressive localization of IgA and C3 in the mesangium as well as in capillary loops was observed more often in these patients. These results clearly indicate that IgA nephropathy may follow a slowly progressive course in about half of the patients, and that marked proteinuria and severe histological changes appear to correlate closely with an unfavorable course.     

Apoptotic cells in six patients with IgA nephropathy in repeat biopsies

SUMMARY: Programmed cell death is a selective process of physiological cell deletion and is known as apoptosis. The purpose of the present study was to determine the relationship between the existence of apoptotic cells in glomeruli and the clinical or histopathological findings obtained in repeat renal biopsies of patients with IgA nephropathy. Repeat renal biopsy specimens were obtained from six patients with IgA nephropathy. The nick end labelling method (TUNEL) was used for the detection of apoptotic cells. Clinical laboratory data, i.e. urinary protein excretion, creatinine clearance (Ccr), blood urea nitrogen (BUN) and serum creatinine, (s‐Cr) were obtained from these patients. At the first renal biopsy, apoptotic cells in the glomeruli were observed in three out of six patients using TUNEL. These patients were classified as the severe glomerular damage group. The other three patients without apoptotic cells were in the mild glomerular damage group. Mean levels of urinary protein excretion at the first renal biopsy in the patients with apoptotic cells were slightly higher than those in patients without apoptotic cells. Levels of Ccr in patients with apoptotic cells were lower than those in patients without apoptotic cells. There were no significant differences in the levels of BUN and s‐Cr in patients with or without apoptotic cells. Two patients with apoptotic cells in glomeruli at the first renal biopsy did not show apoptotic cells at the second renal biopsy. These two patients showed improvement not only in clinical laboratory findings but also in histological findings at the second biopsy. Only one patient with apoptotic cells at the first and second biopsies exhibited deterioration at the second biopsy. All three patients without apoptotic cells at the first renal biopsy also showed deterioration of the clinical laboratory and histopathological findings. It is postulated that various factors other than apoptosis might induce progression of renal injuries in such patients. It appears that the clinical laboratory data, i.e. proteinuria, renal function and histopathological findings, might be influenced by apoptosis in patients with IgA nephropathy. It is postulated that apoptosis may induce reduction of excess proliferative glomerular mesangial cells and/or infiltrating cells and tissue repair.     

Steroid therapy in IgA nephropathy: a retrospective study in heavy proteinuric cases

29 patients with IgA nephropathy whose proteinuria persisted at a level of 2.0 g/day or more and who received prednisolone treatment for 1-3 years were retrospectively evaluated on their clinical courses. 13 of 14 patients with renal dysfunction of less than 70 ml/min in initial creatinine clearance (Ccr) values subsequently entered a progressive course during a follow-up period of 47 months, leading to end-stage renal failure in 8 cases. On the other hand, only 1 of the other 15 patients with preserved renal function of 70 ml/min or more ended up with end-stage renal failure during a follow-up period of 74 months, although 7 underwent a progressive course. Three patients in the latter group experienced a prominent reduction in proteinuria to less than 1.0 g/day and maintained renal function. Meanwhile, the steroid group of moderate proteinuric patients with a creatinine clearance greater than 70 ml/min had a benign course, while the nonsteroid group had an unfavorable one. These results suggest that steroid therapy in IgA nephropathy may be able to stabilize a progressive course, especially in the early stage of the disease, although, because they come from an uncontrolled study, a definite conclusion cannot be drawn.     

Three cases of pregnancy in primary glomerulonephritis with successful outcomes in spite of severe histological findings]

