Lipoprotein glomerulopathy with markedly increased arterial stiffness successfully treated with a combination of fenofibrate and losartan: a case report.

BACKGROUND: Lipoprotein glomerulopathy (LPG) is a apolipoprotein E (ApoE)-related glomerular disease and has been associated with type III hyperlipidemia. Without appropriate treatment, chronic kidney disease (CKD) caused by LPG progresses, and approximately half of the patients develop end-stage kidney disease within 1-27 years of disease onset. However, few studies have highlighted the clinical course of cardiovascular diseases (CVDs) in patients with LPG. Herein, we report the first case of LPG in which the CVD risk was assessed using arterial stiffness. CASE PRESENTATION: A 32-year-old Japanese man was referred to our hospital due to persistent proteinuria. Kidney biopsy showed markedly dilated capillary lumens containing pale-stained thrombi, which stained positively with Oil Red O. Electron microscopy revealed the presence of thrombi in the capillary lumen with low electron density and vacuoles of various sizes in part of the thrombi. Toluidine blue and Sudan IV stains were used to stain the thin sections of Epon-embedded tissue samples for electron microscopy. Sudan IV-positive droplets were observed in the capillary lumens, vascular walls, and cytoplasm of tubular cells. Increased serum ApoE concentration was observed. Liquid chromatography-tandem mass spectrometry of laser-microdissected glomeruli from paraffin sections revealed an increase in ApoE. Direct deoxyribonucleic acid sequencing of ApoE revealed a heterozygous ApoE Sendai mutation (Arg145Pro). The patient was finally diagnosed with LPG with heterozygosity for ApoE-Sendai mutation (Arg145Pro). Notably, at the time of diagnosis, he had markedly increased arterial stiffness for his age. Arterial stiffness was measured using brachial-ankle pulse wave velocity (baPWV), which was equivalent to that of a 56-year-old man. After three months of treatment with fenofibrate and losartan, a significant reduction in proteinuria was achieved along with an improvement in baPWV. Furthermore, these effects were maintained despite the lack of decrease in serum ApoE levels. CONCLUSION: Herein, we report the case of a patient with LPG with markedly increased arterial stiffness at the time of diagnosis, in whom combination therapy with fenofibrate and losartan successfully improved proteinuria and arterial stiffness. To the best of our knowledge, this is the first case report of LPG in which CVD risk was assessed using arterial stiffness.

A case report of youth-onset lipoprotein glomerulopathy with APOE Chicago mutation.

BACKGROUND: This article reports an extremely rare case of lipoprotein glomerulopathy (LPG) with apolipoprotein E gene (APOE) Chicago mutation in a young Chinese male. Only five cases or families with APOE Chicago mutations have been reported in the literature. CASE PRESENTATION: The young male patient is manifested with nephrotic syndrome, accompanied by hyperlipidemia with a preferable increase in triglycerides and elevated ApoE level. Renal biopsy of the patient showed highly dilated glomerular capillaries filled with vacuolar lipids, segmentally fused podocyte foot processes, vacuolar degeneration of renal tubular epithelial cells and absence of electron-dense material, which indicates the diagnosis of LPG. Whole-exome gene sequencing identified the heterozygous mutation of NM_000041.4:c.494G > C (p.Arg165Pro), which is in the exon 4 of the APOE gene and also known as APOE Chicago mutation, a rare mutation of LPG. Further family pedigree gene analysis clarified that the mutation was inherited from the patient's mother, who does not have high ApoE levels or renal manifestations. This is also consistent with the incomplete penetrance of APOE gene mutations in LPG. Under lipid-lowering treatments, including a low-fat diet and fenofibrate, the patient's urinary protein was partially controlled, and the albumin level was recovered. CONCLUSION: Patients with nephrotic syndrome and elevated ApoE levels should be prompted into renal biopsy to avoid delay of appropriate treatment and unnecessary use of glucocorticoids. This case of LPG was diagnosed by renal biopsy and further verified with genetic sequencing. The timely diagnosis and treatment improved the patient's symptoms. This case is one of only six reported LPG cases or families with APOE Chicago mutation in the world.

