Membranous lupus nephritis secondary to secukinumab therapy: A case report and literature review.

The interleukin (IL)-17 axis is involved in many inflammatory and autoimmune diseases. Secukinumab, an IL-17 inhibitor, has been approved for psoriasis treatment. There are accumulating cases of lupus erythematosus induced by IL-17 inhibition. Lupus nephritis after IL-17 inhibition has not been reported. We report the case of a 57-year-old man who developed membranous lupus nephritis after secukinumab treatment for psoriasis. Anti-SSA and PM-Scl antibodies were positive. dsDNA, anti-Smith, and anti-histone antibodies were negative, and serum complement was low. Secukinumab was discontinued, while tacrolimus was initiated, subsequently switched to cyclosporin, belimumab, glucocorticosteroid, and hydroxychloroquine with a good response. The relationship between lupus erythematosus and IL-17 inhibition requires further research.

Diosgenin protects against cationic bovine serum albumin-induced membranous glomerulonephritis by attenuating oxidative stress and renal inflammation via the NF-κB pathway.

CONTEXT: Membranous glomerulonephritis (MGN) is a leading cause of nephrotic syndrome in adults. Diosgenin (DG) has been reported to exert antioxidative and anti-inflammatory effects. OBJECTIVE: To investigate the renoprotective activity of DG in a cationic bovine serum albumin-induced rat model of MGN. MATERIALS AND METHODS: Fourty male Sprague-Dawley rats were randomized into four groups. The MGN model was established and treated with a DG dose (10 mg/kg) and a positive control (TPCA1, 10 mg/kg), while normal control and MGN groups received distilled water by gavage for four consecutive weeks. At the end of the experiment, 24 h urinary protein, biochemical indices, oxidation and antioxidant levels, inflammatory parameters, histopathological examination, immunohistochemistry and immunoblotting were evaluated. RESULTS: DG significantly ameliorated kidney dysfunction by decreasing urinary protein (0.56-fold), serum creatinine (SCr) (0.78-fold), BUN (0.71-fold), TC (0.66-fold) and TG (0.73-fold) levels, and increasing ALB (1.44-fold). DG also reduced MDA (0.82-fold) and NO (0.83-fold) levels while increasing the activity of SOD (1.56-fold), CAT (1.25-fold), glutathione peroxidase (GPx) (1.55-fold) and GSH (1.81-fold). Furthermore, DG reduced Keap1 (0.76-fold) expression, Nrf2 nuclear translocation (0.79-fold), and induced NQO1 (1.25-fold) and HO-1 (1.46-fold) expression. Additionally, DG decreased IL-2 (0.55-fold), TNF-α (0.80-fold) and IL-6 (0.75-fold) levels, and reduced protein expression of NF-κB p65 (0.80-fold), IKKß (0.93-fold), p-IKKß (0.89-fold), ICAM-1 (0.88-fold), VCAM-1 (0.91-fold), MCP-1 (0.88-fold) and E-selectin (0.87-fold), and also inhibited the nuclear translocation of NF-κB p65 (0.64-fold). DISCUSSION AND CONCLUSIONS: The results suggest a potential therapeutic benefit of DG against MGN due to the inhibition of the NF-κB pathway, supporting the need for further clinical trials.

An Unusual Case of Anti-Glomerular Basement Membrane Disease and Phospholipase A2 Receptor-Associated Membranous Nephropathy After Exposure to Hydrocarbons.

We present a rare case of a patient with toluene exposure manifesting as anti-glomerular basement membrane (GBM) disease on a background of phospholipase A2 receptor (PLA2R)-associated membranous nephropathy. A 23-year-old man presented to the emergency department with hypertension, headache, hemoptysis, anemia, acute kidney injury, glomerular hematuria, and proteinuria. He endorsed repeated exposure to toluene-containing products while repairing dirt bikes. Serologies were positive for anti-GBM antibodies. Kidney biopsy showed crescentic glomerulonephritis with linear immunoglobulin G and granular PLA2R staining by immunofluorescence. He was initially treated with high-dose steroids, plasmapheresis, and hemodialysis for pulmonary-renal syndrome followed by oral cyclophosphamide and prednisone, which were discontinued after 3 months when follow-up biopsies confirmed little chance for renal recovery. He remained on dialysis 1 year later. This case exhibits a unique presentation of anti-GBM syndrome and underlying membranous nephropathy following repeated hydrocarbon exposure. Inhaled toxins promote recurrent localized inflammation, unmasking previously hidden epitopes. Early diagnosis and appropriate use of immunosuppressive and extracorporeal therapies are necessary to prevent morbidity and to improve survival in this rare condition.

