Effect of Pregnancy and Delivery on the Renal Function and the Prognosis of Patients with Chronic Kidney Disease Stage 3 Caused by Immunoglobulin A Nephropathy.

OBJECTIVE: Immunoglobulin A nephropathy (IgAN) exhibits a peak onset that coincides with the reproductive age. Therefore, many young women with IgAN may become pregnant. However, the outcome of pregnancy in women with renal diseases remains controversial, and the characteristics and outcome of pregnancy in IgAN patients must be further evaluated. METHODS: A prospective follow-up study of 64 pregnant women with IgAN was performed by analyzing the laboratory data and prognosis. To clarify the influence of renal insufficiency, we compared these patients according to the chronic kidney disease (CKD) stage with special attention to CKD stage 3 [N=16 in total, N=9 for estimated glomerular filtration rate (eGFR) ≥45 mL/min, N=7 for <45 mL/min]. RESULTS: We found that pregnancy and delivery did not produce any significant changes in the renal function for patients with CKD stage 3 (≥45 mL/min) at five years after delivery, although proteinuria was elevated at 30 weeks of pregnancy and at three months after delivery. However, only for patients with CKD stage 3 (<45 mL/min) was there a significant deterioration in the eGFR at five years after delivery. Additionally, the data of pregnant women with CKD stage 3 were compared with those of 22 nonpregnant women with similar clinical and demographic characteristics. CONCLUSION: Pregnant patients with IgAN (CKD stage 3, eGFR ≥45 mL/min) did not exhibit any significant reduction in the renal function at five years after delivery as compared with the baseline, which was similar to the findings in nonpregnant patients. Thus, while pregnancy with CKD stage 3 (eGFR ≥45 mL/min) was not a risk factor, patients with CKD stage 3 (eGFR <45 mL/min) showed a worsened renal function five years after delivery.

Combined IgG4κ and IgG1λ deposition in the glomerular and tubular basement membrane accompanied by autoimmune neutropenia (AIN) and immune thrombocytopenia (ITP).

A 48-year-old male was admitted to our hospital with nephrotic syndrome. Light-microscopic examination of a renal biopsy specimen showed almost normal glomerular appearance, however, immunofluorescence examination revealed linear and granular IgG deposits on the glomerular basement membrane (GBM), accompanied by slight IgG deposition in the tubular basement membrane (TBM). Further investigation of the IgG subclass and light chain staining revealed that the glomerular deposits were composed of IgG1 and IgG4, with both κ and λ light chains, while the tubular deposits were composed of only IgG4 and κ light chains. The electron-microscopic findings of small granular deposits in the GBM and TBM closely resembled those of light and heavy chain deposition disease (LHCDD). Immunoelectron microscopy confirmed the presence of κ and λ chains in the GBM and TBM, however, only significant κ chain deposition was found in the TBM. There was no evidence of monoclonal gammopathy. Clinically, the patient subsequently developed neutropenia and thrombocytopenia associated with the presence of anti-neutrophil antibody and anti-GPIIb/IIIa antibody-producing B cells in the blood. Oral steroid administration was initiated, which led to amelioration of the neutropenia, thrombocytopenia and proteinuria. This may be a very rare case of combined IgG4κ and IgG1λ deposition disease accompanied by autoimmune neutropenia (AIN) and immune thrombocytopenia (ITP) suggestive of biclonal immunoglobulin deposition disease (BIDD). Investigation of the IgG subclass and of the light chains was useful for recognizing the clonality of the immunoglobulin deposits in the kidney.

High uric acid level is a risk factor for progression of IgA nephropathy with chronic kidney disease stage G3a.

