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Cited by 2Renal Diseases and GlomerulopathiesSystemic Lupus Erythematosus ResearchComplement system in diseases

Membranous Nephropathy-Like Apolipoprotein E Deposition Disease with Apolipoprotein E Toyonaka and Homozygous Apolipoprotein E2/2 without Dyslipidemia, with Characteristic Electron-Dense Deposits

Open access
Koshino, Akihiko, Takaeda, Chikako, Matsuno, Takahiro, Kitajima, Shinji, Iwata, Yasunori, Sakai, Norihiko, Nagahama, Kiyotaka, Niida, Yo +3 more·2022·Case Reports in Nephrology and Dialysis
DOI 10.1159/000525086PMC PMC9247525
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Abstract

Recently, several cases of novel apolipoprotein E (apoE)-related glomerular disease known as membranous nephropathy (MN)-like apoE deposition disease with apoE Toyonaka (Ser197Cys) and homozygous apoE2/2 have been reported. However, the clinical and pathological characteristics are uncertain due to the small number of reports. Here, we report an additional case with various clinical and pathological characteristics. A 28-year-old Japanese man with mild proteinuria and hematuria underwent a kidney biopsy. Examination under a light microscope revealed mesangial proliferation, mesangial matrix expansion, and segmental spike lesion. An immunofluorescence study showed no immunoglobulin or complement depositions. In the electron microscopic (EM) examination, massive deposits with various electron densities in the subepithelial, subendothelial, and paramesangial areas were more prominent than those reported in previous cases, which resembled microbubbles or microcysts on higher magnification. The glomerular basement membrane (GBM) structure was partly degenerated by these deposits. Serum triglyceride and cholesterol levels were within the normal range. However, the serum apoE concentration was significantly high, and glomerular apoE accumulation was detected in immunohistochemistry. The DNA sequence revealed apoE Toyonaka and homozygous apoE2/2 similar to that of the previous cases with MN-like apoE deposition disease. MN-like apoE deposition disease can manifest as only mild hematuria and proteinuria without dyslipidemia. Various characteristic deposits associated with GBM degeneration can be observed in the EM study.

AI snapshot

Written from the paper’s full text.

TL;DR

This case report describes a 28-year-old Japanese man with mild proteinuria and hematuria without dyslipidemia who was diagnosed with membranous nephropathy-like apolipoprotein E deposition disease carrying apoE Toyonaka (Ser197Cys) and homozygous apoE2/2. Kidney biopsy showed glomerular apoE accumulation and characteristic electron-dense deposits with glomerular basement membrane degeneration.

Key findings

  • The case is reported as the fourth case of MN-like apoE deposition disease with apoE Toyonaka and homozygous apoE2/2; the patient had only mild proteinuria and hematuria, with proteinuria of 0.8 g/day and normal serum triglyceride and cholesterol levels.
  • Serum apoE was elevated at 8.0 mg/dL (reference value 2.7–4.3 mg/dL), and immunohistochemistry showed widespread apoE accumulation in both the glomerular basement membrane and mesangial area.
  • APOE analysis showed cysteine at both codons 112 and 158, indicating apoE2/E2, plus a heterozygous missense mutation c.644C>G resulting in apoE Toyonaka (Ser197Cys).
  • Electron microscopy revealed massive deposits with various electron densities in subepithelial, subendothelial, and paramesangial areas, resembling microbubbles or microcysts on higher magnification, with partial glomerular basement membrane degeneration; no foam cells or lipoprotein thrombi were marked.

Methods

  • Design: single case report of a 28-year-old Japanese man with a 4-year history of proteinuria and hematuria detected on annual health surveillance.
  • Data/sample: kidney biopsy evaluated by light microscopy, immunofluorescence, electron microscopy, and anti-apoE immunohistochemistry; APOE gene analysis used long-range polymerase chain reaction from peripheral blood DNA, next-generation sequencing, and Sanger validation.
  • Main analysis: descriptive clinical, laboratory, histological, immunohistochemical, electron microscopic, and genetic findings.

