Clinical characteristics and APOE variant spectrum in Chinese patients with lipoprotein glomerulopathy
Open accessAbstract
To the Editor: Lipoprotein glomerulopathy (LPG) is a rare renal disorder characterized by lipoprotein thrombi in the glomerular capillaries. Clinically, it presents with proteinuria and frequently progresses to progressive renal insufficiency.[1] Although identified in various populations worldwide, LPG is predominantly reported in Japan and China. Etiologically, the disease is primarily associated with variants in the apolipoprotein E (APOE) gene.[2] Variants in the APOE gene disrupt its normal function, accumulating pathological lipid deposits in glomeruli. Several APOE variants are linked to LPG, including the Tokyo-Maebashi (p.L162_K164del) and Kyoto (p.R43C).[2] These variants exhibit distinct geographical distributions and founder effects, suggesting that genetic drift and population-specific factors may influence the prevalence and clinical presentation.[3,4] With the advancement in molecular diagnostics, the number of identified patients is progressively increasing, necessitating a comprehensive re-evaluation of the spectrum and distribution of variants associated with LPG. Emerging evidence suggests that variants specific to certain gene regions exhibit phenotypic heterogeneity,[2] thereby warranting an analysis of genotype–phenotype correlation in risk stratification and health care optimization. This study evaluated the demographic, genotypic, and clinical characteristics of 27 LPG patients in Northern China. Specifically, we aimed to identify APOE variants, assess clinical features, and estimate progression risks to end-stage kidney disease (ESKD). Furthermore, we investigated genotype–phenotype correlations and potential founder effects, utilizing three-dimensional protein modeling to elucidate functional impacts and characterize a novel pathogenic variant. This retrospective study included 27 LPG patients from 24 families, diagnosed at Peking University First Hospital between January 2000 and August 2023. Diagnostic confirmation was undertaken using kidney biopsy. Whole-exome sequencing (WES) was used to perform genetic analysis. Ethical approval was obtained from the Ethics Committee of Peking University First Hospital (IRB No. 2018Y99), and all participants provided informed consent. For normally distributed variables, t-tests were used; while non-parametric tests, such as the Mann–Whitney U test, were employed for non-normally distributed variables. A linear mixed-effects model was used to construct estimated glomerular filtration rate (eGFR) trajectories to evaluate the progression of renal function over time. Pearson’s and Spearman’s methods were used to calculate the correlation coefficients for normally distributed and non-normally distributed data, respectively. The Kruskal–Wallis test was employed for analyses that involved multiple groups. A significance threshold of P <0.05 was adopted. Detailed methodologies are provided in the Supplementary Materials, https://links.lww.com/CM9/C764. Among the identified variants, the Tokyo-Maebashi genotype was predominant. The variants spectrum included the Tokyo-Maebashi (15 cases), followed by the Kyoto (8 cases) and Chengdu (2 cases). Notably, two patients exhibited typical clinical features of LPG but lacked the common pathogenic variants. Of these, one harbored a novel APOE variant (p.A210P), while the other remained without a molecular diagnosis. The mean age at diagnosis was 34 years. Geographically, the patients were predominantly distributed in North China, with a notable concentration in central and southern Hebei as well as northern Henan [Supplementary Figure 1A, https://links.lww.com/CM9/C764]. Family history data were available from 14 patients, with 50% (7/14) reporting a clear family history. The pedigree charts of six families [Supplementary File, https://links.lww.com/CM9/C764] revealed patterns consistent with autosomal dominant inheritance. Detailed clinical baseline data are summarized in Supplementary Table 1, https://links.lww.com/CM9/C764. The mean eGFR was 79 mL·min−1·1.73 m−2, with 63% (17/27) classified as chronic kidney disease (CKD) stages 1–2. The urinary protein excretion ranged from 0.5 g/24 h to 14.7 g/24 h and the mean value was 3.7 g/24 h. Thirty percent (8/27) of the patients exhibited nephrotic syndrome while 52% (14/27) presented with nephrotic-range proteinuria. Correlation analysis revealed that eGFR was negatively correlated with age and urinary protein, and positively correlated with kidney size [Supplementary Figure 1B, C, https://links.lww.com/CM9/C764]. Microscopic hematuria was observed in 67% (18/27) of the patients, with a median value of 8.0 red blood cells per high power field (RBC/HPF). Regarding treatment history, 52% (14/27) had received glucocorticoid therapy before diagnosis, while 22% (6/27) had been treated with a combination of glucocorticoids and immunosuppressants (e.g., cyclophosphamide and mycophenolate mofetil). One patient developed Pneumocystis pneumonia while undergoing combined gl
AI snapshot
Written from the paper’s full text.
TL;DR
This retrospective single-center study characterizes 27 Chinese patients with lipoprotein glomerulopathy (LPG), finding the APOE Tokyo-Maebashi variant predominant in Northern China and associated with a relatively milder phenotype. It also identifies a novel likely pathogenic APOE p.A210P variant and suggests a founder effect for the Tokyo variant.
Key findings
Among 27 LPG patients from 24 families, APOE variants were Tokyo-Maebashi in 15 cases, Kyoto in 8, and Chengdu in 2; one patient had a novel APOE p.A210P variant classified as likely pathogenic, and one had no molecular diagnosis. The mean age at diagnosis was 34 years; mean eGFR was 79 mL·min⁻¹·1.73 m⁻², 63% (17/27) were CKD stages 1–2, mean urinary protein was 3.7 g/24 h (range 0.5–14.7), and 52% (14/27) had nephrotic-range proteinuria. Over an average 6.5-year follow-up in 11 patients, two progressed to ESKD; two had faster eGFR decline (18 mL·min⁻¹·1.73 m⁻² per year), and excluding them the estimated average annual decline was 4 mL·min⁻¹·1.73 m⁻². The Tokyo variant showed a founder haplotype (GCGATCTA in 36%, 4/11 unrelated carriers; 1.2% in Han Chinese 1000 Genomes) estimated to have originated 203 generations ago (~4060 years), and genotype–phenotype analysis indicated Tokyo carriers had a relatively milder clinical phenotype.