Lipoprotein Glomerulopathy With Complete Resolution With Fenofibrate: Report of First Case From Pakistan.

Background: Lipoprotein glomerulopathy is an infrequent glomerular disorder that culminates in nephrotic syndrome and often progresses to kidney failure. Whereas most patients have been reported in Japan and China, limited reports have been documented outside these regions. This patient represents the first report of lipoprotein glomerulopathy in Pakistan. Case Presentation: A 25-year-old male patient, hypertensive for 2 years, presented with progressive body edema, frothy urine, and fatigue. Examination revealed elevated blood pressure, bilateral pedal edema, and positive shifting dullness. Laboratory results showed significant proteinuria and elevated cholesterol and triglyceride levels. Renal biopsy revealed enlarged glomeruli with a dilated capillary lumen filled with pale-staining mesh-like material "lipoprotein thrombi." Mild tubular atrophy and interstitial inflammation were observed. No interstitial fibrosis was evident. Electron microscopy detailed the lipoprotein thrombi with lipid granules and vacuoles of various sizes. A diagnosis of lipoprotein glomerulopathy was rendered. Treatment with fenofibrate, rosuvastatin, and captopril led to notable improvements in symptoms, blood pressure, and lipid levels during a 6-month follow-up. Subsequent biopsy showed complete resolution of the lipoprotein thrombi and a significant reduction in subendothelial granular densities. However, the flocculent subendothelial material persisted to some extent despite the complete resolution of lipoprotein thrombi. Conclusion: This report underscores the rarity of lipoprotein glomerulopathy in Pakistan and contributes valuable insights into its histopathologic features and global epidemiology. This unique instance aims to raise awareness among healthcare professionals, aiding in improved recognition of this rare entity. The favorable response to fenofibrate treatment underscores its effectiveness in managing lipoprotein glomerulopathy.

Apolipoprotein E-associated Lipoprotein Glomerulo-tubulopathy.

A 32-year-old man was admitted for the evaluation of proteinuria (5.69 g/day). A light microscopic examination showed markedly dilated glomerular capillary loops with vacuolated areas in many glomeruli, and vacuolated areas were seen on peritubular capillaries in the tubulointerstitium. When electron microscopy specimens prepared by pre-fixation with glutaraldehyde and post-fixation with osmium tetroxide were used for oil red staining, the deposition was confirmed on the affected areas. A genetic analysis of apoE showed that the lipoprotein glomerulopathy was due to apoE-Sendai (Arg145Pro, p.R163P) heterozygosity, which was found in not only the patient but also his mother and twin brother.

The first case of lipoprotein glomerulopathy complicated with collagen type III glomerulopathy and literature review.

Lipoprotein glomerulopathy (LPG) is a rare autosomal dominant kidney disease caused by pathogenic mutations in the APOE gene. Collagen type III glomerulopathy (CG) is a sporadic condition in adults characterized by abnormal accumulation of type III collagen in the subendothelial space and mesangium of the glomerulus. We report the first case of both LPG and CG in a 21-year-old male. A search of the literature found no confirmed reports of these two concomitant nephropathies. The patient presented with hypertension, proteinuria, hematuria and hyperlipidemia. Renal pathology showed lipid vacuoles in the enlarged glomerular capillary loops and type III collagen in the segmental mesangial area and on the inner side of the glomerular basement membrane by electron microscopy. Whole-exome sequencing revealed a heterozygous mutation (c.127C>T; p. Arg43Cys) in exon 3 of the APOE gene, known as the APOE-Kyoto of LPG. In addition, two heterozygous COL4A4 mutations (c.4715C>T in exon 47 and c.5065 T>C in exon 48) were observed, the first one was suspected pathogenic and the other one was uncertain significant. There is no special treatment for these diseases. The patient was treated with lipid-lowering agents, renin-angiotensin-aldosterone system inhibition and tripterygium glycosides. The patient received double-filtration plasmapheresis and immunoadsorption therapy when renal function deteriorated dramatically. Immunoadsorption was beneficial for this patient.

