Establishment of Galectin-3 Time-resolved Fluoroimmunoassay and its Application in Idiopathic Membranous Nephropathy.

The aim of this study was to establish a time-resolved fluorescent immunoassay (TRFIA) for the detection of serum Galectin-3 (Gal-3) and apply this method to evaluate the clinical significance of serum Gal-3 in predicting Idiopathic Membranous Nephropathy (IMN) progression. The Gal-3-TRFIA was established using the double antibody sandwich method, with the capture antibodies coated on a 96-well microplate and the detection antibodies chelated with Europium (III) (Eu3+). Serum Gal-3 was detected in 81 patients with IMN and 123 healthy controls to further evaluate the value of the Gal-3 in staging of IMN. The sensitivity of the Gal-3-TRFIA assay was 0.85 ng/mL, and the detection range was 0.85-1000 ng/mL. The Gal-3 intra-batch and inter-batch coefficients of variation were 3.45% and 5.12%, respectively. The correlation coefficient (R) between the Gal-3-TRFIA assay and commercially available enzyme-linked immunosorbent assay kits was 0.83. The serum Gal-3 concentration was higher in patients with IMN (65.57 ± 55.90 ng/mL) compared to healthy controls (16.29 ± 9.91 ng/mL, P < 0.0001). In this study, a wide detection range Gal-3-TRFIA assay was developed using lanthanide (Eu3+) chelates for the detection of Gal-3 concentrations in serum. Gal-3 concentration is elevated in patients with IMN.

Long-term Low-density Lipoprotein Apheresis in a Patient with Refractory Idiopathic Membranous Glomerulonephritis.

A 61-year-old Japanese man developed nephrotic syndrome (NS) due to idiopathic membranous glomerulonephritis (MGN). He received immunosuppressive therapy for two years, including prednisolone, cyclophosphamide, and cyclosporine A, but the NS persisted. Low-density lipoprotein apheresis (LDL-A) was initiated at a frequency of twice a month and continued for 9 years (203 sessions in total). His proteinuria reduced to less than 1 g daily after 9 years. LDL-A was stopped, and the NS has not relapsed for five years. This case suggests that long-term LDL-A therapy may be a treatment option for idiopathic MGN refractory to immunosuppressive therapy or short-term LDL-A.

Phospholipase A2 Receptor-Positive Idiopathic Membranous Glomerulonephritis with Onset at 95 Years: Case Report.

A 95-year-old woman was admitted to our hospital for evaluation of bilateral lower-limb edema persisting for 3 months. Serum creatinine was 1.55 mg/dl, and urinary protein excretion was 9.1 g/day. Renal biopsy revealed stage 1 membranous glomerulonephritis (MGN) with immunoglobulin G4-dominant staining. This patient did not have any underlying disease such as infection with hepatitis B or C virus or malignancy, and anti-phospholipase A2 receptor (PLA2R) antibody was detected in the serum. Accordingly, idiopathic MGN was diagnosed. Corticosteroid therapy was avoided, but hemodialysis was required to treat generalized edema. The patient is currently doing well. This is the oldest reported case of idiopathic MGN with positivity for anti-PLA2R antibody.

Analysis of the prognostic risk factors of idiopathic membranous nephropathy using a new surrogate end-point.

