nephrin and Glomerulonephritis--IGA

Urinary podocalyxin and nephrin are urine markers of podocyte dysfunction that may reflect the integrity of kidney's filtration barrier. Studies on their respective roles in glomerular diseases are still underway. However, the isolated and unsystematic manner in which they are being studied does not permit proper identification of their roles in each glomerular disease. As such, there is little or no appreciation of what research has already achieved and what remains to be achieved as the research direction is not clearly defined. We explored the recent studies and outlined the major findings regarding the value of both biomarkers in each of the three glomerular disease entities. Our review covered diabetic nephropathy, membranous nephropathy and IgA nephropathy.

Topics: Biomarkers; Diabetic Nephropathies; Glomerulonephritis, IGA; Humans; Membrane Proteins; Podocytes; Proteinuria; Sialoglycoproteins

Topics: Animals; Bone Morphogenetic Protein 2; Claudins; Diabetic Nephropathies; Diagnosis, Differential; Glomerulonephritis, IGA; Glomerulosclerosis, Focal Segmental; GTP-Binding Proteins; Humans; Kidney Diseases; Membrane Proteins; Nephrosis, Lipoid; Podocytes; Protein Glutamine gamma Glutamyltransferase 2; Transglutaminases

Extra-capillary hypercellularity is a common finding in crescentic glomerulonephritis (GN) and focal segmental glomerulosclerosis (FSGS). In diabetic nephropathy (DN), extra-capillary hypercellularity is often observed as a finding of complications such as IgA nephropathy or microscopic polyangiitis superimposed on DN. However, in rare cases, epithelial cell proliferation may accompany DN. We experienced a case of nodular diabetic glomerulosclerosis with marked extra-capillary hypercellularity and revealed the origin of this atypical lesion using immunostainings.. A man in his 50 s was admitted to the hospital with nephrotic syndrome, and a renal biopsy was performed. Diffuse nodular lesions and extra-capillary hypercellularity were observed, but the results of serological examination or immunofluorescent assays did not implicate any other crescentic GN. Immunostaining for claudin-1 and nephrin was performed to identify the origin of the extra-capillary lesions. Given the clinical course and pathological findings, a diagnosis of DN-associated extra-capillary cell proliferation was made.. Extra-capillary hypercellularity, which resembles FSGS or crescentic GN, is a rare finding in DN and should therefore be treated with caution. In such cases, co-staining for claudin-1 and nephrin may facilitate the diagnosis of DN.

Topics: Cell Proliferation; Claudin-1; Diabetes Mellitus; Diabetic Nephropathies; Glomerulonephritis, IGA; Glomerulonephritis, Membranoproliferative; Glomerulosclerosis, Focal Segmental; Humans; Male; Membrane Proteins; Microscopic Polyangiitis; Middle Aged

Huangqi Guizhi Wuwu Decoction(HQGZWWD) is a Traditional Chinese Medicine formula from Synopsis of Golden Chamber used to treat blood arthralgia. According to the principle that the same treatment can be used for different diseases, HQGZWWD has proven effective for IgA nephropathy (IgAN) associated with spleen and kidney yang deficiency.. In this study, we investigated the mechanism by which HQGZWWD alleviates proteinuria and protects renal function in rats with IgAN by regulating the AT1R/Nephrin/c-Abl pathway.. Rats were randomly divided into six groups: control, IgAN model, IgAN model treated with low-dose HQGZWWD, IgAN model treated with medium-dose HQGZWWD, IgAN model treated with high-dose HQGZWWD, and IgAN model treated with valsartan. IgAN was induced using bovine γ-globulin. We evaluated the mediating effects of HQGZWWD on podocyte cytoskeletal proteins, the AT1R/Nephrin/c-Abl pathway, upstream tumor necrosis factor-α (TNF-α), and TNF-α receptor-1 (TNFR1).. The IgAN rats displayed proteinuria, IgA deposition in the mesangial region, and podocyte cytoskeletal protein damage. The expression of TNF-α, TNFR1, AT1R, and c-Abl was increased in the IgAN rat kidney, whereas the expression of nephrin, podocin, ACTN4, and phosphorylated nephrin (p-nephrin) was reduced. HQGZWWD treatment significantly alleviated podocyte cytoskeletal protein damage in the IgAN rats, upregulated the expression of nephrin, podocin, and ACTN4, and the colocalized expression of F-actin and nephrin. This study demonstrates that HQGZWWD attenuates podocyte cytoskeletal protein damage by regulating the AT1R-nephrin- c-Abl pathway, upregulating the expression of p-nephrin, and downregulating the expression of AT1R and c-Abl.. These results indicate that HQGZWWD attenuates podocyte cytoskeletal protein damage in IgAN rats by regulating the AT1R/Nephrin/c-Abl pathway, providing a potential therapeutic approach for IgAN.