BACKGROUND: High uric acid level is a known risk factor for deterioration of renal function in chronic kidney disease (CKD), but its influence on the progression of IgA nephropathy (IgAN) remains unclear. METHODS: Adult IgAN patients (n = 611) were classified according to CKD stage. Renal survival rates and clinical and histological findings were compared between patients with high (H-UA) and normal (N-UA) uric acid levels in different CKD stages. RESULTS: The proportion of patients with H-UA increased significantly with increasing CKD stage (stage G1, 12.3%; stage G2, 19.0%; stage G3a, 43.7%; stage G3b-4, 69.0%; P < 0.001). The 30-year renal survival rate was similar in patients with H-UA and N-UA in CKD stages G1, G2, and G3b-4, but was significantly lower in patients with H-UA than with N-UA in CKD stage G3a (24.7 vs. 51.9%; P = 0.0205). The clinical findings were similar in patients with H-UA and N-UA, but the interval from onset to biopsy differed between groups. The proportion of patients with global sclerosis was significantly higher in patients with H-UA than with N-UA in CKD stage G3a (33.3 vs. 11.4%; P = 0.0005), but the Oxford classifications were similar between groups. Multivariate Cox regression analysis identified H-UA (HR 1.36, 95% CI 1.07-1.72, P = 0.011) and a large amount of proteinuria (HR 1.38, 95% CI 1.09-1.74, P = 0.0084) as independent predictors of end-stage renal disease. CONCLUSIONS: H-UA induced global glomerular sclerosis and accelerated the progression of IgAN in CKD stage G3a.

Long-term damage assessment in patients with microscopic polyangiitis and renal-limited vasculitis using the Vasculitis Damage Index.

OBJECTIVES: The Vasculitis Damage Index (VDI) is used to define the degree of damage occurring in patients with systemic vasculitis. We conducted a retrospective study of 30 patients with microscopic polyangiitis (MPA) and renal-limited vasculitis (RLV). METHODS: The clinical data and VDI of the 30 patients enrolled in the study were collected and assessed for a period of 5 years. RESULT: The VDI score, which was 2.5 at 1 year after the initial diagnosis, increased gradually to 4.3 at 5 years post-diagnosis. The degrees of musculoskeletal and ocular damage significantly increased during the 5-year period (p = 0.001 and p = 0.002, respectively). The most frequent damage items in the VDI were cataract (13 %), hypertension (12 %), diabetes mellitus (9 %), and osteoporosis (6 %). The VDI score was significantly higher in the groups of patients who showed relapse or MPA than in the groups of patients who did not show relapse or RLV at 5 years (p = 0.02 and p = 0.03, respectively). In addition, a significant correlation was found between the VDI score at 5 years and the Birmingham Vasculitis Activity Score at diagnosis (p = 0.04, r = 0.4). CONCLUSION: The VDI was found to be a useful tool for determining the severity of damage caused by disease and the effects of treatment. The individual contributions of the VDI items may also be applied to treatment decisions.

Clinical and pathological studies of IgA nephropathy presenting as a rapidly progressive form of glomerulonephritis.

OBJECTIVE: IgA nephropathy (IgAN) is widely regarded as a slowly progressive disease. However, a minor population of patients present with a rapidly progressive form of glomerulonephritis (RPGN). METHODS: We studied 25 cases of IgAN who presented with RPGN. The laboratory data, histology, and five-year prognosis after diagnostic renal biopsy were evaluated. We compared the data of these patients with those of 495 patients with the non-RPGN type. In addition, we divided the patients with the RPGN type of IgAN into a group with reduced renal function and a group with maintained renal function, and compared the data between the two groups. RESULTS: In the 'RPGN type', the serum creatinine levels and a 24-hour urinary protein excretion were significantly higher than in the non-RPGN type. Histological examinations showed that the rates of endocapillary hypercellularity and tubular atrophy/interstitial fibrosis were significantly higher in the patients with the RPGN type. In the comparison between the groups with reduced and maintained renal functions, the former group exhibited higher levels of proteinuria, serum creatinine and crescent formation than the latter group. CONCLUSION: The RPGN type of IgAN was significantly worse in terms of the renal survival rate at five years than the non-RPGN type. Intensive and active treatments are necessary for this minor population, according to the guideline for the management of RPGN.

Effects of combination therapy with renin-angiotensin system inhibitors and eicosapentaenoic acid on IgA nephropathy.