Efficacy and Adverse Reactions of Mycophenolate Mofetil Combined with Hormone in the Treatment of Idiopathic Membranous Nephropathy: A Meta-Analysis.

Background: The detection and prevalence of idiopathic membranous nephropathy in China are increasing yearly. However, the current treatment of idiopathic membranous nephropathy relies on empirical treatment regimens such as hormones and immunosuppressants, with unclear prognosis and easy recurrence. Methods: Eight databases were searched to obtain controlled trials on the effects of mycophenolate mofetil combined with hormones in the treatment of idiopathic membranous nephropathy. After literature quality evaluation, data analysis was performed using RevMan 5.3 software. Results: 12 studies were ultimately included in this meta-analysis. 12 studies reported that, compared with the control group, the effective rate (OR: 1.15; 95% CI: 1.06, 1.26; P < .001), 24hUP (SMD:-0.35; 95% CI: -0.47, -0.23; P < .001), Alb (SMD: 1.92; 95% CI: -0.51, 4.36; P = .122), Scr (SMD: 4.44; 95% CI: -10.26, 1.38; P = .135), TG (SMD: 0.51; 95% CI: 0.88, 0.15; P < .01) and adverse events (OR: 0.86; 95% CI: 0.67,1.11; P = .255) of the test group was significantly higher. Conclusion: The results of this study suggested that mycophenolate mofetil combined with hormone may be effective on patients with idiopathic membranous nephropathy, as evidenced by effective rate, 24hUP, Alb, Scr, TG, adverse events, and the above conclusions need to be verified by more high-quality studies.

Combination of Rituximab and Low-dose Tacrolimus in the Treatment of Refractory Membranous Nephropathy: A Retrospective Cohort Study

Background: Conventional regimens for refractory idiopathic membranous nephropathy (IMN) still have limitations. Rituximab (RTX) has a good effect in the treatment of refractory IMN. However, whether RTX single or combined with immunosuppressive therapy is more effective and whether adverse events will increase are still inconclusive. Aims: To investigate the efficacy and safety of RTX combined with low-dose tacrolimus (TAC) versus RTX alone in the treatment of refractory IMN. Study Design: A retrospective cohort study. Methods: We retrospectively studied 91 cases of refractory IMN diagnosed between January 2018 and June 2021, all of which immunosuppressive regimens had failed. Thirty-four patients received RTX combined with TAC (RTX + TAC group), and 57 patients were treated with RTX alone (RTX group). The RTX + TAC group was given RTX 1 g once every 2 weeks, two times, and TAC 0.03 mg/kg/day orally. In the RTX group, RTX was given at the same dosage as the RTX + TAC group. Clinical data were collected at 12 months of follow-up to compare the complete and partial remission rates and the incidence of adverse reactions between the two groups. Results: The overall effectiveness rate of RTX + TAC in the treatment of refractory IMN was 87.14%, of which the partial and complete remission rates were 50.01% and 37.13%, respectively, and the median time to complete remission was 9 (interquartile range [IQR] 6.0, 12.0) months. The overall effectiveness rate of RTX was 65.87%, of which the partial and complete remission rates were 39.48% and 26.39%, respectively, and the median time to complete remission was 10.5 (IQR 6.0, 12.0) months. Adverse events occurred in 6 (17.65%) patients in the RTX + TAC group and in 11 (19.30%) in the RTX group (P = 0.473). Proteinuria and high titer of PLA2R are risk factors for non-remission. Conclusion: The complete and partial remission rates of RTX combined with low-dose TAC in the treatment of refractory IMN are higher than those of RTX alone, and no significant increase in adverse events was noted.