Methods
Retrospective study of 27 LPG patients from 24 families diagnosed by kidney biopsy at Peking University First Hospital between January 2000 and August 2023. Genetic analysis used whole-exome sequencing; clinical, histological, treatment, and follow-up data were collected, and plasma/urinary APOE levels were compared with healthy controls and IgA nephropathy patients. Statistical analyses included t-tests, Mann–Whitney U tests, linear mixed-effects modeling of eGFR trajectories, Pearson/Spearman correlations, and Kruskal–Wallis tests, with P < 0.05; three-dimensional protein modeling and haplotype analysis were also performed.
Limitations
The authors state the study has a relatively small sample size and single-center retrospective design, inherent to the rarity of LPG, and that structural modeling findings require further in vitro and in vivo validation. Evident from the text: progression analyses relied on only 11 patients with follow-up and two ESKD events, limiting precision of progression-risk estimates; genotype–phenotype correlation and some clinical details are presented mainly in supplementary materials.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
6 of 10 cited sources checked · 4 supported · 0 flagged · accuracy not yet measured
- Premisecitation§ Clinical characteristics and APOE variant spectrum in Chinese patients with lipoprotein glomerulopathy
Several APOE variants are linked to lipoprotein glomerulopathy, including Tokyo-Maebashi (p.L162_K164del) and Kyoto (p.R43C).
“Several APOE variants are linked to LPG, including the Tokyo-Maebashi (p.L162_K164del) and Kyoto (p.R43C).[2]”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [2] Li MS Li Y Liu Y Zhou XJ Zhang H. An updated review and meta analysis of lipoprotein glomerulopathy. Front Med (Lausanne) 2022; 9: 905007. doi: 10.3389/fmed.2022.905007. 35602473 PMC9120586 source
The Epidemiology section (page unavailable) identifies APOE Kyoto and Tokyo-Maebashi as variants observed in LPG, supporting the association. It calls Kyoto Arg25Cys, but our copy does not explicitly give the claimed p.R43C notation or identify Tokyo-Maebashi as p.L162_K164del; those precise variant labels are therefore not established by this source. (LLM, conf=0.83)
Experimental — accuracy not yet measured
- Premisecitation§ Clinical characteristics and APOE variant spectrum in Chinese patients with lipoprotein glomerulopathy
Lipoprotein glomerulopathy is primarily associated with variants in the APOE gene.
“Etiologically, the disease is primarily associated with variants in the apolipoprotein E (APOE) gene.[2]”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [2] Li MS Li Y Liu Y Zhou XJ Zhang H. An updated review and meta analysis of lipoprotein glomerulopathy. Front Med (Lausanne) 2022; 9: 905007. doi: 10.3389/fmed.2022.905007. 35602473 PMC9120586 source
- Premisecitation§ Clinical characteristics and APOE variant spectrum in Chinese patients with lipoprotein glomerulopathy
Variants in APOE disrupt its normal function, leading to accumulation of pathological lipid deposits in glomeruli.
“Variants in the APOE gene disrupt its normal function, accumulating pathological lipid deposits in glomeruli.”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [2] Li MS Li Y Liu Y Zhou XJ Zhang H. An updated review and meta analysis of lipoprotein glomerulopathy. Front Med (Lausanne) 2022; 9: 905007. doi: 10.3389/fmed.2022.905007. 35602473 PMC9120586 source
- Premisecitation§ Clinical characteristics and APOE variant spectrum in Chinese patients with lipoprotein glomerulopathy
Variants specific to certain gene regions exhibit phenotypic heterogeneity in lipoprotein glomerulopathy.
“Emerging evidence suggests that variants specific to certain gene regions exhibit phenotypic heterogeneity,[2] thereby warranting an analysis of genotype–phenotype correlation in risk stratification and health care optimization.”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [2] Li MS Li Y Liu Y Zhou XJ Zhang H. An updated review and meta analysis of lipoprotein glomerulopathy. Front Med (Lausanne) 2022; 9: 905007. doi: 10.3389/fmed.2022.905007. 35602473 PMC9120586 source
- Premisecitation§ Clinical characteristics and APOE variant spectrum in Chinese patients with lipoprotein glomerulopathy
The Kyoto, Tokyo-Maebashi, and Chengdu APOE variants are located within the N-terminal α-helix of the APOE protein.
“Structurally, these variants are located within the N-terminal α-helix of the APOE protein.[2]”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [2] Li MS Li Y Liu Y Zhou XJ Zhang H. An updated review and meta analysis of lipoprotein glomerulopathy. Front Med (Lausanne) 2022; 9: 905007. doi: 10.3389/fmed.2022.905007. 35602473 PMC9120586 source
In Pathogenesis > APOE Gene and apoE Function (page unavailable), the review places apoE’s N-terminal region at amino acids 1–199 and describes four helix regions within amino acids 20–160. It identifies Kyoto as Arg25Cys and discusses Tokyo-Maebashi, but does not establish that Tokyo-Maebashi lies in an α-helix or identify a Chengdu variant there. The claim’s placement of all three variants in an N-terminal α-helix is therefore not fully supported. (LLM, conf=0.82)
Experimental — accuracy not yet measured
- Interpretationreasoning§ Clinical characteristics and APOE variant spectrum in Chinese patients with lipoprotein glomerulopathy
The prevalence of lipoprotein glomerulopathy may have been underestimated, considering that only less than 300 cases have been reported globally.
“This suggests that the prevalence of LPG may have been underestimated, considering that only less than 300 cases have been reported globally.[2]”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [2] Li MS Li Y Liu Y Zhou XJ Zhang H. An updated review and meta analysis of lipoprotein glomerulopathy. Front Med (Lausanne) 2022; 9: 905007. doi: 10.3389/fmed.2022.905007. 35602473 PMC9120586 source
- Findingown data§ Clinical characteristics and APOE variant spectrum in Chinese patients with lipoprotein glomerulopathy
One of the two patients without common pathogenic variants harbored a novel APOE variant (p.A210P).
