Clinicopathological and long-term prognostic features of membranous nephropathy with crescents: a Japanese single-center experience.

BACKGROUND: Three recent studies from the United States and China reported the clinicopathological features and short-term prognosis in patients with membranous nephropathy (MN) and crescents in the absence of secondary MN, anti-glomerular basement membrane (GBM) antibodies, and anti-neutrophil cytoplasmic antibodies (ANCA). METHODS: We compared clinicopathological and prognostic features in 16 MN patients with crescents (crescent group) and 38 MN patients without crescents (control group), in the absence of secondary MN, anti-GBM antibodies, and ANCA. Median follow-up periods in the crescent and control groups were 79 and 50 months, respectively. RESULTS: Decreased estimated glomerular filtration rates (<50 mL/min/1.73 m2), glomerulosclerosis, and moderate-to-severe interstitial fibrosis were more frequently observed in the crescent group than in the control group (P = 0.043, P = 0.004, and P = 0.035, respectively). Positive staining rates for glomerular IgG2 and IgG4 were significantly different between the 2 groups (P = 0.032, P = 0.006, respectively). Doubling of serum creatinine during follow-up was more frequently observed in the crescent group than in the control group (P = 0.002), although approximately two-thirds of patients in the crescent group were treated with immunosuppressive therapy. Crescent formation and interstitial fibrosis were risks for doubling of serum creatinine [hazard ratio (HR) = 10.506, P = 0.012; HR = 1.140, P = 0.009, respectively]. CONCLUSIONS: This is the first Japanese study demonstrating significant differences in clinicopathological and prognostic features between the 2 groups. Most patients in the crescent group may develop a long-term decline in renal function despite immunosuppressive therapy.

Long-term prognosis of AL and AA renal amyloidosis: a Japanese single-center experience.

BACKGROUND: Few studies have been conducted on the long-term prognosis of patients with amyloid light chain (AL) and amyloid A (AA) renal amyloidosis in the same cohort. METHODS: We retrospectively examined 68 patients with biopsy-proven renal amyloidosis (38 AL and 30 AA). Clinicopathological findings at the diagnosis and follow-up data were evaluated in each patient. We analyzed the relationship between clinicopathological parameters and survival data. RESULTS: Significant differences were observed in several clinicopathological features, such as proteinuria levels, between the AL and AA groups. Among all patients, 84.2 % of the AL group and 93.3 % of the AA group received treatments for the underlying diseases of amyloidosis. During the follow-up period (median 18 months in AL and 61 months in AA), 36.8 % of the AL group and 36.7 % of the AA group developed end-stage renal failure requiring dialysis, while 71.1 % of the AL group and 56.7 % of the AA group died. Patient and renal survivals were significantly longer in the AA group than in the AL group. eGFR of >60 mL/min/1.73 m2 at biopsy and an early histological stage of glomerular amyloid deposition were identified as low-risk factors. A multivariate analysis showed that cardiac amyloidosis and steroid therapy significantly influenced patient and renal survivals. CONCLUSIONS: Our results showed that heart involvement was the major predictor of poor outcomes in renal amyloidosis, and that the prognosis of AA renal amyloidosis was markedly better than that in previously reported cohorts. Therapeutic advances in inflammatory diseases are expected to improve the prognosis of AA amyloidosis.

Different Expression Patterns of Toll-Like Receptor mRNAs in Blood Mononuclear Cells of IgA Nephropathy and IgA Vasculitis with Nephritis.

Mucosal immunity may play a key role in IgA nephropathy (IgAN) and IgA vasculitis with nephritis (IgAVN). IgAVN is characterized by the presence of non-thrombocytopenic palpable purpura, associated with glomerulonephritis with IgA-dominant immune deposits. Recent studies have shown the up-regulation of Toll-like receptors (TLRs) in patients with IgAN or IgAVN. Among TLRs that mediate innate immune reactions, TLR2, TLR4, and TRL5 recognize bacterial components, while TLR3, TLR7, and TLR9 recognize viral components. Here we compared the expression levels of TLR mRNAs in peripheral blood mononuclear cells (PBMCs) from 49 IgAN patients, 20 IgAVN patients, and 20 patients with thin basement membrane nephropathy (TBMN), unrelated to immune-mediated pathogenesis, as a control. The real-time RT-PCR analysis revealed the significantly higher expression levels of TLR2, TLR3, TLR5, TLR7, and TLR9 mRNAs in PBMCs of IgAN and IgAVN patients, compared to TBMN patients. Importantly, TLR4 mRNA levels were significantly higher in IgAN patients than in IgAVN patients, while its expression levels were comparable in IgAVN patients and TBMN patients. In contrast, TLR5 and TLR9 mRNA levels were significantly higher in IgAVN patients than in IgAN patients. In IgAN patients, expression levels of TLR2, TLR3, TLR5, or TLR9 mRNA were correlated with proteinuria levels, and TLR4 mRNA levels were correlated with serum IgA levels. In IgAVN patients, however, there was no such correlation. The up-regulated expression of TLR mRNAs in PBMCs may be related to the development of IgAN and IgAVN. The distinct expression patterns between these two diseases may reflect their different pathogenetic mechanisms.

