Tubulointerstitial nephritis and IgA nephropathy in a patient with advanced lung cancer treated with long-term gefitinib

Masutani, Kohsuke; Fujisaki, Kiichiro; Maeda, Hiroshi; Toyonaga, Jiro; Inoshima, Ichiro; Takayama, K.; Katafuchi, Ritsuko; Hirakata, Hideki; Tsuruya, Kazuhiko; Iida, Mitsuo

doi:10.1007/s10157-008-0066-1

Cited by 31 publications

(19 citation statements)

References 14 publications

(12 reference statements)

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“…22 This hypothesis was verified showing that in EBVtransformed B LCL ERK1/2 is hypo-phosphorylated in SPRY2 variant carriers and normal in the only family member, who tested negative for the variant. Moreover, as mentioned above, pERK1/2 is a strong transcriptional activator of SPRY2, 20,23,24 whereas its block causes SPRY2 transcriptional silencing. This tight transcriptional feedback explains the strong reduction observed in SPRY2 transcript, without apparent reduction in the protein levels.…”

Section: Association Of Mapkmentioning

confidence: 83%

A SPRY2 mutation leading to MAPK/ERK pathway inhibition is associated with an autosomal dominant form of IgA nephropathy

Milillo¹,

Carpia²,

Costanzi

et al. 2015

Eur J Hum Genet

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IgA nephropathy (IgAN) represents the most common primary glomerulonephritis worldwide with a prevalence of 25-50% among patients with primary glomerulopathies. In~5-10% of the patients the disease segregates with an autosomal dominant (AD) pattern. Association studies identified loci on chromosomes 1q32, 6p21, 8p23, 17p13, 22q12, whereas classical linkage studies on AD families identified loci on chromosomes 2q36, 4q26-31, 6q22, 17q12-22. We have studied a large Sicilian family where IgAN segregates with an AD transmission. To identify the causal gene, the exomes of two affected and one unaffected individual have been sequenced. From the bioinformatics analysis a p.(Arg119Trp) variant in the SPRY2 gene was identified as the probable disease-causing mutation. Moreover, functional characterization of this variant showed that it is responsible for the inhibition of the MAPK/ERK1/2 pathway. The same effect was observed in two sporadic IgAN patients carriers of wild-type SPRY2, suggesting that downregulation of the MAPK/ERK1/2 pathway represents a common mechanism leading to IgAN.

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Section: Association Of Mapkmentioning

confidence: 83%

A SPRY2 mutation leading to MAPK/ERK pathway inhibition is associated with an autosomal dominant form of IgA nephropathy

Milillo¹,

Carpia²,

Costanzi

et al. 2015

Eur J Hum Genet

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“…3,4 Patients also should be evaluated for malignancy since adenocarcinoma is a known cause of pericardial effusion and nephritis. 5 In addition, uremia can generate a similar clinical picture. Evaluation of our patient revealed no signs of malignancy.…”

Section: Discussionmentioning

confidence: 99%

“…5 In addition, uremia can generate a similar clinical picture. Evaluation of our patient revealed no signs of malignancy.…”

Section: Discussionmentioning

confidence: 99%

Acute Cardiac Tamponade in a 58-Year-Old Male with Poststreptococcal Glomerulonephritis

