Proteinase­3­antineutrophil cytoplasmic antibody­associated vasculitis secondary to subacute infective endocarditis: A case report.

A 58-year-old male patient was admitted to Peking University First Hospital (Beijing, China) due to recurrent hematuria, proteinuria and kidney dysfunction. The patient was positive for proteinase-3 (PR3)-antineutrophil cytoplasmic antibody (ANCA). Pathology of the kidney showed focal proliferative necrotizing glomerulonephritis with crescent formation and immune complex-mediated glomerulonephritis. The patient was diagnosed with PR3-ANCA-associated vasculitis (AAV), received intensive immunosuppressive therapy and experienced two relapses within 1 year. After admission, aortic valve vegetation was observed via echocardiography. The patient subsequently received antibiotic treatment and valve replacement, and achieved complete remission of kidney and cardiac function. The present case emphasized the importance of identifying secondary reasons for ANCA formation, especially infective endocarditis in patients with PR3-AAV.

Light-chain proximal tubulopathy: a retrospective study from a single Chinese nephrology referral center.

Background: Light-chain proximal tubulopathy (LCPT) is a rare disease characterized by the accumulation of monoclonal light chains within proximal tubular cells. This study aimed to investigate the clinical characteristics of LCPT from a single Chinese nephrology referral center.Methods: Patients with kidney biopsy-proven isolated LCPT between 2016 and 2022 at Peking University First Hospital were retrospectively included. Clinical data, kidney pathological type, treatment, and prognosis were analyzed.Results: Nineteen patients were enrolled, the mean age at diagnosis was 57 ± 11 and the sex ratio was 6/13 (female/male). Mean proteinuria was 2.44 ± 1.89 g/24 hr and the mean estimated glomerular filtration rate (eGFR) at the point of biopsy was 59.640 ± 27.449 ml/min/1.73 m2. κ-restriction (84%) was dominant among LCPTs. An abnormal free light chain ratio was observed in 86% of the patients. Proximal tubulopathy with cytoplasmic inclusions accounted for the majority (53%), followed by tubulopathy associated with interstitial inflammation reaction (26%), proximal tubulopathy without cytoplasmic inclusions (16%), and proximal tubulopathy with lysosomal indigestion/constipation (5%). One patient presented with acute kidney injury and 16 patients presented with chronic kidney disease. Regarding follow-up, patients received bortezomib-based or R-CHOP chemotherapy or supportive treatment only. The mean follow-up time was 22 ± 16 months, and the mean eGFR was 63.098 ± 27.439 ml/min/1.73 m2 at the end of follow-up. These patients showed improved or stable kidney function.Conclusions: This is the first case series report of LCPT in four different pathological types in northern China. Clone-targeted chemotherapy may help preserve the kidney function in these patients.

Characteristics of Complement Protein Deposition in Proliferative Glomerulonephritis with Monoclonal Immunoglobulin Deposition.

BACKGROUND: Hypocomplementemia and complement co-deposition with monoclonal immunoglobulins in glomeruli are not rare in proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID). Deposition of monoclonal immunoglobulins in glomeruli has been suggested to activate complement and cause kidney injury. However, the profiles of complement activation in PGNMID and their clinical and pathologic significance need to be clarified. METHODS: Forty-six patients with PGNMID were enrolled. Proteomic analysis of glomeruli using laser microdissection and mass spectrometry was performed for ten patients with PGNMID to determine the composition of glomerular deposits. Kidney deposition of complement components was detected by immunohistochemistry and immunofluorescence. Urinary and plasma levels of complement components were measured by an enzyme-linked immunosorbent assay. Group differences were assessed using t tests or Mann-Whitney U tests depending on the distribution. Correlation analysis was performed using Spearman rank correlation or Pearson correlation. RESULTS: Laser microdissection and mass spectrometry-based proteomic analysis showed that complement components were the most enriched proteins deposited in the glomeruli of patients with PGNMID. Glomerular deposition of C3c, C4d, and C5b-9 was detected in most patients. Levels of urinary and plasma C3a, C5a, soluble C5b-9, C4d, Bb, and C1q as well as urinary mannose-binding lectin were significantly higher in patients with PGNMID compared with healthy controls. The intensity of C3c and C4d deposition in glomeruli correlated with serum creatinine and the percentage of crescents, respectively. Furthermore, levels of urinary complement components correlated positively with serum creatinine, urinary protein excretion, percentage of crescents, and global glomerulosclerosis in kidney biopsies, whereas plasma levels of most complement components did not show a significant correlation with clinicopathologic parameters. In multivariable analysis, a higher level of urinary C4d was identified as an independent risk factor of kidney failure. CONCLUSIONS: The complement system was found to be overactivated in PGNMID, and levels of urinary complements correlated with disease severity. A higher level of urinary C4d was identified as an independent risk factor of kidney failure.