Effect of CYP3A5 and ABCB1 polymorphisms on the interaction between tacrolimus and itraconazole in patients with connective tissue disease.

PURPOSE: The aim of this study was to investigate the effect of itraconazole (ITCZ), a potent inhibitor of CYP3A4 and P-glycoprotein, on the blood concentration 12 h after tacrolimus administration (C 12h) in relation to CYP3A5 6986A>G and ABCB1 3435C>T genotype status in patients with connective tissue disease (CTD). METHODS: Eighty-one CTD patients taking tacrolimus (Prograf®) once daily at night (2100 hours) were enrolled in this study. Whole blood samples were collected 12 h after tacrolimus administration at steady state. RESULTS: The dose-adjusted tacrolimus C 12h with or without ITCZ co-administration was significantly higher in patients with CYP3A5*3/*3 than in those with the CYP3A5*1 allele [CYP3A5 *1/*1 vs. *1/*3 vs. *3/*3 = 1.67 vs. 2.70 vs. 4.83 ng/mL/mg (P = 0.003) and 0.68 vs. 0.97 vs. 2.20 ng/mL/mg (P < 0.001), respectively], but differences were not observed for ABCB1 genotypes. However, there was no difference in the increase rate of the dose-adjusted C 12h of tacrolimus between CYP3A5 or ABCB1 genotypes (P = 0.378 and 0.259). On the other hand, reduction of the estimated glomerular filtration rate exhibited a correlation with the C 12h of tacrolimus after ITCZ co-administration (r = -0.482, P = 0.009). CONCLUSIONS: In CYP3A5*3/*3 patients, because the metabolic pathway for tacrolimus occurs only through CYP3A4, the combination with ITCZ seems to lead to a higher risk of acute renal dysfunction. Therefore, we suggest that the target blood tacrolimus concentration be set as low as possible through dose-adjustment for patients with the CYP3A5*3/*3 allele.

Effects of CYP3A5 polymorphism and the tacrolimus 12 h concentration on tacrolimus-induced acute renal dysfunction in patients with lupus nephritis.

1. The purpose of the present study was to investigate the effect of tacrolimus concentration in blood 12 h after administration (C12h) on acute renal dysfunction in patients with lupus nephritis (LN) taking tacrolimus once daily. 2. Five of the 35 LN patients experienced tacrolimus-induced acute renal dysfunction. 3. The average annual C12h of tacrolimus was higher for patients with events of elevated serum creatinine level than for patients not experiencing these events [6.4 (5.6-8.8) versus 2.8 (2.2-4.6) ng/mL, respectively, p=0.001]. 4. The average annual tacrolimus C12h was higher for patients with CYP3A5*3/*3 (PM) than for patients with the CYP3A5*1 allele (EM) [4.6 (3.2-6.6) versus 2.5 (2.0-3.1) ng/mL, respectively, p=0.002]. 5. The area under the receiver operating characteristic was 0.887, which gave the best sensitivity (80.0%) and specificity (86.7%) at a tacrolimus C12h (average annual C12h or C12h at events) threshold of 5.2 ng/mL. 6. C12h measurements, CYP3A5 genotyping and dose adjustments of tacrolimus should be performed to prevent acute renal dysfunction in LN patients taking tacrolimus once daily.

Validation of the Japanese histologic classification 2013 of immunoglobulin A nephropathy for prediction of long-term prognosis in a Japanese single-center cohort.

