Lipoprotein glomerulopathy associated with the Osaka/Kurashiki APOE variant: two cases identified in Latin America
Open accessAbstract
Background: Lipoprotein glomerulopathy (LPG) is a rare autosomal dominant disease caused by mutations in APOE, the gene which encodes apolipoprotein E. LPG mainly affects Asian individuals, however occasional cases have also been described in Americans and Europeans. Herein we report two unrelated Brazilian patients with LPG in whom genetic analyses revealed the APOE-Osaka/Kurashiki variant. Case presentation - case 1: A 29-year-old Caucasian male sought medical attention with complaints of face swelling and foamy urine for the last 3 months. He denied a family history of kidney disease, consanguinity, or Asian ancestry. His tests showed proteinuria of 12.5 g/24 h, hematuria, serum creatinine 0.94 mg/dL, albumin 2.3 g/dl, total cholesterol 284 mg/dL, LDL 200 mg/dL, triglycerides 175 mg/dL, and negative screening for secondary causes of glomerulopathy. A kidney biopsy revealed intraluminal, laminated deposits of hyaline material in glomerular capillaries consistent with lipoprotein thrombi. These findings were confirmed by electron microscopy, establishing the diagnosis of LPG. His apolipoprotein E serum level was 72 mg/dL and genetic analysis revealed the APOE pathogenic variant c.527G > C, p.Arg176Pro in heterozygosis, known as the Osaka/Kurashiki mutation and positioned nearby the LDL receptor binding site. Case 2: A 34-year-old Caucasian man sought medical assessment for renal dysfunction and hypertension. He reported intermittent episodes of lower-limb edema for 3 years and a family history of kidney disease, but denied Asian ancestry. Laboratorial tests showed BUN 99 mg/dL, creatinine 10.7 mg/dL, total cholesterol 155 mg/dL, LDL 79 mg/dL, triglycerides 277 mg/dL, albumin 3.1 g/dL, proteinuria 2.7 g/24 h, and negative screening for secondary causes of glomerulopathy. His kidney biopsy was consistent with advanced chronic nephropathy secondary to LPG. A genetic analysis also revealed the Osaka/Kurashiki variant. He was transplanted a year ago, displaying no signs of disease relapse. Conclusion: We report two unrelated cases of Brazilian patients with a diagnosis of lipoprotein glomerulopathy whose genetic assessment identified the APOE-Osaka/Kurashiki pathogenic variant, previously only described in eastern Asians. While this is the second report of LPG in Latin America, the identification of two unrelated cases by our medical team raises the possibility that LPG may be less rare in this part of the world than currently thought, and should definitely be considered when nephrotic syndrome is associated with suggestive kidney biopsy findings.
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Written from the paper’s full text.
TL;DR
This case report describes two unrelated Brazilian patients with lipoprotein glomerulopathy (LPG) who both carried the APOE Osaka/Kurashiki variant c.527G>C, p.Arg176Pro in heterozygosity. It is reported as the first identification of this variant in non-eastern Asian patients and supports considering LPG in nephrotic syndrome with suggestive kidney biopsy findings.
Key findings
- Case 1: a 29-year-old Caucasian male presented with facial swelling and foamy urine; 24-h proteinuria was 12.5 g, with hematuria, serum creatinine 0.94 mg/dL, albumin 2.3 g/dL, total cholesterol 284 mg/dL, LDL 200 mg/dL, and triglycerides 175 mg/dL. Kidney biopsy showed lipoprotein thrombi, and genetic testing found APOE c.527G>C, p.Arg176Pro in heterozygosity; serum apolipoprotein E was 7.2 mg/dL (normal range 2.3–6.2 mg/dL). After 3 years on simvastatin and ezetimibe, creatinine was 2.37 mg/dL and 24-h proteinuria was 3.7 g.
- Case 2: a 34-year-old Caucasian male presented with renal dysfunction and hypertension; BUN was 99 mg/dL, creatinine 10.7 mg/dL, 24-h proteinuria 2.7 g, albumin 3.1 g/dL, total cholesterol 155 mg/dL, LDL 79 mg/dL, and triglycerides 277 mg/dL. Biopsy was consistent with advanced chronic nephropathy secondary to LPG, and the same APOE Osaka/Kurashiki variant was identified. He progressed to renal replacement therapy after 2 months and was transplanted a year ago with no signs of disease relapse.
- The authors state this is the first report of the apoE-Osaka/Kurashiki variant in non-eastern Asian patients with LPG and the third report of LPG in Latin Americans or descendants; they suggest LPG may be less rare in Latin America than currently thought. The abstract describes it as the second report of LPG in Latin America, while the discussion calls it the third report in Latin Americans or descendants.
