Lupus Membranous Nephropathy Research Articles

Improvement of proteinuria by upadacitinib in a patient with refractory lupus membranous nephropathy.

Improvement of proteinuria by upadacitinib in a patient with refractory lupus membranous nephropathy.

Single-Center Experience with Exostosin-2 Immunohistochemical Staining in Lupus Membranous Nephropathy

Single-Center Experience with Exostosin-2 Immunohistochemical Staining in Lupus Membranous Nephropathy

#1267 Exostosin 1- and 2-positive membranous nephropathy in Chinese patients

Abstract Background and Aims The exostosin 1 and 2 (EXT1/2) complex was recently identified as a potential antigen associated with systemic autoimmunity in PLA2R-negative membranous nephropathy patients. There are currently no reports of circulating anti-EXT1/2 antibodies and no clinical studies of EXT1/2-positive membranous nephropathy in the Chinese population. Method Immunohistochemical staining for PLA2R, THSD7A and NELL-1 was performed in 1442 consecutive patients with biopsy-proven MN from January 2011 to December 2019 at Beijing Anzhen Hospital. A total of 201 MN patients were PLA2R-, THSD7A- and NELL-1-negative and enrolled in the study. Patient medical records were reviewed for clinical data, including demographics, laboratory tests, treatment, and follow-up. The glomerular expression of EXT1 and EXT2 was screened. The anti-EXT1 and anti-EXT2 antibodies were also detected in the sera of patients with EXT1/2–positive membranous nephropathy by western blot, ELISA and immunoprecipitation separately. Clinical and pathologic features were comparable between PLA2R-, THSD7A- and NELL-1-negative patients with EXT1/2 or without EXT1/2 positive. Results Among these 201 patients, 19 of 83 (22.9%) with lupus membranous nephropathy (class 5 and class 5+3/4), and 13 of 118 (11.0%) with nonlupus membranous nephropathy exhibited positive EXT1/2 staining. Thirteen patients with EXT1/2-positive non-LMN had no definitive secondary cause, but 7 patients (53.8%, 7/13) were seropositive for ANA. Baseline anti–double-stranded DNA antibody and serum antinuclear antibody positivity were independent predictors of glomerular EXT1/2-positive expression in patients with lupus membranous nephropathy (pure class 5, class 5 + 3/4) and nonlupus membranous nephropathy, respectively. In 32 patients with EXT1/2-positive MN, 22 patients with available serum samples collected at the time of biopsy were tested for anti-EXT1 and anti-EXT2 antibodies. Sixteen patients were positive for antibodies. According to the molecular weight of positive bands, we speculated that 5 patients were positive for both anti-EXT1 and anti-EXT2 antibodies, 11 patients were positive only for anti-EXT1 antibodies, and no patients were positive only for anti-EXT2 antibodies. There were no significantly differences between the characteristics of 22 EXT1/2-positive MN patients with or without antibody seropositivity. Two patients with EXT1/2-positive membranous nephropathy underwent repeated renal biopsies. When the pathological type changed to lupus nephritis (LN) or the LN worsened clinically, the renal tissue staining intensity of EXT1/2 increased. Renal EXT1/2 staining positivity occurred earlier than the diagnosis of lupus. Conclusion This is the first study to detect circulating anti-EXT1/2 antibodies, and the functional significance should be further studied. The renal EXT1/2 staining positive was earlier than diagnosis of lupus. whether the level of serum EXT1/2 antibody can be used as a predictor for disease progression and prognosis needs to be further evaluated in larger sample studies.

Tubular expression of Toll-like receptor 9 in lupus and primary membranous nephropathy.

