PMC3859823_01
Pedigree of the family; the proband described in this case report is indicated by the arrow. A mutation in the ApoE gene was found (ApoEMODENA) in this subject.  This subject underwent dialytic treatment: however, clinical, pathological, or molecular data concerning the cause of renal failure are not available; *this subject developed a nephrotic syndrome; the kidney biopsy showed a minimal change glomerulonephritis, and no endoluminal thrombi were found. This subject was not a carrier of ApoEMODENA (see Table 1).
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A deceased first grade cousin (subject III 7 in Fig. 1) had been under dialysis treatment of nephropathy of unknown etiology. With the exception of the proband (subject III1 in Fig. 1 and Table 3), no carrier of the mutation was found.
(A) capillaries in the glomerulus are distended by lipoprotein thrombi (periodic acid Schiff staining x400); (B) the enlarged capillary lumina contain lipid material stained in black (Sudan Black staining x400); (C) lipid thrombus in a capillary lumen (Red Oil staining x1000); (D) electron micrograph showing finely vacuolated intraluminal electrondense material (x2500).
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Glomerular intraluminal thrombi appeared as weakly periodic acid-Schiff (PAS)-positive deposits or pale blue deposits with Masson-trichrome; the lipid nature of the intraluminal deposits was demonstrated using Black Sudan and oil Red-O staining (Fig. 2 panel A-C; Fig. 4:shown in panels A-D). Ultrastructure analysis confirmed the presence of thrombi in the lumina of the glomerular tufts showing finely vacuolated thrombi (Fig. 2 panel D).
The figure shows the frequency of LDL aphaeresis, the creatinine value, and the urine protein to creatinine ratio during treatment. The shadowed region of the panel indicates the period during which the patient switched from HELP aphaeresis to plasma filtration.
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In early 2005, the patient showed a rapid deterioration of the arterial pressure control, a worsening of proteinuria and peripheral oedema associated with a deterioration of renal function (Fig. 3). Subsequently, as this treatment was not well-tolerated by the patient, so the frequency of LDL aphaeresis sessions was reduced as depicted in Figure 3. TEC, Bad Homburg, Germany) until December 2008 (shadowed area in Fig. 3). After this, proteinuria and hypertension worsened, despite medical and aphaeretic treatment. The patient suddenly died of intracranial hemorrhage during an acute episode of malignant hypertension. With the exception of the proband (subject III1 in Fig. 1 and Table 3), no carrier of the mutation was found.
Panels A-D, were obtained from the first biopsy; panels E-H were obtained from the second biopsy; panels I, L, M and N, were obtained from the post-mortem biopsy. Panels A, E, I, D, H and N: (Masson's trichrome x400. Panels B, F and L: MPAS staining, x400. Panels C, G and M periodic acid Schiff staining x400.
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The evaluation of the specimen showed nearly complete disappearance of glomerular intraluminal deposits as an absence of the typical capillary ectasia. (Fig. 4:available online: panels I, L, M and N).
Immunoblot of plasma ApoE. Plasma ApoE was separated by SDS-PAGE either in the absence (left panel) or in the presence of beta-mercaptoethanol (reducing conditions) (right panel). ApoE was electroblotted onto a nitrocellulose membrane and detected with an anti-human ApoE polyclonal antibody.. Abbreviations: C, control subject; PL, LPG patient, heterozygous carrier of ApoEMODENA.
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Under reducing conditions, only the 34 kDa band was detected in the proband as in the control (Fig. 5).