Methods
- Descriptive case report of two unrelated Brazilian patients; evaluation included clinical and laboratory testing, kidney biopsy with light microscopy, immunofluorescence, and electron microscopy, plus genetic analysis.
- Genetic testing used next-generation sequencing with a gene panel directed to familial hypercholesterolemia in case 1 and whole exome sequencing in case 2; the variant was classified per ACMG criteria and in silico scores were reported (SIFT 0.01, DANN 0.996, Polyphen2 0.89).
- No formal statistical analysis is reported; findings are descriptive.
Limitations
- The paper does not include a dedicated limitations section. It notes that asymptomatic carriers of APOE mutations have been identified and that not all mice harboring the apoE-Sendai variant developed LPG, suggesting other factors may also play a role; it also states the authors did not have access to information for one previously reported Osaka/Kurashiki case.
- Evident from the text: conclusions rest on only two cases, with no functional validation or family segregation analysis reported, and follow-up is limited (case 1 reported at 3 years; case 2 after transplantation).
Model-written summary. Check it against the paper before relying on it.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
11 of 26 cited sources checked · 6 supported · 0 flagged · accuracy not yet measured
- Premisecitation
Only five cases harboring the Osaka/Kurashiki APOE variant have been described so far.
“Only five cases harboring the Osaka/Kurashaki variant have been described so far (Table 2) [8–11].”
Quote in the paperNot a substantial claim3 of 4 sources checked- cites [8] Mitani A, Ishigami M, Watase K, Minakata T, Yamamura T. A novel apolipoprotein E mutation, ApoE Osaka (Arg158 pro), in a dyslipidemic patient with lipoprotein glomerulopathy. J Atheroscler Thromb. 2011;18(6):531–5. https://doi.org/10.5551/jat.7377. source
The Discussion reports one patient with the apoE Osaka (Arg158 Pro) variant, so this paper supports one case in the cited group. It does not state that five Osaka/Kurashiki cases had been described; that total is not established by this source. (LLM, conf=0.87)
Experimental — accuracy not yet measured - cites [9] Tokura T, Itano S, Kobayashi S, Kuwabara A, Fujimoto S, Horike H, et al. A novel mutation ApoE2 Kurashiki (R158P) in a patient with lipoprotein glomerulopathy. J Atheroscler Thromb. 2011;18(6):536–41. https://doi.org/10.5551/jat.8102. source
The Results and Case Presentation describe one patient with the newly identified ApoE2 Kurashiki (R158P) variant. The paper does not establish that five cases of the Osaka/Kurashiki variant had been described, so it supports the existence of a case but not the claimed total. (LLM, conf=0.86)
Experimental — accuracy not yet measured - cites [10] Yang M, Weng Q, Pan X, Hussain HMJ, Yu S, Xu J, et al. Clinical and genetic analysis of lipoprotein glomerulopathy patients caused by APOE mutations. Mol Genet Genomic Med. 2020 Aug;8(8):e1281. https://doi.org/10.1002/mgg3.1281. source
The Results > Genotyping section reports two patients with the APOE-Osaka/Kurashiki variant, establishing that this paper describes cases with the variant. It does not state that only five cases had been described overall; the five patients counted in that section had the different APOE-Kyoto variant. No page number is available in our copy. (LLM, conf=0.87)
Experimental — accuracy not yet measured - cites [11] Yang Z, Wu H, Hu Z. Discovery of a Chinese Tibetan patient with lipoprotein glomerulopathy due to APOE Osaka/Kurashiki variant. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2020;37(2):166–9. https://doi.org/10.3760/cma.j.issn.1003-9406.2020.02.017. source
- Findingnone given
The APOE c.527G>C p.Arg176Pro variant is not described in the gnomAD, 1000 genomes or ABRAOM databases.
“This variant is not described in the gnomAD, 1000 genomes or ABRAOM databases, and the corresponding amino acid (aa) position is conserved in mammals.”
Quote in the paperNot a substantial claim - Findingown data
Case 1 genetic analysis revealed the APOE pathogenic variant c.527G>C, p.Arg176Pro in heterozygosis, known as the Osaka/Kurashiki mutation.
“His apolipoprotein E serum level was 72 mg/dL and genetic analysis revealed the APOE pathogenic variant c.527G > C, p.Arg176Pro in heterozygosis, known as the Osaka/Kurashiki mutation and positioned nearby the LDL receptor binding site.”
Quote in the paperSubstantial claim - Findingnone given
The amino acid position corresponding to p.Arg176Pro is conserved in mammals.