Lipoprotein glomerulopathy caused by mutation of apolipoprotein E gene in children: a report of two cases / 中华肾脏病杂志

The paper reports two cases of lipoprotein glomerulopathy (LPG) in children. The Sanger sequencing results in 2 cases indicated apolipoprotein E gene mutation[c.127 (exon3) C>T, p.R43C (p.Arg43Cys); c.494 (exon4) G>C, p.R165P (p.Arg165Pro),respectively]. Renal pathological presentation of two children showed that a large number of lipoprotein emboli were formed in the glomerular capillary loop, and the diagnosis of LPG was confirmed. The onset of LPG has no specific clinical manifestation, which is easy to be undiagnosed or misdiagnosed. Renal biopsy is a diagnostic means, glucocorticoid treatment is ineffective, and long-term lipid-lowering treatment may be required for LPG.

Lipoprotein Glomerulopathy, First Case Report from Canada.

Lipoprotein glomerulopathy (LPG) is caused by a mutation in the apolipoprotein E gene (APOE) gene and is characterized by lipoprotein thrombi in glomerular capillaries. Here, we describe a case of LPG, the first to be reported from Canada and the first case of LPG in North America to be associated with the APOE Tokyo/Maebashi mutation (p.Leu162_Lys164del, traditional nomenclature 142_144del). A 49-year-old man of Chinese descent with a previous diagnosis of dyslipidemia and a new diagnosis of hypertension was found to have proteinuria on routine urinalysis. Renal biopsy showed markedly dilated glomerular capillaries filled with pale staining mesh-like material that stained positive for Oil-Red-O, consistent with lipoprotein thrombi. APOE gene sequencing confirmed the diagnosis of LPG. The patient was treated with fenofibrate and perindopril. His lipid profile normalized and proteinuria dropped to minimal levels. Repeat renal biopsy 2 years after the first showed resolution of lipoprotein thrombi but with rare residual granular densities by electron microscopy consistent with lipoprotein in the subendothelial space, supporting the hypothesis that this subendothelial material contains precursors to lipoprotein thrombi.

An Updated Review and Meta Analysis of Lipoprotein Glomerulopathy.

More than 200 cases of lipoprotein glomerulopathy (LPG) have been reported since it was first discovered 30 years ago. Although relatively rare, LPG is clinically an important cause of nephrotic syndrome and end-stage renal disease. Mutations in the APOE gene are the leading cause of LPG. APOE mutations are an important determinant of lipid profiles and cardiovascular health in the population and can precipitate dysbetalipoproteinemia and glomerulopathy. Apolipoprotein E-related glomerular disorders include APOE2 homozygote glomerulopathy and LPG with heterozygous APOE mutations. In recent years, there has been a rapid increase in the number of LPG case reports and some progress in research into the mechanism and animal models of LPG. We consequently need to update recent epidemiological studies and the molecular mechanisms of LPG. This endeavor may help us not only to diagnose and treat LPG in a more personized manner but also to better understand the potential relationship between lipids and the kidney.

A novel apolipoprotein E mutation, ApoE Ganzhou (Arg43Cys), in a Chinese son and his father with lipoprotein glomerulopathy: two case reports.

