Ruriko Nozawa

Clinicopathological features and the prognosis of IgA nephropathy in Japanese children on long-term observation.

AIMS Clinicopathological features were investigated to clarify the ultimate prognosis and prognostic indicators for patients with IgA nephropathy in Japanese children. METHODS We evaluated the outcomes of 181 patients in whom IgA nephropathy was diagnosed before the age of 15 years since September 1979 and followed-up at least for three years with regard to clinical data at the onset of symptoms and renal histologic data. RESULTS After mean follow-up of 7.3 years from onset, 91 patients of 181 (50.3%) were in clinical remission at the last examination, 24 (13.2%) had isolated hematuria, 59 (32.6%) had hematuria and proteinuria. Eighteen of 59 (9.9%) had proteinuria more than 1 g per 24 hours. Hypertension was observed in 12 cases and 7 (3.9%) developed end-stage renal disease. Except 7, no patient had reduced renal function and elevated serum creatinine at the final follow-up. Predicted renal survival rate from onset was 92.3% at 10 years and 89.1% at 20 years. In multivariable analysis, age at onset and chronic changes of tubulointerstitium were associated with poor outcome. CONCLUSIONS Of 181 children with IgA nephropathy, 50% regressed, remaining 46% had hematuria and/or proteinuria and 4% of patients lapsed into end-stage renal disease. Our results indicate that childhood IgA nephropathy has a benign course and the risk for end-stage renal disease is lower than that of adults. Age at onset and tubulointerstitial lesions were the strong predictors of a progressive course of childhood IgA nephropathy.

Efficacy of Multidrug Therapy Combined with Mizoribine in Children with Diffuse IgA Nephropathy in Comparison with Multidrug Therapy without Mizoribine and with Methylprednisolone Pulse Therapy

Aim: To evaluate the efficacy of prednisolone, warfarin, and dipyridamole therapy combined with mizoribine (PWDM) in the treatment of diffuse immunoglobulin A (IgA) nephropathy in comparison with prednisolone, warfarin, and dipyridamole therapy without mizoribine (PWD) and with methylprednisolone pulse therapy (PWD pulse). Methods: We collected data on 61 patients diagnosed with diffuse IgA nephropathy, and these patients were retrospectively divided into three groups without randomization. Group A included 21 patients before 1987 who were treated with PWD for 24 months, group B included 20 patients from 1987 to 1989 who were treated with PWD pulse therapy for 24 months, and group C included 20 patients after 1990 who were treated with PWDM for 24 months. Clinical features and pathological findings in each group were analyzed retrospectively. Results: The time from initiation of therapy in group A, group B, and group C was 8.9 ± 5.2, 8.1 ± 3.9, and 7.7 ± 3.8 years, respectively. At the latest follow-up examination, the mean urinary protein excretion (mg/m2/h) was 17 ± 10 in group A, 22 ± 20 in group B, and 6 ± 6 in group C and had decreased significantly in group C as compared with the other groups. The activity index in all three groups was lower at the second biopsy than that at the first biopsy (5.1 ± 0.8 vs. 6.5 ± 2.1 in group A, p < 0.05; 5.6 ± 0.9 vs. 6.6 ± 1.7 in group B, p < 0.01, and 4.5 ± 1.0 vs. 6.8 ± 1.9 in group C, p < 0.01). The chronicity index in groups A and B at second biopsy was higher than at first biopsy (7.3 ± 1.4 vs. 4.8 ± 1.0 in group A, p < 0.01, and 8.1 ± 2.0 vs. 5.3 ± 0.9 in group B, p < 0.01), but was unchanged in group C. At the latest follow-up examination, 1 patient (4.8%) in group A, 3 patients (15%) in group B, and none (0%) in group C had renal insufficiency. Conclusion: These results suggest that PWDM appears to be more effective than PWD or PWD pulse in ameliorating proteinuria and histological severity of patients with IgA nephropathy.