Toll-like- receptors (TLR) control important aspects of innate and adaptive immune responses. Renal cells are among the non-immune cells that express (TLR). Therefore, their activation might be implicated in renal tubulo-interstitial injury. The study aimed to compare TLR9 expression in patients with primary membranous nephropathy (MN) to patients with lupus membranous nephropathy. Kidney sections from 10 Lupus nephritis (LN) patients and ten patients with primary MN were analyzed by immunohistochemistry using anti-human TLR9 antibody. Results showed that TLR9 expression was weak and exclusively tubular in primary MN patients' biopsies. There was a significant difference between LN patients' biopsies and primary MN patients' biopsies. TLR9 expression was more diffused in LN patients' specimen than in those with primary MN. This study focuses on molecular level pathogenesis of MN. The data suggest that the receptors TLR9 may play role in tubulointerstitial injury in the pathogenesis of LN but not primary membranous nephropathy.

Rescue From Permanent Kidney Injury in Acute Thrombosis of Both Renal Veins, the Inferior Vena Cava, and Both Iliofemoral Veins by Catheter-Based Thrombectomy.

A 33-year-old man with previously diagnosed lupus membranous nephropathy presented with painful swelling in both legs. Laboratory tests revealed acute kidney injury, and imaging studies by duplex ultrasound and computed tomography scan showed acute thrombosis of both renal veins, the infrahepatic inferior vena cava, and both iliofemoral venous segments. Initially, pharmacomechanical thrombolysis led to an insufficient morphological result. The therapeutic breakthrough was achieved by catheter-based mechanical thrombectomy of the infrarenal vena cava and both renal veins, which successfully cleared all affected venous segments from thrombus, paralleled by improvement of the patient's condition. However, after 1 week, the patient experienced recurrent thrombosis of the right renal vein with hemorrhagic infarction of the right kidney. After further optimization of immunomodulatory and antithrombotic therapy, a repeated catheter-based mechanical thrombectomy resulted in sustained clinical improvement and preservation of renal venous drainage and kidney function. Extensive acute thrombosis of both renal veins, the inferior vena cava, and both iliofemoral venous segments is a rare emergency potentially threatening kidney function. Immediate effective thrombus removal is essential to preserve kidney function and can be achieved by catheter-based mechanical thrombectomy embedded in a comprehensive immunomodulatory and antithrombotic therapeutic concept. This case demonstrated the efficacy of a catheter-based therapeutic approach in patients with extensive thrombosis of the venous system. A catheter-based approach must be embedded in a comprehensive medical therapeutic concept, which is essential to achieve a sustainable result.

Clinical significance of exostosin 1 in confirmed and suspected lupus membranous nephropathy

ObjectiveThis study aimed to investigate the clinical significance of exostosin 1 (EXT1) in confirmed and suspected lupus membranous nephropathy (LMN).MethodsEXT1 was detected in 67 renal tissues of M-type phospholipase A2...

Determination of Anti-Phospholipase A2 and Anti-Thrombospondin Type 1 Domain-Containing Protein 7A in Latin Patients with Membranous Nephropathy

Primary membranous nephropathy (MN) is caused by antibodies against podocyte antigens, especially the type M receptor of phospholipase A2 (PLA2R) and thrombospondin type-1 domain containing 7 A (THSD7A). This study's aim was the determination of anti-PLA2R, anti-THSD7A serum antibodies, and anti-PLA2R renal tissue staining prevalence in a Latin population with MN, as well as evaluating their role as biomarkers for disease activity. The performance of the two anti-PLA2R serum diagnostic methods-ELISA and indirect immunofluorescence (IFI)-was evaluated for the diagnosis of MN. Fifty-nine patients, including 29 with MN, 18 with lupus membranous nephropathy (LMN) and 12 with focal and segmental glomerulosclerosis (FSGS), were evaluated for serum antibodies. Renal biopsies were also evaluated for the presence of anti-PLA2R staining. Twenty-one patients with MN were followed for 1 year. Patients with LMN and FSGS were negative for both antibodies. All 29 MN patients were negative for anti-THSD7A; 16 MN patients were positive for anti-PLA2R by ELISA and/or IFI, and 3 MN patients were positive for anti-PLA2R only by IFI. Thus, the anti-PLA2R ELISA test demonstrated 45% sensitivity and 97% specificity, while the IFI test showed, respectively, 55% and 100% in our MN patients. Among the 28 MN renal biopsies, 20 presented anti-PLA2R positive staining, corresponding to a 72% sensitivity. Positive correlations were observed between the anti-PLA2R ELISA titer and proteinuria. In conclusion, determination of anti-PLA2R antibodies in the MN Latin population showed similar rates to those reported for other populations. The anti-PLA2R serum levels correlated with MN disease activity.