“This variant is not described in the gnomAD, 1000 genomes or ABRAOM databases, and the corresponding amino acid (aa) position is conserved in mammals.”
Quote in the paperNot a substantial claim - Findingown data
Case 2 genetic analysis revealed the APOE c.527G>C, p.Arg176Pro variant in heterozygosity.
“A genetic analysis also revealed the Osaka/Kurashiki variant.”
- Also stated in: § Case 2 · plain
“Whole exome sequencing also revealed the APOE c.527G > C, p.Arg176Pro variant in heterozygosity (Fig. 2).”
Quote in the paperSubstantial claim - Also stated in: § Case 2 · plain
- Findingown data
Case 2 had a kidney biopsy consistent with advanced chronic nephropathy secondary to LPG.
“His kidney biopsy was consistent with advanced chronic nephropathy secondary to LPG.”
Quote in the paperNot a substantial claim - Findingown data
Case 2 displayed no signs of disease relapse after transplantation.
“He was transplanted a year ago, displaying no signs of disease relapse.”
Quote in the paperNot a substantial claim - Findingown data
The two patients are Brazilian.
“Herein we report two unrelated Brazilian patients with LPG in whom genetic analyses revealed the APOE-Osaka/Kurashiki variant.”
Quote in the paperSubstantial claim - Premisecitation
LPG is caused by pathogenic variants in APOE.
“LPG is caused by pathogenic variants in APOE, the gene which encodes apolipoprotein E (ApoE).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [1] Saito T, Matsunaga A, Fukunaga M, Nagahama K, Hara S, Muso E. Apolipoprotein E-related glomerular disorders. Kidney Int. 2020;97(2):279–88. https://doi.org/10.1016/j.kint.2019.10.031. source
- Premisecitation
Lipoprotein glomerulopathy (LPG) is a rare autosomal dominant disease.
“Lipoprotein glomerulopathy (LPG) is a rare autosomal dominant disease caused by mutations in APOE, the gene which encodes apolipoprotein E.”
- Also stated in: § Background · plain
“Lipoprotein glomerulopathy (LPG) is a rare autosomal dominant disease characterized by glomerular accumulation of lipoproteins as intracapillary thrombi [1].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [1] Saito T, Matsunaga A, Fukunaga M, Nagahama K, Hara S, Muso E. Apolipoprotein E-related glomerular disorders. Kidney Int. 2020;97(2):279–88. https://doi.org/10.1016/j.kint.2019.10.031. source
- Also stated in: § Background · plain
- Premisenone given
Morphological findings of intraluminal pale-staining and laminated lipid or lipoprotein thrombi are strongly consistent with APOE glomerulopathy, even if present in only one glomerulus.
“It must be noted that morphological findings of intraluminal pale-staining and laminated lipid or lipoprotein thrombi are strongly consistent with APOE glomerulopathy, even if those findings are only present in one glomerulus.”
Quote in the paperSubstantial claim - Interpretationown data
The identification of two unrelated patients with this disease by our medical group raises the possibility that LPG may be less rare in Latin America than currently thought.
“Despite its rarity, the identification of two unrelated patients with this disease by our medical group raises the possibility that LPG may be less rare in Latin America than currently thought, and therefore should be considered in the differential diagnosis of nephrotic syndrome associated with suggestive findings in kidney biopsy.”
Quote in the paperSubstantial claim- Rests on an assumption: The two patients are unrelated.
- Rests on an assumption: LPG is currently thought to be rare in Latin America.
- Interpretationown data
The APOE Osaka/Kurashiki variant is the disease etiology in these two patients.
“This report presents two cases of unrelated Brazilian patients with nephrotic syndrome whose investigation led to a diagnosis of LPG and identified the very rare Osaka/Kurashiki APOE variant as the disease etiology.”
Quote in the paperSubstantial claim
- Classified as probably not a substantial claim. 10
- May combine two claims. 14
- The quote only partly states this claim. 1
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationLPG is more often reported in eastern Asian countries, but cases have also been observed in Europe and America.
“It is more often reported in eastern Asian countries, however cases have also been observed in Europe and America [2–4].”
Quote in the paperNot a substantial claim1 of 3 sources checked- cites [2] Pegas KL, Rohde R, Garcia CD, Bittencourt Vde B, Keitel E, Poloni JA, et al. Lipoprotein glomerulopathy: a case report of a rare disease in a Brazilian child. J Bras Nefrol. 2014;36(1):93–5. https://doi.org/10.5935/0101-2800.20140015. source
- cites [3] Rovin BH, Roncone D, McKinley A, Nadasdy T, Korbet SM, Schwartz MM. APOE Kyoto mutation in European Americans with lipoprotein glomerulopathy. N Engl J Med. 2007;357(24):2522–4. https://doi.org/10.1056/NEJMc072088. source
- cites [4] Bomback AS, Song H, D'Agati VD, Cohen SD, Neal A, Appel GB, et al. A new apolipoprotein E mutation, apoE Las Vegas, in a European-American with lipoprotein glomerulopathy. Nephrol Dial Transplant. 2010;25(10):3442–6. https://doi.org/10.1093/ndt/gfq389. source
May combine two claims.