Limitations

  • Stated: the report does not include information on the clinical course after diagnosis because the patient stopped visiting the hospital.
  • Evident: as a single case report, it cannot establish prognosis, treatment response, or generalizability; the authors note that clinical suspicion is difficult due to lack of specific laboratory tests and low awareness of the disease.
  • Stated/evident: cryoglobulin was positive, but the type was not assessed, and the relationship of cryoglobulinemia to the kidney findings remains uncertain.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1159/000525086

Cites

15 of 15 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

27 of 40 cited sources checked · 9 supported · 2 flagged · accuracy not yet measured

  • Premisecitation

    This case is the fourth report of MN-like apoE deposition disease with apoE Toyonaka and homozygous apoE2/2 in the literature.

    “this case is the fourth report of MN-like apoE deposition disease with apoE Toyonaka and homozygous apoE2/2 in the literature.”
    Quote in the paperNot a substantial claim3 of 3 sources checked
    • cites [4] Fukunaga M Nagahama K Aoki M Shimizu A Hara S Matsunaga A Membranous nephropathy-like apolipoprotein E deposition disease with apolipoprotein E Toyonaka (Ser197Cys) and a homozygous apolipoprotein E2/2 Case Rep Nephrol Dial 2018 8 (1) 45 55 29692990 PMC5903162 source

      The Introduction (page unavailable) describes a case of MN-like ApoE deposition with ApoE Toyonaka and homozygous ApoE2/2. The paper does not establish that the citing document’s case is the fourth report in the literature; its Discussion instead describes its own case as the first in which ApoE was identified in the subepithelial area. (LLM, conf=0.87)

      Experimental — accuracy not yet measured
    • cites [5] Hirashima H Komiya T Toriu N Hara S Matsunaga A Saito T A case of nephrotic syndrome showing contemporary presence of apolipoprotein E2 homozygote glomerulopathy and membranous nephropathy-like findings modified by apolipoprotein E Toyonaka Clin Nephrol Case Stud 2018 6 45 51 30542638 PMC6287602 source

      The Introduction and case presentation describe this patient as having MN-like lesions, ApoE Toyonaka, and homozygous ApoE2/2. The Discussion identifies one earlier case with the same combination, but the paper does not say this case was the fourth report in the literature. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [6] Kato T Ushiogi Y Yokoyama H Hara S Matsunaga A Muso E A case of apolipoprotein E Toyonaka and homozygous apolipoprotein E2/2 showing non-immune membranous nephropathy-like glomerular lesions with foamy changes CEN Case Rep 2019 8 (2) 106 11 30701487 PMC6450992 source

      The Discussion calls the paper’s case the third report with apoE Toyonaka and homozygous apoE2/2, not the fourth. The Introduction identifies two earlier cases with MN-like histology. (LLM, conf=0.88)

      Checked by a reasoning model — may be wrong.

      Experimental — accuracy not yet measured
  • Premisecitation

    To date, all four cases of MN-like apoE deposition disease have been reported from the west-central part of the mainland of Japan.

    “To date, all the four cases of MN-like apoE deposition disease have been reported from the west-central part of the mainland of Japan.”
    Quote in the paperNot a substantial claim3 of 3 sources checked
    • cites [4] Fukunaga M Nagahama K Aoki M Shimizu A Hara S Matsunaga A Membranous nephropathy-like apolipoprotein E deposition disease with apolipoprotein E Toyonaka (Ser197Cys) and a homozygous apolipoprotein E2/2 Case Rep Nephrol Dial 2018 8 (1) 45 55 29692990 PMC5903162 source

      The Case Presentation describes one Japanese patient admitted to Toyonaka Municipal Hospital, and the Discussion calls this the first case with ApoE identified in subepithelial deposits. Our copy does not give a count of four MN-like ApoE deposition cases or describe where all such cases were reported; searches for the case count and geographic distribution found no such passage. (LLM, conf=0.77)

      Experimental — accuracy not yet measured
    • cites [5] Hirashima H Komiya T Toriu N Hara S Matsunaga A Saito T A case of nephrotic syndrome showing contemporary presence of apolipoprotein E2 homozygote glomerulopathy and membranous nephropathy-like findings modified by apolipoprotein E Toyonaka Clin Nephrol Case Stud 2018 6 45 51 30542638 PMC6287602 source