OBJECTIVE: The beneficial effects of renin-angiotensin-aldosterone system inhibitors (RASI) and the omega-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA) on IgA nephropathy (IgAN) have been reported. However, it is unknown whether these agents have any synergistic interactions. METHODS: We divided 38 IgAN patients into two groups: an EPA group (n=18) treated with RASI plus EPA and a DILAZEP group (n=20) treated with RASI plus dilazep dihydrochloride. We analyzed the clinical and histological background of each patient, any relevant clinical findings obtained one year after treatment and any factors significantly related to decreases in proteinuria. RESULTS: The clinical findings were largely similar between the groups, except for body mass index (24.9±4.5 in the EPA group vs. 21.4±2.1 in the DILAZEP group, p=0.0041) and total cholesterol (median: 206.0 vs. 177.5 mg/dL, p=0.0493). The histological findings, evaluated according to the Oxford classification, were also similar between the groups. At one year after treatment, the EPA group demonstrated a significantly decreased mean blood pressure (from 94.7±9.0 to 86.4±7.2 mmHg, p=0.0007) and a significantly decreased median level of proteinuria (from 0.80 to 0.41 g/g creatinine, p<0.001). In the DILAZEP group, the mean blood pressure significantly decreased (from 95.2±13.2 to 88.1±7.7 mmHg, p<0.001) without any significant decrease in the median level of proteinuria (from 0.88 to 0.60 g/g creatinine). According to a multivariate logistic analysis, EPA was found to be the only independent factor related to decreases in proteinuria (odds ratio = 5.073, 95% CI: 1.18-26.7, p=0.0285). CONCLUSION: We conclude that EPA accelerates the effects of RASI and thus decreases the proteinuria observed in patients with IgAN.

Effect of single-dose rituximab on steroid-dependent minimal-change nephrotic syndrome in adults.

BACKGROUND: Steroid-dependent minimal-change nephrotic syndrome (MCNS) requires administration of prolonged courses of prednisolone (PSL); therefore, a paradigm shift from such toxic 'non-specific' therapies to selective immunomodulating regimens is necessary for these cases. METHODS: To assess the therapeutic effects of rituximab (an anti-CD20 antibody) in adult patients with steroid-dependent MCNS, we performed a prospective trial of the effects of a single dose of rituximab administered twice at an interval of 6 months in 25 MCNS patients. We evaluated the biochemical parameters and compared the clinical findings between the 12-month period before and 12-month period after the first rituximab infusion. RESULTS: A significant reduction in the number of relapses and the total dose and the maintenance dose of PSL administered was observed during the 12-month period after the first rituximab infusion when compared with the findings during the 12-month period before the first rituximab infusion [25 (100%) versus 4 (16%), P < 0.001; 8.2 versus 3.3 g, P < 0.001; 26.4 mg/day at baseline versus 1.1 mg/day at 12-month, P < 0.0001]. Complete remission was achieved/maintained in all patients undergoing B-cell depletion. Four of 17 patients with B-cell repletion developed relapse. CONCLUSIONS: Our results revealed that rituximab therapy was associated with a reduction in the number of relapses and in the total dose of PSL needed. Therefore, rituximab appears to be a useful therapeutic agent for adult patients with steroid-dependent MCNS. These results suggest that this treatment is rational and should be considered as an important option in the management of adult patients with steroid-dependent MCNS.

Positive C1q staining associated with poor renal outcome in membranoproliferative glomerulonephritis.

BACKGROUND: Pathogenesis and clinical prognosis of membranoproliferative glomerulonephritis (MPGN) has not yet been established. METHODS: We conducted a retrospective study of 41 patients with MPGN (type I and III) and examined the renal survival. In addition, factors contributing to survival time were analyzed. RESULTS: Fourteen patients (34 %) were classified into the renal death group. Patients with nephrotic syndrome and positive C1q staining of glomerular deposits showed a particularly poor prognosis. Significantly higher frequency of nephrotic syndrome and higher urinary protein excretion were observed in the renal death group (p = 0.0002, p = 0.0002) than in the renal survival group. The intensity of C1q staining was positively correlated with the severity of the proteinuria (p = 0.004). Factors that influenced the survival time were positive C1q staining of glomerular deposits (p = 0.003), presence of nephrotic syndrome (p = 0.004), serum albumin (p = 0.02), and proteinuria (p = 0.04). CONCLUSIONS: C1q staining in glomerular deposits and nephrotic syndrome were important factors influencing the prognosis and outcome in MPGN patients. C1q deposition may play a key role in the pathogenesis of MPGN, as evidenced by numerous observations, such as induction of proteinuria.