Membranous nephropathy caused by dimercaptosuccinic acid in a patient with Wilson's disease: a case report and literature review.

BACKGROUND: Dimercaptosuccinic acid (DMSA) therapy is a kind of chelation therapy for patients with Wilson 's disease (WD). While there have been reports of side effects associated with DMSA, the development of membranous nephropathy as a result of this therapy is uncommon. CASE PRESENTATION: We present a case of a 19-year-old male patient with Wilson's disease who experienced proteinuria while receiving long-term DMSA treatment. Further evaluation revealed abnormally low levels of serum ceruloplasmin and serum albumin, as well as a 24-hour urinary protein excretion of 4599.98 mg/24 h. A renal biopsy confirmed the presence of membranous nephropathy. After ruling out other potential causes, we determined that the patient's membranous nephropathy was likely caused by DMSA. Following treatment with glucocorticoids, there was a significant reduction in proteinuria. CONCLUSION: This case highlights the possibility of DMSA-induced membranous nephropathy and the importance of considering this diagnosis in patients receiving DMSA treatment. Given the widespread use of DMSA in the treatment of Wilson's disease, further research is needed to fully understand the potential role of this drug in the development of membranous nephropathy.

Mercury-associated neural epidermal growth factor-like 1 protein (NELL-1) positive membranous nephropathy after use of skin lightening creams.

INTRODUCTION: Membranous nephropathy, one of the common causes of glomerulonephritis worldwide, is reported in association with mercury exposure. Neural epidermal growth factor-like 1 protein is a recently described target antigen in membranous nephropathy. CASE SERIES: Three woman (ages 17, 39, and 19 years old) presented sequentially for our evaluation with complaints consistent with nephrotic syndrome. All three had nephrotic range proteinuria, hypoalbuminemia, hypercholesterolemia, hypothyroidism, and inactive urinary sediments. Kidney biopsies were performed in the first two patients, which demonstrated findings consistent with membranous nephropathy and positive staining for neural epidermal growth factor-like 1 protein. On discovery that they were all using the same skin-lightening cream, samples of the cream were tested and found to contain between 2,180 parts per million and 7,698 parts per million of mercury. Elevated urine and blood mercury concentrations were also found in the first two patients. All three patients improved following cessation of use and treatment with levothyroxine (all three patients) and corticosteroids and cyclophosphamide in patients one and two. DISCUSSION: We hypothesize the role of autoimmunity triggered by mercury exposure in the pathogenesis of neural epidermal growth factor-like 1 protein membranous nephropathy. CONCLUSION: Mercury exposure should be carefully assessed as a part of the evaluation of patients with neural epidermal growth factor-like 1 protein positive membranous nephropathy.

Clinicopathological features and long-term prognosis of glomerular diseases associated with mercury-containing cosmetics.

OBJECTIVE: The pathological types and long-term prognosis of glomerular diseases related to mercury exposure are unclear. This study retrospectively examined 41 cases of glomerulonephropathy caused by mercury-containing cosmetics. METHODOLOGY: Forty-one subjects with glomerular diseases presumably caused by mercury-containing cosmetics were selected. Clinical features, kidney biopsy, treatment, and follow-up data were collected. RESULTS: All patients were female with an average age of 39.4 ± 6.6 years at diagnosis. Median time of exposure to mercury-containing cosmetics was six months, and average urine mercury level was 66.80 ± 38.55ug/(g·Cr). Most patients presented with nephrotic syndrome. Renal histopathology showed membranous nephropathy in 22 patients (53.65%), minimal change disease in 13 patients (31.71%), IgA nephropathy with minimal change disease in 5 patients (12.20%), and focal segmental glomerulosclerosis in 1 patient. Median time of exposure to mercury was longer and the proportion of patients with autoantibodies (mainly antinuclear antibodies) was higher in patients with membranous nephropathy. Both blood phospholipase A2 receptor -Ab and kidney tissue phospholipase A2 receptor were negative. Thirty-six patients received glucocorticosteroids and/or immunosuppressants. Five patients were treated with an angiotensin receptor blocker, and nine patients were treated with chelation therapy. The median follow-up time was 40 months (range 27-94). All patients achieved complete remission, and the median time to complete remission was one month. They all successfully discontinued the drugs without relapsing; withdrawal time was 26 months. CONCLUSION: Membranous nephropathy was the most common pathological type in mercury-induced glomerular disease. Patients were sensitive to glucocorticosteroids and immunosuppressants and achieved complete remission quickly. Contrary to primary glomerulonephritides, patients with mercury-induced glomerular diseases had no relapses after withdrawal of the mercury containing cosmetics.