Topics: Actinin; Actins; Animals; Cytoskeletal Proteins; Disease Models, Animal; Down-Regulation; Drugs, Chinese Herbal; Glomerulonephritis, IGA; Immunoglobulin A; Intracellular Signaling Peptides and Proteins; Male; Membrane Proteins; Podocytes; Protective Agents; Proteinuria; Proto-Oncogene Proteins c-abl; Rats, Sprague-Dawley; Receptor, Angiotensin, Type 1; Receptors, Tumor Necrosis Factor, Type I; Signal Transduction; Tumor Necrosis Factor-alpha

Lupus nephritis (LN) is a common and devastating complication caused by systemic lupus erythematosus. In this study, we evaluated the expression and mechanism of Fos-related antigen 2 (Fra-2) in LN. The results showed that Fra-2 was significantly increased in kidney biopsies of LN patients compared with healthy controls and other kidney disease in glomerular podocytes. The MRL/lpr mouse strain is a murine model of lupus, and it was used to study the mechanisms of Fra-2 in LN. The results showed that Fra-2 was expressed in the glomerular podocytes. We investigated the effects of inflammatory stimuli on Fra-2 protein expression in the glomerular podocytes, and found that interferon gamma was most effective at increasing Fra-2 protein expression. Knockdown of Fra-2 using siRNA enhanced the protein expression of nephrin. Therefore, Fra-2 may be a specific drug target for podocyte injury in LN.

Topics: Animals; Antiviral Agents; Fos-Related Antigen-2; Gene Knockdown Techniques; Glomerulonephritis, IGA; Glomerulonephritis, Membranous; Glomerulosclerosis, Focal Segmental; Humans; IgA Vasculitis; Interferon-gamma; Lupus Nephritis; Membrane Proteins; Mice; Mice, Inbred MRL lpr; Nephrosis, Lipoid; Podocytes

We used a rat model to assess the role of nephrin, podocin, and desmin in the pathogenesis of IgA nephropathy (IgAN). A rat IgAN model was established by administration of BSA, CCl(4), and lipopolysaccharide (LPS) and compared with healthy control rats. Urinary protein, urine red blood cells, and biochemical parameters were measured for 12 weeks. Renal morphology and ultrastructure were examined by light and electron microscopy. Immunofluorescence was used to assess IgA deposition in the glomeruli and to measure expression of nephrin, podocin, and desmin. Real-time quantitative PCR was used to measure expression of nephrin, podocin, and desmin mRNAs. IgAN rats developed proteinuria at week-6 and this worsened over time. Pathological changes were evident under light microscopy at week-8 and under electron microscopy at week-4. Immunofluorescence analysis showed deposition of IgA in the kidneys of IgAN rats, but not control rats. IgAN rats had increased expression of glomerular podocin, nephrin, and desmin mRNAs and proteins at week-4. The expression of nephrin, podocin and desmin proteins and the expression of podocin and desmin mRNAs preceded the increase in urinary protein. Taken together, our study of a rat model of IgAN indicates that changes in the expression and distribution of nephrin, podocin, and desmin precede and may cause foot process fusion and proteinuria.

Topics: Animals; Desmin; Disease Models, Animal; Disease Progression; Fluorescent Antibody Technique; Glomerulonephritis, IGA; Hematuria; Intracellular Signaling Peptides and Proteins; Male; Membrane Proteins; Microscopy, Electron, Transmission; Podocytes; Proteinuria; Rats; Rats, Sprague-Dawley; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Time Factors