PremisecitationAsymptomatic carriers of APOE mutations have been identified, and not all mice harboring the apoE-Sendai variant developed LPG, suggesting other factors may play a role in the disease.
“Asymptomatic carriers of APOE mutations have been identified, however, and not all mice harboring the apoE-Sendai variant developed LPG, suggesting that other factors may also play a role in the disease [9].”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [9] Tokura T, Itano S, Kobayashi S, Kuwabara A, Fujimoto S, Horike H, et al. A novel mutation ApoE2 Kurashiki (R158P) in a patient with lipoprotein glomerulopathy. J Atheroscler Thromb. 2011;18(6):536–41. https://doi.org/10.5551/jat.8102. source
The Discussion reports that ApoE-Sendai induced LPG in apoE-knockout mice, but gives no indication that some mice carrying it did not develop the disease. The Case Presentation describes a patient with LPG, not an asymptomatic mutation carrier. Searches for unaffected carriers, incomplete penetrance, and additional factors found no passage establishing the claim. (LLM, conf=0.76)
Experimental — accuracy not yet measured
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationLPG usually manifests in adulthood and predominantly affects males.
“LPG usually manifests in adulthood and predominantly affects males.”
Quote in the paperNot a substantial claim1 of 2 sources checked- cites [1] Saito T, Matsunaga A, Fukunaga M, Nagahama K, Hara S, Muso E. Apolipoprotein E-related glomerular disorders. Kidney Int. 2020;97(2):279–88. https://doi.org/10.1016/j.kint.2019.10.031. source
- cites [5] Cambruzzi E, Pegas KL. Pathogenesis, histopathologic findings and treatment modalities of lipoprotein glomerulopathy: a review. J Bras Nefrol. 2019;41(3):393–9. https://doi.org/10.1590/2175-8239-jbn-2018-0148. source
May combine two claims.
FindingcitationThe APOE c.527G>C p.Arg176Pro variant is classified as likely pathogenic according to ACMG criteria, with high SIFT (0.01) and DANN (0.996) and moderate Polyphen2 (0.89) scores.
“This variant is classified as likely pathogenic according to the American College of Medical Genetics and Genomics criteria [12], reaching high pathogenicity scores on SIFT (0.01) and DANN (0.996), and a moderate score on Polyphen2 (0.89).”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [12] Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17(5):405–24. https://doi.org/10.1038/gim.2015.30. source
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationCurrent treatment of LPG includes hypolipemiants, in particular fibrates.
“Current treatment of LPG includes hypolipemiants, in particular fibrates.”
Quote in the paperNot a substantial claim1 of 2 sources checked- cites [1] Saito T, Matsunaga A, Fukunaga M, Nagahama K, Hara S, Muso E. Apolipoprotein E-related glomerular disorders. Kidney Int. 2020;97(2):279–88. https://doi.org/10.1016/j.kint.2019.10.031. source
- cites [5] Cambruzzi E, Pegas KL. Pathogenesis, histopathologic findings and treatment modalities of lipoprotein glomerulopathy: a review. J Bras Nefrol. 2019;41(3):393–9. https://doi.org/10.1590/2175-8239-jbn-2018-0148. source
May combine two claims.
PremisecitationHyperlipoproteinemia type III, high plasma apolipoproteins, proteinuria and microhematuria are common findings in LPG, and nephrotic syndrome and progressive loss of renal function are often observed.
“Hyperlipoproteinemia type III (increased LDL and triglyceride levels), high levels of plasma apolipoproteins, proteinuria and microhematuria are common findings, and nephrotic syndrome and progressive loss of renal function are often observed.”