“Of these, one harbored a novel APOE variant (p.A210P), while the other remained without a molecular diagnosis.”
Quote in the paperNot a substantial claim - Findingown data§ Clinical characteristics and APOE variant spectrum in Chinese patients with lipoprotein glomerulopathy
Among identified APOE variants in this cohort, the Tokyo-Maebashi genotype was predominant.
“Among the identified variants, the Tokyo-Maebashi genotype was predominant.”
- Also stated in: § Clinical characteristics and APOE variant spectrum in Chinese patients with lipoprotein glomerulopathy · plain
“the APOE Tokyo-Maebashi variant emerges as the predominant variant in Northern China”
Quote in the paperSubstantial claim- Rests on an assumption: The 27 patients from a single center are representative of the lipoprotein glomerulopathy patient population in Northern China.
- Also stated in: § Clinical characteristics and APOE variant spectrum in Chinese patients with lipoprotein glomerulopathy · plain
- Findingown data§ Clinical characteristics and APOE variant spectrum in Chinese patients with lipoprotein glomerulopathy
The other patient without common pathogenic variants remained without a molecular diagnosis.
“Of these, one harbored a novel APOE variant (p.A210P), while the other remained without a molecular diagnosis.”
Quote in the paperNot a substantial claim - Findingown data§ Clinical characteristics and APOE variant spectrum in Chinese patients with lipoprotein glomerulopathy
Two patients exhibited typical clinical features of lipoprotein glomerulopathy but lacked the common pathogenic APOE variants.
“Notably, two patients exhibited typical clinical features of LPG but lacked the common pathogenic variants.”
Quote in the paperNot a substantial claim - Findingown data§ Clinical characteristics and APOE variant spectrum in Chinese patients with lipoprotein glomerulopathy
Microscopic hematuria was observed in 67% (18/27) of patients.
“Microscopic hematuria was observed in 67% (18/27) of the patients, with a median value of 8.0 red blood cells per high power field (RBC/HPF).”
Quote in the paperNot a substantial claim - Findingown data§ Clinical characteristics and APOE variant spectrum in Chinese patients with lipoprotein glomerulopathy
22% (6/27) of patients had been treated with a combination of glucocorticoids and immunosuppressants before diagnosis.
“Regarding treatment history, 52% (14/27) had received glucocorticoid therapy before diagnosis, while 22% (6/27) had been treated with a combination of glucocorticoids and immunosuppressants (e.g., cyclophosphamide and mycophenolate mofetil).”
Quote in the paperNot a substantial claim - Findingown data§ Clinical characteristics and APOE variant spectrum in Chinese patients with lipoprotein glomerulopathy
eGFR was negatively correlated with age.
“Correlation analysis revealed that eGFR was negatively correlated with age and urinary protein, and positively correlated with kidney size”
Quote in the paperNot a substantial claim - Findingnone given§ Clinical characteristics and APOE variant spectrum in Chinese patients with lipoprotein glomerulopathy
Rectifying the diagnosis significantly changed the treatment strategy for all these patients.
“Rectifying the diagnosis significantly changed the treatment strategy for all these patients.”
Quote in the paperNot a substantial claim - Findingown data§ Clinical characteristics and APOE variant spectrum in Chinese patients with lipoprotein glomerulopathy
Urinary protein excretion ranged from 0.5 g/24 h to 14.7 g/24 h.
“The urinary protein excretion ranged from 0.5 g/24 h to 14.7 g/24 h and the mean value was 3.7 g/24 h.”
Quote in the paperNot a substantial claim - Findingown data§ Clinical characteristics and APOE variant spectrum in Chinese patients with lipoprotein glomerulopathy
30% (8/27) of patients exhibited nephrotic syndrome.
“Thirty percent (8/27) of the patients exhibited nephrotic syndrome while 52% (14/27) presented with nephrotic-range proteinuria.”
Quote in the paperNot a substantial claim - Findingown data§ Clinical characteristics and APOE variant spectrum in Chinese patients with lipoprotein glomerulopathy
Upon excluding the two patients with faster decline, the estimated average annual decline in eGFR was 4 mL·min−1·1.73 m−2.
“Upon excluding these two patients, the estimated average annual decline in eGFR was 4 mL·min−1·1.73 m−2.”
Quote in the paperSubstantial claim - Findingown data§ Clinical characteristics and APOE variant spectrum in Chinese patients with lipoprotein glomerulopathy
eGFR was positively correlated with kidney size.
“Correlation analysis revealed that eGFR was negatively correlated with age and urinary protein, and positively correlated with kidney size”
Quote in the paperNot a substantial claim - Findingown data§ Clinical characteristics and APOE variant spectrum in Chinese patients with lipoprotein glomerulopathy
Disease progression was monitored over an average duration of 6.5 years (11 patients with follow-up range 2-16 years).
“Disease progression was monitored over an average duration of 6.5 years (11 patients with a follow-up time range of 2–16 years).”
Quote in the paperSubstantial claim - Findingown data§ Clinical characteristics and APOE variant spectrum in Chinese patients with lipoprotein glomerulopathy
During the follow-up period, two patients progressed to end-stage kidney disease.
“During this period, two patients progressed to ESKD.”
Quote in the paperSubstantial claim - Findingown data§ Clinical characteristics and APOE variant spectrum in Chinese patients with lipoprotein glomerulopathy
63% (17/27) of patients were classified as chronic kidney disease stages 1-2.
“The mean eGFR was 79 mL·min−1·1.73 m−2, with 63% (17/27) classified as chronic kidney disease (CKD) stages 1–2.”
Quote in the paperNot a substantial claim - Findingown data§ Clinical characteristics and APOE variant spectrum in Chinese patients with lipoprotein glomerulopathy
52% (14/27) of patients presented with nephrotic-range proteinuria.