      The Discussion (page not available) describes the authors’ MN-like ApoE case and a similar case reported by Fukunaga et al. The Case presentation places the authors’ patient at a hospital in Osaka. Our copy does not establish that there were four cases or that all four came from west-central mainland Japan. (LLM, conf=0.82)

      Experimental — accuracy not yet measured
    • cites [6] Kato T Ushiogi Y Yokoyama H Hara S Matsunaga A Muso E A case of apolipoprotein E Toyonaka and homozygous apolipoprotein E2/2 showing non-immune membranous nephropathy-like glomerular lesions with foamy changes CEN Case Rep 2019 8 (2) 106 11 30701487 PMC6450992 source

      The Introduction and Discussion describe three reported cases with MN-like lesions, including the paper’s own case, rather than four. The Discussion says the patient was born in a different area from the other two patients; it does not establish that all cases came from west-central mainland Japan. Page numbers are unavailable in our copy. (LLM, conf=0.84)

      Checked by a reasoning model — may be wrong.

      Experimental — accuracy not yet measured
  • Premisecitation

    In Fukunaga et al., the second biopsy revealed a more robust apoE deposition than the first biopsy performed 9 years earlier.

    “In the case reported by Fukunaga et al. [4], the second biopsy revealed a more robust apoE deposition than the first biopsy performed 9 years earlier.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [4] Fukunaga M Nagahama K Aoki M Shimizu A Hara S Matsunaga A Membranous nephropathy-like apolipoprotein E deposition disease with apolipoprotein E Toyonaka (Ser197Cys) and a homozygous apolipoprotein E2/2 Case Rep Nephrol Dial 2018 8 (1) 45 55 29692990 PMC5903162 source
  • Premisecitation

    In all reported cases including ours, the serum apoE concentration was high regardless of the presence of dyslipidemia.

    “In all reported cases, including our case, the serum apoE concentration was high, regardless of the presence of dyslipidemia (Table 2).”
    Quote in the paperSubstantial claim3 of 3 sources checked
    • cites [4] Fukunaga M Nagahama K Aoki M Shimizu A Hara S Matsunaga A Membranous nephropathy-like apolipoprotein E deposition disease with apolipoprotein E Toyonaka (Ser197Cys) and a homozygous apolipoprotein E2/2 Case Rep Nephrol Dial 2018 8 (1) 45 55 29692990 PMC5903162 source

      The Case Presentation (Analysis of ApoE Mutation; page unavailable) reports high plasma ApoE despite normal triglycerides and cholesterol in this patient. The Discussion also mentions several lipoprotein glomerulopathy cases with high serum ApoE without hyperlipidemia. Neither passage establishes that ApoE was high in all reported cases, regardless of dyslipidemia status. (LLM, conf=0.87)

      Experimental — accuracy not yet measured
    • cites [5] Hirashima H Komiya T Toriu N Hara S Matsunaga A Saito T A case of nephrotic syndrome showing contemporary presence of apolipoprotein E2 homozygote glomerulopathy and membranous nephropathy-like findings modified by apolipoprotein E Toyonaka Clin Nephrol Case Stud 2018 6 45 51 30542638 PMC6287602 source

      The Case presentation > Patient section reports elevated serum ApoE (13.6 mg/dL, versus a normal range of 2.8–4.6 mg/dL) in a patient who also had elevated cholesterol and triglycerides. Our copy does not establish that serum ApoE was high in all reported cases or in cases without dyslipidemia. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [6] Kato T Ushiogi Y Yokoyama H Hara S Matsunaga A Muso E A case of apolipoprotein E Toyonaka and homozygous apolipoprotein E2/2 showing non-immune membranous nephropathy-like glomerular lesions with foamy changes CEN Case Rep 2019 8 (2) 106 11 30701487 PMC6450992 source

      The Case presentation reports elevated serum apoE in the authors’ patient (7.5 mg/dL; normal range 2.4–5.2 mg/dL). The Discussion identifies one earlier case as normolipidemic, but neither its text nor Table 1 reports serum apoE concentrations for the two earlier cases. The source therefore does not establish that apoE was high in all reported cases regardless of dyslipidemia (page numbers unavailable in our copy). (LLM, conf=0.86)

      Experimental — accuracy not yet measured
  • Premisecitation

    No lipid abnormalities were observed in one previous case with apoE Toyonaka and homozygous apoE2/2.

