Combined crystal-storing histiocytosis, light chain proximal tubulopathy, and light chain crystalline podocytopathy in a patient with multiple myeloma: a case report and literature review.

BACKGROUND: Crystal-storing histiocytosis (CSH), light chain proximal tubulopathy (LCPT), and light chain crystalline podocytopathy (LCCP) are rare complications of multiple myeloma (MM) or monoclonal gammopathy of renal significance, and their diagnoses are challenging. CASE PRESENTATION: In this case, a 69-year-old Chinese woman presented with suspicious Fanconi syndrome with renal insufficiency. Immunofixation electrophoresis of both serum and urine revealed elevated immunoglobulin G kappa (IgGkappa) and kappa light chain. Bone marrow aspirate revealed 15% plasma cells with considerable cytoplasmic granular inclusions and needle-shaped crystals. Renal biopsy confirmed the final pathologic diagnosis of kappa-restricted CSH, combined LCPT and LCCP by immunoelectron microscopy. A number of special casts were present which could easily be misdiagnosed as light chain cast nephropathy. Immunofluorescence on frozen tissue presented false negative for kappa light chain, as ultimately proven by paraffin-embedded tissue after pronase digestion. MM and CSH were diagnosed, and two cycles of chemotherapy were given. The patient subsequently refused further chemotherapy, and her renal function remained relatively stable during a 2.5-year follow-up period. CONCLUSIONS: In conclusion, we report a rare case of generalized kappa-restricted CSH involving bone marrow and kidney, combined with LCPT and LCCP, provide a comprehensive summary of renal CSH, and propose a new nomenclature of monoclonal immunoglobulin-induced crystalline nephrology. The presentation of monoclonal immunoglobulin and Fanconi syndrome should suggest the presence of monoclonal immunoglobulin-induced crystalline nephrology. Use of paraffin-embedded tissue after pronase digestion and immunoelectron microscopy is beneficial to improve the sensitivity of diagnosis.

Clinicopathological manifestations of coexistent monoclonal immunoglobulin deposition disease and immunotactoid glomerulopathy.

Combination of monoclonal immunoglobulin deposition disease (MIDD) and immunotactoid glomerulopathy (ITG) is a rare form of monoclonal immunoglobulin (MIg)-associated renal disease. We retrospectively reviewed the native kidney biopsy specimens at Peking University People's Hospital from 2011 to 2020. Five patients were diagnosed as MIDD + ITG. Their clinical and pathological characteristics were studied. The typical clinical features were nephritic syndrome and renal dysfunction with prominent anemia, but hematuria was mild. Unlike single MIDD and single ITG, on light microscopy, segmentally distributed mesangial nodular sclerosis on the basis of mesangial matrix hyperplasia was the major lesion. Others including membranoproliferative glomerulonephritis (MPGN)-like lesion, glomerular basement membrane thickness, and mild to moderate mesangial and endothelial proliferations might presented at the same time and in the same glomeruli. On immunofluorescence, MIg, usually monoclonal light chains, deposited along glomerular basement membranes and tubular basement membranes, while the intact MIg or monoclonal heavy chain deposited in the mesangial regions. Corresponding to the depositions on immunofluorescence, punctate "powdery" deposits along glomerular basement membranes and tubular basement membranes under electronic microscopy indicated the presence of MIDD. Microtubular substructures (diameters of 20-50 nm) exhibiting hollow cores arranged in parallel arrays in mesangial regions indicated the presence of ITG. Patients treated with bortezomib-based regimen seemed to have better outcomes. In conclusion, MIDD + ITG is a rare combination form of MIg-associated renal disease. Accurate diagnosis requires the comprehensive pathological investigations.

Anti-glomerular basement membrane disease mediated by IgG and IgA: a case report.

BACKGROUND: Anti-glomerular basement membrane (anti-GBM) disease is a rare autoimmune condition responsible for rapidly progressive glomerulonephritis. This disease is usually mediated by IgG autoantibodies against the noncollagenous domain of the α3(IV) collagen chain. In rare cases, IgA or IgM anti-GBM antibodies are involved. This raises the question of whether there are different types of antibody-mediated anti-GBM disease at the same time. CASE REPORT: A 37-year-old woman with anti-GBM disease mediated by IgG and IgA. The patient developed rapidly progressive glomerulonephritis with nephrotic syndrome. Indirect immunofluorescence analysis indicated the presence of IgG and IgA antibodies reactive with a basement membrane component, identified by enzyme-linked immunoadsorbent assay and Western blotting as the α3(IV) collagen chain. After plasmapheresis and immunotherapy (steroids and cyclophosphamide), much improved the massive proteinuria and renal function. Follow up to date, she had normal renal function without proteinuria. CONCLUSIONS: This is the first case report of anti-GBM disease mediated by IgG and IgA. If the clinical presentation and histopathological findings are suggestive of atypical anti-GBM disease, alternative laboratory tests such as Western blotting analysis can be used to confirm the diagnosis.

