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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Renal Vasculitis and Pauci-immune Glomerulonephritis Associated With Immune Checkpoint Inhibitors.

Immune checkpoint inhibitors are increasingly used to treat a variety of solid-organ and hematologic cancers. However, overactivation of the immune system can lead to immune-related adverse events, which are increasingly recognized in the kidney. There have been only rare reported cases of checkpoint inhibitor-associated glomerulonephritis and renal vasculitis, although vasculitis in other organs has been well described. We report 4 cases of renal vasculitis or pauci-immune glomerulonephritis after checkpoint inhibitor therapy. Three patients had renal small- to medium-vessel vasculitis and 1 had focally crescentic pauci-immune glomerulonephritis. Three patients presented with acute kidney injury, and 1 presented with nephrotic syndrome and hematuria. Three patients were tested for antineutrophil cytoplasmic antibodies, which were negative. The time from checkpoint inhibitor initiation to immune-related adverse event presentation ranged from 2 weeks to 24 months. Three patients were treated with glucocorticoids, resulting in clinical resolution. Our series demonstrates that renal vasculitis and pauci-immune glomerulonephritis are important considerations in the differential diagnosis of checkpoint inhibitor-related reductions in kidney function.

Incidence, management, and outcomes of autoimmune nephropathies following alemtuzumab treatment in patients with multiple sclerosis.

BACKGROUND: Autoimmune disorders including nephropathies have been reported more frequently in alemtuzumab-treated multiple sclerosis (MS) patients than in the general population. OBJECTIVE: Describe instances of autoimmune nephropathy in alemtuzumab-treated MS patients. METHODS: Cases were identified from safety monitoring within the alemtuzumab relapsing-remitting multiple sclerosis (RRMS) clinical development program (CDP) or post-marketing, or following off-label use. RESULTS: As of 16 June 2017, 16 autoimmune nephropathies have occurred following alemtuzumab treatment for MS. The incidence of autoimmune nephropathies was 0.34% within the CDP (5/1485 patients). The five CDP cases (one of anti-glomerular basement membrane (anti-GBM) disease, two of membranous glomerulonephropathy, and two of serum anti-GBM antibody without typical anti-GBM disease) were identified early, responded to conventional therapy (where needed), and had favorable outcomes. Three of 11 cases outside the CDP occurred following off-label alemtuzumab use prior to approval for RRMS and were all anti-GBM disease. Diagnosis was delayed in one of these three cases and another did not receive appropriate treatment; all three cases resulted in end-stage renal failure. All anti-GBM disease cases with documented urinalysis demonstrated prior microscopic hematuria. CONCLUSION: Close monitoring of alemtuzumab-treated MS patients facilitates diagnosis and treatment early in the nephropathy course when preservation of renal function is more likely.

Infliximab-associated focal segmental glomerulosclerosis in a patient with ankylosing spondylitis.

The introduction of tumor necrosis factor-alpha (TNF-α)-targeting drugs has given new opportunities in the treatment of various inflammatory rheumatic diseases and has been the most important development in the treatment of spondyloarthritis (SpA). However, the increasing use and longer follow-up periods of treatment also pose risks of developing various adverse effects ranging from common ones including infections to uncommon renal complications. This report describes a case of infliximab-induced focal segmental glomerulosclerosis (FSGS) in a 40-year-old female patient with ankylosing spondylitis (AS) who presented with asymptomatic proteinuria and microscopic hematuria. To the best of our knowledge, this is the second reported case of FSGS attributed to infliximab (IFX). A review of the English literature was conducted for cases of possible IFX-associated renal disorders in patients with SpA and SpA spectrum diseases. In this respect, the reported renal pathologies were IgA nephropathy, crescentic glomerulonephritis, acute renal artery occlusion, acute tubulointerstitial nephritis (ATIN), FSGS, and membranous glomerulopathy. Furthermore, partial or complete resolution was reported after cessation of therapy. In conclusion, although renal complications of TNF inhibitors (TNFi) are uncommon, spot urine evaluation may be recommended in the follow-up of patients treated with TNFi.