    “In fact, no lipid abnormalities were observed in one of the previous cases with apoE Toyonaka and homozygous apoE2/2 [4].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [4] Fukunaga M Nagahama K Aoki M Shimizu A Hara S Matsunaga A Membranous nephropathy-like apolipoprotein E deposition disease with apolipoprotein E Toyonaka (Ser197Cys) and a homozygous apolipoprotein E2/2 Case Rep Nephrol Dial 2018 8 (1) 45 55 29692990 PMC5903162 source
  • May combine two claims. 12
  • Classified as probably not a substantial claim. 9

  • May combine two claims.

    Premisecitation

    Previous cases showed increases in proteinuria and decreases in renal function in their long-term course.

    “The previous cases showed increases in proteinuria and decreases in renal function in their long-term course.”
    Quote in the paperNot a substantial claim3 of 3 sources checked
    • cites [4] Fukunaga M Nagahama K Aoki M Shimizu A Hara S Matsunaga A Membranous nephropathy-like apolipoprotein E deposition disease with apolipoprotein E Toyonaka (Ser197Cys) and a homozygous apolipoprotein E2/2 Case Rep Nephrol Dial 2018 8 (1) 45 55 29692990 PMC5903162 source

      The Case Presentation’s “Clinical Course after the First Biopsy” reports that renal function declined in the paper’s single patient, although it later stabilized. It describes proteinuria as initially decreasing and then persisting, not increasing; it does not establish the claimed course across multiple previous cases. Page numbers are unavailable in our copy. (LLM, conf=0.84)

      Experimental — accuracy not yet measured
    • cites [5] Hirashima H Komiya T Toriu N Hara S Matsunaga A Saito T A case of nephrotic syndrome showing contemporary presence of apolipoprotein E2 homozygote glomerulopathy and membranous nephropathy-like findings modified by apolipoprotein E Toyonaka Clin Nephrol Case Stud 2018 6 45 51 30542638 PMC6287602 source

      The Case presentation (Patient; page unavailable) records rising proteinuria in this paper’s patient, from 5.4 to 9.15 g/g Cr, and the Clinical course after biopsy reports a later relapse with increased proteinuria. These passages concern one patient, not previous cases, and do not report a long-term decline in renal function. (LLM, conf=0.78)

      Experimental — accuracy not yet measured
    • cites [6] Kato T Ushiogi Y Yokoyama H Hara S Matsunaga A Muso E A case of apolipoprotein E Toyonaka and homozygous apolipoprotein E2/2 showing non-immune membranous nephropathy-like glomerular lesions with foamy changes CEN Case Rep 2019 8 (2) 106 11 30701487 PMC6450992 source

      The Case presentation and clinical-course sections report increasing proteinuria and later renal dysfunction in this paper’s own patient. Discussion Table 1 reports persistent proteinuria in one previous case and relapse in another, but does not document declining renal function in those previous cases. Pages are not specified in our copy. (LLM, conf=0.85)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premiseown data

    The three previously reported cases showed proteinuria ≥2.0 g/day at diagnosis, whereas the present case was 0.8 g/day.

    “The three previously reported cases showed a relatively high amount of proteinuria of ≥2.0 g/day at the time of diagnosis, although it was 0.8 g/day in the present case (Table 2).”
    Quote in the paperNot a substantial claim3 of 3 sources checked
    • cites [4] Fukunaga M Nagahama K Aoki M Shimizu A Hara S Matsunaga A Membranous nephropathy-like apolipoprotein E deposition disease with apolipoprotein E Toyonaka (Ser197Cys) and a homozygous apolipoprotein E2/2 Case Rep Nephrol Dial 2018 8 (1) 45 55 29692990 PMC5903162 source