Rituximab treatment for adult patients with focal segmental glomerulosclerosis.

We present two cases with steroid-resistant nephrotic syndrome (SRNS) and two cases with steroid-dependent nephrotic syndrome (SDNS) due to focal segmental glomerulonephritis (FSGS) who were treated with a single dose of rituximab (375 mg/m(2)). Although the two cases with SRNS showed no response, the two cases with SDNS achieved complete remission. The patients in whom the peripheral B-cell counts subsequently increased after the administration of rituximab demonstrated a relapse. Rituximab may be an effective treatment agent for SDNS with FSGS and the peripheral B-cell count may be a useful marker in such patients for preventing disease relapse.

[Successful rituximab therapy for MALT lymphoma complicating cryoglobulinemic glomerulonephritis].

We report a case of nephrotic syndrome associated with MALT lymphoma. The patient was a 66-year-old woman who had a 21-year history of MALT lymphoma. She was admitted to our hospital for the evaluation of systemic edema and purpura during two months. Urinary protein excretion was quantified at 3.3 g/24h. Serum creatinine was elevated to 1.63 mg/dL. An immunoserological investigation showed the presence of IgM-kappa type monoclonal cryoglobulin accompanied by a decreased serum complement level. HCV infection was negative. A renal biopsy specimen revealed membranoproliferative glomerulonephritis (MPGN) with cryoglobulin deposition and focal atypical lymphoid cells infiltration in the renal interstitium. Immunoperoxidase staining of the atypical lymphoid cell population was positive for CD20 and CD79. Combined therapy with prednisolone, plasma exchange and rituximab was commenced. Her proteinuria disappeared and renal function improved after rituximab therapy. In our case, nephrotic syndrome due to cryoglobulinemic glomerulonephritis was successfully treated mainly by rituximab.

Comparison of steroids and angiotensin receptor blockers for patients with advanced IgA nephropathy and impaired renal function.

BACKGROUND/AIMS: The therapeutic strategy for advanced IgA nephropathy patients with impaired renal function is still controversial. PATIENTS AND METHODS: We divided 44 IgA nephropathy patients with an estimated glomerular filtration rate (eGFR) of less than 60 ml/min/1.76 m(2) and proteinuria greater than 0.5 g/g · creatinine into two groups: the angiotensin receptor blocker (ARB) group (n = 22), treated with ARBs, and the steroid group (n = 22), treated with corticosteroid. We analyzed the clinical and histological background, renal survival rate until progression to end-stage renal disease (ESRD), and the risk factors for progression. RESULTS: The clinical and histological backgrounds were not significantly different between the groups. At 1 and 2 years after treatment, proteinuria tended to be decreased from baseline in both groups, but not significantly, and urinary red blood cells were significantly decreased in the steroid groups (p < 0.001), but not in the ARB group. The eGFR tended to be increased in the steroid group and decreased in the ARB group. However, the renal survival rate until ESRD was not significantly different between the groups. There were no significant independent risk factors for progression. CONCLUSION: The beneficial effect of ARBs on renal survival of advanced IgA nephropathy with impaired renal function is equal to that with steroids.

Long-term beneficial effects of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker therapy for patients with advanced immunoglobulin A nephropathy and impaired renal function.