An early lesion in many kidney diseases is damage to podocytes, which are critical components of the glomerular filtration barrier. A number of proteins are essential for podocyte filtration function, but the signaling events contributing to development of nephrotic syndrome are not well defined. Here we show that class II phosphoinositide 3-kinase C2α (PI3KC2α) is expressed in podocytes and plays a critical role in maintaining normal renal homeostasis. PI3KC2α-deficient mice developed chronic renal failure and exhibited a range of kidney lesions, including glomerular crescent formation and renal tubule defects in early disease, which progressed to diffuse mesangial sclerosis, with reduced podocytes, widespread effacement of foot processes, and modest proteinuria. These findings were associated with altered expression of nephrin, synaptopodin, WT-1, and desmin, indicating that PI3KC2α deficiency specifically impacts podocyte morphology and function. Deposition of glomerular IgA was observed in knockout mice; importantly, however, the development of severe glomerulonephropathy preceded IgA production, indicating that nephropathy was not directly IgA mediated. PI3KC2α deficiency did not affect immune responses, and bone marrow transplantation studies also indicated that the glomerulonephropathy was not the direct consequence of an immune-mediated disease. Thus, PI3KC2α is critical for maintenance of normal glomerular structure and function by supporting normal podocyte function.

Topics: Animals; Antigens, Surface; Bone Marrow Transplantation; Glomerulonephritis; Glomerulonephritis, IGA; Humans; Immunoglobulin A; Immunoglobulin G; Kidney Glomerulus; Membrane Proteins; Mice; Mice, Inbred C57BL; Mice, Knockout; Microfilament Proteins; Phosphatidylinositol 3-Kinases; Podocytes; Renal Insufficiency; Transplantation Chimera

We have previously documented that human mesangial cell (HMC)-derived tumour necrosis factor-alpha (TNF-alpha) is an important mediator involved in the glomerulo-tubular communication in the development of interstitial damage in IgA nephropathy (IgAN). With the strategic position of podocytes, we further examined the function of podocytes in IgAN.. Podocyte markers were examined in renal tissues by immunofluorescence. In vitro experiments were conducted with podocytes cultured with polymeric IgA (pIgA) or conditioned medium prepared from HMC incubated with pIgA (IgA-HMC conditioned medium).. Glomerular immunostaining for nephrin or ezrin was significantly weaker in patients with IgAN. The immunostaining of IgA and nephrin was distinctly separate with no co-localization. In vitro experiments revealed no effect of pIgA on the expression of these podocyte proteins as IgA from IgAN patients did not bind to podocytes. In contrast, IgA conditioned medium prepared from IgAN patients down-regulated the expression of these podocyte proteins as well as other podocyte markers (podocin and synaptopodin) in cultured podocytes. The mRNA expression of nephrin, erzin, podocin but not synaptopodin correlated with the degree of proteinuria and creatinine clearance. The down-regulation was reproducible in podocytes cultured with TNF-alpha or transforming growth factor-beta (TGF-beta) at concentration comparable to that in the IgA-HMC conditioned medium. The expression of these podocyte proteins was restored partially with a neutralizing antibody against TNF-alpha or TGF-beta and fully with combination of both antibodies.. Our finding suggests podocyte markers are reduced in IgAN. An in vitro study implicates that humoral factors (predominantly TNF-alpha and TGF-beta) released from mesangial cells are likely to alter the glomerular permeability in the event of proteinuria and tubulointerstitial injury in IgAN.

Topics: Apoptosis; Base Sequence; Biomarkers; Case-Control Studies; Cell Survival; Cells, Cultured; Culture Media, Conditioned; Cytokines; Cytoskeletal Proteins; DNA Primers; Female; Gene Expression; Glomerulonephritis, IGA; Humans; Immunoglobulin A; Lymphotoxin-alpha; Male; Membrane Proteins; Mesangial Cells; Osteonectin; Podocytes; Receptor-Like Protein Tyrosine Phosphatases, Class 3; RNA, Messenger; Tumor Necrosis Factor-alpha

Abnormal immunoglobulin (Ig)A1 is considered to play a pivotal role in IgA nephropathy. We used mouse podocytes as the experimental model to investigate the effect of aggregated IgA1 (aIgA1) isolated from IgA nephropathy (IgAN) patients on nephrin expression in podocytes through direct and indirect pathways.. Jacalin affinity chromatography and Sephacryl S-200 molecular sieve chromatography were used to isolate IgA1 from blood of IgAN patients which was therefore became aIgA1. Podocytes were incubated with aIgA1 or special mesangial medium. Nephrin expression in podocytes was measured by real-time polymerase chain reaction and western blot analysis.. Aggregated IgA1 from IgAN patients and healthy controls reduced nephrin expression in podocytes at mRNA and protein levels when compared with podocytes incubated with control medium (RPMI-1640 with 0.5% foetal bovine serum) (P<0.05). While medium from mesangial cells incubated with aIgA1 from IgAN inhibited nephrin expression in podocytes at mRNA and protein levels when compared with podocytes incubated with medium from mesangial cells with aIgA1 from healthy controls (P<0.05).. Our findings implicate that aIgA1 from IgAN patients could inhibit nephrin expression through direct and indirect pathways, although these mechanisms remain to be clarified.