The efficacy and safety of Sanqi Qushi Granule in patients with idiopathic membranous nephropathy --protocol of a multicenter, randomized control trial (SQ-AUTUMN).

BACKGROUND: Adult nephropathy is mainly caused by idiopathic membranous nephropathy (IMN). In cases of proteinuria, Modified Ponticelli Regimens (MPR) are often successful. However, it can cause adverse side effects. Oral Sanqi Qushi Granule (SQG) with MPR is effective in patients with IMN. However, whether it can improve the remission rate of IMN and shorten the remission time is unknown. In this trial, SQG with MPR on IMN will be evaluated clinically for its efficacy and safety. METHODS: We will randomly assign IMN patients who meet the criteria to receives SQG plus cyclical Cyclophosphamide (CTX)/steroids or with placebo plus cyclical CTX/steroids for 6 months. A 12-month follow-up will be conducted on them. Status of remission will be used to assess treatment efficacy. DISCUSSION: This study aims to appraise whether treatment with SQG plus cyclical CTX/steroids is superior to placebo plus cyclical CTX/steroids in the remission rate of patients with adult IMN. Adverse events of SQG plus MPR will be also evaluated for further researches about Chinese Medicine and MPR on whether it can improve the remission rate of IMN in half a year and shorten the remission time and relieve adverse effects will also be clarified. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2200061953 . Registered on 13 July 2022.

Case Report: Successful treatment of late-onset immune checkpoint inhibitor-associated membranous nephropathy in a patient with advanced renal cell carcinoma.

Background: Diagnosing immune checkpoint inhibitor (ICI)-associated nephritis can be challenging since it is a rare complication of therapy, associated with a spectrum of immune-mediated pathologies, and can present months after ICI therapy discontinuation (i.e., late-onset). ICIs are increasingly administered in combination with other cancer therapies with associated nephrotoxicity, further obfuscating the diagnosis of ICI-associated nephritis. In this report, we describe the first suspected case of late-onset ICI-associated membranous nephropathy (MN) in a patient with metastatic clear cell renal cell carcinoma (RCC) who had discontinued ICI therapy 6 months prior to presentation. Prompt recognition of the suspected late-onset immune-related adverse event (irAE) resulted in the successful treatment of MN and continuation of RCC therapy. Case presentation: A 57-year-old man with metastatic clear cell RCC was responsive to third-line RCC therapy with lenvatinib (oral TKI) and everolimus (oral mTOR inhibitor) when he presented with nephrotic range proteinuria and acute kidney injury (AKI). His kidney biopsy revealed probable secondary MN with subendothelial and mesangial immune complex deposits and negative staining for both phospholipase A2 receptor (PLA2R) and thrombospondin type-1 domain-containing 7A (THSD7A). While a diagnosis of paraneoplastic MN could not be excluded, the patient was responding to cancer therapy and had tumor regression. However, 6 months prior to presentation, the patient had received pembrolizumab, an ICI, with his first-line RCC treatment. Due to concern that the patient may be presenting with late-onset ICI-associated MN, he was effectively treated with rituximab, which allowed for his continued RCC therapy. Conclusion: This report highlights the first case of suspected late-onset ICI-associated MN and the increasing complexity of recognizing renal irAEs. With the growing indications for the use of ICIs in combination with other cancer therapies, recognizing the various presentations of ICI-immune nephritis can help guide patient management and treatment.

Investigation of pharmacologic interactions between omeprazole and tacrolimus in a membranous nephropathy patient with CYP3A5 nonexpresser: a case report.

