IgG4相关性肾病的临床病理特征分析

目的探究本中心中国人群IgG4相关性肾病的发病情况、临床病理特征及预后。 方法回顾性分析2010年1月至2019年1月在东部战区总医院国家肾脏疾病临床医学研究中心行肾穿刺活检患者的临床病理资料，对肾组织中有大量浆细胞浸润的患者，重新测定肾活检时血清IgG4水平及肾组织IgG4阳性浆细胞浸润数目，结合肾外表现，筛选出确诊为IgG4相关性肾病的病例，并分析IgG4相关性肾病的临床特点、病理特征及肾脏预后。 结果44 784例肾活检患者中有22例确诊为IgG4相关性肾病。IgG4相关性肾病最常表现为蛋白尿(86.4%)及肾功能不全(81.8%)，约68.2%患者存在肾外累及。高IgG血症、高IgG4血症、低补体血症的发生率分别为86.4%、84.2%、45.5%。肾脏组织学最常见的病理类型为IgG4相关间质性肾炎(90.9%)，其次为膜性肾病(13.6%)。肾间质席纹状纤维化、鸟眼样改变分别占40.9%、54.5%。22例患者中，21例接受糖皮质激素治疗，2例失访，余20例中位随访时间为12个月，9例肾功能好转，10例肾功能平稳，1例肾功能减退并进展至终末期肾病。 结论IgG4相关性肾病发病率低，好发于中老年男性，最常表现为肾功能不全及蛋白尿。半数以上的患者有肾外表现。高IgG血症、高IgG4血症和低补体血症是其血清学特征。最常见的肾脏病理类型为间质性肾炎；大量IgG4阳性浆细胞浸润、肾间质席纹状纤维化或鸟眼样改变是其典型的病理特征。糖皮质激素仍是IgG4相关性肾病治疗首选的一线药物。     

Glomerulonephritis in children with mixed connective tissue disease

AIMS: Mixed connective tissue disease (MCTD) has overlapping clinical features with systemic lupus erythematosus (SLE). Renal biopsy is necessary for all children with SLE to evaluate the prognosis, because they are at a quite high risk of developing renal complications. Furthermore, lupus nephritis and hypocomplementemia usually precede the appearance of clinical manifestations. Immune complex-mediated nephritis is one of the major complications of MCTD. Juvenile MCTD is known to be associated with a higher risk of nephritis than adult MCTD. However, it is uncertain whether all children with MCTD should be subjected to a renal biopsy, and whether most of those with hypocomplementemia present nephropathy, as in patients with SLE. We examined the histopathological characteristics of juvenile MCTD nephritis, the importance of renal biopsy and the implications of hypocomplementemia in our patients and reported cases of MCTD. MATERIAL AND METHODS: We performed renal biopsy in 11 children with MCTD and found 6 patients with glomerulonephritis. In addition, we studied the frequency and the characteristics of glomerulonephritis in 71 cases of juvenile MCTD (our 11 patients and 60 reported cases). We also analyzed the relationship between hypocomplementemia and pathological features in 41 cases of MCTD nephritis (23 adults, 18 children). RESULTS: 6 of our 11 patients had glomerulonephritis, but of them four had no abnormality in urinalysis at the time of biopsy. In 5 patients renal biopsy showed normal findings. Review of 71 cases of juvenile MCTD showed that of them 28% presented latent asymptomatic nephritis at the time of biopsy. Membranous nephropathy (MN) and mesangial proliferative glomerulonephritis (MPG) were common in MCTD. Interestingly, hypocomplementemia was more frequently observed in patients with MN or mixed form of MN and MPG (MPG/MN) than simple MPG based on our review of 41 cases (p < 0.01). CONCLUSION: A more aggressive indication of renal biopsy should be considered in children with MCTD because of the high incidence of non-clinical nephritis. The hypocomplementemia observed in patients with MCTD suggests the high frequency of glomerulonephritis, including membranous lesions.     