When women with kidney disease wish to have children, concerns are raised about the adverse effect on their renal function. Although the situation is less clear in regard to the effects, there is general agreement that a moderately severe decrease in renal function, especially in the presence of significant hypertension, reduces the chance of conception, and a successful outcome of gestation. On the other hand, several reports maintain that in most patients, pregnancy does not change the natural history of glomerular disease. Accordingly, we reported successful cases in whom renal function remained preserved. The three cases suffered from different types of glomerulonephritis (GN) and percutaneous renal biopsies were conducted before pregnancy. All biopsy specimens were examined by light and immunofluorescence microscopy, and were diagnosed as IgA nephropathy, sclerosing GN and membranoproliferative GN, respectively. Since severe histological findings were found and their data worsened (serum creatinine > 1.3 mg/dl, 24-hr creatinine clearance < 70 ml/min), their chance of having children appeared low. However, as we did not observe deterioration of clinical findings and hypertension over the ten-year follow-up, we allowed conception resulting in the birth of normal children. Thus we should mention the relatively favourable courses of nephropathy in some patients with GN, particularly in patients with stable renal disease and normal blood pressure, it should not be considered an indication for termination. It is important to observe the status of glomerular disease for as long as possible.     

Therapy of IgA nephropathy with mycophenolate mofetil--report of 3 cases

Mycophenolate mofetil is an immunosuppressive agent in transplantation which inhibits the purin neogenesis. Proliferating lymphocytes are suppressed and antibody production is decreased. Many cases of successful therapy in different kidney diseases are reported, such as diffuse proliferative lupus nephritis, pauci-immune necrotizing glomerulonephritis, focal segmental glomerular sclerosis and IgA nephropathy. We report 3 patients with IgA nephropathy who were treated with mycophenolate mofetil for more than 1 year. In all patients, proteinuria decreased significantly and the renal function remained stable. In 2 patients, kidney biopsy was repeated after 12 months and 18 months, respectively. There were no histological signs of progression of the disease. Two patients developed infections during treatment. One patient had a pneumonia, and a second patient an infection with varizella zoster. Based on our data, mycophenolate mofetil can be a potential treatment of IgA nephropathy. Further controlled studys are warranted to investigate the role of mycophenolate mofetil in IgA nephropathy.     

强直性脊柱炎肾损害的临床病理特点

目的探讨强直性脊柱炎（AS）合并肾损害的临床及病理特点。方法回顾性分析18例经肾脏活体组织检查的AS患者的临床及肾脏病理表现。结果18例患者中,9例呈隐匿性肾小球肾炎表现,5例呈慢性肾小球肾炎表现,1例呈肾病综合征表现,3例为慢性肾功能不全;4例血压增高,14例血压正常。24h尿蛋白定量平均为（1．17±1．39）g。15例肾功能正常,3例肾功能异常患者血肌酐平均为（153．2±36．8）umol／L。8例患者血清IgA水平升高,10例c反应蛋白升高,13例红细胞沉降率（EsR）增快,且血清IgA水平和C反应蛋白呈正相关（r=0．707,P=0．001）,血清IgA水平和ESR呈正相关（r=0．858,P〈0．001）。病理检查结果发现15例为IgA肾病（其中10例为轻度系膜增生性肾炎,1例为轻度系膜增生性肾炎并慢性肾小管间质肾病,2例为局灶增生性肾炎,1例为局灶增生坏死性肾炎,1例为局灶节段性肾小球硬化症）,1例为膜性肾病,1例为局灶增生性肾炎伴慢性肾小管间质肾病,1例为慢性。肾小管间质肾病。有慢性肾小管间质肾病者均有服中药史。结论AS相关性肾损伤的病理改变多样,但主要为IgA肾病,也可表现为膜性肾病、局灶增生性肾炎和慢性肾小管间质。肾病,其肾损伤可能与AS疾病本身和（或）治疗用药相关。     

Crescentic, proliferative IgA nephropathy: clinical and histological response to methylprednisolone and intravenous cyclophosphamide.