Mercury Intoxication as a Rare Cause of Membranous Nephropathy in a Child.

In adults, membranous nephropathy is the second most common cause of nephrotic syndrome. In contrast, minimal change disease and focal segmental glomerulosclerosis constitute the most common forms of nephrotic syndrome in children, while membranous nephropathy accounts for <5% of cases. In adults, causes of membranous nephropathy include autoantibodies directed against phospholipase A2 receptor and thrombospondin type 1 containing 7A, various infections, environmental toxicities, autoimmune disorders, malignancies, and other secondary forms. The most common causes of secondary membranous nephropathy in children are infections, autoimmune diseases, and neoplasia. We discuss an unusual presentation of new-onset membranous nephropathy due to mercury toxicity in a 14-year-old male with reflux nephropathy. This case underscores the importance of a high index of suspicion for uncommon causes of nephrotic syndrome in pediatric patients with membranous nephropathy.

Therapeutic Effect of a Novel Nano-Drug Delivery System on Membranous Glomerulonephritis Rat Model Induced by Cationic Bovine Serum.

In order to explore a novel high efficacy drug delivery system for membranous glomerulonephritis (MGN), a complex chronic inflammation, methylprednisolone bovine serum albumin nanoparticles (ME BSA NPs) were designed. The nanoparticles were prepared by desolvation-chemical crosslinking method and its physicochemical characterizations were conducted. The experimental MGN rat models induced by cationic bovine serum albumin were established by a modified Border's method and applied in the pharmacodynamics study of ME BSA NPs. The results showed that the particle size, particle dispersion index, and entrapment efficiency of ME BSA NPs were 131.1 ± 3.4 nm, 0.159 ± 0.036, and 71.51 ± 1.74%, respectively. In addition, the image of transmission electron microscopy showed that the ME BSA NPs were the relatively uniform spherical particles. In the in vivo pharmacodynamics study, compared with saline group and SOLU-MEDROL® group, that the ME BSA NPs group was significantly reduced the levels of 24 h urinary protein (P < 0.01) and serum creatinine (P < 0.05). Consequently, these outcomes indicated that the nanoparticles we studied were a promising drug delivery system for the MGN disease, and it may be also useful for other complex chronic inflammations.

Glomerulopathy induced by immunization with a peptide derived from the goodpasture antigen α3IV-NC1.

Mouse experimental autoimmune glomerulonephritis, a model of human antiglomerular basement membrane disease, depends on both Ab and T cell responses to the Goodpasture Ag noncollagenous domain 1 of the α3-chain of type IV collagen (α3IV-NC1). The aim of our study was to further characterize the T cell-mediated immune response. Repeated immunization with mouse α3IV-NC1 caused fatal glomerulonephritis in DBA/1 mice. Although two immunizations were sufficient to generate high α3IV-NC1-specific IgG titers, Ab and complement deposition along the glomerular basement membranes, and a nephrotic syndrome, two additional immunizations were needed to induce a necrotizing/crescentic glomerulonephritis. Ten days after the first immunization, α3IV-NC1-specific CD4(+) cells producing TNF-α, IFN-γ, or IL-17A were detected in the spleen. With the emergence of necrotizing/crescentic glomerulonephritis, ∼0.15% of renal CD4(+) cells were specific for α3IV-NC1. Using peptides spanning the whole α3IV-NC1 domain, three immunodominant T cell epitopes were identified. Immunization with these peptides did not lead to clinical signs of experimental autoimmune glomerulonephritis or necrotizing/crescentic glomerulonephritis. However, mice immunized with one of the peptides (STVKAGDLEKIISRC) developed circulating Abs against mouse α3IV-NC1 first detected at 8 wk, and 50% of the mice showed mild proteinuria at 18-24 wk due to membranous glomerulopathy. Taken together, our results suggest that autoreactive T cells are able to induce the formation of pathologic autoantibodies. The quality and quantity of α3IV-NC1-specific Ab and T cell responses are critical for the phenotype of the glomerulonephritis.