BACKGROUND: Lipoprotein glomerulopathy is a rare and newly recognized glomerular disease that can lead to kidney failure. Its pathological features include the presence of lipoprotein embolus in the loop cavity of glomerular capillaries. It is believed that apolipoprotein E gene mutation is the initiator of the disease. Since the discovery of lipoprotein glomerulopathy, 16 different apolipoprotein E mutations have been reported worldwide, but most of these cases are sporadic. Here we report two cases of lipoprotein glomerulopathy, a Chinese son and his father, with a novel apolipoprotein E mutation, ApoE Ganzhou (Arg43Cys). CASE PRESENTATION: Case 1, a 33-year-old Chinese man, was hospitalized on 3 March 2014 owing to edema and weakness of facial and lower limbs for 1 month. Laboratory data showed urine protein 3+, hematuria 2+, serum creatinine 203 µmol/L, uric acid 670 µmol/L, total cholesterol 12.91 mmol/L, triglyceride 5.61 mmol/L, high-density lipoprotein 1.3 mmol/L, low-density lipoprotein 7.24 mmol/L, apolipoprotein B 2.48 g/L, and lipid protein (a) 571 mg/L. Renal tissue examined by immunofluorescence and electron microscopy indicated lipoprotein glomerulopathy. Case 2, 55-year-old father of case 1, was hospitalized on 12 January 2016 owing to edema of his lower extremities for 6 months. Laboratory data showed urine protein 2+, hematuria 2+, serum creatinine 95 µmol/L, uric acid 440 µmol/L, total cholesterol 4.97 mmol/L, triglyceride 1.91 mmol/L, high-density lipoprotein 1.18 mmol/L, low-density lipoprotein 3.12 mmol/L, apolipoprotein B 2.48 g/L, and lipid protein (a) 196 mg/L. Renal tissue examined by immunofluorescence and electron microscopy indicated lipoprotein glomerulopathy. Apolipoprotein E mutation test showed that they had the same gene mutation, a novel type of apolipoprotein E mutation. Based on their clinical presentation and examination findings, they were diagnosed with lipoprotein glomerulopathy. Case 1 was treated with prednisone and dual plasma replacement, followed by simvastatin, nifedipine, triptolide, and angiotensin II receptor blocker drug therapy. After 1 month, the edema symptoms of the patient were alleviated, and urinary protein, serum creatinine, and uric acid were quantitatively reduced. Case 2 was treated with Tripterygium wilfordii and angiotensin II receptor blocker drugs for 3 weeks, and his edema symptoms were alleviated, and urinary protein, serum creatinine, and uric acid were quantitatively reduced. CONCLUSIONS: The apolipoprotein E mutation in the two cases we reported was a familial aggregation phenomenon, and the mutation is a novel type, which we named ApoE Ganzhou (Arg43Cys). The location of the gene mutation is close to the most common mutation type of lipoprotein glomerulopathy, ApoE Kyoto (Arg25Cys), so we speculate that its pathogenic role might be the similar to that of ApoE Kyoto (Arg25Cys).

Unusual late presentation of lipoprotein glomerulopathy recurrence in a Chinese kidney transplant recipient.

Lipoprotein glomeurulopathy (LPG) is an uncommon cause of end stage kidney disease (ESKD). The long-term outcome of kidney transplantation in patients with LPG remains largely unknown and early recurrence of LPG in the allograft kidney appears to be the rule. Here we report a young Chinese patient with ESKD due to rare coexisting LPG and fibrillary glomerulonephritis, who received deceased kidney transplantation, was diagnosed to have LPG recurrence after 20 years of post-transplant follow-up. With the longest follow-up duration after kidney transplantation in literature, our case shows that the prognosis of kidney transplantation in patients with LPG can still be good. Kidney transplantation should remain a therapeutic option for patients with ESKD due to LPG.

Lipoprotein Glomerulopathy-Like Lesions in Atherosclerotic Mice Defected With HDL Receptor SR-B1.