Quote in the paperNot a substantial claim1 of 2 sources checked- cites [1] Saito T, Matsunaga A, Fukunaga M, Nagahama K, Hara S, Muso E. Apolipoprotein E-related glomerular disorders. Kidney Int. 2020;97(2):279–88. https://doi.org/10.1016/j.kint.2019.10.031. source
- cites [5] Cambruzzi E, Pegas KL. Pathogenesis, histopathologic findings and treatment modalities of lipoprotein glomerulopathy: a review. J Bras Nefrol. 2019;41(3):393–9. https://doi.org/10.1590/2175-8239-jbn-2018-0148. source
The Clinical findings section identifies type III hyperlipoproteinemia, increased serum apolipoproteins, and proteinuria as features of LPG. The Introduction describes steroid-resistant nephrotic syndrome and progression to kidney failure in approximately 50% of patients. Our copy does not describe microhematuria as common; it mentions hematuria only in a treatment-section case report. It also does not establish increased triglyceride levels as part of the claim’s parenthetical definition. (LLM, conf=0.88)
Experimental — accuracy not yet measured
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationTypical LPG histology comprises glomeruli with increased size due to ectasia of capillary loops, filled with light and lamellated eosinophilic thrombi; electron microscopy confirms small lipid vacuoles typical of lipoproteins.
“The typical LPG histology comprises glomeruli with increased size due to ectasia of capillary loops, filled with light and lamellated eosinophilic thrombi. Electron microscopy confirms small lipid vacuoles typical of lipoproteins.”
Quote in the paperNot a substantial claim1 of 2 sources checked- cites [1] Saito T, Matsunaga A, Fukunaga M, Nagahama K, Hara S, Muso E. Apolipoprotein E-related glomerular disorders. Kidney Int. 2020;97(2):279–88. https://doi.org/10.1016/j.kint.2019.10.031. source
- cites [5] Cambruzzi E, Pegas KL. Pathogenesis, histopathologic findings and treatment modalities of lipoprotein glomerulopathy: a review. J Bras Nefrol. 2019;41(3):393–9. https://doi.org/10.1590/2175-8239-jbn-2018-0148. source
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationImmunoadsorption with staphylococcal protein A and LDL apheresis using a heparin-induced extracorporeal lipoprotein precipitation system has yielded positive results in LPG.
“Immunoadsorption with staphylococcal protein A and LDL apheresis using a heparin-induced extracorporeal lipoprotein precipitation system has also yielded positive results [1, 5].”
Quote in the paperNot a substantial claim1 of 2 sources checked- cites [1] Saito T, Matsunaga A, Fukunaga M, Nagahama K, Hara S, Muso E. Apolipoprotein E-related glomerular disorders. Kidney Int. 2020;97(2):279–88. https://doi.org/10.1016/j.kint.2019.10.031. source
- cites [5] Cambruzzi E, Pegas KL. Pathogenesis, histopathologic findings and treatment modalities of lipoprotein glomerulopathy: a review. J Bras Nefrol. 2019;41(3):393–9. https://doi.org/10.1590/2175-8239-jbn-2018-0148. source
May combine two claims.
Findingown dataCase 1 had a kidney biopsy with intraluminal laminated deposits of hyaline material in glomerular capillaries consistent with lipoprotein thrombi, confirmed by electron microscopy, establishing the diagnosis of LPG.
“A kidney biopsy revealed intraluminal, laminated deposits of hyaline material in glomerular capillaries consistent with lipoprotein thrombi. These findings were confirmed by electron microscopy, establishing the diagnosis of LPG.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataCase 1 patient remains on simvastatin and ezetimib after 3 years, with serum creatinine 2.37 mg/dL and 24-h proteinuria 3.7 g.
“The patient remains on simvastatin 20 mg qd and ezetimib 10 mg qd after 3 years, with serum creatinine of 2.37 mg/dL and 24-h proteinuria of 3.7 g.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing). The quote only partly states this claim.
Findingown dataBoth patients denied Asian ancestry.
“He denied a family history of kidney disease, consanguinity, or Asian ancestry”
- Also stated in: § Case 2 · plain
“He denied Asian ancestry”
Quote in the paperNot a substantial claim- Also stated in: § Case 2 · plain
May combine two claims.
Findingown dataCase 2 progressed to renal replacement therapy after 2 months of conservative management and was transplanted a year ago after 4 years on RRT.
“The patient progressed to renal replacement therapy after 2 months of conservative management.”
- Also stated in: § Case 2 · plain
“The patient was transplanted a year ago after 4 years on RRT.”
Quote in the paperNot a substantial claim- Also stated in: § Case 2 · plain
Probably not a substantial claim: may not pass S3 (load-bearing).
Premisenone givenFifteen APOE mutations have been described associated with LPG.
“Fifteen mutations have been described up until now.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationThe APOE mutations most frequently associated with LPG are the Sendai and Kyoto variants.