Clinicopathological and immunological features of new onset kidney disease: a rare event after SARS-CoV-2 vaccination.

The onset of various kidney diseases has been reported after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. However, detailed clinical and pathological features are lacking. We screened and analyzed patients with newly diagnosed kidney diseases after inactivated SARS-CoV-2 vaccination in Peking University First Hospital from January 2021 to August 2021, and compared them with the reported cases in the literature. We obtained samples of blood, urine and renal biopsy tissues. Clinical and laboratory information, as well as light microscopy, immunostaining and ultrastructural observations, were described. The SARS-CoV-2 spike protein and nucleoprotein were stained using the immunofluorescence technique in the kidney biopsy samples. SARS-CoV-2 specific antibodies were tested using magnetic particle chemiluminescence immunoassay. The study group included 17 patients with a range of conditions including immune-complex-mediated kidney diseases (IgA nephropathy, membranous nephropathy and lupus nephritis), podocytopathy (minimal change disease and focal segmental glomerulosclerosis) and others (antineutrophil-cytoplasmic-antibody-associated vasculitis, anti-glomerular basement membrane nephritis, acute tubulointerstitial nephritis and thrombotic microangiopathy). Seven patients (41.18%) developed renal disease after the first dose and ten (58.82%) after the second dose. The kidney disease spectrum as well as clinicopathological features are similar across different types of SARS-CoV-2 vaccines. We found no definitive evidence of SARS-CoV-2 spike protein or nucleoprotein deposition in the kidney biopsy samples. Seropositive markers implicated abnormal immune responses in predisposed individuals. Treatment and follow-up (median = 86 days) showed that biopsy diagnosis informed treatment and prognosis in all patients. In conclusion, we observed various kidney diseases following SARS-CoV-2 vaccine administration, which show a high consistency across different types of SARS-CoV-2 vaccines. Our findings provide evidence against direct vaccine protein deposition as the major pathomechanism, but implicate abnormal immune responses in predisposed individuals. These findings expand our understanding of SARS-CoV-2 vaccine renal safety.

Primary membranous nephropathy in two siblings with one combined with anti-glomerular basement membrane disease: a case report.

BACKGROUND: The phospholipase A2 receptor (PLA2R) associated with membranous nephropathy (MN) is an organ-specific autoimmune disease associated with PLA2R and human leukocyte antigen (HLA) genes. Familial PLA2R-related MN is rarely reported. The combination of anti-GBM disease and MN has been well documented, though the mechanism behind it remains unclear. CASE PRESENTATION: We describe two siblings diagnosed with pathology-confirmed PLA2R-related MN 1 year apart. And one of the two siblings developed an anti-GBM disease. The high-resolution HLA typing showed identical alleles in both siblings, specifically heterozygotes of DRB1*15:01/*03:01. CONCLUSION: We describe a familial case of PLA2R-related MN supporting the role of genetic factors that HLA-DRB1*15:01 and DRB1*03:01 predispose patients in the development of PLA2R-related MN in the Han Chinese population. The combination of MN and anti-GBM disease may also partially be associated with the same susceptible HLA allele DRB1*15:01.

Clinicopathological Spectrum of Cryoglobulinemic Glomerulonephritis without Evidence of Autoimmunity Disorders: A Retrospective Study from a Single Institute of China.