BACKGROUND: A new Japanese histologic classification (JHC) of immunoglobulin A nephropathy (IgAN) for prediction of long-term prognosis was proposed in 2013. The goal of this study was to validate the JHC system in a Japanese single-center cohort. METHODS: A retrospective study was conducted in 198 Japanese adult patients with IgAN. Clinical findings including blood pressure, urinary protein, estimated glomerular filtration rate (eGFR), and outcomes were evaluated in these patients. The glomerular lesion percentage score (GLPS) [number of glomeruli with cellular crescents, fibrocellular crescents, global sclerosis, segmental sclerosis, or fibrous crescents/number of total obtained glomeruli × 100 (%)] was assessed in each patient and categorized into histologic grades (HGs) of HG1 (<25 %), HG2 (25-49 %), and HG3/4 (≥50 %). Associations of GLPS (HG) with disease progression (50 % eGFR decline or end-stage renal disease requiring dialysis) within 10 years after biopsy and the rate of annual eGFR decline were examined. RESULTS: During a median follow-up period of 12.0 years after biopsy, disease progression occurred in 12.8 % (12/94) of HG1 patients, 32.3 % (21/65) of HG2 patients, and 46.2 % (18/39) of HG3/4 patients. The risk of disease progression was significantly higher in the HG2 and HG3/4 groups than in the HG1 group (odds ratios: 3.3 and 5.9 vs. 1). A higher GLPS was significantly associated with a higher risk of disease progression and a greater annual eGFR decline. CONCLUSION: The newly proposed JHC system 2013 based on GLPS (HG) was well correlated with long-term prognosis in our cohort of Japanese adult patients with IgAN.

Validation of the 2010 histopathological classification of ANCA-associated glomerulonephritis in a Japanese single-center cohort.

OBJECTIVES: To validate the 2010 histopathological classification system of anti-neutrophil cytoplasmic antibodies (ANCA)-associated glomerulonephritis (GN) in a Japanese single-center cohort. METHODS: We retrospectively studied 54 patients (28 renally limited pauci-immune GN, 25 microscopic polyangiitis, and one Churg-Strauss syndrome). RESULTS: There were 17 patients with focal GN, eight patients with crescentic GN, 19 patients with mixed GN, and 10 patients with sclerotic GN. Detailed information regarding treatment was available in 39 patients. All these patients were treated with steroids with or without immunosuppressive agents. Hemodialysis was introduced in two patients with crescentic GN and three patients with sclerotic GN. During the follow-up period, 27 of 54 patients died. The major cause of death was pneumonia. Significant differences were observed in estimated glomerular filtration rate among patients with focal, crescentic, mixed, and sclerotic GN at entry and 1- and 5-year follow-up. Patients with focal GN had preserved renal function and favorable outcome. CONCLUSIONS: Our validation study suggests that the 2010 histopathological classification of ANCA-associated GN might aid in prognostication of patients at the time of diagnosis and in therapy selection.

Serum interleukin 6 levels as a useful prognostic predictor of clinically amyopathic dermatomyositis with rapidly progressive interstitial lung disease.

OBJECTIVES: Rapidly progressive interstitial lung disease (RP-ILD) is life-threatening in patients with clinically amyopathic dermatomyositis (CADM). Useful prognostic markers are necessary for treatment selection. This study aimed to investigate differences in clinical and laboratory characteristics between surviving and non-surviving patients. METHODS: Twelve CADM patients with RP-ILD were enrolled. Six patients lived (Group A) and six patients died (Group B) after immunosuppressive treatment for RP-ILD. Clinical manifestations and laboratory data before treatment were compared between the two groups. RESULTS: Among the clinical manifestations and laboratory data examined, serum interleukin 6 (IL-6) levels in Group B were significantly higher than those in Group A (mean ± SD 28.5 ± 21.0 vs. 7.2 ± 1.6 pg/mL; p = 0.009). Simple regression analysis showed that serum IL-6 was the only significant prognostic factor (p = 0.032). Kaplan-Meier estimates showed that the cumulative survival rate was significantly lower in patients with serum IL-6 levels of ≥ 9 pg/mL than in patients with those of < 9 pg/mL (p = 0.04). CONCLUSIONS: Serum IL-6 levels may predict the prognosis of CADM patients with RP-ILD. The intensity of immunosuppressive treatment can be decided according to serum IL-6 levels at an early phase of the disease.

Proliferative glomerulonephritis with monoclonal IgG deposits in a patient with autoimmune hemolytic anemia.