Soluble Urokinase Receptor Levels in Secondary Focal Segmental Glomerulosclerosis.

BACKGROUND: Soluble urokinase receptor (suPAR) has been reported to be a possible permeability factor causing primary focal segmental glomerulosclerosis (FSGS) in recent years. We investigated the plasma and urinary suPAR levels in patients with 3 common types of secondary FSGS: Alport's syndrome (Alport-FSGS), obesity-related FSGS, and diabetic nephropathy. METHODS: Fifty-two secondary FSGS patients diagnosed by kidney biopsy, including 8 with Alport-FSGS, 20 with obesity-related FSGS, and 24 with diabetic nephropathy, were enrolled in the study in the period from January 2008 to June 2014 at the Renal Division, Peking University First Hospital. Fifty-six healthy donors and 74 patients with primary FSGS, 14 with minimal-change disease, and 29 with membranous nephropathy were used as healthy controls and disease controls, respectively. Plasma and urinary suPAR concentrations were measured with commercial ELISA kits, and their correlations with clinical and pathological data were analyzed. RESULTS: Both plasma and urinary suPAR levels in the total secondary FSGS group were significantly higher than in healthy controls (p < 0.0001 and p< 0.001, respectively). There was no significant difference in levels of plasma and urinary suPAR in the Alport-FSGS, obesity-related FSGS, and diabetic nephropathy groups (p = 0.64 and p = 0.72, respectively). The plasma suPAR level was not correlated with estimated glomerular filtration rate and urine protein. CONCLUSIONS: The levels of plasma and urinary suPAR in patients with Alport-FSGS, obesity-related FSGS, and diabetic nephropathy were increased. Plasma suPAR might be a pathogenetic participation factor or a useful marker of glomerular diseases with FSGS-associated podocytopathy but is not necessarily a circulating permeability factor.

IgG4-related kidney disease (IgG4-RKD) with membranous nephropathy as its initial manifestation: report of one case and literature review.

BACKGROUND: IgG4-related disease (IgG4-RD) often affects multiple organs and tissues, especially the kidneys, and is characterized by interstitial nephritis, obstructive nephropathy, and in rare cases glomerulopathy (including membranous nephropathy). CASE PRESENTATION: In this article, we report a patient with nephrotic syndrome as the only initial manifestation. Membranous nephropathy was confirmed by renal biopsy, but without any renal interstitial lesions. The nephrotic syndrome completely resolved after treatment with immunosuppressants but recurred after drug withdrawal, which was accompanied by acute kidney injury. Ultimately, IgG4-related interstitial nephritis with membranous nephropathy was confirmed by a second renal biopsy. After routine administration of steroids and cyclophosphamide, renal function returned to normal after 2 months, and nephrotic syndrome was ameliorated after 5 months. CONCLUSION: Special attention should be paid to this rare condition in the clinical setting. In patients with membranous nephropathy (MN) that is accompanied by multi-system damage, impaired renal function, elevated IgG4 levels (absolute or relative value), negative PLA2R, and/or renal interstitial plasma cell infiltration, the possibility of IgG4-related kidney disease (IgG4-RKD) should be carefully assessed.

The Clinical and Immunologic Features of Patients With Combined Anti-GBM Disease and Castleman Disease.

Patients with both anti-glomerular basement membrane (anti-GBM) disease and Castleman disease have been rarely reported. In this study, we report 3 patients with this combination. They had immunologic features similar to patients with classic anti-GBM disease. Sera from the 3 patients recognized the noncollagenous (NC) domain of the α3 chain of type IV collagen (α3(IV)NC1) and its 2 major epitopes, EA and EB. All 4 immunogloblin G (IgG) subclasses against α3(IV)NC1 were detectable, with predominance of IgG1. In one patient with lymph node biopsy specimens available, sporadic plasma cells producing α3(IV)NC1-IgG were found, suggesting a causal relationship between the 2 diseases. One patient, who achieved remission with antibody clearance and normalization of serum creatinine and interleukin 6 concentrations after plasma exchange and 3 cycles of chemotherapy, experienced recurrence of anti-GBM antibodies and an increase in interleukin 6 concentration after chemotherapy discontinuation because of adverse effects, but both returned to normal after another cycle of chemotherapy. This clinical course and the pathologic findings support the hypothesis that the Castleman disease-associated tumor cells are the source of the anti-GBM autoantibodies.