“The APOE mutations most frequently associated with LPG are the Sendai [6] and Kyoto [7] variants (p.Pro163Arg and p.Arg43Cys, respectively), but other variants have been reported (Table 1) [8–10].”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [6] Oikawa S, Matsunaga A, Saito T, Sato H, Seki T, Hoshi K, et al. Apolipoprotein E Sendai (arginine 145-->proline): a new variant associated with lipoprotein glomerulopathy. J Am Soc Nephrol. 1997;8(5):820–3. https://doi.org/10.1681/ASN.V85820. source
- cites [7] Matsunaga A, Sasaki J, Komatsu T, Kanatsu K, Tsuji E, Moriyama K, et al. A novel apolipoprotein E mutation, E2 (Arg25Cys), in lipoprotein glomerulopathy. Kidney Int. 1999;56(2):421–7. https://doi.org/10.1046/j.1523-1755.1999.00572.x. source
May combine two claims.
PremisecitationAPOE mutations can lead to specific glomerular diseases, including APOE homozygote glomerulopathy, membranous nephropathy-like apoE deposition disease and lipoprotein glomerulopathy.
“As a result, APOE mutations can lead to specific glomerular diseases, including APOE homozygote glomerulopathy, membranous nephropathy-like apoE deposition disease and lipoprotein glomerulopathy [1].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [1] Saito T, Matsunaga A, Fukunaga M, Nagahama K, Hara S, Muso E. Apolipoprotein E-related glomerular disorders. Kidney Int. 2020;97(2):279–88. https://doi.org/10.1016/j.kint.2019.10.031. source
May combine two claims.
PremisereasoningThe only differential diagnosis for these morphological findings is fat emboli; LPG presents as a proteinuric disease and fat emboli as acute kidney injury.
“The only differential diagnosis is fat emboli; however, the clinical presentation is completely distinct as LPG presents itself as a proteinuric disease (most often nephrotic syndrome) and fat emboli as an acute kidney injury.”
Quote in the paperNot a substantial claimMay combine two claims.
PremisecitationStructural abnormalities in apoE reduce its capacity to bind LDL and IDLs, impairing catabolism and clearance, while increasing binding affinity to heparin.
“Structural abnormalities in apoE reduce its capacity to bind LDL and IDLs, impairing catabolism and their clearance, while increase its binding affinity to other molecules such as heparin.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [1] Saito T, Matsunaga A, Fukunaga M, Nagahama K, Hara S, Muso E. Apolipoprotein E-related glomerular disorders. Kidney Int. 2020;97(2):279–88. https://doi.org/10.1016/j.kint.2019.10.031. source
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Premisenone givenThe p.Arg176Pro substitution hits repeat domain 5, located near the K175 succinylation site and the LDL receptor-binding site.
“The p.Arg176Pro substitution hits the repeat domain 5, located near the K175 succinylation site and the LDL receptor-binding site.”
Quote in the paperNot a substantial claimMay combine two claims.
Interpretationown dataThis is the first report of the apoE-Osaka/Kurashiki variant in non-eastern Asian patients with LPG and the third report of this disease in Latin Americans or descendants.
“This is the first report of the apoE-Osaka/Kurashiki variant in non-eastern Asian patients with LPG and the third report of this disease in Latin Americans or descendants.”
Quote in the paperSubstantial claim- Rests on an assumption: The patients' denial of Asian ancestry accurately reflects their genetic ancestry.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationLPG relapse in the graft has been reported in cases of kidney transplantation.
“As expected, LPG relapse in the graft has been reported in cases of kidney transplantation [16].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [16] Foster K, Matsunaga A, Matalon R, Saito T, Gallo G, D'Agati V, et al. A rare cause of posttransplantation nephrotic syndrome. Am J Kidney Dis. 2005;45(6):1132–8. https://doi.org/10.1053/j.ajkd.2004.08.048. source
The paper relies on this without support.
The two patients are unrelated.
“Herein we report two unrelated Brazilian patients with LPG in whom genetic analyses revealed the APOE-Osaka/Kurashiki variant.”
“We report two unrelated cases of Brazilian patients with a diagnosis of lipoprotein glomerulopathy whose genetic assessment identified the APOE-Osaka/Kurashiki pathogenic variant, previously only described in eastern Asians.”
“This report presents two cases of unrelated Brazilian patients with nephrotic syndrome whose investigation led to a diagnosis of LPG and identified the very rare Osaka/Kurashiki APOE variant as the disease etiology.”
The paper relies on this without support.
The patients' denial of Asian ancestry accurately reflects their genetic ancestry.
“He denied a family history of kidney disease, consanguinity, or Asian ancestry”
“He denied Asian ancestry”
The paper relies on this without support.
LPG is currently thought to be rare in Latin America.