BACKGROUND: There are few reports analyzing the effects of angiotensin-converting enzyme inhibitors (ACEIs) and/or angiotensin receptor blockers (ARBs) on the long-term renal survival of advanced immunoglobulin A nephropathy (IgAN) patients. PATIENTS AND METHODS: In this retrospective cohort analysis, we divided 66 IgAN patients with an estimated glomerular filtration rate (eGFR) <60 ml/min into three groups: ACEI group (n = 20, treated with ACEIs), ARB group (n = 23, treated with ARBs), and control group (n = 23, treated with antiplatelet agents), and analyzed the clinical and histological background, renal survival rate until the primary endpoint of 50% decrease of eGFR from baseline, and the secondary endpoint of progression to end-stage renal disease, and the risk factors for progression. RESULTS: The clinical and histological background without serum IgA and C3 were not significantly different among the three groups. The renal survival rate until the primary and secondary endpoints was significantly higher in the ACEI and ARB groups than in the control group. The independent risk factors for progression were higher mean blood pressure (hazard ratio [HR] 1.76, P = 0.04), higher histological grade (HR 2.54, P = 0.0184) at baseline, and without ACEIs or ARBs (HR 7.09, P = 0.001), but decreased proteinuria and blood pressure. The risk factors with resistance to ACEIs or ARBs were higher blood pressure and lower eGFR at baseline. There was no difference regarding the survival rate and the risk for progression between ACEI s and ARBs. CONCLUSION: ACEIs or ARBs were effective for long-term renal survival of advanced IgAN, although proteinuria and blood pressure did not decrease.

The significance of caveolae in the glomeruli in glomerular disease.

AIMS: The aim of this study was to demonstrate expression of cell membrane invagination 'caveolae' in glomeruli and to correlate this with functional and structural characteristics of the human glomerular diseases. METHODS: The expression of caveolin-1 (Cav-1), which is the main component of caveolae, was examined in the glomeruli, and the relationship between Cav-1 expression and pathological and clinical findings was determined in 99 patients with glomerular disease and in 50 renal transplantation donors as controls. RESULTS: Cav-1 was expressed very weakly in the controls, and the area of Cav-1 expression relative to the total glomerular area was 0.57±0.65%. However, the area of Cav-1 expression was significantly larger in each glomerular disease (IgA nephropathy, 1.05±1.36%, p<0.05; crescent glomerulonephritis, 1.86±1.19%, p<0.001; minimal change disease, 2.38±1.24%, p<0.001; focal segmental glomerulosclerosis, 2.88±2.05%, p<0.01; membranous nephritis, 4.27±2.95%, p<0.001; membranoproliferative glomerulonephritis, 4.49±3.15%, p<0.001; and diabetic nephropathy, 2.45±1.52%, p<0.001; compared with the controls. Cav-1 expression was significantly decreased in glomerular disease treated with steroids. Co-localisation of Cav-1 and the endothelial marker 'pathologische anatomie leiden-endothelium' was prominent in an immunofluorescence study, and caveolae on the glomerular endothelial cells were observed in electron microscopy. CONCLUSIONS: The expression of Cav-1 was significantly increased in the glomeruli of patients with glomerular disease, and it was related to urinary albumin excretion. Cav-1 expression and caveolae were observed in glomerular endothelial cells. It is hypothesised that they play a role in the recovery phase of capillary injury or endocytosis of albumin into endothelial cells. Basic research should be performed to elucidate the role played by Cav-1 and caveolae.

Effect of single-dose rituximab on primary glomerular diseases.

BACKGROUND: A paradigm shift from such toxic 'nonspecific' therapies to selective immunomodulating regimens is necessary for glomerular diseases. Rituximab, which acts by inhibiting CD20-mediated B cell proliferation and differentiation, could be effective in the treatment of nephrotic syndrome as shown in recent reports. DESIGN: To assess the effects of rituximab in patients with primary glomerular diseases, including minimal-change disease, immunoglobulin A (IgA) nephropathy, focal segmental glomerulonephritis, membranous nephropathy and membranoproliferative glomerulonephritis, we performed a prospective trial of the effects of single-dose rituximab therapy in 24 patients. We prospectively evaluated the serum and urinary biochemical parameters before and after 6 months of therapy. RESULTS: In all of the patients studied, depletion of CD19 and CD20 cells was noted, with significant reduction in the degree of proteinuria from 3.7 ± 3.4 g/day at baseline to 1.3 ± 2.0 g/day at 6 months after the drug administration (p = 0.002). However, no significant changes of the serum creatinine, urinary RBC sediment, serum CD4/8 or serum IL-4 levels were observed at 6 months after the drug administration. In subjects with IgA nephropathy, while depletion of CD19 and CD20 cells was noted, no significant change in the severity of proteinuria was observed at 6 months after the drug administration as compared with the level at the baseline. CONCLUSION: For the treatment of primary glomerular diseases, the use of a single dose of rituximab is demonstrated with no serious adverse events. Further study of the mechanism of action of rituximab in successfully treated patients could encourage new perspectives in the treatment of primary glomerular diseases.