Topics: Angiotensin II; Animals; Cells, Cultured; Culture Media; Glomerulonephritis, IGA; Humans; Immunoglobulin A; Membrane Proteins; Mice; Podocytes; RNA, Messenger

IgA nephropathy (IgAN) is characterized by mesangial deposition of polymeric IgA1, and podocyte injury plays an important role in glomerulosclerosis of the disease. Our previous study indicated that medium of mesangial cells co-incubated with aggregated IgA1 (aIgA1), isolated from IgAN patients, down-regulated nephrin expression. Yet the mechanism remains unclear.. Podocytes were incubated with a medium of mesangial cells co-incubated with aIgA1, which was isolated from IgAN patients, and enalaprilat (10(-5) M), valsartan (10(-5) M) and anti-mouse tumour necrosis factor-alpha antibody (50 ng mL(-1)) separately. Nephrin expression in podocytes was measured by real-time polymerase chain reaction and Western blot analysis.. The level of angiotensinogen and angiotensin-converting enzyme mRNAs in podocytes, as well as angiotensin, was also increased by a medium of mesangial cells co-incubated with aIgA1 from IgAN patients (P<0.05). Enalaprilat or valsartan partly improved nephrin expression when compared with that by podocytes exposed to the mesangial medium (P<0.05), while the nephrin expression of podocytes with enalaprilat or valsartan was lower than that of podocytes exposed to medium of mesangial cells stimulated by aIgA1 from healthy control (P<0.05). However, anti-mouse tumour necrosis factor-alpha antibody did not show any improvement in nephrin expression.. Our findings implicate that local renin angiotensin system activation in podocytes is partly involved in down-regulation of nephrin by mesangial medium in IgA nephropathy.

Topics: Animals; Cells, Cultured; Down-Regulation; Gene Expression; Glomerulonephritis, IGA; Humans; Immunoglobulin A; Membrane Proteins; Mesangial Cells; Mice; Podocytes; Reference Values; Renin-Angiotensin System

To investigate the association of the polymorphism of NPHS1, coding gene of nephrin, with the degree of proteinuria, renal function, and prognosis of IgA nephropathy (IgAN) in patients in north China.. Peripheral blood samples were collected from 532 patients with IgAN confirmed by biopsy, 285 males and 230 females, aged (31+/-11). Genomic DNA was isolated from the peripheral blood leucocytes. Polymorphism of the exon G349A of NPHS1 was detected by polymerase chain reaction combined with restriction fragment length polymorphism (PCR-RFLP). 138 patients were followed up for 4-99 months. The correlation between the NPHS1 polymorphism and renal function at the time of renal biopsy, and that between NPHS1 polymorphism and the prognosis were analyzed.. The frequency of the genotype with the allele G (AG/GG) in the patients with the estimated glomerular filtration rate (eGFR)<60 mlxmin(-1)x(1.73 m2)(-1) was significantly higher than that of the patients with the eGFR>60 ml.min(-1)x(1.73 m2)(-1) (P=0.008). Even after adjusting for the effects of proteinuria, hypertension, and age, AG/GG genotype was an independent risk factor of the exacerbation of renal damage at the time of diagnosis (P=0.011), and GG genotype was an independent risk factor of the prognosis (P<0.001).. G allele and AG/GG genotype are associated with the severity of renal function at the time of diagnosis the GG genotype is associated with the prognosis of IgAN patients.

Topics: Adult; Alleles; Female; Gene Frequency; Genotype; Glomerulonephritis, IGA; Humans; Male; Membrane Proteins; Polymorphism, Genetic; Prognosis; Young Adult