BACKGROUND: IgA nephropathy is an immune-complex glomerulopathy that can result in capillary or extra-capillary proliferation. Previous attempts to correlate specific histological findings including cellular crescents or endocapillary proliferation, with clinical outcomes, have produced conflicting results. METHODS: We conducted a prospective open-labelled trial of 12 patients with crescentic, proliferative IgA nephropathy and clinically progressive disease and treated them with pulse steroids and intravenous cyclophosphamide. Therapy included pulse solumedrol at 15 mg/kg/day for 3 days, followed by monthly intravenous cyclophosphamide at 0.5 g/m(2) body surface area for 6 months. Clinically significant proteinuria (>1.0 g/24 h) was present in all patients, while nephrotic-range proteinuria (>3.0 g/24 h) was observed in eight of 12 patients. All patients were hypertensive (BP >140/90 mmHg). RESULTS: After 6 months of treatment, the mean serum creatinine was reduced from a maximum of 2.65+/-0.39 to 1.51+/-0.10 mg/dl (P<0.03), while proteinuria was reduced from 4.04 to 1.35 g/24 h (P<0.01). The mean slope of 1/serum creatinine increased from -0.0398+/-0.02 to 0.0076+/-0.01 after 6 months of therapy, but this trend did not reach statistical significance (P<0.08). A repeat kidney biopsy was performed in all treated patients. Endocapillary proliferation, cellular crescents and karyorrhexis were eliminated in all 12 patients after 6 months of therapy, while interstitial fibrosis and tubule dropout remained unchanged. To determine the long-term efficacy of the treatment, treated patients were compared to 12 historical controls matched for severity of IgA on initial biopsy. After 36 months, the rate of end-stage renal disease in the treated group was lower (1/12) than in the historical controls (5/12). CONCLUSIONS: We conclude that steroids and intravenous cyclophosphamide reduce proliferative lesions, reduce proteinuria and stabilize renal function in patients with crescentic IgA nephropathy.     

Glomerular nephropathy associated with chronic Q fever

Of three patients with Coxiella burnetii endocarditis, two developed focal segmental proliferative glomerulonephritis (GN), and the third developed diffuse intracapillary proliferative glomerulonephritis. In one case, a good therapeutic response was followed by partial remission of the renal alterations, but 10 months later there were clinical and histological signs of active glomerular nephropathy, suggesting that the antigenic stimulus persisted. In another case, poor evolution of the infection was accompanied by clinically and histologically aggressive glomerular nephropathy, and advanced renal failure. The third patient, who had diffuse proliferative glomerulonephritis, underwent renal biopsy earlier than the other two cases, and the behavior of the nephropathy has not been aggressive to date. Immunohistopathologic study revealed a diffuse granular deposit of IgM and C3 in all three cases; the first two also presented a discrete linear IgG deposit in the capillary loops. Attempts to identify C burnetii antigen at the glomerular level by immunohistologic techniques failed in two patients. The literature on the association of chronic Q fever with glomerulonephritis is briefly reviewed.     

C1q nephropathy: do C1q deposits have any prognostic significance in the nephrotic syndrome?

C1q deposits are usually found in association with other complement components and immunoglobulins in proliferative glomerulonephritis and may predominate in systemic lupus erythematosus (SLE). We report the clinical outcome of four patients who developed a nephrotic syndrome associated with C1q nephropathy unrelated to SLE. On presentation the mean urinary protein loss was 6.8 g/24 h (range 4-10), and renal function impaired, mean serum creatinine 201 mumol/l (150-400). Over a mean follow up period of 6.5 years (1.7-19), all four patients improved, three spontaneously and one treated with steroids and cyclosporin, to a current urinary protein loss of 0.3 g/24 h (less than 0.2-0.9) and serum creatinine 98 mumol/l (68-115). C1q nephropathy was confirmed in each biopsy by conventional immunohistology. C1q deposits were demonstrated within the glomerular basement membrane of three biopsies and the mesangium in two samples. One patient had been categorized on light- and electron-microscopy as having mesangiocapillary glomerulonephritis, one membranous glomerulonephritis, one proliferative glomerulonephritis with focal segmental glomerulosclerosis, and one diffuse proliferative glomerulonephritis with both subendothelial and mesangial dense deposits. In view of the expected progressive nature of the underlying renal histopathological appearance, the presence of predominant C1q deposits would appear to be associated with a better clinical outcome.     