Prediagnostic Appearance of Thrombospondin Type-1 Domain 7A Autoantibodies in Membranous Nephropathy.

Key Points The entire extracellular domain of thrombospondin type-1 domain 7A (THSD7A) in the luciferase immunoprecipitation system immunoassay was required to detect autoantibodies with high sensitivity in membranous nephropathy (MN).In THSD7A-seropositive MN patients, changes in antibody levels precede changes in clinical status.Seropositive THSD7A antibodies were detected in some patients with MN considered to be secondary to autoimmunity or cancer. Background Pathogenic autoantibodies against thrombospondin type-1 domain 7A (THSD7A) are present in approximately 3% of patients with membranous nephropathy (MN). Compared with PLA2R antibodies, less is known about THSD7A autoantibodies (ABs) because of the relative rarity and the lack of a commercially available quantitative immunoassay. Methods In this study, we describe the development and validation of a highly quantitative luciferase immunoprecipitation system (LIPS) assay for detecting THSD7A ABs and used it to study dominant THSD7A epitopes, disease associations, and monitoring disease activity. The Department of Defense Serum Repository (DODSR) was then used to analyze THSD7A AB in 371 longitudinal serum samples collected before clinical diagnosis of MN from 110 PLA2R-negative MN subjects. Results LIPS analysis demonstrated that a near full-length THSD7A (amino acids 1–1656) detected robust autoantibody levels in all known seropositive MN patients with 100% sensitivity and specificity compared with ELISA and/or Western blotting. Most of the THSD7A-seropositive subjects in our pilot cohort had evidence of coexisting autoimmunity or cancer. Moreover, three THSD7A-seropositive patients undergoing immunosuppressive therapy showed longitudinal autoantibody levels that tracked clinical status. Additional epitope analysis of two smaller protein THSD7A fragments spanning amino acids 1-416 and 1-671 demonstrated lower sensitivity of 32% and 44%, respectively. In the DODSR cohort, THSD7A seropositivity was detected in 4.5% of PLA2R-negative MN patients. In one primary and in one secondary MN-associated with cancer, THSD7A ABs were detectable <1 month before biopsy-proven diagnosis. In addition, three patients with lupus membranous nephropathy had detectable THSD7A ABs years before hypoalbuminemia and biopsy-proven diagnosis. Conclusions Although further studies are needed to explore the significance of THSD7A ABs in lupus membranous nephropathy, this study describes a novel, highly sensitive LIPS immunoassay for detecting THSD7A ABs and adds to the existing literature on THSD7A-associated MN. Clinical Trial registry name and registration number: NCT00977977; registration date: September 16, 2009.

Apixaban Prophylactic Anticoagulation in Patients with Nephrotic Syndrome.

Background Nephrotic syndrome (NS) is associated with an increased risk of thromboembolic events (TEs), due to hemostatic derangements. The use of direct oral anticoagulants (DOACs) in the prevention of TE has not been studied intensively in patients suffering from NS. Methods The method included retrospective analysis of consecutive incident patients with NS due to glomerular disease, receiving apixaban for thromboprophylaxis. It is an uncontrolled, single-center study. Results We identified 27 patients treated with apixaban for the prevention of TEs, in the context of NS. During follow-up, apixaban minimal blood concentration (trough level; Cmin) and maximum blood concentration (Cmax) levels were measured. The mean duration of the anticoagulant treatment was 153 days (±132). Patients were followed for a mean of 14.7 months (±8.4) since the introduction of apixaban. Three patients had a TE at the time of NS diagnosis. Two patients had pulmonary embolism (PE) and one patient presented a stroke in a lupus membranous nephropathy context. One patient developed PE approximately 2 months after the introduction of apixaban treatment. No minor or major bleeding events were noticed. Conclusion The present study shows that patients, suffering from severe NS under anticoagulant therapy with apixaban had a reduced risk of venous and arterial TEs compared with patients previously described in the literature, without increased risk of bleeding.