Background: Cryoglobulinemic glomerulonephritis (Cryo-GN), caused by circulating cryoglobulins, has varied etiology and clinical-pathologic manifestations. This study aimed to investigate the clinicopathological spectrum and outcome of patients with various Cryo-GN in China. Methods: A retrospective review of 74 Chinese patients with biopsy-proven cryoglobulin-related renal lesions in Peking University First Hospital from 2010 to 2020 was performed. Results: The mean age at diagnosis was 52.9 ± 15.0 years, and the female-to-male ratio was about 2/5. For the etiology screening, serum/urine monoclonal immunoglobulin could be detected on immunofixation electrophoresis in 34% of patients, including 6 patients who had hematological malignancies. Fifty-seven percent of patients had HBV infection, far more than HCV infection (5%). Ten percent of patients had other infections, and 27% of patients were classified as essential or idiopathic. Eleven out of the 15 patients with type II cryoglobulinemia had a consistent monotype of serum monoclonal immunoglobulins and monoclonal cryoprecipitate. The clinical manifestations were similar between various types of cryoglobulinemia. Hematuria, proteinuria, hypertension, anemia, and chronic renal insufficiency were the most common features. Fifty-three percent of patients presented with nephrotic syndrome, and 32% experienced acute kidney injury. Hypocomplementemia, serum-positive rheumatoid factor activity, and skin lesions were reported in 45%, 29%, and 28% of patients, respectively. After a median of 24 months follow-up, 18 patients reached end-stage kidney disease. The clone-targeted treatment could retard the renal deterioration compared with immunosuppressive therapy. Conclusions: This was the largest single-center, clinicopathological retrospective study of Cryo-GN in China. Our data strongly support the association between monoclonal gammopathy and type II Cryo-GN. The renal responsive rate of immunosuppressant therapy is still suboptimal. The clone-targeted treatment shows promising effects in patients with type I or II Cryo-GN.

Fibrinogen A Alpha-Chain Amyloidosis in Two Chinese Patients.

Objectives: Fibrinogen A alpha-chain amyloidosis (AFib amyloidosis) is the most common form of hereditary renal amyloidosis in the United Kingdom and Europe, but has rarely been reported in Asia. In this study, we reported two AFib amyloidosis patients in China, reviewing the literature and summarizing main characteristics of AFib amyloidosis in Asia. Methods: Two unrelated Chinese patients were diagnosed with AFib amyloidosis by clinical presentation, renal biopsy, mass spectrometry and DNA sequencing in Peking University First Hospital of China from 2014 to 2016. Results: Both of the patients presented with proteinuria, edema and hypertension. Renal biopsies of two patients showed extensive amyloid deposits (Congo red positive) in glomeruli, and focal tubulointerstitial amyloid deposits was also found in patient 1. Besides, hepatic involvement of amyloidosis has been detected by liver biopsy in patient 1. By electron microscopy, randomly arranged fibrils in a diameter of 8-12 nm was identified in mesangial matrix and subendothelial area of glomeruli. Immunohistochemistry demonstrated amyloid deposits were strongly positive for fibrinogen Aα in glomeruli and positive for LECT2 in the interstitium of renal medulla and the liver in Patient 1. Unevenly positive staining for both fibrinogen Aα and ApoA-I were found in Patient 2. Fibrinogen Aα was the most abundant amyloidogenic protein in both patients identified by laser microdissection and mass spectrometry-based proteomic analysis. Genetic analysis revealed the fibrinogen A a-chain gene (FGA) mutation in both patients, including a new deletion mutation [c.1639delA (p.Arg547Glyfs*21; NM_000508)] in Patient 2. Genetic analysis of the LECT2 gene in patient 1 revealed a codon change from ATC to GTC at position 172 [c.172A>G (p.Ile58Val; NM_002302)], which is a common polymorphism (SNP rs31517) in all ALECT2 amyloidosis patients. Conclusions: We reported two AFib amyloidosis patients in China, one of them coexisted with ALECT2 amyloidosis simultaneously.

Kidney Histopathologic Spectrum and Clinical Indicators Associated with MGRS.