High-density lipoprotein (HDL) homeostasis is important in maintaining both cardiovascular and renal health. Scavenger receptor class B type 1 (SR-B1), the major HDL receptor in mammals, plays a crucial role in reverse cholesterol transport and HDL metabolism. Evidence from mouse study has well demonstrated that HDL disorders caused by Srb1 inactivation accelerate atherosclerosis and even induce lethal cardiovascular diseases. However, the renal consequences of Srb1 dysfunction are still unknown. Here we explored this issue in both Srb1 knockout (Srb1-/-) mice and atherosclerotic low-density lipoprotein receptor knockout (Ldlr-/-) mice with Srb1 deletion. Our data showed that no apparent renal damage was observed in 5-month-old Srb1-/- mice fed on standard rodent chow diet as well as Srb1-/- mice fed on a high-fat diet (HFD) for 12 weeks. However, 5-month-old Srb1/Ldlr-/- mice fed on rodent chow had increased urinary albumin excretion and developed spontaneous intraglomerular Oil-red O (ORO)-positive lipoprotein deposition that is similar to lesions observed in human lipoprotein glomerulopathy (LPG). HFD feeding accelerated LPG-like lesions in Srb1/Ldlr-/- mice, inducing severe proteinuria and significantly promoting intraglomerular ORO-positive lipoprotein deposition. Interestingly, probucol reversed HFD-induced HDL disorders and almost fully abrogated LPG-like lesions in Srb1/Ldlr-/- mice. In conclusion, the present study demonstrates that SR-B1 dysfunction leads to LPG-like lesions in atherosclerotic mice, which could be rescued by probucol. SR-B1 loss-of-function mutant carriers therefore might be susceptible to developing metabolic nephropathy in addition to cardiovascular diseases, and probucol might be a potential therapeutics.

Case Report: A Pediatric Case of Lipoprotein Glomerulopathy in China and Literature Review.

Background: Lipoprotein glomerulopathy is a rare kidney disease characterized by lipoprotein thrombi in the glomerulus. Here, we report a case of lipoprotein glomerulopathy in a Chinese pediatric patient. Furthermore, we summarized the clinical features and genetic characteristics of lipoprotein glomerulopathy in China. Case Presentation: An 11-year-old Chinese girl presented with nephrotic syndrome with anemia (98 g/L). After excluding secondary causes, primary nephrotic syndrome was considered. Treatment with prednisone (60 mg/day) did not improve her condition. Renal biopsy showed marked dilation of the capillary lumen with lipoprotein thrombi and positive oil red O staining. Genetic testing revealed the genetic variant c.127C > T (p.R43C), known as the Kyoto mutation of the APOE gene. These findings are consistent with the diagnosis of lipoprotein glomerulopathy. Prednisone was gradually tapered and captopril was initiated. A 2-year follow-up revealed elevated urine protein and serum creatinine levels. We also reviewed 17 pediatric and 156 adult cases of lipoprotein glomerulopathy reported in China from the year of creation to 2021. The most common clinical features were edema, hematuria, hypertriglyceridemia, and increased serum apoE levels. Extra-renal manifestations included anemia, splenomegaly, and cardiac lipoprotein deposition. Conclusion: APOE Kyoto is the most common mutation in patients with lipoprotein glomerulopathy. In China, homozygosity for E3 (E3/3) is the most common isoform.

Case Report: Lipoprotein Glomerulopathy Complicated by Atypical Hemolytic Uremic Syndrome.

Lipoprotein glomerulopathy (LPG) is a rare inherited disease caused by mutations in the APOE gene, encoding apolipoprotein E (apoE). Atypical hemolytic uremic syndrome (aHUS) is a thrombotic microangiopathy (TMA) characterized by overactivation of the alternative complement pathway. Here we report the case of a 21-year-old man with LPG who developed aHUS. A functional complement assay demonstrated an overactivation of the complement system. Complementary genetic analysis revealed a homozygous aHUS risk allele for complement factor-H related 1 (CFHR1), CFHR1*B. To the best of our knowledge, this is the first report of an aHUS in a patient with LPG.

APOE gene variants in primary dyslipidemia.