      The Case Presentation reports proteinuria in this patient but gives no 0.8 g/day value in the retrieved passage. The Clinical Course after the First Biopsy gives a later range of 0.5–2.5 g/gCr, not proteinuria at diagnosis. Searches for 0.8 g/day, three previously reported cases, and Table 2 found no passage in our copy establishing the claimed comparison. (LLM, conf=0.76)

      Experimental — accuracy not yet measured
    • cites [5] Hirashima H Komiya T Toriu N Hara S Matsunaga A Saito T A case of nephrotic syndrome showing contemporary presence of apolipoprotein E2 homozygote glomerulopathy and membranous nephropathy-like findings modified by apolipoprotein E Toyonaka Clin Nephrol Case Stud 2018 6 45 51 30542638 PMC6287602 source

      The Case presentation > Patient section reports substantial proteinuria in this paper’s patient: 5.4 g/g Cr at initial admission and 9.15 g/g Cr at the second hospitalization. It does not establish that all three previously reported cases had proteinuria ≥2.0 g/day at diagnosis; its measurements are also in g/g Cr, not g/day. The 0.8 g/day figure describes the citing authors’ present case, not this source’s patient. (LLM, conf=0.76)

      Experimental — accuracy not yet measured
    • cites [6] Kato T Ushiogi Y Yokoyama H Hara S Matsunaga A Muso E A case of apolipoprotein E Toyonaka and homozygous apolipoprotein E2/2 showing non-immune membranous nephropathy-like glomerular lesions with foamy changes CEN Case Rep 2019 8 (2) 106 11 30701487 PMC6450992 source

  • May combine two claims.

    Premisecitation

    One previous case showed no dyslipidemia and the other two showed both hypertriglyceridemia and hypercholesterolemia.

    “one of the previous cases showed no dyslipidemia and the other two cases showed both hypertriglyceridemia and hypercholesterolemia (Table 2).”
    Quote in the paperNot a substantial claim3 of 3 sources checked
    • cites [4] Fukunaga M Nagahama K Aoki M Shimizu A Hara S Matsunaga A Membranous nephropathy-like apolipoprotein E deposition disease with apolipoprotein E Toyonaka (Ser197Cys) and a homozygous apolipoprotein E2/2 Case Rep Nephrol Dial 2018 8 (1) 45 55 29692990 PMC5903162 source

      The Case Presentation and Analysis of ApoE Mutation report normal lipid levels in this paper’s patient, supporting the case without dyslipidemia. The paper does not report that two other cases had both hypertriglyceridemia and hypercholesterolemia; that part of the three-case comparison is unsupported by this source. (LLM, conf=0.82)

      Experimental — accuracy not yet measured
    • cites [5] Hirashima H Komiya T Toriu N Hara S Matsunaga A Saito T A case of nephrotic syndrome showing contemporary presence of apolipoprotein E2 homozygote glomerulopathy and membranous nephropathy-like findings modified by apolipoprotein E Toyonaka Clin Nephrol Case Stud 2018 6 45 51 30542638 PMC6287602 source

      The Case presentation (Patient; page not available) reports elevated triglycerides and total cholesterol in this paper’s patient, supporting one case with both conditions. Our copy does not establish the lipid status of the other two previous cases or the claimed one-without-dyslipidemia, two-with-both breakdown. (LLM, conf=0.85)

      Experimental — accuracy not yet measured
    • cites [6] Kato T Ushiogi Y Yokoyama H Hara S Matsunaga A Muso E A case of apolipoprotein E Toyonaka and homozygous apolipoprotein E2/2 showing non-immune membranous nephropathy-like glomerular lesions with foamy changes CEN Case Rep 2019 8 (2) 106 11 30701487 PMC6450992 source

      The Discussion (Table 1; page unavailable) describes one of the three cases as normolipidemic and marks hypertriglyceridemia in the other two. The Case presentation reports elevated triglycerides and total cholesterol in the paper’s own case, but the copy does not give a cholesterol result for the Hirashima case. Thus, it does not establish that both remaining cases had hypercholesterolemia. (LLM, conf=0.85)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Findingown data

    Serum creatinine, triglyceride, and cholesterol levels were within the normal range.

    “the levels of serum creatinine, triglyceride, and cholesterol were within the normal range.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    Cryoglobulin was positive.