A 25-year-old woman was admitted because of proteinuria. A renal biopsy showed mesangial/endocapillary proliferative glomerulonephritis with IgG2-κ deposits. Electron microscopy showed immune complex-type deposits. She also had Coombs-positive hemolytic anemia, anticardiolipin antibodies, and antinuclear antibodies. Middle-dose steroid therapy led to improvement of proteinuria and hemolytic anemia. Six years later, she developed crescentic glomerulonephritis with IgG2-κ deposits during pregnancy. Middle-dose steroid therapy improved renal dysfunction. This is an exceptional case of proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID), a recently described rare dysproteinemia-related glomerulonephritis, associated with autoimmune disease. This case also suggests that crescentic glomerulonephritis can be superimposed on PGNMID.

Validation of the 2010 histopathological classification of ANCA-associated glomerulonephritis in a Japanese single-center cohort.

OBJECTIVES: To validate the 2010 histopathological classification system of anti-neutrophil cytoplasmic antibodies (ANCA)-associated glomerulonephritis (GN) in a Japanese single-center cohort. METHODS: We retrospectively studied 54 patients (28 renally limited pauci-immune GN, 25 microscopic polyangiitis, and one Churg-Strauss syndrome). RESULTS: There were 17 patients with focal GN, eight patients with crescentic GN, 19 patients with mixed GN, and 10 patients with sclerotic GN. Detailed information regarding treatment was available in 39 patients. All these patients were treated with steroids with or without immunosuppressive agents. Hemodialysis was introduced in two patients with crescentic GN and three patients with sclerotic GN. During the follow-up period, 27 of 54 patients died. The major cause of death was pneumonia. Significant differences were observed in estimated glomerular filtration rate among patients with focal, crescentic, mixed, and sclerotic GN at entry and 1- and 5-year follow-up. Patients with focal GN had preserved renal function and favorable outcome. CONCLUSIONS: Our validation study suggests that the 2010 histopathological classification of ANCA-associated GN might aid in prognostication of patients at the time of diagnosis and in therapy selection.

Distribution of glomerular IgG subclass deposits in patients with membranous nephropathy and anti-U1 ribonucleoprotein antibody.

BACKGROUND: It is known that a predominant glomerular deposition of IgG4 is characteristic of idiopathic membranous nephropathy (MN) and that significant deposition of other IgG subclasses is also observed in lupus MN. However, there is no report focusing on the distribution of glomerular IgG subclass deposits in MN patients with anti-U1 ribonucleoprotein (RNP) antibody. METHODS: We evaluated clinicopathological features and the distribution patterns of glomerular IgG subclass deposits in seven MN patients with positive anti-RNP antibody and negative antibodies to double-stranded DNA (dsDNA) and Smith antigen (Sm) (RNP-MN group) and in seven age- and sex-matched lupus MN patients with positive anti-dsDNA antibody and negative antibodies to RNP and Sm (L-MN group). RESULTS: Mixed connective tissue disease was diagnosed in four patients in the RNP-MN group. Two patients in the RNP-MN group and three patients in the L-MN group developed nephrotic syndrome. Renal insufficiency was not present in all patients in both groups. Hypocomplementemia was found in two patients in the RNP-MN group and six patients in the L-MN group. In the RNP-MN group, positive stainings for glomerular IgG1, IgG2, IgG3 and IgG4 were observed in one, seven, zero and five patients, respectively. On the contrary, in the L-MN group, positive stainings for glomerular IgG1, IgG2, IgG3 and IgG4 were observed in seven, seven, seven, and six patients, respectively. CONCLUSIONS: This is the first study showing striking differences in the distribution of glomerular IgG subclass deposits between RNP-MN and L-MN groups. RNP-MN and L-MN may result from different immunological mechanisms.

Renal biopsy in patients aged 80 years and older: a single-center experience in Japan.