BACKGROUND AND OBJECTIVES: Patients with monoclonal gammopathy and concomitant kidney diseases are frequently found in clinical practice. Some of them are diagnosed with monoclonal gammopathy of renal significance (MGRS) due to the presence of monoclonal Ig-related kidney injuries. This study aimed to investigate the histopathologic spectrum and clinical characteristics associated with MGRS in a large cohort of patients with monoclonal gammopathy and biopsy-proven kidney diseases from a single Chinese nephrology referral center. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Patients who presented with monoclonal gammopathy (monoclonal spike on serum and/or urine immunofixation tests) and underwent kidney biopsy in the Peking University First Hospital from January 1, 1999 to December 31, 2020 were enrolled in this retrospective study. Patients with malignant hematologic diseases were excluded. Clinical and laboratory data were collected from the electronic medical record system. Comparisons of patients with and without MGRS and with and without amyloidosis were performed. The clinical characteristics associated with MGRS were identified using multivariable logistic regression. RESULTS: A total of 700 patients with monoclonal gammopathy and kidney biopsy were identified. Thirteen patients with repeat kidney biopsies were analyzed separately. For the remaining 687 patients with one kidney biopsy, 261 patients (38%) had MGRS lesions, and the rest (426 patients, 62%) had non-MGRS kidney diseases. Ig-related amyloidosis accounted for the most MGRS cases (n=164, 63%), followed by monoclonal Ig deposition disease (n=23, 9%) and thrombotic microangiopathy (n=22, 8%). In the non-MGRS group, membranous nephropathy was the most common diagnosis (n=171, 40%). In the multivariable logistic regression model, the presence of abnormal serum free light chain ratio, older age, and greater proteinuria were independently associated with MGRS. CONCLUSIONS: Monoclonal Ig amyloidosis is the leading cause of MGRS in Chinese patients with monoclonal gammopathy. The presence of abnormal free light chain ratio, older age, and greater proteinuria were associated with MGRS.

C3 glomerulonephritis associated with monoclonal gammopathy: a retrospective case series study from a single institute in China.

OBJECTIVE: To investigate the demographic and clinicopathological features and renal outcomes of Chinese patients with C3 glomerulonephritis in the setting of monoclonal gammopathy. METHODS: Patients with renal biopsy-proven C3 glomerulonephritis and detectable serum and/or urine monoclonal immunoglobulin from 2006 to 2018 in Peking University First Hospital were included, their clinical data, renal pathology type, treatment, and prognosis were collected and analyzed. RESULTS: Nineteen patients were enrolled, accounting for 24% of C3GN patients in the study period. The mean age of onset was 55 years old and the gender ratio was 4/15 (female/male). The mean eGFR at biopsy was 49.55 ± 29.81 ml/min/1.73m2. The prominent clinical manifestations included nephrotic syndrome (58%), anemia (68%), microscopic hematuria and leukocyturia (58%), and hypocomplementemia (13, 68%). The IgG was the most common isotype of monoclonal Ig on immunofixation electrophoresis. Kidney biopsies revealed a relatively prominent MPGN pattern. Only two patients had direct evidence of monocle immunoglobulins acting as C3GN pathogenic factors. Two patients had concurrent TMA-like renal injuries. The median renal survival was 12 and 15 months, respectively in patients receiving conservative therapy and immunosuppressant therapy, without statistical significance. The efficacy of clone-targeted therapy needed further investigation. Plasma exchange therapy only improved one patient's renal outcome. CONCLUSIONS: This is the first case series report of C3GN combined with monoclonal Ig in northern China. The renal prognosis of these patients is poor, and immunosuppressant therapies show no advantage over supportive therapy in renal prognosis, while the benefit of clone-targeted chemotherapy is still requiring investigation.

Case Report: Lenalidomide as a Second-Line Treatment for Bortezomib-Ineffective Nephrotic Syndrome Caused by LCDD: 2 Case Reports and a Literature Review.

Background: Light-chain deposition disease (LCDD) is a rare systemic disorder characterized by the deposition of monoclonal light chains in organs. The kidney is a prominent target of light-chain deposition, with a median time to end-stage renal disease (ESRD) of 2.7 years and 5-year ESRD-free survival of 37%. The therapeutic management of LCDD remains ill-defined. In addition to bortezomib-based therapy as first-line therapy, the effect of lenalidomide on LCDD is rarely reported. Case Presentation: This study describes two male LCDD patients in their 60s with nephrotic syndrome and moderately impaired renal function. One patient had monoclonal IgGλ with underlying MGRS, and another had monoclonal IgGκ with underlying monoclonal gammopathy that developed into symptomatic MM during follow-up. The hallmarks of this disease were consistent with previous reports. Both patients initially received BCD therapy, but no hematological response was observed. Consequently, the nephrotic syndrome was refractory. Sequential Rd therapy was initiated, and partial hematological response and nephrotic remission were observed in the IgGλ patient but absent in the IgGκ patient. Conclusion: Limited reports have demonstrated the effect of lenalidomide in LCDD. We report the outcome of lenalidomide in two cases of bortezomib-resistant LCDD. This treatment might be a beneficial supplement for those unresponsive or intolerant to bortezomib in LCDD, but the effect should be prospectively investigated.