A case of Mikulicz’s disease complicated with severe interstitial nephritis associated with IgG4

A 48-year-old woman who had bilateral swelling in the eyelids and submandibular region was admitted. Clinical findings suggested that her renal function had deteriorated. Laboratory data showed renal insufficiency (2.52 mg/dl), hypergammaglobulinemia (IgG 3,729 mg/dl, IgA 124 mg/dl, IgM 73 mg/dl). Gallium-67 scintigram indicated abnormal uptake in bilateral lacrimal glands, submandibular glands, and kidneys. A diagnosis of Mikulicz’s disease and interstitial nephritis was made, since biopsy specimens of her lacrimal gland and minor salivary gland showed diffuse infiltration of lymphocytes. In addition, renal biopsy specimens showed diffuse severe interstitial infiltration of IgG4-positive mononuclear cells. Symptoms and laboratory data normalized in response to methylprednisolone semi-pulse therapy and prednisolone 50 mg/day. Mikulicz’s disease was recently reported to be IgG4 associated disease. In our case, Mikulicz’s disease complicated with diffuse severe interstitial nephritis was successfully treated by corticosteroid. The present case supports the hypothesis that IgG4-related autoimmune disease could be causes of Mikulicz’s disease and interstitial nephritis.     

Renal involvement in IgG4-related disease

IgG4-RD may affect several organs including kidneys. The kidney is involved in approximately 20% of patient with IgG4-RD. The most common intrinsic kidney disease is tubulointerstitial nephritis (IgG4-TIN). Retroperitoneal fibrosis (IgG4-RPF) may induce obstructive acute renal failure. More rarely, IgG4-RKD can manifest as a glomerular disease, in particular as a membranous nephropathy (MN). It mostly affects middle-aged to elderly men and causes acute or chronic renal dysfunction, multiple hypodense lesions on CT-Scan and various extra-renal lesions. Increased serum IgG4 and hypocomplementemia are the most important serological findings for the diagnosis of IgG4-RD and thus should be systematically assessed when IgG4-RKD is suspected. Specific diagnosis criteria for IgG4-TIN including interstitial infiltration of IgG4-positive plasma cells, storiform fibrosis and tubular basement membrane immune complex deposits have been proposed. Corticosteroids are effective and remain the first-line therapy but relapses or severe forms could respond to immunosuppressive therapy.     

Diagnosis of IgG4-related tubulointerstitial nephritis

IgG4-related systemic disease is an autoimmune disease that was first recognized in the pancreas but also affects other organs. This disease may manifest as tubulointerstitial nephritis (IgG4-TIN), but its clinicopathologic features in the kidney are not well described. Of the 35 patients with IgG4-TIN whose renal tissue specimens we examined, 27 (77%) had acute or progressive chronic renal failure, 29 (83%) had involvement of other organ systems, and 18 of 23 (78%) had radiographic abnormalities. Elevated total IgG or IgG4 serum levels were present in 79%. All pathologic specimens featured plasma cell-rich TIN, with most showing diffuse, expansile interstitial fibrosis. Immune complexes along the tubular basement membranes were present in 25 of 30 (83%). All specimens had a moderate to marked increase in IgG4+ plasma cells by immunohistochemistry. We used a control group of 175 pathologic specimens with plasma cell-rich interstitial infiltrates that can mimic IgG4-TIN to examine the diagnostic utility of IgG4 immunostaining. Excluding pauci-immune necrotizing and crescentic glomerulonephritis, IgG4 immunohistochemistry had a sensitivity of 100% (95% CI 90-100%) and a specificity of 92% (95% CI 86-95%) for IgG4-TIN. Of the 19 patients with renal failure for whom treatment and follow-up data were available, 17 (89%) responded to prednisone. In summary, because no single test definitively diagnoses IgG4-related systemic disease, we rely on a combination of histologic, immunophenotypic, clinical, radiographic, and laboratory features. When the disease manifests in the kidney, our data support diagnostic criteria that can distinguish IgG4-TIN from other types of TIN.     

Perirenal capsule involvement in IgG4-related chronic interstitial nephritis: a case report and literature review

Objective To explore the clinicopathological features and the renal biopsy process of a case of IgG4-related chronic interstitial nephritis with perirenal capsule involved and review associated literature to improve the clinician's understanding for this disease and to perform a better renal biopsy. Methods The onset, diagnosis and treatment course of the disease were described and associated literature were reviewed to summary the clinicopathologic features and key points in renal biopsy. Results The data of the patient showed that the urine specific gravity was 1.011, with urine protein ± and urine sugar 3+. The concentration of hemoglobin was 53 g/L, serum creatinine was 1665 μmol/L, and IgG4 was 9.39 g/L. Computed tomography showed that both kidneys enlarged slightly with decreased density and low density shadow around the kidneys. On contrast-enhanced scan, irregular low-density enhancement areas were found in both kidneys, and the edge of the boundary was not clear. For the first renal biopsy, no renal parenchyma was found except mainly hyaline collagen fibrils. At the second time, 3 pieces of tissues were obtained, which showed chronic interstitial glomerulonephritis. The IgG4 positive plasma cells were about 60/HPF and the IgG4+/IgG+cells ratio was more than 40%. The diagnosis of IgG4-related chronic interstitial glomerulonephritis was confirmed. After corticosteroid treatment, the serum creatinine decreased to 502 μmol/L after the patient got rid of dialysis. Conclusions There are various manifestations of renal damage caused by IgG4-related disease. It is necessary to pay attention to the involvement of the perirenal capsule, and to balance the risk of bleeding and poor sampling in renal biopsy.     