“Thirty percent (8/27) of the patients exhibited nephrotic syndrome while 52% (14/27) presented with nephrotic-range proteinuria.”
Quote in the paperNot a substantial claim - Findingown data§ Clinical characteristics and APOE variant spectrum in Chinese patients with lipoprotein glomerulopathy
The mean age at diagnosis was 34 years.
“The mean age at diagnosis was 34 years.”
Quote in the paperNot a substantial claim - Findingown data§ Clinical characteristics and APOE variant spectrum in Chinese patients with lipoprotein glomerulopathy
Family history data were available from 14 patients, with 50% (7/14) reporting a clear family history.
“Family history data were available from 14 patients, with 50% (7/14) reporting a clear family history.”
Quote in the paperNot a substantial claim - Findingown data§ Clinical characteristics and APOE variant spectrum in Chinese patients with lipoprotein glomerulopathy
The patients were predominantly distributed in Northern China, with a notable concentration in central and southern Hebei as well as northern Henan.
“Geographically, the patients were predominantly distributed in Northern China, with a notable concentration in central and southern Hebei as well as northern Henan”
Quote in the paperNot a substantial claim- Rests on an assumption: The 27 patients from a single center are representative of the lipoprotein glomerulopathy patient population in Northern China.
- Findingown data§ Clinical characteristics and APOE variant spectrum in Chinese patients with lipoprotein glomerulopathy
The mean eGFR was 79 mL·min−1·1.73 m−2.
“The mean eGFR was 79 mL·min−1·1.73 m−2, with 63% (17/27) classified as chronic kidney disease (CKD) stages 1–2.”
Quote in the paperNot a substantial claim - Findingown data§ Clinical characteristics and APOE variant spectrum in Chinese patients with lipoprotein glomerulopathy
eGFR was negatively correlated with urinary protein.
“Correlation analysis revealed that eGFR was negatively correlated with age and urinary protein, and positively correlated with kidney size”
Quote in the paperNot a substantial claim - Findingown data§ Clinical characteristics and APOE variant spectrum in Chinese patients with lipoprotein glomerulopathy
52% (14/27) of patients had received glucocorticoid therapy before diagnosis.
“Regarding treatment history, 52% (14/27) had received glucocorticoid therapy before diagnosis, while 22% (6/27) had been treated with a combination of glucocorticoids and immunosuppressants (e.g., cyclophosphamide and mycophenolate mofetil).”
Quote in the paperNot a substantial claim - Findingown data§ Clinical characteristics and APOE variant spectrum in Chinese patients with lipoprotein glomerulopathy
Two patients exhibited a significantly faster decline in eGFR, with mean rates of 18 mL·min−1·1.73 m−2 per year (patients 8 and 11).
“Two of the patients exhibited a significantly faster decline in eGFR, with mean rates of 18 mL·min−1·1.73 m−2 per year (patients 8 and 11).”
Quote in the paperSubstantial claim - Findingown data§ Clinical characteristics and APOE variant spectrum in Chinese patients with lipoprotein glomerulopathy
The mean urinary protein excretion was 3.7 g/24 h.
“The urinary protein excretion ranged from 0.5 g/24 h to 14.7 g/24 h and the mean value was 3.7 g/24 h.”
Quote in the paperNot a substantial claim - Findingown data§ Clinical characteristics and APOE variant spectrum in Chinese patients with lipoprotein glomerulopathy
The GCGATCTA haplotype was the most prevalent (36%, 4/11) among 11 unrelated patients who carried the Tokyo variant.
“The GCGATCTA haplotype was the most prevalent (36%, 4/11) among 11 unrelated patients who carried the Tokyo variant.”
Quote in the paperSubstantial claim - Findingown data§ Clinical characteristics and APOE variant spectrum in Chinese patients with lipoprotein glomerulopathy
Mesangiolysis was observed in 38% (9/24) of patients.
“Other findings included mesangial interposition (33%, 8/24), mesangiolysis (38%, 9/24), and basement membrane thickening with double contours (46%, 11/26).”
Quote in the paperNot a substantial claim - Findingnone given§ Clinical characteristics and APOE variant spectrum in Chinese patients with lipoprotein glomerulopathy
The GCGATCTA haplotype was present in only 1.2% of individuals from the Han Chinese population in the 1000 Genomes Project.
“This haplotype was present in only 1.2% of individuals from the Han Chinese population in the 1000 Genomes Project.”
Quote in the paperSubstantial claim - Findingown data§ Clinical characteristics and APOE variant spectrum in Chinese patients with lipoprotein glomerulopathy
Proliferation of segmental endothelial cells, mesangial cells, and the mesangial matrix was observed.
“The proliferation of segmental endothelial cells, mesangial cells, and the mesangial matrix was also observed.”
Quote in the paperNot a substantial claim - Findingown data§ Clinical characteristics and APOE variant spectrum in Chinese patients with lipoprotein glomerulopathy
Mesangial interposition was observed in 33% (8/24) of patients.
“Other findings included mesangial interposition (33%, 8/24), mesangiolysis (38%, 9/24), and basement membrane thickening with double contours (46%, 11/26).”
Quote in the paperNot a substantial claim - Findingown data§ Clinical characteristics and APOE variant spectrum in Chinese patients with lipoprotein glomerulopathy
Positive immunofluorescence was observed in 54% (13/24) of patients.
“Positive immunofluorescence was observed in 54% (13/24) of the patients, with segmental granular deposits of immunoglobulin M (IgM) (42%, 10/24) and C3 (13%, 3/24) in the capillary walls and mesangial areas.”
Quote in the paperNot a substantial claim - Findingown data§ Clinical characteristics and APOE variant spectrum in Chinese patients with lipoprotein glomerulopathy
Patients harboring the Tokyo variant exhibited a relatively milder clinical phenotype.