Update on New Antigens in the Pathogenesis of Membranous Nephropathy

Previously, membranous nephropathies were divided into primary and secondary categories when the exact mechanism or pathogenetic factor were unknown. Approximately 70% accounted for primary membranous nephropathies. The remaining 30% were called secondary because they developed due to well-known diseases such as autoimmune diseases, tumours, infections, or drug assumptions. The discoveries of the M-type phospholipase A2 receptor and of thrombospondin type 1 domain containing 7A as causative antigens in a part of the so-called primary membranous nephropathies opened new knowledge on the effective causes of a large part of these diseases. The availability of novel techniques such as laser micro-dissection and tandem mass spectrometry, as well as immunochemistry with antibodies directed against novel proteins, allowed the confirmation of new antigens involved. The use of confocal microscopy and Western blot allowed detection of the new antigen on glomerular membrane, and the same antigen and relative antibodies have been detected in serum samples. Through these techniques, four new antigens were first detected, including neural epidermal growth factor 1 and semaphorin 3B in the so-called primary membranous nephropathy, and exostosin 1 and 2 and neural cell adhesion molecule 1 in lupus membranous nephropathy. The aim of this study is to describe the characteristics of the new antigens discovered and their association with other diseases. In addition, new antigens are on the horizon, and the story of primary membranous nephropathy is still to be completely written and understood.

Kidney biopsy during pregnancy: a difficult decision. A case series reporting on 20 patients from Mexico.

Kidney biopsy is a routine procedure in the diagnosis of kidney disease, but during pregnancy it carries potential adverse effects for both mother and child, aside from the challenges of obtaining adequate tissue samples. Nevertheless, a precise diagnosis is necessary when specific and potentially toxic treatments are to be used during pregnancy. The present report presents our experience with regard to the usefulness and safety of kidney biopsies during pregnancy. Retrospective analysis of clinical indications, complications, histopathological diagnoses, and treatment of patients who had kidney biopsies done at a single academic center during gestation weeks 11-30 between January 2015 and January 2019. Kidney biopsies were carried out in 20 pregnant patients with nephrotic proteinuria. Biopsy was adequate in all patients. The histological diagnoses included focal segmental glomerulosclerosis (collapsing, tip and perihiliar varieties), membranous lupus nephropathy, diabetic nephropathy, and IgA nephropathy. Treatment was associated with reduction of proteinuria in 17 patients and reduction of serum creatinine in 9 out of 11 patients who had serum creatinine ≥ 1mg/dl at the time of biopsy. There was one major bleeding complication that required transfusion of one unit of blood. There was a high incidence of preeclampsia, preterm delivery, and low birth weight despite appropriate kidney disease therapy. Kidney biopsy may be done during pregnancy when therapeutic decisions depend on a precise pathologic diagnosis.

Advances in Membranous Nephropathy.