Crescentic glomerulonephritis associated with totally implantable central venous catheter-related Staphylococcus epidermidis infection

A 59-year-old woman was admitted to our hospital for treatment of acute renal insufficiency. She had been under home intravenous hyperalimentation therapy through a totally implantable central venous catheter for 2 years because of post-radiation enteritis. Clinical examination on admission revealed severe renal insufficiency complicated with hypocomplementemia, marked proteinuria and hematuria. Chest roentgenography demonstrated moderate pulmonary congestion. Hemodialysis was initiated and her pulmonary congestion improved. On the 14th and 21st hospital day, blood culture revealed Staphylococcus epidermidis colonization. Cefazolin was administered and C-reactive protein decreased, however, renal insufficiency and hypocomplementemia did not improve. To investigate the genesis of renal insufficiency, renal biopsy was performed. Light microscopic findings of the kidney revealed severe crescentic glomerulonephritis complicated with moderate tubulointerstitial damage. Immunofluorescence-microscopic findings of the kidney revealed positive IgG, IgM, C3 deposition along the capillary lumen. From these laboratory findings and the clinical course, we diagnosed her renal disease as crescentic glomerulonephritis induced by catheter-related bloodstream infection, and the central venous catheter was removed. After removal, urinary output and hypocomplementemia remarkably improved, however, unfortunately, her renal dysfunction did not improve and maintenance hemodialysis needed to be continued. Although her renal disease was not caused by ventriculo-atrial shunt but by central venous catheter-related bloodstream infection, we supposed that the pathogenesis was a closely similar entity to shunt nephritis.     

Tubulointerstitial nephritis associated with IgG4-related systemic disease

We report three patients with tubulointerstitial nephritis (TIN) with high serum IgG4 concentrations. None of the patients had notable pancreatic lesions when the TIN developed, although one had a history of autoimmune pancreatitis (AIP). Nevertheless, the clinicopathological findings were quite similar to those of AIP. They were all middle-aged to elderly men. Sialadenitis and lymphadenopathy were often evident. Serum total IgG and IgG4 concentrations were elevated and hypocomplementemia was observed. Although antinuclear antibodies were positive, anti-Ro and anti-La antibodies were negative. Renal biopsy showed dense lymphoplasmacytic infiltration with fibrosis in the renal interstitium, and the infiltrated plasma cells had strong immunoreactivity for IgG4. Furthermore, lymphoplasmacytic infiltration and abundant IgG4-positive plasma cells were observed in the salivary glands of a patient. Steroid therapy was effective for TIN in all three patients. The present findings support the recently proposed concept of IgG4-related systemic disease, and suggest that IgG4 is associated not only with AIP but also with other systemic lymphoplasmacytic diseases, including TIN. The conditions responsible for the pathogenesis of TIN need to be considered, irrespective of the presence of AIP.     

Clinicopathological findings of immunoglobulin G4-related kidney disease

Immunoglobulin (Ig) G4-related kidney disease characterizing tubulointerstitial nephritis (TIN) is an organ complication recognized in IgG4-related systemic diseases that has some unique aspects compared to other types of TIN. TIN lesions in the kidney can be tumor-like, focal or diffuse. Abnormal urinalysis is usually mild or absent even in the cases with deteriorated renal dysfunction. Some cases are accidentally diagnosed from radiological findings without renal dysfunction and/or abnormal urinalysis. The typical pathological findings of TIN are unique fibrosis and infiltration of massive lymphocytes and IgG4-positive plasma cells. Glomerular lesions are rare but the complication of mesangial proliferative glomerulonephritis and membranous nephropathy is occasionally reported. Pathogenic mechanisms are unclear until now; however, auto-immune and allergic mechanisms have been suspected from laboratory data. The initial response to steroid agents is generally favorable; however, recurrence is possible after the discontinuation of steroid treatment. Long-term follow-up is necessary with continuous systemic checks for organ disorders due to IgG4-related systemic diseases.     