“Genotype–phenotype correlation analysis [Supplementary Figure 3 and Supplementary Table 2, http://links.lww.com/CM9/C764] indicated that patients harboring the Tokyo variant exhibited a relatively milder clinical phenotype.”
- Also stated in: § Clinical characteristics and APOE variant spectrum in Chinese patients with lipoprotein glomerulopathy · plain
“associated with relatively milder clinical manifestations”
Quote in the paperSubstantial claim - Also stated in: § Clinical characteristics and APOE variant spectrum in Chinese patients with lipoprotein glomerulopathy · plain
- Findingreasoning§ Clinical characteristics and APOE variant spectrum in Chinese patients with lipoprotein glomerulopathy
The Tokyo variant modifies the ionic associations in the APOE-LDLR complex from Aspartate-Arginine to Aspartate-Lysine.
“Additionally, the variant modifies the ionic associations in the APOE–LDLR complex from Aspartate–Arginine to Aspartate–Lysine.”
Quote in the paperNot a substantial claim- Rests on an assumption: The 3D protein modeling predictions reflect the actual structural and functional effects of the APOE variants.
- Findingown data§ Clinical characteristics and APOE variant spectrum in Chinese patients with lipoprotein glomerulopathy
The average glomerulosclerosis rate was 14% (range 3-41%).
“Nineteen patients (79%) exhibited varying degrees of glomerulosclerosis, with an average sclerosis rate of 14% (range: 3–41%).”
Quote in the paperNot a substantial claim - Findingown data§ Clinical characteristics and APOE variant spectrum in Chinese patients with lipoprotein glomerulopathy
Podocyte foot process effacement was noted in all patients.
“According to electron microscopy results, podocyte foot process effacement was noted in all patients, with 52% (13/24) of them showing glomerular basement membrane thickening.”
Quote in the paperNot a substantial claim - Findingown data§ Clinical characteristics and APOE variant spectrum in Chinese patients with lipoprotein glomerulopathy
Nineteen patients (79%) exhibited varying degrees of glomerulosclerosis.
“Nineteen patients (79%) exhibited varying degrees of glomerulosclerosis, with an average sclerosis rate of 14% (range: 3–41%).”
Quote in the paperNot a substantial claim - Findingown data§ Clinical characteristics and APOE variant spectrum in Chinese patients with lipoprotein glomerulopathy
C3 deposits were observed in 13% (3/24) of patients.
“Positive immunofluorescence was observed in 54% (13/24) of the patients, with segmental granular deposits of immunoglobulin M (IgM) (42%, 10/24) and C3 (13%, 3/24) in the capillary walls and mesangial areas.”
Quote in the paperNot a substantial claim - Findingcitation§ Clinical characteristics and APOE variant spectrum in Chinese patients with lipoprotein glomerulopathy
The allele frequencies of the Kyoto variant in the Chinamap, Westlake, and gnomAD databases range between 8/106 and 1/104.
“The allele frequencies of the Kyoto variant in the Chinamap, Westlake, and gnomAD databases range between 8/106 and 1/104.”
Quote in the paperSubstantial claim - Findingown data§ Clinical characteristics and APOE variant spectrum in Chinese patients with lipoprotein glomerulopathy
52% (13/24) of patients showed glomerular basement membrane thickening.
“According to electron microscopy results, podocyte foot process effacement was noted in all patients, with 52% (13/24) of them showing glomerular basement membrane thickening.”
Quote in the paperNot a substantial claim - Findingown data§ Clinical characteristics and APOE variant spectrum in Chinese patients with lipoprotein glomerulopathy
Three known APOE variants were identified: Kyoto (p.R43C), Tokyo-Maebashi (p.L162_K164del), and Chengdu (p.L173P).
“In this study, three known APOE variants were identified: the Kyoto (p.R43C), Tokyo-Maebashi (p.L162_K164del), and Chengdu (p.L173P) variants.”
Quote in the paperSubstantial claim - Findingown data§ Clinical characteristics and APOE variant spectrum in Chinese patients with lipoprotein glomerulopathy
Segmental granular immunoglobulin M deposits were observed in 42% (10/24) of patients.
“Positive immunofluorescence was observed in 54% (13/24) of the patients, with segmental granular deposits of immunoglobulin M (IgM) (42%, 10/24) and C3 (13%, 3/24) in the capillary walls and mesangial areas.”
Quote in the paperNot a substantial claim - Findingown data§ Clinical characteristics and APOE variant spectrum in Chinese patients with lipoprotein glomerulopathy
Basement membrane thickening with double contours was observed in 46% (11/26) of patients.
“Other findings included mesangial interposition (33%, 8/24), mesangiolysis (38%, 9/24), and basement membrane thickening with double contours (46%, 11/26).”
Quote in the paperNot a substantial claim - Findingreasoning§ Clinical characteristics and APOE variant spectrum in Chinese patients with lipoprotein glomerulopathy
AggreProt supported that protein aggregation peaks at the Kyoto variant site.
“AggreProt (Masaryk University, Brno, Czech Republic) supported that protein aggregation peaks at the variant site.”
Quote in the paperSubstantial claim- Rests on an assumption: The 3D protein modeling predictions reflect the actual structural and functional effects of the APOE variants.
- Findingown data§ Clinical characteristics and APOE variant spectrum in Chinese patients with lipoprotein glomerulopathy
Conservation analysis indicates that the sites for the Tokyo and Chengdu variants are evolutionarily conserved across species.
“Conservation analysis indicates that the sites for the Tokyo and Chengdu variants are evolutionarily conserved across species.”
Quote in the paperNot a substantial claim - Findingown data§ Clinical characteristics and APOE variant spectrum in Chinese patients with lipoprotein glomerulopathy
Plasma and urinary APOE levels were significantly elevated in lipoprotein glomerulopathy patients compared to healthy controls.
“We observed that these levels were significantly elevated in LPG patients compared to healthy controls (HCs) but showed no significant difference versus IgA nephropathy (IgAN) patients.”