Tacrolimus has been widely used in membranous nephropathy in recent years. The drug interactions of the coadministration of tacrolimus with omeprazole in CYP3A5 nonexpresser membranous nephropathy patients have not been demonstrated. Here, we report an idiopathic membranous nephropathy patient who was with CYP2C19*2/*2, CYP3A5*3/*3 (nonexpresser) and ABCB1 (3435 TT, 1236 computed tomography, 2677 TT) genotype requiring treatment with tacrolimus and omeprazole and found to have fluctuating metabolism of tacrolimus. This study shows that tacrolimus and omeprazole have pharmacologic drug interactions in CYP3A5 nonexpressers, implying that the CYP3A and ABCB1 gene mutations linked to tacrolimus metabolism may alter tacrolimus levels in the blood. The observed concentrations of tacrolimus were decreased after the discontinuation of omeprazole therapy. It demonstrates that, in addition to genotype, clinical covariates, such as omeprazole are important when it comes to better understanding and prediction of tacrolimus dosage. It is deemed necessary to monitor tacrolimus blood concentrations and make dose adjustments when patients were coadministered with omeprazole.

Cyclosporine A-Induced Conchal Hyperplasia with Nasal Obstruction in a Patient with Membranous Nephropathy.

BACKGROUND The immunomodulatory and pharmacokinetic effects of cyclosporine A are used to treat diverse disease entities in different medical fields, including organ transplantation and/or autoimmune diseases. It is also applied in patients with nephrotic range proteinuria as an adjunct to steroids and supportive antihypertensive/antiproteinuric medications. Cyclosporine has a small therapeutic window and is dosed with respect to the underlying disease entity and severity via trough level adaptations. Among its most frequent adverse effects are hypertension, nephrotoxicity, neurotoxicity, and electrolyte disturbances. Hypertrichosis and gingival hyperplasia are obvious and widely recognized adverse effects. CASE REPORT We report on a 66-year-old woman who was treated with cyclosporine A for primary membranous nephropathy. During treatment with cyclosporine, she developed hirsutism and gingival hyperplasia. Later, she reported having impaired nasal breathing and dyspnea on mild physical exercise. Clinical, rhinoscopic, and radiological evaluations showed marked conchal hyperplasia as a potential cause of her symptoms. An extensive medical work-up did not show evidence of allergic, immunologic, or other drug adverse effects, suggesting cyclosporine-induced hyperplasia of the turbinates as a hypothetical causative factor. Dose reductions did not lead to resolution of symptoms but resulted in increasing proteinuria. Therefore, cyclosporine was stopped, and the patient was treated with rituximab. Thereafter, hirsutism and gingival and conchal hyperplasia gradually regressed over 2-4 months, showing complete resolution of conchal hyperplasia on computed-tomography follow-up after 6 months. CONCLUSIONS Cyclosporine can not only result in gingival hyperplasia but also in hyperplasia of the turbinates leading to impaired nasal breathing and shortness of breath on exertion. An extensive search for many other known causes of conchal swelling is warranted to finally suggest an adverse effect of cyclosporine. Discontinuation of cyclosporine resulted in complete remission of conchal hyperplasia as well as other adverse effects.

Treatment of Idiopathic Membranous Nephropathy for Moderate or Severe Proteinuria: A Systematic Review and Network Meta-Analysis.

Objective: Numerous studies have demonstrated that the efficacy of drugs differs in idiopathic membranous nephropathy (IMN) patients with moderate or high proteinuria. However, there is no systematic comparison confirming it. This network meta-analysis (NMA) was performed to respectively compare the efficacy of ten IMN treatments in patients with moderate and high proteinuria and compare the risk of adverse events with 10 IMN regimens. Methods: Randomized controlled trials (RCTs) and observational studies analyzing the main therapeutic regimens for IMN were included from some databases. Network comparisons were performed to analyze the rates of total remission (TR), bone marrow suppression, and gastrointestinal symptoms. The surface under the cumulative ranking area (SUCRA) was calculated to rank interventions. Results: Seventeen RCTs and eight observational studies involving 1778 patients were pooled for comparison of ten interventions. Steroid + tacrolimus (TAC) showed the highest probabilities of TR whether patients had severe proteinuria or not (SUCRA 89.5% and 88.9%, separately). Rituximab (RTX) was more beneficial for TR on patients with proteinuria <8 g/d (SUCRA 66.0%) and was associated with a lower risk of bone marrow suppression and gastrointestinal symptoms (SUCRA 21.7% and 21.4%, separately). TAC + RTX and steroids + cyclophosphamide induced the highest rates of bone marrow suppression (SUCRA 90.6% and 88.3%, separately) and gastrointestinal symptoms (SUCRA 86.0% and 72.1%, separately). Conclusions: Steroids + TAC showed significant efficacy in patients with all degrees of proteinuria, while RTX was more effective in patients with moderate proteinuria and was safer in bone marrow suppression and gastrointestinal symptoms.