IgG4-related tubulointerstitial nephritis presenting with psychiatric manifestations and skin lesions

We describe a 21-year male with mood disorder on lithium therapy and psoriasis-like skin lesions presenting with rapidly progressive renal failure. The kidney biopsy showed acute tubulointerstitial nephritis with immunoglobulin G4-positive plasma cell infiltration. He was started on oral steroids with a provisional diagnosis of IgG4-related tubulointerstitial nephritis. All dermatological, psychiatric and renal manifestations dramatically improved, and he was taken off lithium. He had a relapse of his psychiatric symptoms on stopping steroids, and they again responded to steroids.     

Predominant tubulointerstitial nephritis in a patient with systemic lupus nephritis

In most cases of systemic lupus erythematosus (SLE), glomerular lesions are the main renal complication. Although tubulointerstitial lesions are often associated with severe glomerular lesions, predominant or isolated tubulointerstitial injury in the presence of minimal glomerular abnormalities with SLE, so-called predominant tubulointerstitial lupus nephritis, is rare. Only ten cases are reported in the English literature. Herein, we describe the case of a 64-year-old man with SLE who presented with acute renal deterioration attributable to acute tubulointerstitial nephritis. Renal biopsy showed diffuse infiltration of inflammatory mononuclear cells in the interstitium and tubulitis without significant glomerular lesions. Immunofluorescence study revealed positive staining for IgG, C3, and C1q along the renal tubular basement membrane (TBM). Electron microscopy also showed electron-dense deposits in the TBM. Other causes of tubulointerstitial injury, such as drug use and infection, were ruled out. Taking these findings together with the presence of antitubular basement membrane antibody, predominant tubulointerstitial lupus nephritis was diagnosed. Treatment with oral corticosteroids for 6 weeks improved renal function. Even after tapering of the corticosteroid, renal function and serological markers of SLE activity have remained stable in this patient for more than 12 months.     

Predominant tubulointerstitial nephritis in a patient with systemic lupus erythematosus: phenotype of infiltrating cells

A 63-year-old man with systemic lupus erythematosus developed tubular proteinuria. All subclasses of serum IgG increased, and the largest IgG subclass increase was IgG4. A renal biopsy showed lupus nephritis (Class II) with severe tubulointerstitial nephritis (so-called predominant tubulointerstitial lupus nephritis, an unusual form of lupus nephritis). Immunofluorescence microscopy revealed positive granular staining for IgG, C3 and C1q in the mesangium and peritubular interstitium, and along the tubular basement membranes (TBM). Electron microscopy also showed electron-dense deposits in the mesangium and TBM. Immunophenotyping of interstitial infiltrating cells disclosed a predominance of T cells. CD8-positive cytotoxic T cells infiltrated the peritubular interstitium, and some of these cells infiltrated the tubules. B cell-rich lymphoid follicles were also observed. IgG subclass analyses showed glomerular IgG1, IgG2 and IgG4 deposition, positive staining of IgG4 in the peritubular interstitium and along the TBM, and abundant IgG1-, IgG3- and IgG4-positive plasma cells in the interstitium. The patient responded well to moderate-dose steroid therapy. This is the first report of immunophenotyping of interstitial infiltrates in predominant tubulointerstitial lupus nephritis. The results suggest CD8-positive cytotoxic T cell-mediated tubular injury. Furthermore, immune complexes containing IgG4 might be one of etiologic factors.     

IgG4-related tubulointerstitial nephritis presented with multiple renal nodular lesions

A 66-year-old man presented with multiple bilateral renal nodular lesions demonstrated by enhanced computed tomographic scan. He had a history of autoimmune pancreatitis and renal cell carcinoma, which had been treated with partial nephrectomy. We performed renal biopsy under ultrasound guidance. Pathological examination revealed plasma cell infiltration to the renal interstitium. Serum IgG4 level was high and we diagnosed as IgG4-related tubulointerstitial nephritis. After one month of oral steroid therapy the multiple nodular lesions disappeared.     