    “Cryoglobulin was positive, although the type of cryoglobulin was not assessed and complement levels were not low.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    EM revealed massive deposits with various electron densities in the subepithelial, subendothelial, and paramesangial areas, accompanied by foot process effacement.

    “The EM study revealed massive deposits with various electron densities in the subepithelial, subendothelial, and paramesangial areas, accompanied by foot process effacement”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingown data

    The patient had no significant medical history including low birth weight, kidney disease, and dyslipidemia.

    “The patient was a 28-year-old Japanese man without significant medical history and family history, including low birth weight, kidney disease, and dyslipidemia.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Neither foam cells nor lipoprotein thrombi were marked.

    “Neither foam cells nor lipoprotein thrombi were marked.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The patient was a 28-year-old Japanese man with mild proteinuria and hematuria.

    “A 28-year-old Japanese man with mild proteinuria and hematuria underwent a kidney biopsy.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingnone given

    This case presented with cryoglobulinemia without any clinical or hematological evidence of vasculitis.

    “This case presented with cryoglobulinemia without any clinical or hematological evidence of vasculitis.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The apoE molecule comprises an N-terminal domain (amino acids 1-191), a hinge region (amino acids 192-215), and a C-terminal domain (amino acids 216-299).

    “The apoE molecule comprises an N-terminal domain (NT; amino acids 1–191), a hinge region (amino acids 192–215), and a C-terminal domain (CT; amino acids 216–299).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [10] Narayanaswami V Szeto SS Ryan RO Lipid association-induced N- and C-terminal domain reorganization in human apolipoprotein E3 J Biol Chem 2001 276 (41) 37853 60 11483594 source

      Checked before — its earlier verdict is held back until a new check runs.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    NT includes an LDL receptor and heparan sulfate proteoglycan-binding region, and CT is critical for lipid binding.

    “NT includes an LDL receptor and heparan sulfate proteoglycan-binding region, and CT is critical for lipid binding [10].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [10] Narayanaswami V Szeto SS Ryan RO Lipid association-induced N- and C-terminal domain reorganization in human apolipoprotein E3 J Biol Chem 2001 276 (41) 37853 60 11483594 source

      Checked before — its earlier verdict is held back until a new check runs.

  • Classified as probably not a substantial claim.

    Premisecitation

    Animal experiments revealed the importance of podocyte injury in foam cell formation based on hypercholesterolemia.

    “Animal experiments revealed the importance of podocyte injury in foam cell formation based on hypercholesterolemia [14].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [14] Hara S Kobayashi N Sakamoto K Ueno T Manabe S Takashima Y Podocyte injury–driven lipid peroxidation accelerates the infiltration of glomerular foam cells in focal segmental glomerulosclerosis Am J Pathol 2015 185 (8) 2118 31 26072030 PMC4530130 source

      Checked before — its earlier verdict is held back until a new check runs.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The hinge region plays an indispensable role in the binding of both domains.

    “The hinge region plays an indispensable role in the binding of both domains [10].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [10] Narayanaswami V Szeto SS Ryan RO Lipid association-induced N- and C-terminal domain reorganization in human apolipoprotein E3 J Biol Chem 2001 276 (41) 37853 60 11483594 source

      Checked before — its earlier verdict is held back until a new check runs.

  • May combine two claims.

    Interpretationcitation

    The deformed hinge region may markedly affect the three-dimensional structure of apoE and cause dysfunction of both NT and CT.

    “The deformed hinge region may markedly affect the three-dimensional structure of apoE and cause dysfunction of both NT and CT [7].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [7] Saito T Matsunaga A Fukunaga M Nagahama K Hara S Muso E Apolipoprotein E-related glomerular disorders Kidney Int 2020 97 (2) 279 88 31874799 source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    This case report does not include information regarding the clinical course after diagnosis because the patient stopped visiting the hospital.

    “A limitation of this case report is that it does not include information regarding the clinical course after diagnosis as the patient stopped visiting the hospital.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Cryoglobulin can be detected in the serum of healthy individuals with normal levels of complement.