Assessment of KDIGO definitions in patients with histopathologic evidence of acute renal disease.

BACKGROUND AND OBJECTIVES: AKI is a clinical syndrome with various causes involving glomerular, interstitial, tubular, and vascular compartments of the kidney. Acute kidney disease (AKD) is a new concept that includes both AKI and the conditions associated with subacute decreases in GFR (AKD/non-AKI). This study aimed to investigate the correlation between AKI/AKD defined by clinical presentation and diffuse histologic criteria for acute abnormalities based on renal biopsy. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: All 303 patients who were histologically diagnosed as having acute tubular necrosis (ATN), acute tubulointerstitial nephritis, cellular crescentic GN, acute thrombotic microangiopathy, or complex lesions on renal biopsy from January 2009 to December 2011 were enrolled in the study. The 2012 Kidney Disease Improving Global Outcomes AKD/AKI definitions were applied to classify patients as follows: AKI, AKD/non-AKI, non-AKD, or unclassified. RESULTS: A total of 273 patients (90.1%) met the AKD criteria; 198 patients (65.3%) were classified as having AKI according to serum creatinine (SCr) and urine output criteria. The urine output criteria added 4.3% to the SCr criteria and reclassified 6.7% of the AKI cases into higher stages. Of patients with ATN on pathology, 79.2% met AKI criteria; this was a higher percentage than for those who had other individual pathologic lesions (50%-64%). The major cause of not being defined as having AKI was a slower SCr increase than that required by the definition of AKI (98, 93.3%). Patients with AKI had more severe clinical conditions and worse short-term renal outcome than those in the non-AKI group. CONCLUSIONS: Diffuse, acute abnormality defined by renal biopsy and AKI defined by clinical presentation are two different entities. Most patients who have diffuse acute histologic findings met the criteria for AKD, whereas only two thirds met the definition of AKI.

[Clinicopathologic features of collagen III glomerulopathy].

OBJECTIVE: To study the clinicopathologic features of collagen III glomerulopathy and its cause, pathogenesis and prognosis. METHODS: Five cases of collagen III glomerulopathy that collected from 2005 to 2014 were observed by renal biopsy. The morphologic characteristics were studied by light microscopy, immunofluorescence, immunohistochemical and electron microscopy. RESULTS: The glomerular mesangium became expansion but no hypercellularity, basement membrane appeared thickened. The glomeruli showed collagen type III deposit by immunohistochemistry method, and collagen fibers increased by electron microscopy. The patients often show serious proteinuria, nephrotic syndrome and renal function damage. CONCLUSIONS: Collagen III glomerulopathy is an idiopathic glomerular disease, characterized by massive accumulation of collagen type III within the glomerular mesangial areas and basement membrane. Collagen III glomerulopathy is extremely rare. The etiology and pathogenesis may relate to the abnormality of collagen III gene. There is no specific treatment for it and its prognosis is poor.

Immunofixation electrophoresis was highly specific for the diagnosis of renal light-chain amyloidosis.

BACKGROUND: Renal light-chain amyloidosis (AL) is one of the common causes of massive proteinuria and nephrotic syndrome, especially in elderly patients. This study aimed to evaluate the sensitivity and specificity of serum and urine using immunofixation electrophoresis (IFE) in the diagnosis of renal AL amyloidosis in patients older than 40 years. METHODS: Patients receiving native renal biopsy in the hospital who meet the following criteria were recruited in this retrospective study: (1) proteinuria excretion ≥3.5 g/24 hr; (2) age ≥ 40 years when receiving renal biopsy and (3) biopsy-proven glomerulopathy. Serum and urine monoclonal free immunoglobulin light chains were detected using IFE. RESULTS: A total of 625 patients were recruited. Of them, 32 patients (5.12%) were diagnosed as renal AL amyloidosis. The specificities of serum, urine and serum combined urine IFE in the total 625 patients (ie, monoclonal free immunoglobulin light chain in serum or urine) for diagnosis of renal AL amyloidosis were 98.6%, 98.0% and 97.6%, respectively. For patients older than 60 years, the specificities of serum, urine and serum combined urine IFE for diagnosis of renal AL amyloidosis were 98.5%, 98.0% and 97.6%, respectively and the sensitivity of serum, urine and serum combined urine IFE for diagnosis of renal AL amyloidosis were 68.6%, 81.3% and 81.3%, respectively. CONCLUSION: Serum or urine IFE was highly specific for renal AL amyloidosis for patients older than 40 years with nephrotic-range proteinuria. In older patients (>60 years), both the sensitivity and specificity of IFE for renal AL amyloidosis were high. Combination of serum and urine IFE could improve the sensitivity with comparable specificity.