BACKGROUND: There is a paucity of data on renal biopsy in a large number of the very elderly (age ≥ 80 years) worldwide. METHODS: Clinicopathological features in 73 patients aged ≥ 80 years were evaluated and compared with control groups of 172 patients aged 60 - 61 years and 128 patients aged 70 - 71 years. RESULTS: The common indications for biopsy in the very elderly were nephrotic syndrome (NS), followed by proteinuria without NS and/or hematuria, and acute kidney injury (AKI). Histological diagnoses were considered to potentially modify treatment in 57 cases (78.1%): the most frequent diagnosis was membranous nephropathy, followed by minimal change disease, and various other diseases. There were no biopsy procedure-related serious complications. Clinical assessment of treatments was evaluated in 38 of 54 patients with AKI and/or NS. Improvement in renal dysfunction or NS was observed in 24 of 30 (80%) patients who received immunosuppressive therapy. There were statistically significant differences in the disease spectrum between the very elderly and control groups. CONCLUSIONS: This is the first report of renal biopsy findings in a relatively large number of Japanese very elderly patients. Histological observations are useful aids in estimating the prognosis and therapy selection for renal disorders, even in the very elderly.

Angioimmunoblastic T-cell lymphoma and membranous nephropathy: a still unreported association.

A 21-year-old man with lymphadenopathy and Coombs-positive hemolytic anemia had been treated with steroid maintenance therapy. He developed nephrotic syndrome with size increase of lymphadenopathy. Lymph node examination disclosed angioimmunoblastic T-cell lymphoma (AITL). Light microscopy of a renal biopsy specimen showed typical features of membranous nephropathy (MN), such as bubbling appearance and spike formation. Immunofluorescence studies revealed no significant deposition of immunoglobulins. Electron microscopy showed sparse degenerative materials on the epithelial side of the glomerular basement membranes, with intervening spikes. These unique histological findings suggested secondary MN. High-dose steroid therapy followed by six courses of cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) therapy improved his symptoms. One-year follow-up revealed the patient in good health without any signs of relapse. Glomerular manifestations have rarely been reported in association with AITL. To our knowledge, this is the first reported case of nephrotic syndrome due to MN associated with AITL.

Simultaneous herpes simplex virus esophagitis and lupus enteritis in a patient with systemic lupus erythematosus.

A 52-year-old woman with a 6-year history of systemic lupus erythematosus (SLE) developed acute abdominal pain, nausea, vomiting, and diarrhea accompanied by hypocomplementemia. Herpes simplex virus (HSV) esophagitis and lupus enteritis were diagnosed on the basis of the results of endoscopic and histological examinations and abdominal computed tomography (CT) findings. Treatment with acyclovir followed by high-dose intravenous steroids improved her symptoms. To our knowledge, this is the first case of simultaneous HSV esophagitis and lupus enteritis.

High-throughput sequencing of IgG B-cell receptors reveals frequent usage of the rearranged IGHV4-28/IGHJ4 gene in primary immune thrombocytopenia.

Primary immune thrombocytopenia (ITP) is an acquired form of thrombocytopenia caused by IgG anti-platelet autoantibodies and represents an organ-specific autoimmune disorder. Although the glycoprotein (GP)IIb/IIIa and GPIb/IX have been shown to be targets for autoantibodies, the antigen specificity of autoantibodies is not fully elucidated. To identify the characteristics of IgG B-cell receptor (BCR) repertoires in ITP, we took advantage of adaptor-ligation PCR and high-throughput DNA sequencing methods for analyzing the clone-based repertoires of IgG-expressing peripheral blood B cells. A total of 2,009,943 in-frame and 315,469 unique reads for IGH (immunoglobulin heavy) were obtained from twenty blood samples. Comparison of the IGHV repertoires between patients and controls revealed an increased usage of IGHV4-28 in ITP patients. One hundred eighty-six distinct IGHV4-28-carrying sequences were identified in ITP patients and the majority of these clones used an IGHJ4 segment. The IGHV4-28/IGHJ4-carrying B-cell clones were found in all ITP patients. Oligoclonal expansions of IGHV4-28/IGHJ4-carrying B cells were accompanied by multiple related clones with single amino substitution in the CDR3 region suggesting somatic hypermutation. Taken together, the expansion of IGHV4-28/IGHJ4-carrying IgG-expressing B cells in ITP may be the result of certain antigenic pressure and may provide a clue for the immune pathophysiology of ITP.

Monoclonal immunoglobulin deposition disease associated with membranous features.