    “Cryoglobulin can be detected in the serum of healthy individuals with normal levels of complement”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [15] Muchtar E Magen H Gertz MA How I treat cryoglobulinemia Blood 2017 129 (3) 289 98 27799164 source

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductown data

    DNA sequences were screened by next-generation sequencing and validated by Sanger sequencing.

    “DNA sequences were screened by next-generation sequencing and validated by Sanger sequencing.”
    Quote in the paperSubstantial claim
18 of 18

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • APOE Toyonaka (Ser197Cys) was considered to be in linkage disequilibrium with apoE2 (Arg158Cys).

    “This variant was considered to be in linkage disequilibrium with apoE2 (Arg158Cys).”

    From Impact of Apolipoprotein E Variants: A Review of Naturally Occurring Variants and Clinical Features (2025) · cites this paper as [103]

    The Case Report/Case Presentation section reports both apoE Toyonaka (Ser197Cys) and apoE2/E2 in the patient, and the Introduction notes other cases with both. Neither section states that Toyonaka is in linkage disequilibrium with apoE2; co-occurrence in cases does not establish that genetic association. Page numbers are unavailable in our copy. (LLM, conf=0.81)

    Experimental — accuracy not yet measured

  • A new glomerular disease was identified in four non-consanguineous carriers possessing the novel variant APOE Toyonaka (Ser197Cys).

    “A new glomerular disease was identified in four non-consanguineous carriers possessing the novel variant APOE Toyonaka (Ser197Cys) (Fig.5, Table 3)99, 101-103).”

    From Impact of Apolipoprotein E Variants: A Review of Naturally Occurring Variants and Clinical Features (2025) · cites this paper as [103]

    The Discussion/Conclusion identifies this as the fourth reported case of MN-like apoE deposition disease with apoE Toyonaka, and the Case Report/Case Presentation confirms the Ser197Cys variant in this patient. Our copy does not establish that the four carriers were non-consanguineous; it reports only that this patient had no significant family history. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • Glomerular lesions only occurred in APOE Toyonaka (Ser197Cys, Arg158Cys) when the other allele was ApoE2.

    “It was reported that glomerular lesions only occurred in APOE Toyonaka (Ser197Cys, Arg158Cys) when the other allele was ApoE2.”

    From Impact of Apolipoprotein E Variants: A Review of Naturally Occurring Variants and Clinical Features (2025) · cites this paper as [103]

    The Case Presentation reports glomerular apoE accumulation in a patient with heterozygous apoE Toyonaka (Ser197Cys) and apoE2/E2, while the Introduction describes similar lesions in earlier cases with that genotype. The paper does not establish that lesions occur only when the other allele is apoE2; its Discussion notes that only four cases had been reported. Page numbers are unavailable in our copy. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

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Authors
Koshino, A., Takaeda, C., Matsuno, T., Kitajima, S., Iwata, Y., Sakai, N., Nagahama, K., Niida, Y., Saito, T., Yokoyama, H., & Wada, T.
Affiliations
  • Kanazawa University (JP)
  • Public Central Hospital of Matto Ishikawa (JP)
  • Kyorin University (JP)
  • Kanazawa Medical University Hospital (JP)
  • Kanazawa Medical University (JP)
Corresponding author
Koshino, Akihiko
ORCID
Venue
Case Reports in Nephrology and Dialysis
Publisher
S. Karger AG
Published
2022-06-10
Volume
12
Issue
2
Pages
96-104
ISSN
2296-9705 (ISSN-L)
DOI
10.1159/000525086
PMC
PMC9247525
OpenAlex
W4281641925
Cited by
2
References
15
Citations by year
2025: 1 · 2024: 1
FWCI
0.32
Type
journal article
Language
en
Open access
Licence
Locations
  • Case Reports in Nephrology and Dialysis (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Nephrology › Renal Diseases and Glomerulopathies
  • Health Sciences › Medicine › Rheumatology › Systemic Lupus Erythematosus Research
  • Life Sciences › Immunology and Microbiology › Immunology › Complement system in diseases
Keywords
apolipoprotein E, glomerular deposition, electron-dense deposits, proteinuria, hematuria, mesangial cell proliferation, dyslipidemia, renal biopsy

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-31.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-31.

Cited sources are checked by gpt-6-sol.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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