Role of Rituximab in Patients with Resistant Nephrotic Syndrome.

Resistant nephrotic syndrome is a group of disorders with diverse histological findings, which are by definition resistant to corticosteroids given in adequate dose for adequate duration and many are resistant to other therapy as well. In many patients progression to end-stage renal disease is the ultimate outcome. The role of B cells has not been fully explained in man, agents that specifically interfere with B cells would ideally represent the first step toward selective therapy. We studied short term and long term effects of rituximab in patients with resistent primary nephrotic syndrome. MATERIAL: Study was conducted at SMS-medical college and Hospital Jaipur, four doses of rituximab were given weakly, in fixed dose of 500 mg per dose and proteinuria was evaluated before start of therapy and at 3 months, 6 months and 12 months of therapy. Patients with resistant primary nephrotic syndrome who failed to respond to other therapies, with stable eGFR >30, and controlled BP were included in study. Patients with Active infection, Uncontrolled hypertension, pregnancy were excluded from study. OBSERVATION: 10 patients were enrolled in study out of which 7 FSGS (focal segmental glomeruloscllerosis) and 3 were IMN (idiopathic membranous nephropathy), 5 were female and 5 were male, age 17-61years (average 34.6), weight were 48-70 kg (avg 57.9), BMI 19.4-23 (AVG 21.18), all patients have normal renal function (average creatinine value of 0.8, range= 0.5 to 1.1). At 3 months 1 patient had partial response and 9 had no response. At 6 months of treatment 2 patients had partial response, 3 had complete response and 5 no response. At 12 months of treatment 4 had partial response, 5 had complete response and 1 no response. Out of 10 patients no one had relapse of Nephrotic syndrome at 12 month of therapy. Renal function remain normal in all patients over 12 months followup. CONCLUSION: This prospective, observational study evaluated 3 month, 6 month, and 12 month outcome of 3 IMN and 7 FSGS patients, with persistent nephrotic range proteinuria and showed that rituximab promoted sustained remission in proteinuria in resistent nephrotic syndrome with normal renal function.

Clinical Outcome of Idiopathic Membranous Nephropathy-A Single Centre Study.

INTRODUCTION: Idiopathic Membranous nephropathy (IMN) is one of the most common causes of adult onset nephrotic syndrome worldwide. About 50% will slowly progress to renal failure if untreated. METHODS: We did a retrospective study in patients with Idiopathic membranous nephropathy who were on follow-up between 2016-2018 at Madras medical college, Chennai. Clinical records, investigations, treatment and treatment response were analyzed. Risk stratification was done according to urine protein estimation, Modified Ponticelli regimen was administered in patients with high risk of renal failure and those with complications. They were followed up 6-12 months. RESULTS: Among 61 patients with IMN, 37 were treated with Modified Ponticelli regimen after 6months of supportive treatment. Spontaneous remission was 14%, after mean follow up of 3.14 yrs total remission was 64.86 %( CR 43.24%; PR-21.62%) and 35.14% had no remission. Three patients progressed to CKD. Tacrolimus was initiated in non responders to IST. Analysis between IST responders and non responders shows those who presented with lesser proteinuria had statistically better outcome. CONCLUSION: This retrospective study of IMN showed a reasonably better outcome. Seventeen per cent of patients had spontaneous remission and 64.86% achieved remission with Modified Ponticelli regimen.