“raises the possibility that LPG may be less rare in Latin America than currently thought”
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Sendai substitution is reversed
MinorThe background describes the Sendai variant as Pro163Arg, but Table 1 lists it as R163P (Arg163Pro).
“the Sendai [6] and Kyoto [7] variants (p.Pro163Arg and p.Arg43Cys, respectively)”
“| c.488G>C | p.R163P | R145P (Sendai) | Heparan sulphate proteoglycan binding site |”
Case 1 apolipoprotein E level differs tenfold
MinorThe abstract reports 72 mg/dL for case 1, while the case presentation reports 7.2 mg/dL.
“His apolipoprotein E serum level was 72 mg/dL”
“Serum apolipoprotein E was 7.2 mg/dL (normal range: 2.3–6.2 mg/dL).”
Cites
Richards, S., Aziz, N., Bale, S., Bick, D., Das, S., Gastier-Foster, J., Grody, W. W., Hegde, M., Lyon, E., Spector, E., et al. (2015) · Genetics in Medicine · doi:10.1038/gim.2015.30 · Cited by 32,594 · see citing works
Oikawa, S., Matsunaga, A., Saito, T., Sato, H., Seki, T., Hoshi, K., Hayasaka, K., Kotake, H., Midorikawa, H., Sekikawa, A., et al. (1997) · Journal of the American Society of Nephrology · doi:10.1681/asn.v85820 · Cited by 103 · see citing works
A novel apolipoprotein E mutation, E2 (Arg25Cys), in lipoprotein glomerulopathy
Matsunaga, A., Sasaki, J., Komatsu, T., Kanatsu, K., Tsuji, E., Moriyama, K., Koga, T., Arakawa, K., Oikawa, S., Saito, T., et al. (1999) · Kidney International · doi:10.1046/j.1523-1755.1999.00572.x · Cited by 91 · see citing works
Apolipoprotein E–related glomerular disorders
Saito, T., Matsunaga, A., Fukunaga, M., Nagahama, K., Hara, S., & Muso, E. (2020) · Kidney International · doi:10.1016/j.kint.2019.10.031 · Cited by 77 · see citing works
Lipoprotein Glomerulopathy: A New Apolipoprotein E Mutation With Enhanced Glomerular Binding
Sam, R., Wu, H., Yue, L., Mazzone, T., Schwartz, M. M., Arruda, J. A. L., Dunea, G., & Singh, A. K. (2006) · American Journal of Kidney Diseases · doi:10.1053/j.ajkd.2005.12.031 · Cited by 53 · see citing works
Georgiadou, D., Stamatakis, K., Efthimiadou, E. K., Kordas, G., Gantz, D., Chroni, A., & Stratikos, E. (2013) · Journal of Lipid Research · doi:10.1194/jlr.m030965 · Cited by 37 · see citing works
<i>APOE</i>Kyoto Mutation in European Americans with Lipoprotein Glomerulopathy
Rovin, B. H., Roncone, D., McKinley, A., Nadasdy, T., Korbet, S. M., & Schwartz, M. M. (2007) · New England Journal of Medicine · doi:10.1056/nejmc072088 · Cited by 35 · see citing works
A Novel Mutation ApoE2 Kurashiki (R158P) in a Patient with Lipoprotein Glomerulopathy
Tokura, T., Itano, S., Kobayashi, S., Kuwabara, A., Fujimoto, S., Horike, H., Satoh, M., Komai, N., Tomita, N., Matsunaga, A., et al. (2011) · Journal of Atherosclerosis and Thrombosis · doi:10.5551/jat.8102 · Cited by 28 · see citing works
Bomback, A. S., Song, H., D'Agati, V. D., Cohen, S. D., Neal, A., Appel, G. B., & Rovin, B. H. (2010) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gfq389 · Cited by 25 · see citing works
Mitani, A., Ishigami, M., Watase, K., Minakata, T., & Yamamura, T. (2011) · Journal of Atherosclerosis and Thrombosis · doi:10.5551/jat.7377 · Cited by 24 · see citing works
Katsarou, M., Stratikos, E., & Chroni, A. (2018) · Journal of Lipid Research · doi:10.1194/jlr.m088732 · Cited by 22 · see citing works
Clinical and genetic analysis of lipoprotein glomerulopathy patients caused by <i>APOE</i> mutations
Yang, M., Weng, Q., Pan, X., Hussain, H. M. J., Yu, S., Xu, J., Yu, X., Liu, Y., Jin, Y., Zhang, C., et al. (2020) · Molecular Genetics & Genomic Medicine · doi:10.1002/mgg3.1281 · Cited by 15 · see citing works
A Rare Cause of Posttransplantation Nephrotic Syndrome