Quote in the paperNot a substantial claim - Findingown data§ Clinical characteristics and APOE variant spectrum in Chinese patients with lipoprotein glomerulopathy
Plasma and urinary APOE levels showed no significant difference between lipoprotein glomerulopathy patients and IgA nephropathy patients.
“We observed that these levels were significantly elevated in LPG patients compared to healthy controls (HCs) but showed no significant difference versus IgA nephropathy (IgAN) patients.”
Quote in the paperNot a substantial claim - Findingown data§ Clinical characteristics and APOE variant spectrum in Chinese patients with lipoprotein glomerulopathy
A novel APOE variant (c.628G>C, p.A210P) was identified in a 34-year-old female with lipoprotein glomerulopathy.
“In addition to these established genotypes, we identified a novel variant associated with LPG in a 34-year-old female, who carried a heterozygous variant (c.628G >C, p.A210P) in the APOE gene.”
Quote in the paperSubstantial claim - Findingown data§ Clinical characteristics and APOE variant spectrum in Chinese patients with lipoprotein glomerulopathy
After normalizing for urinary protein excretion, the median urinary APOE-to-protein ratio was significantly lower in lipoprotein glomerulopathy patients (0.06) compared to IgA nephropathy (0.13) and healthy control (0.17) groups.
“However, after normalizing for urinary protein excretion, the median urinary APOE-to-protein ratio was significantly lower in LPG patients (0.06) compared to the IgAN (0.13) and HC (0.17) groups”
Quote in the paperNot a substantial claim - Interpretationcitation§ Clinical characteristics and APOE variant spectrum in Chinese patients with lipoprotein glomerulopathy
Genetic drift and population-specific factors may influence the prevalence and clinical presentation of lipoprotein glomerulopathy.
“These variants exhibit distinct geographical distributions and founder effects, suggesting that genetic drift and population-specific factors may influence the prevalence and clinical presentation.[3,4]”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [3] Hu Z Huang S Wu Y Liu Y Liu X Su D,. Hereditary features, treatment, and prognosis of the lipoprotein glomerulopathy in patients with the APOE Kyoto mutation. Kidney Int 2014; 85: 416– 424. doi: 10.1038/ki.2013.335. 24025644 source
- cites [4] Toyota K Hashimoto T Ogino D Matsunaga A Ito M Masakane I,. A founder haplotype of APOE-Sendai mutation associated with lipoprotein glomerulopathy. J Hum Genet 2013; 58: 254– 258. doi: 10.1038/jhg.2013.8. 23407349 source
- Interpretationown data§ Clinical characteristics and APOE variant spectrum in Chinese patients with lipoprotein glomerulopathy
Pedigree charts of six families revealed patterns consistent with autosomal dominant inheritance.
“The pedigree charts of six families [Supplementary File, http://links.lww.com/CM9/C764] revealed patterns consistent with autosomal dominant inheritance.”
Quote in the paperNot a substantial claim - Interpretationown data§ Clinical characteristics and APOE variant spectrum in Chinese patients with lipoprotein glomerulopathy
The estimated average annual eGFR decline suggests a possible lifetime risk of lipoprotein glomerulopathy progression to end-stage kidney disease by the time patients reach around 50 years of age.
“This result suggests a possible lifetime risk of LPG progression to ESKD by the time the patients reach around 50 years of age”
Quote in the paperSubstantial claim- Rests on an assumption: The observed average annual decline in eGFR can be extrapolated linearly to estimate lifetime risk of end-stage kidney disease by age 50.
- Interpretationown data§ Clinical characteristics and APOE variant spectrum in Chinese patients with lipoprotein glomerulopathy
The Tokyo variant in northern Chinese has a founder effect.
“It suggested a founder effect of Tokyo variant in northern Chinese.”
Quote in the paperSubstantial claim - Interpretationown data§ Clinical characteristics and APOE variant spectrum in Chinese patients with lipoprotein glomerulopathy
The LRKLRK sequence affected by the Tokyo variant might play a crucial role in receptor binding.
“Structural analysis confirmed that the LRKLRK sequence affected by the Tokyo variant might play a crucial role in receptor binding”
Quote in the paperNot a substantial claim- Rests on an assumption: The 3D protein modeling predictions reflect the actual structural and functional effects of the APOE variants.
- Interpretationown data§ Clinical characteristics and APOE variant spectrum in Chinese patients with lipoprotein glomerulopathy
The Tokyo variant most likely originated 203 generations ago, extrapolated to approximately 4060 years ago.
“DMLE+ (University of Alberta, Edmonton, Alberta, Canada) was used to estimate that this variant most likely originated 203 generations ago, which is extrapolated to approximately 4060 years ago”
Quote in the paperNot a substantial claim - Interpretationreasoning§ Clinical characteristics and APOE variant spectrum in Chinese patients with lipoprotein glomerulopathy
The protein aggregation for the Kyoto variant is likely attributable to cysteine's propensity to form disulfide bonds, as illustrated by the protein dimer model.
“This phenomenon is likely attributable to cysteine’s propensity to form disulfide bonds, as illustrated by the protein dimer model.”
Quote in the paperNot a substantial claim- Rests on an assumption: The 3D protein modeling predictions reflect the actual structural and functional effects of the APOE variants.
- Interpretationnone given§ Clinical characteristics and APOE variant spectrum in Chinese patients with lipoprotein glomerulopathy
According to American College of Medical Genetics and Genomics guidelines, the p.A210P variant is classified as likely pathogenic based on criteria PM1, PM2, PP2, PP3, and PP4.
“According to American College of Medical Genetics and Genomics guidelines, this variant is classified as likely pathogenic (LP) based on the criteria PM1, PM2, PP2, PP3, and PP4.”
Quote in the paperSubstantial claim - Interpretationreasoning§ Clinical characteristics and APOE variant spectrum in Chinese patients with lipoprotein glomerulopathy
The electrostatic interaction between arginine and negatively charged aspartate is more robust compared to the interaction involving lysine.