Nephropathy in IgG4-related systemic disease

Lymphoplasmacytic sclerosing pancreatitis ("autoimmune" pancreatitis) is the best-known manifestation of an unusual corticosteroid-sensitive systemic fibrosclerotic disease that is associated with high plasma immunoglobulin G4 (IgG4) and tissue infiltration with IgG4-secreting plasma cells. Pancreatic and biliary manifestations of this condition are well-reported, but reports of other systemic involvement are few. We report here a case of initially unrecognized autoimmune pancreatitis followed 5 years later by a focal sclerosing lymphoplasmacytic tubulointerstitial nephritis and concurrent membranous nephropathy. The patient presented with hypertension, a raised serum creatinine, proteinuria, elevated serum IgG4, and eosinophilia. Immunolabeling of renal tissue showed numerous IgG4 positive plasma cells with peritubular and glomerular subepithelial IgG4 deposition. On steroid therapy serum IgG4 levels normalized, the eosinophilia resolved, and there was improvement in symptomatic wheeze, dry eyes, serum creatinine, and liver function tests. This case highlights a distinctive and potentially treatable form of interstitial nephritis manifesting from a systemic immune disorder, and provides circumstantial evidence to support the notion that dysregulated IgG4 can precipitate the development of a form of membranous nephropathy.     

Les atteintes uro-néphrologiques au cours de la maladie associée aux IgG4

Hyper-IgG4 syndrome, or IgG4-related disease, is an emerging disorder, involving one or more organ(s), and characterized by “storiform” fibrosis and inflammatory lesions with a predominance of IgG4+ plasma cells and increased IgG4 serum levels. Since the first report of auto-immune pancreatitis, numerous organ lesions have been reported and have been found to occur in a same patient including: sialadenitis, dacryoadenitis, lymphadenopathy, liver and biliary tract involvement, and renal and retroperitoneal lesions. Renal involvement was first described in 2004 and usually presents as functional and/or morphological abnormalities. In most cases, renal pathological analysis reveals tubulointerstitial nephritis that is rarely associated with glomerular lesions. Retroperitoneal fibrosis is also a typical feature that may be associated with periaortitis or inflammatory abdominal aortic aneurysm. First line treatment is based on corticosteroid therapy. Short-term outcome is usually favorable. However, patients should be carefully monitored for relapses and long-term complications. Although the multiple organ lesions share common clinical, biological, radiological and pathological features, no consensus diagnostic criteria have yet been validated for IgG4-related disease. Ruling out differential diagnoses is thus mandatory. Our literature review provides nephrologists, urologists and pathologists with key elements that will help in the early diagnosis and proper management of this new and emerging disorder.     

Late flare-up of nephrotic lupus nephritis transforming histological pattern and autoantibody reactions

A 15-year-old boy developed a nephrotic syndrome. At that time, autoantibodies related to systemic lupus erythematosus (SLE) had been persistently negative, even on repeated evaluation. C1q was normal, but C4, C3 and CH50 were low. Renal biopsy revealed membranous lupus nephritis (LN) based on the new classification of glomerulonephritis in SLE [Weenig et al. 2004]. We did not establish our diagnosis of SLE on the criteria of the American Rheumatism Association (ARA). The patient showed complete remission ofnephrotic syndrome treated with prednisolone and cyclophosphamide. Thereafter, he had no proteinuria and clinical evidence of SLE for 22 years. At the age of 37, however, he developed facial discoid eruption, proteinuria in the nephrotic range, hypocomplementemia and positive reaction to autoantibodies of SLE. Light microscopic findings of renal biopsy indicated mesangial LN, which showed "full-house" immunofluorescence and mesangial dense deposits associated with diffuse epithelial cell foot process effacement in electron microscopy. Steroid therapy was very effective. This case initially showed autoantibody-negative and hypocomplementemic LN with membranous type, and transformed to SLE with mesangial LN after a long interval.     

Repeat renal biopsy in a girl with tubulointerstitial nephritis and uveitis syndrome

A Japanese girl aged 8 years who presented with a 2-month history of uveitis subsequently developed tubulointerstitial nephritis. A percutaneous renal biopsy revealed massive interstitial mononuclear cell infiltrates consisting of CD4-positive T cells. Despite administration of topical corticosteroids, the ocular symptoms persisted. Systemic corticosteroid therapy dramatically reduced the ocular symptoms and urinary β₂-microglobulin (β 2MG) concentration. However, reducing the prednisolone dosage induced recurrence of uveitis associated with increased levels of urinary β 2MG. The CD4-positive T cell infiltration persisted in the second renal biopsy performed 6 months after the first renal biopsy. These observations suggest that the interstitial cell infiltration persists for a relatively long time in a proportion of patients with tubulointerstitial nephritis and uveitis syndrome (TINU). Although the renal outcome of TINU has been reported to be favorable, prolonged interstitial cell infiltration may affect long-term renal outcome. Selected patients with TINU should be followed with close observation. Received: 7 February 2001 / Revised: 8 June 2001 / Accepted: 27 June 2001     