Foster, K., Matsunaga, A., Matalon, R., Saito, T., Gallo, G., D’Agati, V., & Stokes, M. B. (2005) · American Journal of Kidney Diseases · doi:10.1053/j.ajkd.2004.08.048 · Cited by 14 · see citing works
Cambruzzi, E., & Pêgas, K. L. (2019) · Brazilian Journal of Nephrology · doi:10.1590/2175-8239-jbn-2018-0148 · Cited by 14 · see citing works
Lipoprotein glomerulopathy: a case report of a rare disease in a brazilian child
Pêgas, K. L., Rohde, R., Garcia, C. D., Bittencourt, V. D. B., Keitel, E., Poloni, J. A. T., & Cambruzzi, E. (2014) · Jornal Brasileiro de Nefrologia · doi:10.5935/0101-2800.20140015 · Cited by 8 · see citing works
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Sorted by citations
Lipoprotein Glomerulopathy, First Case Report from Canada
Ting, J. A., McRae, S. A., Schwartz, D., Barbour, S. J., & Riazy, M. (2022) · International Journal of Nephrology and Renovascular Disease · doi:10.2147/ijnrd.s364890 · Cited by 7 · see citing works
Post-transplantat recurrence of lipoprotein glomerulopathy: report of 4 cases and literature review
Neves, P. D. M. D. M., Mansur, J., Neto, M. M., Rohde, R. W., Poli‐de‐Figueiredo, C. E., Araújo, S. D. A., Wanderley, D. C., Proença, H., Pêgas, K. L., Watanabe, A., et al. (2025) · American Journal of Transplantation · doi:10.1016/j.ajt.2025.04.018 · Cited by 1 · see citing works
Self-citationFingerprints of lipoprotein glomerulopathy – An addition to the list of rare diseases in India
Walia, G. K., Munjappa, B. C., Kumar, R., & Vankalakunti, M. (2025) · Indian Journal of Pathology and Microbiology · doi:10.4103/ijpm.ijpm_79_25 · Cited by 1 · see citing works
Apolipoprotein E Dyslipidemia and Nephrotic Syndrome: A Rare Connection
Tito, S., Atri, A., Patil, S. P., Dean, S., & Carpenter, S. (2023) · Annals of Internal Medicine Clinical Cases · doi:10.7326/aimcc.2023.0059
The diagnostic and therapeutic significance of apolipoprotein E in personalized medicine
Kumar, M., Suryavanshi, A., Mahapatra, D. K., Jaiswal, M., Mandal, V., & Bharti, S. K. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-40563-1.00007-7
An Updated Review and Meta Analysis of Lipoprotein Glomerulopathy
Li, M.-S., Li, Y., Liu, Y., Zhou, X.-J., & Zhang, H. (2022) · Frontiers in Medicine · doi:10.3389/fmed.2022.905007 · Cited by 25 · see citing works
- Authors
- da Silveira-Neto, J. N., de Oliveira Ahn, G. J., de Menezes Neves, P. D. M., Baptista, V. A. F., de Almeida Araújo, S., Wanderley, D. C., Watanabe, A., Watanabe, E. H., Murai, N. M., Bertollo, E. M. G., Vieira-Neto, O. M., Dantas, M., de Antônio, S. R., Costa, R. S., Baptista, M. A. S. F., Moysés-Neto, M., & Onuchic, L. F.
- Affiliations
- Universidade Federal de Minas Gerais (BR)
- Universidade de São Paulo (BR)
- Faculdade de Medicina de São José do Rio Preto (BR)
- ORCID
- Venue
- Diagnostic Pathology
- Published
- 2021-07-26
- Volume
- 16
- Issue
- 1
- Pages
- 65-65
- ISSN
- 1746-1596 (ISSN-L)
- PMC
- PMC8314595
- OpenAlex
- W3187021820
- Semantic Scholar
- 511d4747fa367f8ae16f8239e09f994b3e899cf9
- Cited by
- 6
- References
- 16
- Citations by year
- 2026: 1 · 2025: 2 · 2023: 1 · 2022: 2
- FWCI
- 0.51
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Diagnostic Pathology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Health Sciences › Medicine › Nephrology › Renal Diseases and Glomerulopathies
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Keywords
- lipoprotein glomerulopathy, apolipoprotein E, autosomal dominant disorder, proteinuria, chronic nephropathy, kidney transplantation, Brazilian patients, genetic diagnosis, hypertriglyceridemia, hypertension, hematuria
- MeSH terms
- Adult, Apolipoproteins E, Brazil, Genetic Markers, Heterozygote, Humans, Kidney Diseases, Male, Mutation
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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