Apolipoprotein E (apoE) is a major apolipoprotein involved in lipoprotein metabolism. It is a polymorphic protein and different isoforms are associated with variations in lipid and lipoprotein levels and thus cardiovascular risk. The isoform apoE4 is associated with an increase in LDL-cholesterol levels and thus a higher cardiovascular risk compared to apoE3. Whereas, apoE2 is associated with a mild decrease in LDL-cholesterol levels. In the presence of other risk factors, apoE2 homozygotes could develop type III hyperlipoproteinemia (familial dysbetalipoproteinemia or FD), an atherogenic disorder characterized by an accumulation of remnants of triglyceride-rich lipoproteins. Several rare APOE gene variants were reported in different types of dyslipidemias including FD, familial combined hyperlipidemia (FCH), lipoprotein glomerulopathy and bona fide autosomal dominant hypercholesterolemia (ADH). ADH is characterized by elevated LDL-cholesterol levels leading to coronary heart disease, and due to molecular alterations in three main genes: LDLR, APOB and PCSK9. The identification of the APOE-p.Leu167del variant as the causative molecular element in two different ADH families, paved the way to considering APOE as a candidate gene for ADH. Due to non mendelian interacting factors, common genetic and environmental factors and perhaps epigenetics, clinical presentation of lipid disorders associated with APOE variants often strongly overlap. More studies are needed to determine the spectrum of APOE implication in each of the diseases, notably ADH, in order to improve clinical and genetic diagnosis, prognosis and patient management. The purpose of this review is to comment on these APOE variants and on the molecular and clinical overlaps between dyslipidemias.

Lipoprotein glomerulopathy induced by ApoE Kyoto mutation in ApoE-deficient mice.

BACKGROUND: Lipoprotein glomerulopathy (LPG) is a rare autosomal dominant kidney disease that is most commonly caused by mutations in ApoE Kyoto (p.R43C) and ApoE Sendai (p.R163P). Differences in phenotype among the various ApoE mutations have been suggested, but the pathogenic role of ApoE Kyoto has not been validated in an animal model. This study intended to establish an ApoE Kyoto murine model and to further compare the pathologic differences between ApoE Kyoto and ApoE Sendai. METHOD: Male ApoE-deficient mice, 3 months of age, were divided into five groups, including the AD-ApoE Sendai, AD-ApoE Kyoto, AD-ApoE3, AD-eGFP, and ApoE (-/-) groups. The first four groups received recombinant adenovirus that contained the entire coding regions of the human ApoE Sendai and ApoE Kyoto, apoE3, and eGFP genes, respectively. Fasting blood and urine samples were collected at multiple time points. Lipid profiles and urine albumin-creatinine ratio were measured. Renal and aortic histopathologic alterations were analyzed. RESULTS: After virus injection, plasma human ApoE was detected and rapidly reached the maximum level at 4-6 days in the AD-ApoE Kyoto and AD-ApoE Sendai groups (17.4 ± 3.1 µg/mL vs.: 22.2 ± 4.5 µg/mL, respectively) and at 2 days in the AD-ApoE3 group (38.4 µg/mL). The serum total cholesterol decreased by 63%, 65%, and 73% in the AD-ApoE Kyoto, AD-ApoE Sendai and AD-ApoE3 groups, respectively. There were no significant changes in serum triglyceride and urinary albumin-creatinine ratio among the five groups. Typical lipoprotein thrombi with positive ApoE staining were detected in the AD-ApoE Kyoto and AD-ApoE Sendai groups. The Oil-red O-positive glomerular area tended to be higher in the AD-ApoE Kyoto group (9.2%) than in the AD-ApoE Sendai (3.9%), AD-ApoE3 (4.8%), AD-eGFP (2.9%), and ApoE (-/-) (3.6%) groups. The atherosclerotic plaque area in the aorta was lower in the group injected with various ApoE mutations than in the group without injection of ApoE mutation. CONCLUSIONS: In this animal study, we first established an ApoE Kyoto mutation murine model and confirmed its pathogenic role in LPG. Our results suggested that LPG may be more severe with the ApoE Kyoto than with the ApoE Sendai.