Tiopronin-induced membranous nephropathy: a case report.

BACKGROUND: Tiopronin, a glycine derivative extensively used to treat cystinuria and hepatic cell injury, can give rise to rare complications such as proteinuria and nephrotic syndrome. However, the pathological characteristics of this secondary nephropathy are poorly understood. Here, we report a case of tiopronin-induced nephrotic syndrome. CASE PRESENTATION: A 65-year-old Chinese man with a history of myasthenia gravis admitted tiopronin for hepatoprotection therapy. After 3 months later, he presented with rapid weight gain, massive peripheral edema, and proteinuria in the nephrotic range. Laboratory findings included serum albumin (20 g/L), total protein (38 g/L), and total cholesterol (11.78 mmol/L). A 24-hour urine protein collection contained 8620 mg. Percutaneous renal biopsy revealed a uniformly thickened glomerular and rigid basement membrane with immunoglobulin G (IgG) and complement C3 deposited along the glomerular capillary wall. Withdrawal of tiopronin-induced proteinuria complete remission and clinical resolution of nephrotic syndrome. CONCLUSIONS: Potential risk of kidney injury exists with long-term tiopronin treatment. Membranous nephropathy was a common renal pathologic feature. Proteinuria in the nephrotic range may spontaneously remit after tiopronin withdrawal. Periodic urine analysis and patient follow-up are recommended with tiopronin therapy.

Membranous nephropathy and nonsteroidal anti-inflammatory agents.

Membranous nephropathy presents clinically as nephrotic syndrome, with subepithelial immune complex deposits seen on biopsy. Historically, in about three-quarters of membranous cases, no obvious etiologic agent or condition can be identified. More recently, serum antibodies to the phospholipase A2 receptor have been discovered in many patients with primary/idiopathic membranous nephropathy. About one-quarter of patients have membranous nephropathy as a manifestation of another systemic disorder, such as autoimmune conditions, infection, malignancy, toxin exposure, or drugs (classically gold or penicillamine). In this report, we present a case of recurrent nephrotic syndrome with biopsy-proven membranous nephropathy closely associated with use of the nonsteroidal anti-inflammatory drugs (NSAIDs) naproxen and piroxicam. Characterization of the immunoglobulin G (IgG) subclass profile of the deposits showed abundant IgG1, weak IgG4, and positive staining for phospholipase A2 receptor. This case serves to highlight membranous nephropathy as an under-recognized renal complication of NSAID use. Other kidney effects of NSAIDs, such as hemodynamic compromise, interstitial nephritis, and minimal change disease, are more broadly recognized.

Varenicline induced acute interstitial nephritis in the setting of idiopathic membranous glomerulonephritis.

BACKGROUND: Varenicline is a nicotinic receptor partial agonist indicated for the cessation of smoking. It is regarded as having no or minimal renal toxicity. A single case report has linked it to acute interstitial nephritis. CASE PRESENTATION: A 56 year-old female with a long-standing history of idiopathic membranous glomerulonephritis presented on routine follow-up with an unexpected rise in her serum creatinine from a stable baseline of 225 umol/L to 319 umol/L Biopsy revealed acute interstitial nephritis. There were no preceding clinical events other than the initiation of varenicline therapy three months prior. This was discontinued with no improvement in renal function. A ten week course of prednisone was initiated and creatinine levels returned to baseline. Shortly after prednisone therapy was completed, renal function worsened but the patient declined further immunosuppressive therapy. Exposure to varenicline therapy two years prior had also resulted in a reversible decline in kidney function. CONCLUSION: This is only the second case report to document varenicline-induced acute interstitial nephritis. A careful medication history and renal biopsy were essential in identifying the etiology of the acute kidney injury in this patient with a complex renal history.