Membranous nephropathy (MN) is a rare auto-immune disease where the glomerulus is targeted by circulating auto-antibodies mostly against podocyte antigens, which results in the formation of electron-dense immune complexes, activation of complement and massive proteinuria. MN is the most common cause of nephrotic syndrome in adults leading to severe thrombotic complications and kidney failure. This review is focused on the recent therapeutic and pathophysiological advances that occurred in the last two years. For a long time, we were lacking a head-to-head comparison between cyclophosphamide considered as the gold standard therapy and other medications, notably rituximab. Substantial progress has been achieved owing to three randomized controlled trials. MENTOR (Membranous Nephropathy Trial of Rituximab) and STARMEN (Sequential Therapy with Tacrolimus and Rituximab in Primary Membranous Nephropathy) conclusively established that calcineurin inhibitor-based regimens are slower to result in an immunologic response than rituximab or cyclophosphamide, achieve fewer complete clinical remissions, and are less likely to maintainremission. Rituximab Versus Steroids and Cyclophosphamide in the Treatment of Idiopathic Membranous Nephropathy (RI-CYCLO) suggested that competition between cyclophosphamide and rituximab remains open. Given the technological leap combining laser microdissection of glomeruli and mass spectrometry of solubilized digested proteins, four “new antigens” were discovered including NELL-1 and Semaphorin 3B in so-called primary MN, and exostosins 1 and 2 and NCAM 1 in lupus MN. NELL-1 is associated with about 8% of primary MN and is characterized by segmental immune deposits and frequent association with cancer (30%). Semaphorin 3B-associated MN usually occurs in children, often below the age of two years, where it is the main antigen, representing about 16% of non-lupus MN in childhood. Exostosins 1/2 and NCAM 1 are associated with 30% and 6% of lupus MN, respectively. Exostosins 1/2 (EXT1/2) staining is associated with a low rate of end-stage kidney disease (ESKD) even in mixed classes III/IV+V. These findings already lead to revisiting the diagnostic and therapeutic algorithms toward more personalized medicine.

Phase II, randomised, double-blind, multicentre study evaluating the safety and efficacy of filgotinib and lanraplenib in patients with lupus membranous nephropathy

ObjectivesPatients with lupus membranous nephropathy (LMN) are at risk for prolonged proteinuria and progressive chronic kidney disease. There are no proven effective treatments for LMN, and controlled trials are lacking....

Profile of Indian Patients With Membranous Nephropathy

IntroductionThe majority of primary membranous nephropathy (MN) cases are no longer considered idiopathic with the discovery of the podocytic autoantigens: phospholipase A2 receptor (PLA2R) and thrombospondin type 1 domain–containing 7A (THSD7A). Limited data on PLA2R-related MN in Indians exist in literature, and THSD7A-related MN remains undocumented in this population. We aimed to characterize the baseline PLA2R and THSD7A profile of adult and pediatric membranous nephropathy (MN) in a large Indian single-institution cohort.MethodsA retrospective analysis of all cases of MN (primary and secondary) between 2014 and 2017 was performed with PLA2R direct immunofluorescence and THSD7A immunohistochemistry on the biopsies and anti-PLA2R enzyme-linked immunosorbent assay (ELISA) on baseline sera.ResultsMN constituted 10% of kidney biopsies received in the study period. A total of 216 cases with adequate tissue underwent PLA2R direct immunofluorescence, and 110 of them had available sera for PLA2R ELISA. Combining both testing methods, the prevalence of PLA2R-related primary MN was 72.8%, with moderate concordance between the 2 methods (kappa 0.61). PLA2R was also detected in 16.7% cases of secondary MN, most commonly lupus MN. THSD7A immunohistochemistry performed on 176 cases showed a prevalence of 3.4% in primary MN. One case of lupus MN was also positive for THSD7A. Dual positivity (PLA2R and THSD7A) was noted in 2 cases. The large pediatric cohort tested showed a prevalence of 44% of PLA2R based on tissue testing, whereas 1 case demonstrated THSD7A positivity.ConclusionThis study in a large cohort of Indian patients demonstrates prevalence rates of PLA2R- and THSD7A-related MN similar to world literature, including the substantial cohort of pediatric MN. It also confirms variation in MN in the form of outliers within PLA2R (related to tissue and serum testing), dual positivity for PLA2R and THSD7A, and PLA2R/THSD7A-positive secondary MN.