Case Report: Predominant Tubulointerstitial Lupus Nephritis or the Combination With IgG4-Related Disease?

Isolated or dominant tubulointerstitial lupus nephritis is rare. Here, we reported a 67-year-old man diagnosed with systemic lupus erythematosus (SLE) based on clinical and laboratory criteria, who was showing impaired renal function and non-nephrotic range proteinuria in the past 2 years. Renal biopsy showed almost normal glomeruli, but the tubulointerstitium showed "storiform" pattern with interstitial infiltration of IgG3 predominant plasma cells. Immunofluorescence showed linear and granular staining of IgG and C1q along TBM and interstitium. He started on medium dose of oral steroids and mycophenolate mofetil, which were gradually tapered. As a result, his renal function improved over a few days. Now, he continued on low dose steroids and mycophenolate mofetil with no evidence of relapse.

Rituximab Therapy for Primary Membranous Nephropathy in a Chinese Cohort.

Background: Rituximab has become one of the first-line therapies for the treatment of moderate and high-risk primary membranous nephropathy (pMN). We retrospectively reviewed 95 patients with pMN who received rituximab therapy and focused on the therapeutic effects and safety of this therapy in a Chinese cohort. Methods: Ninety-five consecutive patients with pMN diagnosed by kidney biopsy received rituximab and were followed up for >6 months. Four weekly doses of rituximab (375 mg/m2) was adopted as the initial administration. Repeated single infusions were administrated to maintain B cell depletion levels of <5 cells/mL. Results: A total of 91 patients completed rituximab therapy with the total dose of 2.4 (2.0, 3.0) g; 64/78 (82.1%) patients achieved anti-PLA2R antibody depletion in 6.0 (1.0, 12.0) months; 53/91 (58.2%) patients achieved clinical remission in 12.0 (6.0, 24.0) months, including complete remission in 18.7% of patients and partial remission in 39.6% of patients. Multivariate logistic regression analysis showed that severe proteinuria (OR = 1.22, P = 0.006) and the persistent positivity of anti-PLA2R antibodies (OR = 9.00, P = 0.002) were independent risk factors for no-remission. The remission rate of rituximab as an initial therapy was higher than rituximab as an alternative therapy (73.1 vs. 52.3%, P = 0.038). Lastly, 45 adverse events occurred in 37 patients, but only one patient withdrew from treatment due to severe pulmonary infection. Conclusion: Rituximab is a safe and effective treatment option for Chinese patients with pMN, especially as an initial therapy.

Crystalline appearance in light chain cast nephropathy is associated with higher early mortality in patients with newly diagnosed multiple myeloma.

BACKGROUND: Light chain cast nephropathy (LCCN) is the most common kidney lesion in multiple myeloma patients. LCCN may exhibit a crystalline appearance. The frequency and clinical significance of crystalline LCCN are not well understood. Here, we report the first retrospective study of crystalline LCCN. METHODS: Twenty-six patients with LCCN were enrolled. We studied the clinicopathological features and outcomes of LCCN patients and compared ordinary LCCN patients (n = 18) with crystalline LCCN patients (n = 8). RESULTS: Crystalline LCCN was not rare (8/26, 30.8%) in our study. The median age of LCCN patients was 57.5 (range, 41-75) years. No patients presented with nephrotic syndrome. No significant differences in clinical features were observed between the two groups. All crystalline LCCN patients suffered from advanced multiple myeloma and acute kidney injury. There was a dominance of the λ isotype (7/8, 87.5%) in patients with crystalline LCCN. Patients with ordinary LCCN had significantly higher scores of tubular atrophy and acute tubular injury than those with crystalline LCCN. The crystalline casts of 5 crystalline LCCN patients stained negative with antihuman Tamm-Horsfall glycoprotein. There were no significant differences in the median overall survival between the crystalline LCCN group and the ordinary LCCN group (6.0 months vs. 35.0 months, p = 0.173). However, crystalline LCCN patients had higher early mortality than ordinary LCCN patients (50.0% vs 11.1%, p = 0.03). CONCLUSION: Crystalline LCCN patients had higher early mortality than ordinary LCCN patients. Thus, for patients with LCCN, crystalline appearance should be screened carefully.