Efficacy of Prednisolone and Mizoribine Therapy for Diffuse IgA Nephropathy

Objective: There have been only a few studies concerning oral prednisolone and mizoribine therapy for diffuse IgA nephritis (IgAN). We evaluated the efficacy of prednisolone and mizoribine therapy for diffuse IgAN. Methods: We enrolled 34 patients who had been diagnosed as having diffuse IgAN with severe proteinuria during the period from 1992 to 1999. Following diagnostic renal biopsy, the patients were treated with prednisolone, mizoribine, warfarin and dilazep dihydrochloride. The clinical features, laboratory data and pathological findings between pre- and post-therapy were investigated. Results: The mean urinary protein excretion after 6 months of treatment had decreased significantly compared to pre-therapy. The incidence of hematuria in post-therapy was lower than that of pre-therapy. The grading index decreased significantly from 4.8 ± 2.1 at the first biopsy to 2.3 ± 1.7 at the second biopsy (p < 0.001) and the staging index decreased significantly from 4.1 ± 1.9 at the first biopsy to 2.7 ± 2.4 at the second biopsy (p < 0.05). Macrophage infiltration and α-smooth muscle actin-positive cells in the glomerulus and interstitial region decreased significantly in post-therapy compared with pre-therapy. At the most recent follow-up, none of the 34 patients had renal insufficiency. Conclusions: Our study suggested that prednisolone and mizoribine therapy is effective for those patients with the risk of progression of IgAN.

Efficacy of school urinary screening for membranoproliferative glomerulonephritis type 1

Aims: In order to evaluate the efficacy of a school urinary screening programme, children with membranoproliferative glomerulonephritis (MPGN) type 1 were studied. Methods: A total of 52 patients who had been diagnosed with MPGN type 1 from 1970 to 1997 were studied; 35 were identified after 1974 on screening (group S), and 17 were identified by presenting symptoms (group N), mostly before 1989. Results: Mean blood pressure was 89 mm Hg in group S and 104 mm Hg in group N; urinary protein excretion was 0.9 g/day in group S and 3.0 g/day in group N. Histopathological evidence of chronic changes was found in six group S and 15 group N patients. No patients in group S had renal insufficiency, but five patients in group N required regular haemodialysis. Conclusions: Results suggest that early identification by school urinary screening may enable early management and so improve prognosis of MPGN.

A 12-year-old girl with hemolytic uremic syndrome as initial symptom of systemic lupus erythematosus and a literature review

We describe a 12-year-old girl with systemic lupus erythematosus (SLE) who first presented with an atypical hemolytic uremic syndrome (HUS) associated with hypocomplementemia, and compare the clinical manifestations and prognosis between SLE patients with HUS and thrombotic thrombocytopenic purpura in the reported literature. Diagnoses were based on renal failure, hemolytic anemia, and thrombocytonemia, including the observation of fragmented red blood cells, hypocomplementemia and on the American College of Rheumatology criteria for SLE. Cocktail therapy may have been effective against the pathological condition of SLE. In 4 patients with SLE and HUS, prednisolone and immunosuppressive drugs were administered, and none of the patients suffered from chronic renal insufficiency. The prognosis for SLE patients with HUS is good. These findings suggest that SLE should be suspected in any HUS patient presenting with hemolytic anemia, thrombocytopenia, acute renal failure and hypocomplementemia, and the therapeutic response and prognosis for SLE with HUS are good.

Glomerulonephritis associated with chronic infection from long-term central venous catheterization

There have been few reports on immune complex-mediated glomerulonephritis associated with chronic infection from long-term central venous catheterization in adulthood. We report here on a 13-year-old boy with nephritis who exhibited glomerulonephritis that had been induced by the long-term use of central venous catheters, and its resolution after extraction of the central venous catheter. A diagnosis of glomerulonephritis associated with chronic infection caused by long-term central venous catheterization was made, based on the absence of clinical findings after removal of the catheter, hypocomplementemia, pathology findings resembling membranoproliferative glomerulonephritis, and detection of Staphylococcus epidermidis from culture of the removed catheter culture. For clinicians using long-term central venous access for parenteral feeding, rapid catheter exchange is necessary for patients with fever of unknown origin.