Significance of tubulointerstitial lesions in biopsy specimens of glomerulonephritic patients

To evaluate the significance of tubulointerstitial lesions in the cortical area of renal biopsy specimens, clinicopathological studies were performed on 101 cases of IgA nephropathy, 31 cases of IgA-negative (non-IgA) proliferative glomerulonephritis and 75 cases of idiopathic membranous glomerulonephritis. The degree of tubulointerstitial lesions was assessed semiquantitatively by light microscopic observation and was correlated with the several histopathological and clinical parameters at biopsy, as well as with status at final follow-up (average follow-up period: 72 months). In these three types of glomerulonephritis, the degree of tubulointerstitial lesions in the cortical area was clearly correlated with the severity of glomerular injury, the prevalence of segmental sclerosis, global sclerosis, arteriolosclerosis, decreased renal function (GFR less than 70 ml/min) and hypertension (greater than 150/90 mm Hg) at the time of biopsy. The prevalence of stable renal function at final follow-up was statistically higher in the cases without tubulointerstitial lesions or with those whose lesions included less than 20% of the cortical area. From the above data, it was concluded that a semiquantitative evaluation of tubulointerstitial lesions in the cortex would reflect the severity of glomerular injury and also contribute to the assessment of prognosis in such primary glomerulonephritic patients.     

Treatment of IgA nephropathy with eicosapentanoic acid (EPA): a two-year prospective trial

Thirty-seven patients with biopsy proven mesangial IgA nephropathy were prospectively allocated to either two years of treatment with eicosapentanoic acid (EPA) 10 g per day or no treatment. At entry treated and untreated patients with renal dysfunction (Group A) or patients with normal serum creatinine less than 0.12 mmol/l (Group B) did not differ in serum creatinine, creatinine clearance, urinary protein excretion, or quantitative urinary red cell counts. Compliance with EPA therapy was excellent as assessed by plasma fatty acid profiles. At the end of the trial creatinine clearance in treated patients had gone from 80 +/- 16 to 57 +/- 17 ml/min (p less than 0.05) and in untreated patients from 76 +/- 18 to 55 +/- 14 (p less than 0.05). There were no beneficial effects in either Group A or Group B patients. The only two patients who had improvement in renal function were in the EPA treatment group. Although no side effects of treatment were noted, EPA does not alter the course of established mesangial IgA nephropathy.     

Clinical presentation, natural history, and treatment of crescentic proliferative IgA nephropathy

IgA nephropathy is one of the most common causes of glomerulonephritis in the world and is characterized histologically by the deposition of polymeric forms of IgA within the mesangium and in some cases along the glomerular capillary wall.(1) Proliferative and crescenteric forms of IgA are associated with nephrotic range proteinuria, accelerated hypertension, and a more rapid decline toward end-stage renal disease. Previous attempts to categorize the incidence and clinical significance of proliferative IgA nephropathy have given conflicting results. This is in part the result of the lack of a uniform nomenclature and the failure of clinical therapies to prolong renal survival in specific subgroups. In the present study, we performed a prospective open-label trial of pulse solumedrol and intravenous cyclophosphamide in 20 patients with IgA nephropathy and at least 10% cellular crescents or endocapillary proliferation on renal biopsy. Seventeen patients underwent repeat kidney biopsies after 6 months of therapy, and the morphologic response to treatment was assessed using a modified systemic lupus erythematosis (SLE) histologic activity and chronicity index score. To determine the long-term efficacy of intravenous cyclophosphamide on renal survival, the results of the treated patients were compared with 12 untreated historical controls. Pulse solumedrol and intravenous cyclophosphamide effectively reduced peak serum creatinine, degree of proteinuria, the rate of decline in renal function, and the incidence of end-stage renal disease at 36 months.     

Histological features of IgA glomerulonephritis as predictors of pregnancy outcome

116 pregnancies undertaken by 70 women with IgA glomerulonephritis and their diagnostic renal biopsies have been reviewed. An IgA diffuse mesangial proliferative lesion with superimposed focal and segmental proliferative lesions (IgA FSP) on diagnostic renal biopsy was associated with a greater incidence of maternal complications than IgA diffuse mesangial proliferative glomerulonephritis with no superimposed lesions (IgA DMP) and IgA diffuse mesangial proliferative glomerulonephritis with superimposed focal and segmental hyalinosis and sclerosis (IgA FSHS) (p less than 0.025). Patients with severe vessel lesions had a significantly greater incidence of fetal loss than those with only mild to moderate lesions (p less than 0.025).     

