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Contains fulltext : 71431.pdf (Publisher’s version ) (Closed access) Podocyte foot process effacement is characteristic of proteinuric renal diseases. In minimal change nephrotic syndrome (MCNS) foot processes are diffusely effaced whereas the extent of effacement varies in focal segmental glomerulosclerosis (FSGS). Here we measured foot process effacement in FSGS and compared it to that in MCNS and in normal kidneys. A clinical diagnosis was used to differentiate idiopathic FSGS from secondary FSGS. Median foot process width, determined morphometrically by electron microscopy, was 3236 nm in 17 patients with idiopathic FSGS, 1098 nm in 7 patients with secondary FSGS, and 1725 nm in 15 patients with MCNS, as compared to 562 nm in 12 control patients. Multivariate analysis showed that foot process width did not correlate with proteinuria or serum albumin levels but was significantly associated as an independent factor with the type of disease. Foot process width over 1500 nm differentiated idiopathic from secondary FSGS with high sensitivity and specificity. Our results show that quantitative analysis of foot processes may offer a potential tool to distinguish idiopathic from secondary FSGS.

Contains fulltext : 49831.pdf (Publisher’s version ) (Closed access) Collapsing focal segmental glomerulosclerosis (cFSGS) is characterized by hyperplasia of glomerular epithelial cells. In a mouse model of FSGS and in a patient with recurrent idiopathic FSGS, we identified the proliferating cells as parietal epithelial cells (PECs). In the present study, we have evaluated the origin of the proliferating cells in cFSGS associated with human immunodeficiency virus (HIV) and pamidronate. We performed a detailed study of glomerular lesions in biopsies of two patients with HIV-associated cFSGS and a nephrectomy specimen of a patient with pamidronate-associated cFSGS. Glomeruli were studied by serial sectioning using light and electron microscopy and immunohistochemistry to determine the epithelial cell phenotype. We used Synaptopodin, vascular endothelial growth factor, and CD10 as podocyte markers, CK8 and PAX2 as PEC markers and Ki-67 as marker of cell proliferation. The newly deposited extracellular matrix was characterized using antiheparan sulfate single-chain antibodies. The proliferating cells were negative for the podocyte markers, but stained positive for the PEC markers and the cell proliferation marker Ki-67. The proliferating PAX-2 and CK8 positive cells that covered the capillary tuft were always in continuity with PAX-2/CK8 positive cells lining Bowman's capsule. The matrix deposited by these proliferating cells stained identically to Bowman's capsule. Our study demonstrates that PECs proliferate in HIV and pamidronate-associated cFSGS. Our data do not support the concept of the proliferating, dedifferentiated podocyte.

Distribution of GBM heparan sulfate proteoglycan core protein and side chains in human glomerular diseases. Using monoclonal antibodies (mAbs) recognizing either the core protein or the heparan sulfate (HS) side chain of human GBM heparan sulfate proteoglycan (HSPG), we investigated their glomerular distribution on cryostat sections of human kidney tissues. The study involved 95 biopsies comprising twelve different glomerulopathies. Four normal kidney specimens served as controls. A homogenous to linear staining of the GBM was observed in the normal kidney with anti-HSPG-core mAb (JM-72) and anti-HS mAb (JM-403). In human glomerulopathies the major alteration was a segmental or total absence of GBM staining with anti-HS mAb JM-403, which is most pronounced in lupus nephritis, membranous glomerulonephritis (GN), minimal change disease and diabetic nephropathy, whereas the HSPG-core staining by mAb JM-72 was unaltered. In addition we found HSPG-core protein in the mesangial matrix when this was increased in membranoproliferative GN Type I, Schonlein-Henoch GN, IgA nephropathy, lupus nephritis, diabetic nephropathy and in focal glomerulosclerosis. Also staining with the anti-HS mAb JM-403 became positive within the mesangium, although to a lesser extent. Furthermore, amyloid deposits in AL and AA amyloidosis clearly stained with anti-HSPG-core mAb JM-72, and to a lesser degree with anti-HS mAb JM-403. Finally, in membranous GN (stage II and III), the GBM staining with anti-HSPG-core mAb JM-72 became irregular or granular, probably related to the formation of spikes. In conclusion, major alterations were observed in the glomerular distribution of HS and HSPG-core in various human glomerulopathies. The mAbs can be useful to further delineate the significance of HSPG and HS for glomerular diseases.

INJECTION of HgCl2 into Brown Norway (BN) rats induces systemic autoimmunity, involving high production of (auto-)antibodies and immunoglobulin E (IgE), multi-organ inflammation, and proteinuria. Induction of disease is dependent on activation of T lymphocytes of the Th2-type, which produce a.o. interleukin 4 (ILA). In contrast, Lewis rats develop generalized immunosuppression on exposure to HgCl2, which is probably dependent on activation of Thl cells. In both rat strains, HgCl2 induces an early and transient increase in expression of the major histocompatibility complex class II (MHCII) molecule RT1.B on B lymphocytes.' This increase is possibly mediated by cytokines such as IL4, which is a potent inducer of MHCII expression on B lymphocytes. In vitro, HgCl2 was shown to induce enhanced expression of RT1.B but not of RT1.D on splenic B lymphocytes from BN and Lewis rats, which was partially inhibited by anti-IL4 only in cell cultures from BN rats.2 To get more insight into the relationship between HgCl2-induced enhancement of MHCII expression and IL4 production, we compared the effects of HgCl2 and IL4 on expression of the rat MHCII molecules RT1.B and RT1.D.

Environmental, occupational and therapeutic exposure to nephrotoxic compounds may cause different forms of renal disease and constitutes a major health problem. This paper discusses pathogenetic mechanisms leading to impairment of renal function and early detection of its symptoms, with special emphasis on immunopathology. Finally, it focuses on ways of identifying potentially nephrotoxic compounds.

Eighteen patients with melanoma of the vulva are reported, 16 with a primary tumor and 2 with a recurrent tumor. Radical vulvectomy with en bloc inguinal and femoral lymph node dissection seems to be the best treatment, though prognosis for patients with positive nodes is poor. Nine of 16 patients with primary tumor were eligible for 5-yr survival. Five of them had no evidence of disease, but a 5-yr survival does not mean a cure.

The immunogenicity of the minor histocompatibility antigen Eag-1 of the rat kidney endothelium was studied in renal allografts mismatched for antigens of the major histocompatibility complex (MHC). The rejection rates of BN.1L (RT1(1), Eag-1+), (BN.1LXMAXX)F1 (RT1l/n, Eag-1+), and LEW (RT1l, Eag-1-) kidneys transplanted into unsensitized, bilaterally nephrectomized MAXX (RT1n, Eag-1-) recipients were comparable, indicating that incompatibility for Eag-1 has no effect on the survival of MHC-incompatible kidney grafts. Transplantation of BN (RT1n, Eag-1+) and WKY (RT1k, Eag-1+) kidneys into unilaterally nephrectomized MAXX recipients led to a weak and inconsistent antibody response against Eag-1, indicating that MHC incompatibility does not influence the formation of antibodies against Eag-1.

A patient is described who developed cavitary Legionella pneumonia 2 weeks after kidney transplantation. The initial pulmonary symptoms were followed by severe thrombocytopenia and acute renal failure. Although acute irreversible graft rejection was suspected, this was not supported by the pathology findings in the resected kidney, which were compatible with tubular damage. We presume that the extrapulmonary symptoms were caused by Legionellosis.