Clinicopathological features and outcomes of coexistent light chain cast nephropathy and light chain deposition disease in patients with newly diagnosed multiple myeloma.

AIMS: A varying proportion of patients with multiple myeloma suffer from more than one type of kidney disease simultaneously, of which the most common pattern is coexistent light chain cast nephropathy and light chain deposition disease (LCCN+LCDD). We investigated clinicopathological characteristics and outcomes of LCCN+LCDD in comparison with pure LCCN and pure LCDD. METHODS: We retrospectively analysed 45 newly diagnosed multiple myeloma patients with pure LCCN (n=26), LCCN +LCDD (n=9) and pure LCDD (n=10) between 2000 and 2019 at Peking University First Hospital. RESULTS: Pathologically, patients with LCCN+LCDD were more likely to have λ light chain isotype and presented atypical features of LCDD including less nodular glomerulosclerosis and less deposit distribution than patients with pure LCDD. In clinical characteristics, patients with LCCN +LCDD and patients with pure LCCN shared similar features. The death-censored renal survival in patients with LCCN +LCDD was similar to patients with pure LCCN but worse than patients with pure LCDD, but the overall survival was much better than patients with LCCN alone and similar to patients with pure LCDD. For patients with pure LCCN, the independent predictor of death-censored renal survival was lactate dehydrogenase, and the independent predictors of overall survival were the mean number of casts and serum albumin. CONCLUSIONS: Patients with LCCN+LCDD had similar renal outcome compared with patients with pure LCCN but the overall survival is much better. Thus, for patients with LCCN, especially those with λ restriction, pathologists should carefully evaluate the kidney specimens to exclude the possibility of combined LCDD.

Monoclonal Immunoglobulin-Associated Renal Lesions in Patients with Newly Diagnosed Multiple Myeloma: A Report from a Single Center.

BACKGROUND: Monoclonal immunoglobulin-associated renal lesions in patients with newly diagnosed myeloma vary. We aimed to determine the pathological spectrum and analyze associated prognostic factors. METHODS: Fifty-six patients with newly diagnosed multiple myeloma and biopsy-proven renal lesions were enrolled. Kidney biopsies were reanalyzed, and the baseline clinical characteristics, treatments and outcomes were recorded. RESULTS: Fifty-one patients had monoclonal immunoglobulin-associated renal lesions, with myeloma cast nephropathy (MCN) being the most common pattern. We divided our cohort into pure MCN, MCN+ other pathologies and non-MCN. Patients with MCN had more severe renal injury than those with non-MCN. In our cohort, none of the patients with pure MCN or MCN + other pathologies presented with nephrotic syndrome. Patients with non-MCN had better renal and overall survival than those with pure MCN but similar survivals to those with MCN + other pathologies. Number of myeloma casts (HR 1.08, p = 0.012) was the only independent prognostic factor for renal survival. Male sex (HR: 3.64; p = 0.015) and number of casts (HR: 1.17; p = 0.001) were independent prognostic factors for overall survival. CONCLUSION: Patients with MCN had more severe renal injury than those with non-MCN. Patients with non-MCN had better renal and overall outcomes than those with pure MCN, but their outcomes were similar to those with MCN + other pathologies. The independent predictors of overall survival were male sex and number of myeloma casts.

Unveiling the Features of Mercury-Associated Minimal Change Disease: Comparison with Primary Minimal Change Disease.