A clinicopathological analysis in a large cohort of Chinese patients with renal amyloid light-chain amyloidosis.

BACKGROUND: The aim of the study is to investigate the association between clinical and pathological features in a large cohort of Chinese patients with renal immunoglobulin light-chain amyloidosis (AL). METHODS: A series of 186 patients with renal AL amyloidosis diagnosed between 1990 and 2011 were retrospectively reviewed. The extent of amyloid deposition in glomeruli, blood vessels and tubulointerstitium were evaluated semiquantitatively. The renal amyloid load was defined by the sum of glomerular, vascular and interstitial deposits. The associations between the clinical manifestations and pathological features were analyzed. RESULTS: The extent of glomerular amyloid deposition was positively correlated with the level of proteinuria. Patients with codeposition of amyloid and immune complexes (ICs) in glomeruli had higher levels of proteinuria than those without ICs. Advanced glomerular amyloid deposition was an independent pathological factor associated with renal insufficiency at diagnosis. The degree of vascular amyloid (VA) deposition was positively correlated with cardiac involvement and hepatic involvement. Patients with AL-κ showed a higher prevalence of hepatic involvement and more severe VA deposition than patients with AL-λ. High renal amyloid load independently predicted the increased risk for overall death after adjusting for recognized confounders. CONCLUSIONS: The degree and localization of amyloid deposits in the kidney of AL patients were associated with the degree of proteinuria and renal insufficiency, as well as extrarenal organs involvement. There were some differences between AL-κ and AL -λ in clinical and pathological characteristics. The renal amyloid load was an independent predictor for overall mortality.

Acute kidney injury and bilateral symmetrical enlargement of the kidneys as first presentation of B-cell lymphoblastic lymphoma.

Lymphoblastic lymphoma is an uncommon subtype of lymphoid neoplasm in adults. Acute kidney injury at initial presentation due to lymphoblastic lymphoma infiltration of the kidneys has rarely been described. We report a 19-year-old woman who presented with acute kidney injury due to massive lymphomatous infiltration of the kidneys. The diagnosis of B-cell lymphoblastic lymphoma was established by immunohistochemical study of the biopsied kidney. The patient had an excellent response to the VDCLP protocol (vincristine, daunomycin, cyclophosphamide, asparaginase, and dexamethasone) with sustained remission. We recommend that lymphomatous infiltration be considered in patients presenting with unexplained acute kidney injury and enlarged kidneys.

Renal involvement in a large cohort of Chinese patients with Castleman disease.

BACKGROUND: The association of kidney disease with Castleman disease (CD) is uncommon. To date, most studies have been based on single-case reports. Here, we describe renal involvement in CD in a large Chinese cohort. METHODS: Seventy-six CD patients were identified in one clinical center. Clinical and pathological characteristics of patients with renal involvement were described, which were also compared with cases identified through a systematic literature review. RESULTS: Nineteen patients (25%) exhibited renal involvement. Patients with multicentric clinical type (59 versus 0%) or plasma cell (PC)/mixed cellularity histological variant (61.5 versus 6%) were more likely to have renal involvement (P < 0.001). Proteinuria (with 7/19 reaching nephrotic range) and acute renal failure (12/19, 63%) were the main clinical presentations. Kidney biopsy revealed various glomerular diseases (10/11) and interstitial nephritis (1/11), while with 'thrombotic microangiopathy-like' lesions were the most common pathological characteristics (6/11, 55%). This contrasted significantly with the literature in which amyloidosis was the most reported. Renal outcomes responded well to chemotherapy. Nine (9/12, 75%) patients with acute renal failure recovered completely, one recovered partially. Overall, only three (3/19, 16%) patients progressed to end-stage kidney disease. Renal involvement did not influence survival rate (log-rank test, P = 0.73) in the follow-up. CONCLUSIONS: CD with multicentric type and PC or mixed cellularity variant are often associated with renal complications. Thrombotic microangiopathy-like lesions are the most common pathological characteristics. Chemotherapy can reverse kidney damage in most cases.