There have been many exciting advances in our understanding of genetic causes of nephrotic syndrome since 1998 when nephrin was first found. The mRNA expressions of nephrin and CD2AP were studied by quantitative real-time polymerase chain reaction (PCR) in aspirated renal biopsy tissues from 9 subjects with minimal change nephrotic syndrome (MCNS), 6 with primary IgA nephropathy (IgAN), and 15 controls. Protein expression of nephrin, podocin, and CD2AP were analyzed by immunohistochemistry, indirect immunofluorescence, and laser confocal microscope. Compared with controls, the CD2AP mRNA level was significantly downregulated in renal samples from MCNS and IgAN patients (p=0.001 in MCNS, p=0.046 in IgAN), though no significant downregulation was found in the mRNA level of nephrin (p=0.346 in MCNS, p=0.311 in IgAN). The expression levels of protein CD2AP and nephrin were significantly reduced in MCNS and IgAN (MCNS: nephrin, p=0.034, CD2AP, p=0.005; IgAN: nephrin, p=0.021, CD2AP, p=0.025). The podocin staining did not differ significantly between controls and disease groups (p value 0.340 and 0.787, respectively). The results suggest that transcript and translation expression changes of nephrin and CD2AP may have pathogenetic roles in some patients with MCNS and IgAN in Chinese, though no correlation was found in podocin with proteinuria in this study.

Topics: Adaptor Proteins, Signal Transducing; Child; China; Cytoskeletal Proteins; Female; Glomerulonephritis, IGA; Humans; Immunohistochemistry; Intracellular Signaling Peptides and Proteins; Kidney; Male; Membrane Proteins; Nephrosis, Lipoid; Polymerase Chain Reaction; RNA, Messenger

Proteinuria is a poorly understood feature of many acquired renal diseases. Recent studies concerning congenital nephrotic syndromes and findings in genetically modified mice have demonstrated that podocyte molecules make a pivotal contribution to the maintenance of the selective filtration barrier of the normal glomerulus. However, it is unclear what role podocyte molecules play in proteinuria of acquired renal diseases. This study investigated the mRNA and protein expression of several podocyte-associated molecules in acquired renal diseases. Forty-eight patients with various renal diseases were studied, including minimal change nephropathy, focal segmental glomerulosclerosis, IgA nephropathy, lupus nephritis, and diabetic nephropathy, together with 13 kidneys with normal glomerular function. Protein levels of nephrin, podocin, CD2-associated protein, and podocalyxin were investigated using quantitative immunohistochemical assays. Real-time PCR was used to determine the mRNA levels of nephrin, podocin, and podoplanin in microdissected glomeruli. The obtained molecular data were related to electron microscopic ultrastructural changes, in particular foot process width, and to clinical parameters. In most acquired renal diseases, except in IgA nephropathy, a marked reduction was observed at the protein levels of nephrin, podocin, and podocalyxin, whereas an increase of the glomerular mRNA levels of nephrin, podocin, and podoplanin was found, compared with controls. The mean width of the podocyte foot processes was inversely correlated with the protein levels of nephrin (r = -0.443, P < 0.05), whereas it was positively correlated with podoplanin mRNA levels (r = 0.468, P < 0.05) and proteinuria (r = 0.585, P = 0.001). In the diseases studied, the decrease of slit diaphragm proteins was related to the effacement of foot processes and coincided with a rise of the levels of the corresponding mRNA transcripts. This suggests that the alterations in the expression of podocyte-associated molecules represent a compensatory reaction of the podocyte that results from damage associated with proteinuria.

Topics: Adaptor Proteins, Signal Transducing; Adult; Aged; Blotting, Western; CD2 Antigens; Cytoskeletal Proteins; DNA, Complementary; Female; Glomerulonephritis, IGA; Humans; Image Processing, Computer-Assisted; Immunohistochemistry; Intracellular Signaling Peptides and Proteins; Kidney; Kidney Diseases; Lupus Nephritis; Male; Membrane Proteins; Microscopy, Electron; Microscopy, Fluorescence; Middle Aged; Models, Statistical; Oligonucleotide Probes; Protein Biosynthesis; Proteins; Reverse Transcriptase Polymerase Chain Reaction; RNA; RNA, Messenger; Sialoglycoproteins

Nephrin, the molecule responsible for congenital nephrotic syndrome of Finnish type, is crucial in maintaining the glomerular filtration barrier. Recently, its complete gene structure and common gene polymorphisms in its exons have been reported, although the functional and clinical significance of these polymorphisms has not yet been elucidated. We investigated a possible association of the NPHS1 polymorphisms with the development of Ig A nephropathy (IgAN), as well as the clinical and histologic manifestations in IgAN. A total of 464 Japanese subjects, including 267 patients with histologically proven IgAN and 197 healthy controls with normal urinalysis, were genotyped for the NPHS1 G349A, G2289A, and T3315C polymorphisms. The frequencies of the genotypes, alleles, and estimated haplotypes of NPHS1 polymorphisms were no different between patients with IgAN and the controls. Within the IgAN group, patients carrying at least one G allele of G349A tended to present with more proteinuria, lower renal function, and more severe histopathologic injury than those with the AA genotype, although the time from the first urinary abnormality to the renal biopsy was no different between both groups. The logistic regression analysis indicated that even after adjusting for the effect of proteinuria and hypertension the GG genotype of NPHS1 G349A was an independent risk factor for the deteriorated renal function at the time of diagnosis. This study suggests that the NPHS1 G349A polymorphism may be associated with heavy proteinuria and a decline in renal function in patients with IgAN.