Bottinor

Fronk

Sadruddin

et al. 2016

Methodist DeBakey Cardiovascular Journal

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A 58-year-old male with diabetes and chronic kidney disease presented with a history of malaise, fatigue, and sore throat. He also had experienced intermittent nausea, vomiting, and diarrhea over the prior 2 weeks and reported subjective fevers and chills. Physical examination was unremarkable. Basic metabolic panel demonstrated acute kidney injury (AKI).The patient was administered intravenous saline. A renal ultrasound demonstrated normal anatomy, and Clostridium difficile antigen was negative. He was started on ceftriaxone and metronidazole for bacterial intestinal overgrowth. Emesis and diarrhea improved after 24 hours of antibiotics; however, renal function continued to worsen. The patient developed volume overload and ultimately required hemodialysis. Transthoracic echocardiogram showed low normal left ventricular systolic function with a trivial pericardial effusion. Urinalysis revealed proteinuria, hematuria, and pyuria. Urine culture was negative. Complement 3 level was low at 47.6 mg/dL (lower limit 90 mg/dL). Complement 4 level was normal. Both erythrocyte sedimentation rate and C-reactive protein were markedly elevated. Antinuclear antibody, antineutrophil cytoplasmic antibody, anti-double-stranded DNA, anti-Ro, anti-La, and antiglomerular basement membrane antibody were negative. Serum protein electrophoresis and urine protein electrophoresis were negative. Creatinine kinase was within normal limits. Hepatitis B and C antibodies were nonreactive, as were HIV antibodies, rheumatoid factor, and cryoglobulins. Serum IgA was 582 mg/dL (upper limit 400 mg/dL) and IgG was 3190 mg/ dL (upper limit 1523 mg/dL). Antistreptolysin O titer was 2484 IU/mL (upper limit of normal 200 IU/mL). The patient was diagnosed with poststreptococcal glomerulonephritis and continued to tolerate dialysis well. Before discharge, the patient developed intractable hiccups. Chest X-ray revealed only resolving pulmonary edema. He was discharged with plans for outpatient chest and abdominal computed tomography (CT) to further evaluate his hiccups.The following day, he presented to the emergency department with acute dyspnea after routine hemodialysis. He had tachypnea and hypoxia that responded to supplemental oxygen. Systolic blood pressure decreased by 10 mm Hg with inspiration. Chest CT demonstrated a moderate pericardial effusion. A repeat transthoracic echocardiogram (online video) showed a pericardial effusion with right atrial and right ventricular diastolic collapse. The patient underwent urgent pericardiocentesis with removal of 700 mL of sanguineous fluid. Bacterial, fungal, mycobacterial cultures, and cytology were negative. His blood urea nitrogen was 39 mg/dL on re-presentation to the hospital. Nine months later, the patient has had no recurrence of pericardial effusion. He has recovered kidney function and no longer requires hemodialysis. DiscussionPericarditis in conjunction with nephritis presents as an interesting clinical picture, leading one to consider a robust list of differential diagnoses that includes autoim...

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“…Although rare, both solid tumor such as renal cell cancer, lung cancer, pancreas cancer, and hematological malignancies such as Hodgkin's and non-Hodgkin's diseases, could induce IgA nephropathy, termed paraneoplastic IgA nephropathy [15,16]. Interestingly, a case is recently reported that IgA nephropathy occurs in gefitinib treatment for lung cancer [17].…”

Section: Discussionmentioning

confidence: 99%

A case of gefitinib-associated membranous nephropathy in treatment for pulmonary adenocarcinoma

et al. 2014

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We experienced a case that was considered as gefitinib-associated membranous nephropathy (MGN) in treatment for pulmonary adenocarcinoma. A female patient aged 80 who had been treated for lung cancer was referred and hospitalized at our hospital, because of nephrotic syndrome. The patient had pulmonary adenocarcinoma (cT4N2M1a) with positive for epidermal growth factor receptor (EGFR) mutation. Gefitinib, EGFR tyrosine kinase inhibitor, was initiated from 1 year and 2 months ago. At that time, proteinuria was negative. The treatment effect on lung cancer was so favorable that partial response had been maintained. However, from 4 months ago, edema of legs appeared, leading to become nephrotic syndrome. Renal biopsy was performed, and secondary MGN was diagnosed, because of deposition of peripheral IgG, mesangial IgA, and C3, as well as the deposition of peripheral IgG4, IgG1, IgG2, and weak IgG3. We considered druginduced MGN and discontinued the administration of gefitinib. Subsequently, the proteinuria tended to decrease gradually and became negative 10 months later. However, the lung cancer recurred 3 months after discontinuation of gefitinib and another molecular target drug, erlotinib, was administered. At present, 13 months after discontinuation of gefitinib, absence of proteinuria is maintained. It has been generally considered that secondary MGN can be induced by both malignant tumor and their treatment. In the present case, the clinical course and pathological characteristics showed the secondary MGN that might be associated with gefitinib during the treatment for pulmonary adenocarcinoma. The present case, to our knowledge, may be a first case of gefitinib-associated MGN.

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Tubulointerstitial nephritis and IgA nephropathy in a patient with advanced lung cancer treated with long-term gefitinib

Cited by 31 publications

References 14 publications

A SPRY2 mutation leading to MAPK/ERK pathway inhibition is associated with an autosomal dominant form of IgA nephropathy

A SPRY2 mutation leading to MAPK/ERK pathway inhibition is associated with an autosomal dominant form of IgA nephropathy

Acute Cardiac Tamponade in a 58-Year-Old Male with Poststreptococcal Glomerulonephritis

A case of gefitinib-associated membranous nephropathy in treatment for pulmonary adenocarcinoma

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