Aristolochic acid nephropathy: variation in presentation and prognosis.

BACKGROUND: Aristolochic acid nephropathy (AAN) is a worldwide problem and one of the common causes of chronic kidney disease (CKD) in China. METHODS: Three hundred patients diagnosed as AAN from 1997 to 2006 were enrolled. Medical histories of Chinese herb ingestion, clinical-pathological features and risk factors for renal failure were recorded. Patients were followed up for 2-156 months. Factors involved in the prognosis of AAN were investigated. RESULTS: The 300 patients with AAN manifested three clinical subtypes, including acute kidney injury (acute AAN) in 13 patients, abrupt tubular dysfunction with normal serum creatinine (Scr) levels in seven cases and chronic tubulointerstitial nephropathy with decreased estimated glomerular filtration rate (eGFR) (chronic AAN) in 280 cases. The acute AAN cases had the highest aristolochic acid (AA)-I intake per day and developed progressive kidney failure during 1-7 years follow-up. The tubular dysfunction AAN patients had the lowest cumulative AA-I intake and were able to keep normal Scr levels during 2-8 years follow-up. The chronic AAN patients took the lowest AA-I dose per day but with the longest period and the highest cumulative dosage and exhibited a very large range of eGFR changing rate (from -21.6 to 5.2, median -3.5 mL/min/year). The cumulative AA-I intake (r = 0.330, P = 0.045) and the time course from the termination of AA medication to the start of follow-up (r = -0.430, P = 0.009) were found to be independent factors correlated with the decrease rate of eGFR in the chronic AAN patients. AA and the metabolites could be detected in a high frequency in patients who had stopped herbal medication for 1 year, which indicates a rather long washout time for these chemicals. CONCLUSIONS: AAN has variant phenotypes with distinct prognosis, which is determined by the variable AA medications. With better understanding of toxic and environmental causes for kidney injury, there would be a better chance to uncover the causal factors of cases of 'CKD without known causes' which is crucial for improving the disease outcomes.

Pathologic predictors of renal outcome and therapeutic efficacy in IgA nephropathy: validation of the oxford classification.

BACKGROUND AND OBJECTIVES: The Oxford classification of IgA nephropathy (IgAN) may aid in predicting prognosis and providing therapeutic strategy but must be validated in different ancestry. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A total of 410 patients with IgAN, enrolled from one of the largest renal centers in China, were evaluated for the predictive value of the Oxford classification to prognosis defined as end stage renal disease. A total of 294 of these patients were prospectively treated with renin-angiotensin system blockade and immunosuppressants sequentially and were evaluated separately to assess the predictive value to therapeutic efficacy (defined as time-averaged proteinuria <1 g/d). Three pathologists reviewed specimens independently according to the Oxford classification and were blinded to clinical data. RESULTS: Segmental glomerulosclerosis and tubular atrophy and interstitial fibrosis were independent predictive factors of end stage renal disease. Patients who had >25% of glomeruli with endocapillary hypercellularity showed higher proteinuria, lower estimated GFR, and higher mean BP than patients with less endocapillary hypercellularity. Immunosuppressive therapy showed a protective effect to prognosis of endocapillary hypercellularity in patients with endoncapillary hypercellularity could benefit from immunosuppressive therapy. Mesangial hypercellularity and tubular atrophy and interstitial fibrosis were independent factors of inefficiency of renin-angiotensin system blockade alone. Crescents were not significant in predicting prognosis or in therapeutic efficacy. CONCLUSIONS: The Oxford classification may aid in predicting prognosis and providing a therapeutic strategy in Chinese patients with IgAN.

The renal histopathological spectrum of patients with nephrotic syndrome: an analysis of 1523 patients in a single Chinese centre.