“Consequently, the electrostatic interaction between arginine and the negatively charged aspartate is more robust compared to the interaction involving lysine.”
Quote in the paperSubstantial claim- Rests on an assumption: The 3D protein modeling predictions reflect the actual structural and functional effects of the APOE variants.
- May combine two claims. 8
- Classified as probably not a substantial claim. 10
May combine two claims.
Findingown data§ Clinical characteristics and APOE variant spectrum in Chinese patients with lipoprotein glomerulopathyThe APOE variant spectrum in this cohort included Tokyo-Maebashi (15 cases), Kyoto (8 cases), and Chengdu (2 cases).
“The variants spectrum included the Tokyo-Maebashi (15 cases), followed by the Kyoto (8 cases) and Chengdu (2 cases).”
Quote in the paperSubstantial claimClassified as probably not a substantial claim.
Findingown data§ Clinical characteristics and APOE variant spectrum in Chinese patients with lipoprotein glomerulopathyPatient 8 had concurrent hepatitis B virus infection.
“Patient 8 had concurrent hepatitis B virus (HBV) infection while patient 11 experienced fungus Pneumocystis jirovecii infection as aforementioned.”
Quote in the paperSubstantial claimMay combine two claims.
Findingnone given§ Clinical characteristics and APOE variant spectrum in Chinese patients with lipoprotein glomerulopathyAll patients received fenofibrate lipid-lowering therapy and renin-angiotensin-aldosterone system inhibitors following diagnosis.
“All patients received fenofibrate lipid-lowering therapy and renin–angiotensin–aldosterone system inhibitors following their diagnosis.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Findingown data§ Clinical characteristics and APOE variant spectrum in Chinese patients with lipoprotein glomerulopathyThe median microscopic hematuria value was 8.0 red blood cells per high power field.
“Microscopic hematuria was observed in 67% (18/27) of the patients, with a median value of 8.0 red blood cells per high power field (RBC/HPF).”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Findingown data§ Clinical characteristics and APOE variant spectrum in Chinese patients with lipoprotein glomerulopathyOne patient developed Pneumocystis pneumonia while undergoing combined glucocorticoid and cyclophosphamide therapy before enrollment.
“One patient developed Pneumocystis pneumonia while undergoing combined glucocorticoid and cyclophosphamide therapy before enrollment.”
Quote in the paperNot a substantial claimClassified as probably not a substantial claim.
Findingown data§ Clinical characteristics and APOE variant spectrum in Chinese patients with lipoprotein glomerulopathyRenal biopsies were performed on 24 patients.
“Histologically, renal biopsies were performed on 24 patients.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Findingown data§ Clinical characteristics and APOE variant spectrum in Chinese patients with lipoprotein glomerulopathyPatient 11 experienced fungus Pneumocystis jirovecii infection.
“Patient 8 had concurrent hepatitis B virus (HBV) infection while patient 11 experienced fungus Pneumocystis jirovecii infection as aforementioned.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown data§ Clinical characteristics and APOE variant spectrum in Chinese patients with lipoprotein glomerulopathyAlthough renal function remained stable during the initial years, a gradual decline in eGFR was evident with extended follow-up.
“Although renal function remained stable during the initial years, a gradual decline in eGFR was evident with extended follow-up, highlighting an unmet need for novel or additional therapy.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown data§ Clinical characteristics and APOE variant spectrum in Chinese patients with lipoprotein glomerulopathyRenal biopsies consistently revealed key pathological features of glomerular capillary dilation and the presence of oil-red O-positive lipid thrombi in capillary lumens.
“It consistently revealed key pathological features of glomerular capillary dilation and the presence of oil-red O-positive lipid thrombi in capillary lumens.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Findingown data§ Clinical characteristics and APOE variant spectrum in Chinese patients with lipoprotein glomerulopathyOne patient presented with immunoglobulin M, C1q, and fibrinogen-fibrin-related antigen deposits.
“Three patients presented with distinct immunofluorescent patterns: IgM, C1q, and fibrinogen-fibrin-related antigen (FRA) deposits in one patient; and IgM and C3 deposits in two patients.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingnone given§ Clinical characteristics and APOE variant spectrum in Chinese patients with lipoprotein glomerulopathyThe Tokyo variant is a deletion variant that does not cause significant changes in the local hydrophobicity or surface charge.
“Conversely, the Tokyo variant is a deletion variant that does not cause significant changes in the local hydrophobicity or surface charge.”
Quote in the paperNot a substantial claim- Rests on an assumption: The 3D protein modeling predictions reflect the actual structural and functional effects of the APOE variants.
Probably not a substantial claim: may not pass S3 (load-bearing).
Findingown data§ Clinical characteristics and APOE variant spectrum in Chinese patients with lipoprotein glomerulopathyTwo patients presented with immunoglobulin M and C3 deposits.
“Three patients presented with distinct immunofluorescent patterns: IgM, C1q, and fibrinogen-fibrin-related antigen (FRA) deposits in one patient; and IgM and C3 deposits in two patients.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Findingown data§ Clinical characteristics and APOE variant spectrum in Chinese patients with lipoprotein glomerulopathyThe arginine at position 43 (Kyoto) appears evolutionarily recent, being present in higher primates whereas proline is found in other species.
“In contrast, the arginine at position 43 (Kyoto) appears evolutionarily recent, being present in higher primates whereas proline is found in other species”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown data§ Clinical characteristics and APOE variant spectrum in Chinese patients with lipoprotein glomerulopathyFor the Kyoto variant, the amino acid change alters local surface hydrophilicity and electronic charge.
“For the Kyoto variant, the amino acid change alters local surface hydrophilicity and electronic charge.”
Quote in the paperSubstantial claim- Rests on an assumption: The 3D protein modeling predictions reflect the actual structural and functional effects of the APOE variants.
Probably not a substantial claim: may not pass S3 (load-bearing).
Findingown data§ Clinical characteristics and APOE variant spectrum in Chinese patients with lipoprotein glomerulopathyMesangial electron-dense deposits were observed in four patients.