Topics: Adolescent; Adult; Aged; Case-Control Studies; Child; DNA Primers; Female; Gene Frequency; Genotype; Glomerulonephritis; Glomerulonephritis, IGA; Humans; Male; Membrane Proteins; Middle Aged; Nephrotic Syndrome; Polymorphism, Genetic; Proteins; Proteinuria

Recently, nephrin, podocin, alpha-actinin, and WT1, which are located at the slit diaphragm and expressed by the podocyte, were found to be causative in congenital/familial nephrotic syndrome (NS), but their role in acquired NS remains unclear. We studied their expression in NS with the aim of disclosing their possible role in the development of proteinuria. Immunofluorescence, confocal microscopy, and image analysis were used to study the expression and the distribution in 19 children with primary NS, 9 with isolated hematuria, and 9 controls. All the children with NS presented with heavy proteinuria and foot process effacement was identified by electron microscopy. No proteinuria and foot process effacement was seen in the group with hematuria. A dramatic decrease of podocin expression was found in NS (86.66+/-22.74) compared with control groups ( P=0.014). Furthermore, we also found the pattern of distribution of nephrin, podocin, and alpha-actinin changed in children with NS. In conclusion, a dramatic decrease of podocin expression and abnormal distribution of nephrin, podocin, and alpha-actinin were found in children with NS. No differences were found in children with isolated hematuria, suggesting involvement of these molecules in the development of proteinuria in primary NS.

Topics: Actinin; Adolescent; Case-Control Studies; Child; Female; Glomerulonephritis, IGA; Hematuria; Humans; Intracellular Signaling Peptides and Proteins; Male; Membrane Proteins; Nephrosis, Lipoid; Nephrotic Syndrome; Proteins; Tissue Distribution; WT1 Proteins

Nephrin is a recently identified protein, which is synthesized in the podocytes and localized in the slit diaphragm area. Nephrin is a cell adhesion molecule of the immunoglobulin superfamily, and presumably is a part of the zipper-like structure of the slit membrane. As the mutation of the gene coding nephrin induces congenital nephrotic syndrome of Finnish type, which is a prototype of nephrotic syndrome, it has been suggested that nephrin also plays a role in acquired proteinuric kidney disease.. To address the above issue, the expression of nephrin in acquired human glomerular disease was studied by immunoelectron microscopy employing a polyclonal antibody against nephrin. Four normal human kidneys from nephrectomy specimens and eight kidney biopsy specimens from glomerular disease patients (one minimal change disease, one membranous glomerulonephritis (GN), one membranoproliferative GN, four IgA nephropathy, and one lupus nephritis) were studied. Proteinuria of the patients ranged from 448 to 11725 mg/day. Effacement of the foot processes was observed in all patients.. The study demonstrated that the number and distribution of gold particles in the glomerular region, where the podocyte foot process was well preserved, were similar to that found in normal kidneys; however, gold particles were almost always absent in regions where the foot processes were effaced. The number of gold particles per foot process interspace was not different between normal controls and GN patients; however, the number of gold particles per defined length (1000 nm) of the glomerular basement membrane underlying the foot processes was significantly reduced in GN patients.. Using immunoelectron microscopy, we observed that the expression of nephrin in GN was lower in regions where the foot processes were effaced, and comparable with that of normal controls where the foot process interspaces were preserved. The significance of our observation in the context of proteinuria in acquired GN needs further clarification.

Topics: Adult; Case-Control Studies; Female; Gene Expression; Glomerulonephritis; Glomerulonephritis, IGA; Glomerulonephritis, Membranoproliferative; Glomerulonephritis, Membranous; Humans; Kidney Glomerulus; Lupus Nephritis; Male; Membrane Proteins; Microscopy, Fluorescence; Microscopy, Immunoelectron; Middle Aged; Nephrosis, Lipoid; Proteins