Characteristics of immunoglobulin A nephropathy with mesangial immunoglobulin G and immunoglobulin M deposition.

AIM: There are immunoglobulin (Ig)A nephropathy (IgAN) cases showing mesangial IgG and/or IgM deposition, however, their characteristics have remained unknown. METHODS: Three hundred and eighty-four IgAN patients were divided according to the existence of mesangial IgG and/or IgM deposition: IgA deposition only (A group, n = 77); IgA and IgM deposition (AM group, n = 114); IgA and IgG deposition (AG group, n = 36); and IgA, IgG and IgM deposition (AGM group, n = 157). Clinical and histological findings, and outcomes were examined and compared among these four groups. RESULTS: At the time of renal biopsy, serum creatinine was significantly higher in the A and AM group, however, creatinine clearance did not differ among the four groups. The ratio of glomerular obsolescence was significantly higher in the AM group than in the A and AGM group, and the ratio of glomerular tuft adhesion was significantly higher in the AM, AG and AGM group than in the A group. However, the other clinical and histological findings, electron microscopic findings and renal survivals did not differ among the four groups. Proteinuria was independently associated with an increase in risk of doubling of creatinine (P = 0.005), however, IgG and IgM depositions were not by multivariate Cox regression. CONCLUSION: The presence of other Ig classes, besides IgA deposits, was found to be associated with glomerular obsolescence and tuft adhesions, however, without any effect on renal survival in IgAN.

Risedronate therapy for the prevention of steroid-induced osteoporosis in patients with minimal-change nephrotic syndrome.

BACKGROUND: Minimal-change nephrotic syndrome (MCNS) is treated by the administration of prednisolone (PSL) at high doses. Steroid-induced osteoporosis is a serious adverse effect of this drug. METHODS: Patients with MCNS were randomly assigned to two groups, the risedronate (2.5 mg/day) + alfacalcidol (0.25 µg/day) group (n=20) and the alfacalcidol (0.25 µg/day)-alone group (n=20). All the patients had received PSL and the clinical characteristics were compared between the two groups at baseline and at 12 months. RESULTS: A significant decrease of the mean bone mineral density (BMD) of the lumbar spine from 0.710±0.162 (g/cm(2)) to 0.588±0.125 was observed in the alfacalcidol-alone group (p=0.02), while no such decrease of the bone mineral density was found in the risedronate + alfacalcidol group (0.663±0.169 at baseline and 0.626±0.129 at 12 months). No significant differences in the results of other biochemical tests performed at the baseline and at 12 months were observed between the two groups. The likelihood of development of steroid-induced osteoporosis was influenced by the cumulative dose of PSL, the mean BMD at the baseline, occurrence of disease relapse, and risedronate therapy. CONCLUSION: Risedronate appears to be effective in preventing steroid-induced osteoporosis. It is necessary to use bisphosphonates to maintain the BMD in patients with MCNS receiving prolonged steroid therapy.

Effect of kidney disease stage on pregnancy and delivery outcomes among patients with immunoglobulin A nephropathy.

BACKGROUND: Immunoglobulin A nephropathy (IgAN) has a peak onset that coincides with the reproductive age. Therefore, many young women who are affected become pregnant. The effects and outcome of pregnancy in women with renal diseases remain controversial, and the characteristics and outcome of pregnancy in IgAN patients must be further evaluated. METHODS: A prospective follow-up study of 29 pregnant women with IgAN was performed by analyzing laboratory data, histology and prognosis. To clarify the influence of renal insufficiency, we compared these patients according to the chronic kidney disease (CKD) stage. RESULTS: We found that pregnancy and delivery did not produce any significant changes of the renal function in any of the patients at 3 years after delivery, although the proteinuria was elevated at 30 weeks of pregnancy and at 3 months after delivery. Finally, the data of pregnant women with IgAN were compared with those of 45 nonpregnant women who had similar clinical and demographic characteristics. CONCLUSION: The pregnant patients with IgAN did not exhibit any significant reduction of renal function at 3 years after delivery as compared with the baseline, which is similar to the findings in nonpregnant patients. Furthermore, pregnancy with stage 2 or 3 CKD was not a risk factor for renal dysfunction or delivery.