Renal Effects of Coxsackie B4 Virus in Hyper-IgA Mice

For clarification of the pathogenetic role of viral infection in chronic glomerulonephritis, the renal effects of Coxsackie B4 virus (CB4) were examined in hyper-IgA (HIGA) mice. In experiment 1, HIGA mice (n = 75) were inoculated intravenously with live CB4 and inactivated CB4 once a month from 1 to 12 mo of age. In experiment 2, HIGA mice (n = 45) were inoculated intravenously with live CB4 and inactivated CB4 once at 6 wk of age. In experiment 3, 60 mice were inoculated intravenously with carbon and live or inactivated CB4 once at 6 wk of age. Mice in the control group were inoculated with vehicle. The kidneys were extirpated from five mice of each group killed with time after inoculation for histologic evaluation. The scores for mesangial IgA deposition, PCNA-positive cells, and matrix at 20 wk were higher in mice with live CB4 than in mice with inactivated CB4 or without CB4. On electron microscopic examination, swelling and detachment of endothelial cells from 24 h after inoculation and increase of serum IFN-gamma concentration were found in mice with live CB4. Many carbon particles were present in peripheral and central zones of the mesangium from 5 to 10 d in mice with carbon and live CB4. These results suggest that CB4 provokes exacerbation of renal pathologic findings in HIGA mice via endothelial injury, IFN-gamma production, and dysfunction of the mesangial pathway.

Poor Renal Accumulation of 99mTc-DMSA in Idiopathic Tubular Proteinuria

In Japanese patients idiopathic tubular proteinuria presents mainly as asymptomatic tubular low molecular weight proteinuria. This disease has recently been shown to resemble Dent’s disease which is characterized by tubular proteinuria, hypercalciuria, rickets and eventual renal failure. We report on 4 children with idiopathic tubular proteinuria. Although they had normal renal function, as evidenced by serum creatinine or creatinine clearance, they had very poor renal accumulation of 99mTc-DMSA and the presence of large amounts of tracer in the bladder. Additionally, the patient with the largest amounts of tubular proteinuria had the poorest renal accumulation of the 4 patients. The renal accumulation of tracer decreased with time from a maximum at 10 min after injection. These findings demonstrate that the tracer, once taken to be confined to the proximal tubular cells, is immediately excreted to the tubular lumen. We suggest that poor renal accumulation of 99mTc-DMSA is very important in elucidating the mechanism of idiopathic tubular proteinuria, and that 99mTc-DMSA renoscintigraphy is useful in the evaluation of the patient’s renal function over time.

Epstein-Barr virus-associated hemophagocytic syndrome in a patient with lupus nephritis

Hemophagocytic syndrome (HPS) is an unusual but severe illness associated with a variety of infections, as well as genetic, malignant tumors, and autoimmune diseases. We report an 11-year-old girl with systemic lupus erythematosus and nephritis who developed HPS associated with Epstein-Barr virus reactivation. In our patient, the onset of reactive HPS might be related to immunosuppressive treatment during the course of lupus nephritis.

Prediction of Relapse by Plasma Lipoprotein(a) Concentration in Children with Steroid-Sensitive Nephrotic Syndrome

Aim: To clarify whether plasma lipoproteins, including Lp(a), can predict relapse pattern in the first years after diagnosis of nephrotic syndrome (NS), we evaluated them in patients with steroid-sensitive NS. Methods: We analyzed the medical records of 35 patients with steroid-sensitive NS who were seen by us from January 1992 to December 1999 followed for at least 1 year. These patients were divided into two groups. Group 1 consisted of 20 patients who infrequently relapse (IR: <2 in 6 months or <3 in a year), group 2 consisted of 15 patients who frequently relapse (FR: ≥2 in 6 months or ≥3 in a year). Clinical and laboratory findings such as age at onset, gender, urinalysis, serum level of total protein, albumin, and concentrations of serum lipid including lipoprotein(a) (Lp(a)) were investigated between group 1 and group 2. Results: The concentration of plasma Lp(a) in group 2 was higher than that in group 1 (81.0 ± 35.2 vs. 35.9 ± 26.5 mg/dl, p < 0.01). On multivariate analysis using logistic regression model, the concentration of plasma Lp(a) was an independent risk factor for relapse of NS. Conclusions: Our findings suggest that of all the laboratory data examined, high values of Lp(a) can predict future relapse of NS and should be well documented.