BACKGROUND: Nephrotic syndrome is caused by a variety of glomerulopathy. The current study investigated the renal histopathological spectrum of patients with nephrotic syndrome who received a renal biopsy in our department within the last 15 years. METHODS: One thousand five hundred and twenty-three consecutive patients (≥14 years old at renal biopsy) with nephrotic syndrome were recruited. Patients were divided into four groups according to age at the time of renal biopsy. The renal histopathological spectrum was also compared between nephrotic-range proteinuria patients with and without hypoalbuminaemia. RESULTS: Among the 1523 patients, the most common cause of nephrotic syndrome was idiopathic membranous nephropathy (IMN) (20.7%), followed by minimal change disease (MCD) (20.4%). Among the patients aged 14-24, 25-44, 45-59 and ≥60 years, the most common cause of nephrotic syndrome was MCD (33.0%), lupus nephritis (LN) (23.0%), IMN (37.9%) and IMN (42.3%), respectively. Among the female patients aged 14-24 and 25-44 years, LN was the leading cause of nephrotic syndrome (35.8 and 36.2%, respectively). The proportion of patients with renal amyloidosis increased in parallel with patient age. The comparison between nephrotic patients with and without hypoalbuminaemia suggests that patients with MCD, LN or renal amyloidosis were more likely to develop hypoalbuminaemia. CONCLUSIONS: The renal histopathological spectrum of nephrotic syndrome differs between ages. MCD, LN and IMN were the main cause of nephrotic syndrome among younger patients, and IMN was the main cause of nephrotic syndrome among older patients. The proportion of patients with renal amyloidosis increased in parallel with patient age.

Urinary kidney injury molecule-1 in patients with IgA nephropathy is closely associated with disease severity.

BACKGROUND: The pathological characteristics of IgA nephropathy (IgAN) are highly variable. Urinary kidney injury molecule-1 (KIM-1) is a sensitive biomarker for proximal tubule injury. The aim of the study is to investigate the value of KIM-1 as a biomarker for assessing the renal injury in IgAN. METHODS: The levels of urinary KIM-1 in 202 patients with IgAN, 46 patients with other renal diseases as disease controls and 60 healthy blood donors as normal controls were measured. Correlations with clinical and histopathological features of patients with IgAN were evaluated. RESULTS: The levels of urinary KIM-1 were significantly higher in patients with IgAN than in normal controls (P < 0.001) and in patients with non-IgAN (P = 0.011). Urinary levels of KIM-1 in IgAN positively correlated with levels of serum creatinine and proteinuria and negatively with creatinine clearance. The more severe the tubulointerstitial injury was, the higher the levels of urinary KIM-1. Patients with severe mesangial proliferation, crescents formation or endocapillary proliferation had higher levels of urinary KIM-1 than those without. The levels of tubular KIM-1 expression in immunohistochemistry closely correlated with the levels of urinary KIM-1 (r = 0.553, P = 0.032). Renal survival was significantly worse in patients with elevated urinary KIM-1 (P = 0.020). CONCLUSION: Urinary KIM-1 may be a useful biomarker to evaluate kidney injury in IgAN.

[Cellular components of crescents in four common types of crescentic glomerulonephritis].

OBJECTIVE: To examine the cellular components at different stages of the crescent formation in four most common types of human crescentic glomerulonephritis (CGN), including anti-GBM disease (GBM-CGN), crescentic IgA nephropathy (IgA-CGN), ANCA associated pauci-immune CGN (ANCA-CGN) and crescentic lupus glomerulonephritis (LN-CGN). METHODS: Renal biopsy specimens of patients with GBM-CGN (n = 10), IgA-CGN (n = 12), ANCA-CGN (n = 12), and LN-CGN (n = 11) were selected. Immunohistochemistry was adopted to identify the cellular components using different cell markers including cytokeratin (PEC), CD68 (macrophage), nestin (podocyte), podocalyxin (podocyte), CD3 (lymphocyte), CD15 (neutrophil) and PCNA. RESULTS: There were different subtypes of cell components identified during the formation of a cellular crescent in 4 different types of human CGN. Mainly of PEC 11.4 (0.0, 95.0)%, macrophage 8.0 (0.0, 35.0)% and podocyte 5.5 (0.0, 22.0)% and their constitutive percentages were different among various CGNs (P < 0.01). In all the CGNs studied, there were 50% of cells were negative to all the cell markers adopted for this expeiment. Podocalyxin positive cells 0.5 (0.0, 9.6)% were significantly less than nestin positive cells 5.5 (0.0, 22.0)% in all CGNs. PCNA positive cells were 44.7 (16.7, 83.3)% in the cellular crescent of all CGNs and co-localized with nestin (38/45 cases), CK (42/45 cases) or CD68 (24/45 cases). CONCLUSIONS: PEC, macrophage and podocyte might play important roles in the formation of crescents. The staining disparity of nestin and podocalyxin indicates that podocyte dedifferentiation may occur during the crescent formation. PEC, podocytes and macrophages may participate in the formation of crescent in common CGNs through active cellular proliferation.