Idiopathic membranous nephropathy (IMN) is one of the most common causes of nephrotic syndrome (NS) in adults. The latest study of the chronic kidney disease-prognosis consortium showed that a 30% decrease in the estimated glomerular filtration rate (eGFR) within 2 years could cover more patients and showed a better correlation with end-stage renal disease (ESRD), as compared with serum creatinine (SCr). The aim of the present study was to analyze prognostic factors of ESRD using a 30% decrease in eGFR within 2 years as the end-point. The medical records of patients who were diagnosed as having IMN by clinical pathology between February 2011 and August 2012 and had been followed up for ≥24 months were analyzed retrospectively. A 30% decrease in eGFR or the occurrence of ESRD were the end-points. Factors affecting the prognosis were analyzed by the χ2 test and multivariate logistic regression analysis, and the cumulative risk of risk factors was analyzed by Kaplan-Meier curve. A total of 73 patients with IMN were confirmed by clinical pathology. Blood pressure, tubulointerstitial injury area (TIA), glomerular sclerosis ratio, SCr, blood urea nitrogen, cystatin C, serum albumin and 24-h urine protein. In total, 28 patients (38.4%) reached the observation end-point. Multivariate logistic regression analysis showed that only age ≥60 years, serum albumin <25 g/l and TIA >25% were independent risk factors for predicting the occurrence of end-point events in the two groups (P<0.05), which increased the risk of the occurrence of end-point events in IMN patients by 3.471-, 3.195- and 6.724-fold, respectively. Kaplan-Meier curve showed that the occurrence of end-point events within 2 years was significantly higher in IMN patients whose age was ≥60 years, serum albumin <25 g/l and TIA >25% (log-rank P=0.004, P=0.024 and P=0.001). The results of the present study revealed that age ≥60 years, low serum albumin concentrations and severe tubulointerstitial injury are independent risk factors for the occurrence of ESRD in IMN patients.

A new rescue regimen with plasma exchange and rituximab in high-risk membranous glomerulonephritis.

BACKGROUND: Even though current treatment guidelines for idiopathic membranous glomerulonephritis (iMGN) exist, many questions regarding an optimal therapy remain unanswered. Complete remission cannot be achieved in all patients; relapses occur, in some cases frequently, and side effects from the immunosuppressive therapy are common. Therapeutic options in high-risk patients not responding to standard immunosuppressive therapies are limited. Recent research reveals that the human M-type phospholipase A2 receptor (PLA2 R) is a causative factor in iMGN that parallels clinical disease activity. However, in some patients, this correlation is not evident and additional undetermined factors seem to play a role. DESIGN: We evaluated a new rescue protocol including plasma exchanges (PE) against albumin, intravenous immunoglobulins (IVIGs) and rituximab for 10 patients with a biopsy-proven diagnosis of iMGN who were therapy-resistant to all conventional regimens and had a urinary protein to creatinine ratio of more than 10 000 mg/g Crea. We compared this protocol with standard immunosuppressive protocols including monthly alternating prednisolone plus cyclophosphamide (18 patients), cyclosporine plus prednisolone (23 patients) and rituximab alone (eight patients) in a retrospective design. RESULTS: Our rescue regimen with PE, IVIGs and rituximab achieved partial remission in 90% of patients who had been otherwise refractory to therapy. The mean time to partial remission was 2·1 months. Furthermore, two anti-PLA2 R-antibody negative patients were also treated with this rescue regimen, achieving partial remission after 1 and 4 months. CONCLUSION: A combination of PE, IVIGs and rituximab is a treatment option to consider for high-risk patients with iMGN who are refractory to conventional therapy.

A Case of Idiopathic Membranous Glomerulonephritis in association with Thin Glomerular Basement Membrane Nephropathy / 대한신장학회잡지

We report a rare case of the idiopathic membranous glomerulonephritis (IMGN) in association with the thin glomerular basement membrane nephropathy (TGBMN) in a 63-year-old female with hematuria. This is the first case reported in Korea. In renal biopsy of this case, direct immunofluorescence demonstrated anti-IgG Ab along the glomerular capillary wall with granular pattern. The basement membrane was thin, about 170-220 nm and small epimembranous electron dense deposits were observed by electron microscopy. As this case, the combination of TGBMN and IMGN is very uncommon because the IMGN is characterized morphologically by diffuse global thickening of the glomerular capillary wall, while the TGBMN is defined as an extreme thinning of the glomerular basement membrane, less than 200 nm. Our case showed no renal function deterioration and benign prognosis as other reports showed.