[Three adult cases of severe acute glomerulonephritis with acute renal failure requiring hemodialysis].

Acute poststreptococcal glomerulonephritis (APSGN) typically recovers within 2 weeks with conservative therapy, but severe cases are known to develop acute renal failure and or nephrotic syndrome. We experienced 3 adult cases of APSGN with acute renal failure. All 3 cases required hemodialysis, 2 cases received double filtration plasmapheresis, and 2 cases received steroid therapy. In all cases, renal biopsy specimens showed endocapillary proliferative glomerulonephritis. One case had 25% cellular crescents and the others showed wide subendothelial deposits. There were no tubulointerstitial lesions. These 3 cases of severe APSGN with acute renal failure showed the benefits of combination therapy, hemodialysis, double filtration plasmapheresis and steroid therapy. Further clinical study is required to determine which therapy, double filtration plasmapheresis or steroid therapy, is useful.

Predictors of poor outcomes in steroid therapy for immunoglobulin A nephropathy.

BACKGROUND: Steroid therapy appears to be beneficial in patients of immunoglobulin A nephropathy (IgAN), as it causes a reduction in the proteinuria and improves the renal survival. METHODS: A retrospective review of the 5 year follow-up data of 60 patients with IgAN who were treated with steroids was conducted. Steroid non-responders were defined as patients in whom the primary end-point of a 30% decrease of the estimated glomerular filtration rate from baseline was reached. The patients were divided into two groups, namely, the steroid responder group (n = 47) and the steroid non-responder group (n = 13), and the clinicopathophysiological characteristics were compared between the two groups. RESULTS: Significant decrease of the proteinuria was observed in the responder group over the 5 year follow-up period, whereas no significant change of the urinary protein excretion was observed in the non-responder group during the same period. In regard to the pathological findings, significantly higher ratios of glomerular obsolescence and glomerular tuft adhesion to the Bowman's capsule, and significantly higher severity of interstitial fibrosis at the time of diagnosis in the non-responder group than in the responder group were found. The rates of glomerular obsolescence and glomerular tuft adhesion to the Bowman's capsule, the severity of interstitial fibrosis, serum albumin and urinary protein excretion were identified as independent risk factors influencing the rate of renal function deterioration. CONCLUSION: To develop effective therapeutic modalities, it is important to have a thorough understanding of the clinicopathophysiological characteristics of IgAN patients showing poor treatment response to steroids (non-responder group in this study).

Low-dose losartan therapy reduces proteinuria in normotensive patients with immunoglobulin A nephropathy.

The present study was designed to assess the antiproteinuric effects of a low dose of an angiotensin II-receptor blocker, losartan, in normotensive patients with immunoglobulin A (IgA) nephropathy. We performed a prospective, controlled trial of losartan (12.5 mg/d) therapy to assess the effects on mild proteinuria and renal function. The study subjects were 18 normotensive and proteinuric patients with IgA nephropathy in the losartan group and 18 IgA nephropathy patients treated with antiplatelet agents in the control group. We prospectively evaluated blood pressure, proteinuria, renal function, and biochemical parameters before and after 12 months of therapy. Blood pressure was kept constant during the 12-month period. Serum creatinine levels and estimated glomerular filtration rate did not significantly change during the 12 months in any of the patients studied. Systolic and diastolic blood pressures did not differ significantly between the losartan and control groups. However, low-dose losartan significantly reduced proteinuria from 0.8+/-0.5 g/d at baseline to 0.4+/-0.4 g/d at 12 months (p=0.006). Proteinuria was significantly lower at 12 months in the losartan group than in the control group (p=0.04). In addition, urinary N-acetyl-beta-D-glucosaminidase (NAG) levels in the losartan group at 12 months were significantly lower than those in the control group (p=0.009). Our data suggest that low-dose losartan therapy for normotensive patients with IgA nephropathy could reduce the amount of urinary protein and NAG excretion without affecting systemic blood pressure.