Clinical and genetic analysis of lipoprotein glomerulopathy patients caused by APOE mutations.

BACKGROUND: Lipoprotein glomerulopathy (LPG) is a rare kidney disease caused by APOE mutations. The aim of this study was to correlate the genetic and clinical features of LPG. METHODS: Totally eight LPG patients were recruited in this study and Sanger sequencing of APOE was performed for all available family members. Clinical and histological features were analyzed. A literature review of LPG was also conducted. RESULTS: Genetic analysis revealed five patients with APOE-Kyoto, two with APOE-Osaka/Kurashiki, and one with APOE-Chicago mutations. LPG patients with urine protein reduced more than 50% had a slower decrease in renal function than those with less urine protein reduction (estimated glomerular filtration rate reduction rate -5.0 ± 0.8 vs. 1.5 ± 0.7 ml/min per 1.73 m2 ⋅month-1 , p = .03). We then enrolled 95 LPG patients from previous studies and this study. LPG patients had higher blood pressure (mean arterial pressure: 109.4 ± 19.4 vs. 94.4 ± 11.1 mmHg, p < .001) than the control group. Interestingly, patients with APOE mutations in the LDL receptor binding region had higher serum apolipoprotein E (apoE) levels [ln(apoE): 2.7 ± 0.4 vs. 2.0 ± 0.5 mg/dl, p < .001] in comparison to other domains. CONCLUSION: Here, we report for the first time APOE-Osaka/Kurashiki and APOE-Chicago mutations in the Chinese population. LPG was associated with higher blood pressure and serum apoE levels were higher in patients with mutations in LDL receptor binding region. In addition, the findings further indicated that treatment of proteinuria might slow down renal function progression in these patients.

Apolipoprotein E-related glomerular disorders.

Of the glomerular disorders that occur due to apolipoprotein E (apoE) mutations, apoE2 homozygote glomerulopathy and lipoprotein glomerulopathy (LPG) have been characterized. ApoE2 homozygote glomerulopathy has been found in individuals expressing homozygous apoE2/2. This was characterized histologically by glomerulosclerosis with marked infiltration of foam cells derived from macrophages, and occasionally with non-lamellated lipoprotein thrombi. Recently, several cases of apoE Toyonaka (Ser197Cys) combined with homozygous apoE2/2 have been reported, in which non-immune membranous nephropathy-like features were observed in glomeruli. Interestingly, in these cases, apoE accumulation was identified by tandem mass spectrometry. Therefore, it is speculated that these findings may arise from apoE molecules without lipids, which result from hinge damage by apoE Toyonaka and may cross the glomerular basement membrane as small molecules. LPG is primarily associated with heterozygous apoE mutations surrounding the low-density lipoprotein-receptor binding site, and it is histologically characterized by lamellated lipoprotein thrombi that lack foam cells. Recent studies have suggested that LPG can be induced by thermodynamic destabilization, hydrophobic surface exposure, and the aggregation of apoE resulting from the incompatibility of apoE mutated residues within helical regions. Additionally, apoE5 may play a supporting role in the development of LPG and in lipid-induced kidney diseases via hyperlipoproteinemia. Thus, it is interesting that many apoE mutations contribute to characteristic glomerular disorders through various mechanisms. In particular, macrophages may uptake lipoproteins into the cytoplasm and contribute to the development of apoE2 homozygote glomerulopathy as foam cells, and their dysfunction may contribute to the accumulation of lipoproteins in the glomerulus, causing lipoprotein thrombi in LPG.

Lipoprotein Glomerulopathy in a Hispanic Female: A Case Report and Literature Review.