INTRODUCTION: Long-term exposure to mercury can cause minimal change disease. However, the current understanding of mercury-associated minimal change disease (M-MCD) is inadequate. To improve the understanding of M-MCD, this study retrospectively analyzed the clinicopathological, ultrastructural, and prognostic features of M-MCD, in comparison with primary minimal change disease (P-MCD). METHODS: We retrospectively analyzed the clinicopathological data of 21 M-MCD patients and 21 P-MCD patients. Electron micrographs of glomerular capillaries were taken, and the foot process width (FPW) was measured. A receiver operating characteristics (ROC) curve analysis was performed to determine the optimum cutoff value of FPW that can differentiate the M-MCD from P-MCD. RESULTS: M-MCD patients presented similar clinical and routine pathological characteristics with P-MCD patients but had lower levels of FPW (935.0 [interquartile range (IQR) 853.7-1,176.7] nm vs. 1,403.2 [IQR 1,089.2-1,841.8] nm, p = 0.002). ROC curve analysis showed that FPW value below 1,385 nm might help to differentiate M-MCD from P-MCD (area under the curve of 0.787, sensitivity of 94.7%, and specificity of 52.4%). For patients with M-MCD, 77.8% achieved complete remission after mercury detoxification monotherapy. Patients with M-MCD had a lower relapse rate than patients with P-MCD (0 vs. 47.1%, p = 0.003). In addition, there was no significant difference in remission time between M-MCD patients treated with mercury detoxification monotherapy and those initially treated with immunosuppressive therapy (2.0 [IQR 1.0-6.0] months vs. 2.0 [IQR 1.5-2.5] months, p = 0.606). CONCLUSIONS: M-MCD patients showed similar clinicopathological features with P-MCD patients, but with less severe foot process effacement, suggesting different pathogenesis of these 2 disease entities. The treatment of mercury detoxification was highly effective for patients with M-MCD and can be considered as a primary choice in clinical practice.

Comparison of Ultrastructural Features Between Patients with Mercury-associated Membranous Nephropathy and Idiopathic Membranous Nephropathy.

BACKGROUND: Prolonged exposure to mercury can cause membranous nephropathy. Mercury-associated membranous nephropathy (M-MN) and idiopathic membranous nephropathy (I-MN) have similar clinical manifestations, making misdiagnoses likely. We compared the clinicopathological and ultrastructural features of M-MN and I-MN. METHODS: We retrospectively analyzed the clinicopathological data of 13 M-MN patients and 13 I-MN patients. Electron micrographs of glomerular capillaries were taken, and foot process width (FPW) and the number of foot processes per 10 µm glomerular basement membrane (GBM) were calculated. The presence and location of electron-dense deposits were recorded. RESULTS: Compared with I-MN patients, M-MN patients were younger (38.7 ±â€¯8.5 versus 45.8 ±â€¯5.7 years, P = 0.020), achieved complete remission more quickly (9.0 ±â€¯6.1 versus 20.3 ±â€¯9.8 months, P = 0.004), and had a lower relapse rate (0 versus 45.5%, P = 0.014). Patients with M-MN also had lower FPW (974.3 [interquartile range or IQR, 791.2-1504.4] nm versus 2370.6 [IQR, 2219.4-2559.1] nm, P = 0.001), more foot processes per 10 µm GBM (8.1 [IQR, 5.2-10.0] versus 3.3 [IQR, 3.1-3.5], P = 0.001), and a higher rate of mesangial electron-dense deposits (41.7% versus 0, P = 0.015). A cut-off FPW of <1654 nm differentiated M-MN from I-MN with high sensitivity (92.3%) and specificity (83.3%). CONCLUSIONS: Foot process effacement was less severe in M-MN than in I-MN. In patients with mercury toxic exposure, MN with less severe foot processes effacement suggested mercury could be the cause. Better prognosis in patients with M-MN may be associated with minor podocyte damage.

Pregnancy-associated proliferative glomerulonephritis with monoclonal immunoglobulin deposits.

We report a young woman presented with nephrotic syndrome and normotension during every pregnancy and achieved complete remissions after the deliveries. We thus inferred that her nephrotic syndrome was closely associated with pregnancy. Kidney biopsies were perfromed and showed different histologic patterns: the first biopsy showed a pattern of endocapillary proliferative glomerulonephritis; the second biopsy revealed proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID) with features of membranous nephropathy. With regard to presentation during the second trimester of pregnancy, achieving complete remission after delivery, and no relapse during the follow-up period, pregnancy associated PGNMID is suggested. To our best knowledge, this is the first reported case of PGNMID associated with pregnancy.