“Mesangial electron-dense deposits were observed in four patients.”
Quote in the paperNot a substantial claimMay combine two claims.
Premisecitation§ Clinical characteristics and APOE variant spectrum in Chinese patients with lipoprotein glomerulopathyAPOE variants linked to lipoprotein glomerulopathy exhibit distinct geographical distributions and founder effects.
“These variants exhibit distinct geographical distributions and founder effects, suggesting that genetic drift and population-specific factors may influence the prevalence and clinical presentation.[3,4]”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [3] Hu Z Huang S Wu Y Liu Y Liu X Su D,. Hereditary features, treatment, and prognosis of the lipoprotein glomerulopathy in patients with the APOE Kyoto mutation. Kidney Int 2014; 85: 416– 424. doi: 10.1038/ki.2013.335. 24025644 source
- cites [4] Toyota K Hashimoto T Ogino D Matsunaga A Ito M Masakane I,. A founder haplotype of APOE-Sendai mutation associated with lipoprotein glomerulopathy. J Hum Genet 2013; 58: 254– 258. doi: 10.1038/jhg.2013.8. 23407349 source
Classified as probably not a substantial claim.
Premisereasoning§ Clinical characteristics and APOE variant spectrum in Chinese patients with lipoprotein glomerulopathyThe guanidinium group of arginine possesses a concentrated positive charge, facilitating a stronger ionic bond than the amino group of lysine, which has a less focused charge distribution.
“The guanidinium group of arginine possesses a concentrated positive charge, facilitating a stronger ionic bond than the amino group of lysine, which has a less focused charge distribution.”
Quote in the paperSubstantial claimMay combine two claims.
Study design and conductreasoning§ Clinical characteristics and APOE variant spectrum in Chinese patients with lipoprotein glomerulopathyThe study had a relatively small sample size and a single-center retrospective design.
“The limitations of this study include the relatively small sample size and single-center retrospective design, which are inherent to the rarity of LPG.”
Quote in the paperNot a substantial claim
The paper relies on this without support.
The 27 patients from a single center are representative of the lipoprotein glomerulopathy patient population in Northern China.
“This retrospective study included 27 LPG patients from 24 families, diagnosed at Peking University First Hospital between January 2000 and August 2023.”
“the APOE Tokyo-Maebashi variant emerges as the predominant variant in Northern China”
The paper relies on this without support.
The observed average annual decline in eGFR can be extrapolated linearly to estimate lifetime risk of end-stage kidney disease by age 50.
“Upon excluding these two patients, the estimated average annual decline in eGFR was 4 mL·min−1·1.73 m−2. This result suggests a possible lifetime risk of LPG progression to ESKD by the time the patients reach around 50 years of age”
The paper relies on this without support.
The 3D protein modeling predictions reflect the actual structural and functional effects of the APOE variants.
“To elucidate the underlying molecular mechanisms, we investigated the structural impact of the Tokyo and Kyoto variants using 3D protein modeling”
“further in vitro and in vivo studies are warranted to fully validate the functional impact of these variants.”
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.
Podocyte finding percentage does not match the stated fraction
MinorThirteen of 24 patients is 54.2%, not 52%.
Reported 52 · recomputed 54.166667
“with 52% (13/24) of them showing glomerular basement membrane thickening.”
Basement membrane thickening percentage does not match the stated fraction
MinorThe stated 11/26 is 42.3%, not 46%. The denominator of 26 also exceeds the 24 patients reported to have undergone renal biopsy.
Reported 46 · recomputed 42.307692
“Other findings included mesangial interposition (33%, 8/24), mesangiolysis (38%, 9/24), and basement membrane thickening with double contours (46%, 11/26).”
Biopsy confirmation conflicts with the reported biopsy count
MinorThe methods say the 27 patients' diagnoses were confirmed using kidney biopsy, but the results say biopsies were performed on only 24 patients.
“This retrospective study included 27 LPG patients from 24 families, diagnosed at Peking University First Hospital between January 2000 and August 2023. Diagnostic confirmation was undertaken using kidney biopsy.”
“Histologically, renal biopsies were performed on 24 patients.”
Cites
Hu, Z., Huang, S., Wu, Y., Liu, Y., Liu, X., Su, D., Tao, Y., Fu, P., Zhang, X., Peng, Z., et al. (2014) · Kidney International · doi:10.1038/ki.2013.335 · Cited by 60 · 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
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
Self-citationA founder haplotype of APOE-Sendai mutation associated with lipoprotein glomerulopathy
Toyota, K., Hashimoto, T., Ogino, D., Matsunaga, A., Ito, M., Masakane, I., Degawa, N., Sato, H., Shirai, S., Umetsu, K., et al. (2013) · Journal of Human Genetics · doi:10.1038/jhg.2013.8 · Cited by 19 · see citing works
Flagged first, then by citations
Cited by
Still being checked.
- Authors
- Li, M., Li, Y., Jiang, L., Wang, X., Liu, Z., Song, Z., You, R., Chen, Y., Zhou, X., & Zhang, H.
- Affiliations
- Peking University (CN)
- Corresponding author
- Zhou, Xujie
- Venue
- Chinese Medical Journal
- Published
- 2026-03-06
- Volume
- 139
- Issue
- 8
- Pages
- 1245-1247
- ISSN
- 0366-6999 (ISSN-L)
- 2542-5641
- PMC
- PMC13090053
- OpenAlex
- W7134242770
- Cited by
- 0
- References
- 3
- FWCI
- 0.00
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Chinese Medical Journal (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Health Sciences › Medicine › Nephrology › Renal Diseases and Glomerulopathies
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Keywords
- lipoprotein glomerulopathy, APOE gene, genotype-phenotype correlation, founder effect, novel pathogenic variant, renal function decline, end-stage renal disease, proteinuria, Chinese patients, northern China, genetic risk stratification
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 ›
Are you an author, or do you see a problem with this page? Request a review