RATIONALE: Lipoprotein glomerulopathy (LPG) is a rare renal disorder that features glomerular capillary lipoprotein thrombi, proteinuria, and progressive renal failure. Although most reported cases describe involvement in Asian patients, occurrence in Caucasian and other ethnicities has also been reported. PRESENTING CONCERN: A 28-year-old Hispanic female with a past medical history of hypertension, high cholesterol, gastritis, and a strong family history of renal disease presented with abdominal pain. On admission, her blood pressure was elevated. A computed tomography scan was unremarkable. Her laboratory studies showed proteinuria, high creatinine level, and an abnormal lipid profile. DIAGNOSIS: The kidney biopsy showed glomerular capillary lipoprotein thrombi that stained positively for Oil-Red-O, confirming the lipid nature of the material consistent with LPG. INTERVENTION: After stabilizing her blood pressure, the patient was started on fenofibrate to treat her high cholesterol and improve her renal function. OUTCOME: Her lipid profile and renal function were initially improved. However, after one year of treatment, her renal function started to decline and the patient was referred to a transplant center for further management. NOVEL FINDING: To the best of our knowledge, this the first reported incidence of LPG in a Hispanic female.

JUSTIFICATION: La glomérulopathie lipoprotéique (GLP) est une pathologie rénale rare caractérisée par des thrombus au niveau des capillaires glomérulaires, une protéinurie et une insuffisance rénale progressive. Bien que la plupart des cas rapportés concernent des patients d'origine asiatique, quelques cas ont été observés chez des patients caucasiens ou d'origines ethniques autres. PRÉSENTATION DU CAS: Une patiente de 28 ans d'origine hispanique a consulté à l'urgence pour un tableau de douleurs abdominales. Elle présentait des antécédents d'hypertension, d'hypercholestérolémie et de gastrite, en plus d'importants antécédents familiaux de néphropathies. À son admission, sa pression artérielle était élevée. La tomodensitométrie était normale. Les résultats de laboratoire indiquaient une protéinurie, un taux élevé de créatinine et un profil lipidique anormal. DIAGNOSTIC: La biopsie rénale a montré des thrombus lipoprotéiniques au niveau des capillaires glomérulaires. Leur nature lipidique, cohérente avec une GLP, a été confirmée par la coloration Oil-Red-O. INTERVENTION: Après stabilisation de la pression artérielle, un traitement au fénofibrate a été initié pour abaisser le taux de cholestérol et améliorer la fonction rénale. RÉSULTATS: Le profil lipidique et la fonction rénale de la patiente se sont améliorés initialement. Cependant, après un an de traitement, la fonction rénale a commencé à décliner et la patiente a été aiguillée vers un centre de transplantation pour prise en charge. CONCLUSION: À notre connaissance, ce cas constitue la première incidence d'une GLP chez une femme d'origine hispanique.

A novel apolipoprotein E mutation caused by a five amino acid deletion in a Chinese family with lipoprotein glomerulopathy: a case report.

BACKGROUND: Lipoprotein glomerulopathy (LPG) is a rare kidney disease with a poor prognosis that is related to mutation of the apoE gene. More than 10 variants of apoE associated with LPG have currently been identified. CASE PRESENTATION: A male and his mother presented with proteinuria during a health examination. They went to hospital for further examination. Renal biopsy was performed, and the diagnosis was lipoprotein glomerulopathy (LPG), which is a rare, inherited renal disease. Medical histories were collected from the 2 LPG patients and their family members. The patients and family members underwent a routine urine test, and their renal function, blood lipids, and lipoprotein levels were examined. Genomic DNA was extracted from the peripheral blood of 7 family members, and exon 2, exon 3 and exon 4 of apoE were amplified by polymerase chain reaction (PCR). The purified PCR products were sequenced. Sequence analysis identified a 15 bp deletion (GCGCAAGCTGCGTAA) in exon 4 of the apoE gene that results in a novel 5 amino acid deletion in apoE (143 K-147R → 0). No mutations were found in exon 2 and exon 3 of the apoE gene. CONCLUSIONS: This family study suggests that a novel ApoE mutation (143 K-147R → 0) may be etiologically related to LPG, and other genetic or environmental factors may be associated with the occurrence of LPG.