Significance of levels of circulating IgA-class immune complex in discriminant analysis of patients with IgA nephropathy before renal biopsy

Discriminant analysis of clinical markers including circulating IgA-class immune complex (IgA-CIC) before renal biopsy in patients with IgA nephropathy is described. Fifty-six patients with IgA nephropathy (IgA nephropathy group) and 54 patients with other primary chronic glomerulonephritis (non-IgA nephropathy group) were examined. Discriminant analysis was applied to separate these two groups by using 21 clinical markers including levels of IgA-CIC. The levels of IgA-CIC in sera were measured by a solid-phase anti-C3 Facb enzyme immunoassay (EIA). Among these clinical markers, the levels of serum IgA, IgA-CIC and creatinine, and the degree of microhematuria in the IgA nephropathy group were significantly higher than those in the non-IgA nephropathy group. Contributions of IgA and IgA-CIC to the classification were very high and both had almost the same effect. The correct classification rate was 80.00% using five clinical markers: serum IgA, microhematuria, IgA-CIC, serum creatinine, and blood urea nitrogen. It was shown that the levels of serum IgA and IgA-CIC were major markers for the clinical diagnosis of patients with IgA nephropathy. It was concluded that discriminant analysis before renal biopsy was useful for the diagnosis of IgA nephropathy.     

Discriminant analysis of clinical markers before renal biopsy in patients with IgA nephropathy

Discriminant analysis of clinical markers before renal biopsy in patients with IgA nephropathy is described. Sixty eight patients with IgA nephropathy (IgA nephropathy group) and 66 patients with other chronic glomerulonephritis (non-IgA nephropathy group) were examined. The discriminant analysis was applied to separate those two groups by using twenty clinical parameters as well as binding capacity of serum IgA to the glomeruli of renal specimens. Binding of serum IgA of patients to the glomeruli obtained from patients with IgA nephropathy was performed using avidin-biotin immunofluorescence. Among twenty clinical markers, the levels of serum IgA and creatinine, and degree of microhematuria in IgA nephropathy group were significantly higher than those in non-IgA nephropathy group Furthermore, the positive incidence of serum IgA binding of IgA nephropathy group was significantly higher than that of serum IgA binding of non-IgA nephropathy group. The correct classification rate were 79.10% using five clinical markers including serum IgA, microhematuria, serum C4, quantitation of proteinuria and degree of proteinuria. It is indicated that the levels of serum IgA and the binding of serum IgA to the glomeruli were considered to be major markers for clinical diagnosis of patients with IgA nephropathy It was concluded that the discriminant analysis before renal biopsy was useful for diagnosis of IgA nephropathy.     

Strong association between IgA nephropathy and hepatitis B surface antigenemia in endemic areas

The frequency of hepatitis B surface antigen (HBsAg) was studied in the sera of 122 patients with primary IgA nephropathy. Hepatitis B surface (HBs) antigenemia was detected in 21 patients (17.2%) and this was significantly higher than the prevalence of HBsAg carrier in the general population (p less than 0.01). These patients had no clinical or laboratory findings to suggest acute or chronic liver diseases. Two glomerulopathic entities: mesangial proliferative glomerulonephritis with predominant mesangial IgA deposits and a mixed picture of membranous nephropathy with capillary IgG deposits and mesangial proliferative glomerulonephritis with mesangial IgA deposits, were observed in this group of patients. Glomerular deposits of HBsAg, hepatitis B core antigen (HBcAg), and both HBsAg and HBcAg were detected in three, five and four renal biopsy specimens respectively. Replication of hepatitis B virus (HBV) was suggested in two of the six renal biopsy specimens examined by HBV DNA gene probe. During the mean study period of 40 months (range 12-84), 19% of these patients with hepatitis B virus-associated IgA nephropathy developed progressive renal deterioration and one required maintenance dialysis therapy. Our study suggests that hepatitis B virus antigenemia may play a significant pathogenetic role in the development of IgA nephropathy in areas of high HBV endemicity and these HBV-associated IgA nephropathies can run an indolent but relentless slowly progressive clinical course.