Clinical usefulness of anti-M-type phospholipase-A-receptor antibodies in patients with membranous nephropathy and the comparison of three quantification methods

Associations between anti-M-type phospholipase A2 receptor (PLA2R) antibodies and disease activity and prognosis have been suggested in primary membranous nephropathy (MN); however, more evidence is needed. We aimed to establish a clinically useful method to measure anti-PLA2R antibodies. We developed a western blot assay and a cell-based enzyme-linked immunosorbent assay (ELISA). Anti-PLA2R antibodies were evaluated retrospectively using these assays and the commercial solid-phase ELISA. Anti-PLA2R antibodies were detected in 12, 6, and 12 out of 23 Japanese patients with biopsy-proven primary MN using the western blot, the cell-based ELISA, and the solid-phase ELISA, respectively. The samples of the lupus MN patients tested negative. The levels of proteinuria correlated moderately with the titres of anti-PLA2R antibodies measured by the three methods (r = 0.39–0.47). Anti-PLA2R antibodies were significantly associated with physicians’ decisions on immunosuppressive treatment without prior knowledge of anti-PLA2R antibody positivity (p < .01). In the longitudinal analysis, the titres of anti-PLA2R antibodies measured by the solid-phase ELISA declined significantly following treatment (p = .03). In conclusion, these results suggest the usefulness of anti-PLA2R antibody as a diagnostic, prognostic, and surrogate biomarker in primary MN. The three methods proved to be reliable for measuring anti-PLA2R antibody titres, but their performances differ.

Exostosin 1/Exostosin 2-Associated Membranous Nephropathy.

In membranous nephropathy (MN), which is characterized by deposition of immune complexes along the glomerular basement membrane (GBM), phospholipase A2 receptor (PLA2R) and thrombospondin type 1 domain-containing 7A are target antigens in approximately 70% and 1%-5% of cases of primary MN, respectively. In other cases of primary MN and in secondary MN, the target antigens are unknown. We studied 224 cases of biopsy-proven PLA2R-negative MN and 102 controls (including 47 cases of PLA2R-associated MN) in pilot and discovery cohorts. We also evaluated 48 cases of PLA2R-negative presumed primary MN and lupus MN in a validation cohort. We used laser microdissection and mass spectrometry to identify new antigens, which were localized by immunohistochemistry. Mass spectrometry detected exostosin 1 (EXT1) and exostosin 2 (EXT2) in 21 cases of PLA2R-negative MN, but not in PLA2R-associated MN and control cases. Immunohistochemistry staining revealed bright granular GBM staining for EXT1 and EXT2. Clinical and biopsy findings showed features of autoimmune disease, including lupus, in 80.7% of the 26 EXT1/EXT2-associated MN cases we identified. In the validation cohort, we confirmed that EXT1/EXT2 staining was detected in pure class 5 lupus nephritis (eight of 18 patients) and in presumed primary MN associated with signs of autoimmunity (three of 16 patients); only one of the 14 cases of mixed class 5 and 3/4 lupus nephritis was positive for EXT1/EXT2. Tests in seven patients with EXT1/EXT2-associated MN found no circulating anti-exostosin antibodies. A subset of MN is associated with accumulation of EXT1 and EXT2 in the GBM. Autoimmune disease is common in this group of patients.

Annals for Educators - 19 February 2019.

Annals for Educators - 19 February 2019.

Mannose-Binding Lectin2 Gene Polymorphism and IgG4 in Membranous Nephropathy

Background: Idiopathic membranous nephropathy (IMN) has been linked to the lectin pathway, IgG4 and genetic susceptibility. We investigated the frequency of mannose-binding lectin2 (MBL2) gene polymorphisms and the serum ratio of IgG4 in patients with membranous nephropathy (MN). Methods: Polymorphisms in the exon 1 of the MBL2 gene (codons 52, 54, and 57) and single base polymorphisms at positions –550 (HL) and –221 (XY) in the promoter region were evaluated in 60 patients compared to a control group (CG) of 101 blood donors. It established the frequency of polymorphisms and the serum ratio of IgG4 comparing 2 etiologies of MN: idiopathic (35 patients) and secondary to systemic lupus erythematosus (25 patients). Results: Patients with MN had a 2.54-fold higher probability (95% CI 1.51–4.31) of carrying the O alelle, exon 1 variant, and 11.16-fold higher probability (95% CI 4.77–28.41) of having A/O genotype when compared to CG. The frequency of polymorphisms in the promoter region was similar between the groups. Combined genotypes generally related to the defective production of MBL (YA/O, XA/O and O/O) were more frequent in patients with MN (OR 7.11; 95% CI 2.69–21.27), when compared to controls. The median of serum ratio IgG4 was 5% for idiopathic MN and 3% for lupus MN patients (p = 0.016). Conclusions: Our data suggests that MBL2 polymorphisms may be associated with the activation of the lectin pathway by IgG4 subclass antibodies in MN.