BACKGROUND: Very few cases of non-organized and non-Randall-type monoclonal immunoglobulin deposition disease (MIDD) associated with membranous features have been reported. Information on clinicopathological features and prognosis in this entity is limited. METHODS: We reviewed 5443 renal biopsies processed at our department, and identified three patients with MIDD associated with membranous features. We evaluated clinicopathological features and outcomes in these patients. RESULTS: All patients had proteinuria, and one patient developed nephrotic syndrome. Renal insufficiency was not observed. Cryoglobulin or monoclonal protein in serum and urine was not detected. A renal biopsy showed thickening of the glomerular capillary walls and spike formation. Tubulointerstitial and vascular alterations were mild or absent. Immunofluorescence studies revealed granular IgG3-kappa deposits in two patients and IgG1-kappa deposits in one patient, along the glomerular capillary walls. Immunofluorescence studies using antibodies specific for gamma-heavy chain Fab containing C(H)1 domain, C(H)2 domain and C(H)3 domain did not show any apparent deletion. On confocal microscopy, glomerular colocalization of light and heavy chains was observed. Electron microscopy showed predominant subepithelial granular deposits without distinct ultrastructural organization. All patients were treated with steroids, and good effects were observed. A follow-up renal biopsy performed in one patient showed histological improvements. No patient developed myeloma or other haematological malignancy during the course of follow-up (mean 44 months). CONCLUSIONS: MIDD associated with membranous features is an extremely rare but distinctive entity. Our study suggests glomerular deposition of a nondeleted whole immunoglobulin molecule. Patients with this entity appear to respond well to steroid therapy.

Disappearance of a thrombotic microangiopathy-like glomerular lesion in a patient with a placental site trophoblastic tumor after hysterectomy.

A 32-year-old woman presented with amenorrhea after a normal childbirth and subsequently developed nephrotic syndrome. Renal biopsy showed a thrombotic microangiopathy (TMA)-like glomerular lesion with deposits of immunoglobulins, complements, and fibrinogen. Increased serum levels of the beta subunit of human chorionic gonadotropin, abnormal uterine findings from imaging studies, and endometrial biopsy findings suggested gestational trophoblastic disease. She was diagnosed with a placental site trophoblastic tumor (PSTT) after hysterectomy and, following treatment, her proteinuria disappeared. Follow-up renal biopsy showed the disappearance of the TMA-like lesion. To our knowledge, this is the first case report of the pathological remission of renal disease associated with PSTT.

Anti-neutrophil Cytoplasmic Antibody-associated Vasculitis Complicated by Periaortitis and Cranial Hypertrophic Pachymeningitis: A Report of an Autopsy Case.

Anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) is a systemic inflammatory disorder categorized as small-vessel vasculitis. We herein report an elderly Japanese man with AAV (granulomatosis with polyangiitis affecting the eyes, nose, lungs, and kidneys) who also showed periaortitis at the diagnosis and developed cranial hypertrophic pachymeningitis (HP) during steroid maintenance therapy. His consciousness disturbance caused by HP improved after steroid pulse therapy, but he died of aspiration pneumonia. Autopsy findings showed giant cells in the thickened pachymeninges and obsolete inflammatory lesions in the aortic adventitia and renal tubulointerstitium. This is the first case of AAV complicated by periaortitis and cranial HP.

Interaction of alpha-actinin-4 with class I PxxP motif-containing OK/SW-CL.16 protein.

BACKGROUND: The aim of this study was to identify novel binding partners for alpha-actinin-4 (actinin-4), an essential component of the glomerular filtration barrier. METHODS: We performed bacterial two-hybrid screenings of a human kidney cDNA library using as a bait human actinin-4 containing the spectrin-like repeat R1. The identified interactions were further verified by in vitro affinity assays. To investigate the expression of the identified molecules in the kidney and other tissues, a human tissue cDNA panel screening and in situ hybridization were performed. RESULTS: One isolated cDNA from the library encoded OK/SW-CL.16 protein with a segment similar to known actinin-interacting regions. OK/SW-CL.16 protein also contained the class I PxxP motif, which can participate in binding to Src homology 3 (SH3) domain-containing signaling proteins. In vitro affinity assays showed interactions of recombinant actinin-4 R1 and full-length renal actinin-4 with recombinant OK/SW-CL.16 protein. A tissue cDNA panel screening revealed a ubiquitous expression of OK/SW-CL.16 mRNA. In situ hybridization showed glomerular expression of OK/SW-CL.16 mRNA, mainly in podocytes and mesangial cells. CONCLUSION: Our results suggest that OK/SW-CL.16 protein is a novel binding partner for actinin-4. OK/SW-CL16 protein might act as a linker between actinin-4 and some SH3 domain-containing signaling proteins in podocytes.