Immune-mediated membranous nephropathy: Long term fluconazole usage caused podocyte autophagy.

The primary consequences of membranous nephropathy (MN) are the development of nephrotic syndrome including hypogammaglobulinemia, the increased infectious risk, the loss of protein-bound vitamin D, and, above all, an elevated thromboembolic incidence of up to 50% in severe proteinuria patients. Membrane nephropathy may be either idiopathic or primary, not recognized (70%-80%) or secondary (20%-30%) to pathological sicknesses such as hepatitis B, systemic lupus erythematosus, malignancies, and side-effects of medicines. The immunological responses in MN involve multiple components: immunoglobulin G (IgG), long-escaped antigens, and the membrane attachment complex, formed by the supplement to form C5b-9. In general, IgG4 is the most significant IgG subclass deposited in idiopathic membranous nephropathic disease but fluctuating IgG1 levels also are linked with immunological deposits. In contrast, IgG1, IgG2, and IgG3 deposition are greater than IgG4 deposition in secondary nephropathy. Fluconazole is a synthetic antifungal triazole that is often used. It is well tolerated in general and has never been identified as a cause of nephropathies. We report on the development of MN caused by fluconazole therapy that could potentiate podocyte autophagy.

Worsening membranous nephropathy in a patient with GIST treated with sunitinib.

Tyrosine kinase inhibitors (TKI) are anticancer agents widely used for a variety of malignancies including gastrointestinal stromal tumours (GIST). Although generally well-tolerated, TKIs have been associated with a number of adverse events including hypertension, proteinuria and nephrotic syndrome. We present the case of a 70-year-old patient with metastatic GIST on long-standing sunitinib who developed hypertension, oedema and hypoalbuminemia with a rising serum creatinine and was found to have nephrotic syndrome. Workup revealed elevated antiphospholipase A2 receptor (PLA2R) antibody IgG titres and a kidney biopsy confirmed PLA2R-positive membranous nephropathy without findings of thrombotic microangiopathy. Cessation of sunitinib led to reduction in anti-PLA2R antibody IgG titres while resumption, due to concern for cancer progression, led to worsening symptoms. Treatment with rituximab led to undetectable anti-PLA2R IgG titres. We highlight the importance of maintaining a systematic approach for evaluating nephrotic syndrome and provide a case showing that TKIs can exacerbate underlying nephrotic syndrome.

Neutrophil Gelatinase-Associated Lipocalin as an Early Predictor of Contrast-Induced Nephropathy Following Endovascular Aortic Repair for Abdominal Aortic Aneurysm.

To investigate serum neutrophil gelatinase-associated lipocalin (sNGAL) and urine neutrophil gelatinase-associated lipocalin (uNGAL) as early predictors of contrast-associated acute kidney injury(contrast-induced nephropathy)following endovascular aortic repair for abdominal aortic aneurysm. Prospective cohort study. Subjects included 202 consecutive patients with abdominal aortic aneurysm diagnosed between February 2016 and October 2018. We divided the patients into 2 groups: contrast-induced nephropathy (CIN) (n = 26) and non-CIN (n = 176). We assessed correlations between sNGAL and uNGAL concentrations and standard renal markers at baseline, 6, 24, and 48 hours post-procedure. We constructed conventional receiver operating characteristic (ROC) curves and calculated the area under the curve to assess SCr, eGFR, sNGAL, and uNGAL performance. We derived biomarker cutoff levels from ROC analysis results to maximize sensitivity and specificity values. The CIN incidence within our cohort was 12.9%. sNGAL levels correlated significantly with SCr and eGFR at baseline, 6, and 24 hours post-contrast medium exposure. Similarly, uNGAL levels correlated with SCr and estimated glomerular filtration rate (eGFR) at baseline, 6, and 24 hours post-exposure. sNGAL and uNGAL were significantly elevated as early as 6 hours post-endotherapy in the CIN group; there were only minor changes in the non-CIN group. SCr was also significantly elevated in the CIN group, but not until 48 hours post-catheterization. Both sNGAL and uNGAL may be more accurate than SCr and eGFR as early biomarkers of CIN in patients with abdominal aortic aneurysm undergoing endovascular therapy.