Increased Granulocyte Heparanase Activity in Neutrophils from Patients with Lupus Nephritis and Idiopathic Membranous Nephropathy

Heparanase is a β-glucuronidase that cleaves sugar chains of heparan sulfate proteoglycans. It is believed that heparanase may be involved in the pathogenesis of proteinuria. The aim of this study was to assess the significance of heparanase in the pathogenesis of particular glomerulonephritis types. The evaluation of heparanase activity in serum, urine, and granulocytes and superoxide dismutase (SOD) activity in granulocytes of patients with lupus nephritis (n = 17), membranous nephropathy (n = 11), IgA nephropathy (n = 12), focal and segmental glomerulosclerosis (n = 18), mesangiocapillary glomerulonephritis (n = 12) and in 19 healthy volunteers were performed. The heparanase activity in granulocytes of patients with lupus nephritis and membranous nephropathy was higher than heparanase activity in granulocytes in the control group (p = 0.02 in both cases). This is the first observation of this phenomenon. There was no difference between SOD activity in granulocytes of patients with all assessed types of glomerulonephritis and the control group. A positive correlation between heparanase activity in urine and double-strain DNA antibodies (r = 0.51; p = 0.04), and reverse correlations between heparanase in urine and hemolytic activity of the complement (r = −0.57; p = 0.03) in the lupus nephritis group, and between heparanase activity in granulocytes and serum total protein level (r = −0.69; p = 0.02) in membranous nephropathy were observed. Increase in heparanase activity without changes in superoxide dismutase activity in the granulocytes from patients with lupus nephritis and membranous nephropathy was observed. It may be used as one of the markers of these disease activities.

Resolution of Proteinuria in Lupus Nephritis: Hurry Up and Wait

In this issue of The Journal , Touma and colleagues map out the time to improvement or resolution of proteinuria in a historical cohort of patients with lupus nephritis (LN)1. More than 200 patients entered in the University of Toronto Lupus Clinic database and followed between 1970 and 2011 constituted the cohort for this analysis. Regardless of the time from the original diagnosis of lupus, the first identified onset of proteinuria functioned as the baseline for this study. From that point onward, the time it took for recovery of proteinuria was measured. Recovery was defined as a 24 h urine protein of < 0.5 g. If a 24 h urine collection was not available, urine dipstick for albumin, or a random urine protein to creatinine ratio was used. For the Kaplan-Meier analysis of proteinuria over time, the maximum followup was 5.5 years. If a patient still had proteinuria at this time, the data were censored. Interestingly, the mean duration of lupus before the onset of proteinuria was more than 5 years. None of the baseline characteristics, renal or extrarenal, predicted who would recover from proteinuria. Even the subgroup of patients with true nephrotic-range proteinuria had the same degree of ultimate resolution compared to those with subnephrotic protein excretion. Not surprisingly, the greater the proteinuria at baseline, the longer it took for recovery (the further you live from home, the longer it takes to get there). The presence of persistently low complement levels was associated with increased time to recovery, which again makes sense, as it can reflect either more aggressive, treatment-resistant disease or non-adherence to therapy. Biopsy class also did not appear to influence resolution or time to resolution, although it is regrettable that 20 patients with biopsy-proven lupus membranous nephropathy were excluded from analysis because of the … Address correspondence to Dr. Bargman, University Health Network, 200 Elizabeth Street, 8N-840, Toronto, ON CANADA M5G 2C4. E-mail: joanne.bargman{at}uhn.ca