Membranous nephropathy: a rare renal manifestation of IgG4-related systemic disease

This is a case of IgG4-related systemic disease (ISD) and its rare renal manifestation as membranous nephropathy (MGN). The patient presented with peripheral edema, hematuria and proteinuria. 24-h urine revealed proteinuria of up to 15 g/d. Renal biopsy revealed MGN and many IgG4-positive plasma cells. Serum IgG4 levels were elevated at 750 mg/dl (9 - 89 mg/d). Biopsies of multiple tissues revealed many IgG4-positive plasma cells. Prednisone was initiated after making the diagnosis of ISD. However, the patient progressed into renal failure and eventually needed dialysis despite rituximab therapy. The renal manifestation of ISD typically shows tubulointerstitial nephritis, but, rarely, it may include glomerular abnormalities such as MGN or membranoproliferative glomerulonephritis. Castleman disease (CD) and ISD share similarities in pathology, particularly in the lymph nodes. Rituximab has shown promising results in some patients with ISD, CD, and MGN, and its use should be considered in steroid-resistant cases. Clinicians need to be made aware of ISD and its varied presentations. Timely initiation of steroid therapy can induce remission, and delay in therapy can cause permanent organ damage. Therefore, clinicians must have a high index of suspicion to make an early diagnosis of ISD in order to initiate appropriate treatment.     

Recurrent lupus nephritis in the second allograft of a patient with systemic lupus erythematosus

Lupus glomerulonephritis is a common and serious complication of systemic lupus erythematosus (SLE) affecting up to 50% of lupus patients. Recurrent lupus nephritis is rare, complicating as low as 1% of the lupus transplant population according to some authors. However, it may be underreported with more realistic recurrent rates oscillating from 2.8 to 8.7%. We report the case of a patient with SLE who lost her first allograft 4 years after transplantation with a diagnosis of de novo fibrillary glomerulopathy. She underwent a second renal transplantation and her renal function was stable for the past 5 years. She now presented with skin rash, arthralgias and positive lupus serologies. Her creatinine was slightly elevated and proteinuria was also noted. A renal biopsy performed revealed a recurrent focal proliferative lupus nephritis (WHO III). Retrospectively, we believe that her first allograft was also lost to recurrent lupus nephritis. This is a unique case of recurrent lupus nephritis in the second allograft of a patient with SLE.     

Proposal for diagnostic criteria for IgG4-related kidney disease

Background

IgG4-related disease has attracted wide attention recently. It is characterized by a high level of serum IgG4 and dense infiltration of IgG4-positive plasma cells into multiple organs, with the kidney being one representative target. Although several sets of diagnostic criteria for autoimmune pancreatitis (AIP) are available and renal lesion is recognized as an extra-pancreatic manifestation of AIP, it is difficult to differentiate IgG4-related tubulointerstitial nephritis (TIN) without AIP from other types of TIN. To clarify the entity of IgG4-related kidney disease (IgG4-RKD) and support in-depth studies, the Japanese Society of Nephrology has established a working group to prepare diagnostic criteria for IgG4-RKD.

Method

The working group analyzed 41 patients with IgG4-RKD, and collected the following data to devise a diagnostic algorithm and diagnostic criteria for IgG4-RKD: clinical features including extra-renal organ involvement, urinalysis and serological features including serum IgG4 levels, imaging findings demonstrated by computed tomography (CT), renal histology with IgG4 immunostaining, and response to steroid therapy.

Results

The conditions for criteria are as follows. (1) Presence of some kidney damage, as manifested by abnormal urinalysis or urine marker(s) and/or decreased kidney function with either elevated serum IgG level, hypocomplementemia, or elevated serum IgE level. (2) Kidney imaging studies showing abnormal renal imaging findings, i.e., multiple low density lesions on enhanced CT, diffuse kidney enlargement, hypovascular solitary mass in the kidney, and hypertrophic lesion of the renal pelvic wall without irregularity of the renal pelvic surface. (3) Serum IgG4 level exceeding 135?mg/dl. (4) Renal histology showing two abnormal findings: (a) dense lymphoplasmacytic infiltration with infiltrating IgG4-positive plasma cells >10/high power field (HPF) and/or ratio of IgG4-positive plasma cells/IgG positive plasma cells >40%. (b) Characteristic ??storiform?? fibrosis surrounding nests of lymphocytes and/or plasma cells. (5) Extra-renal histology showing dense lymphoplasmacytic infiltration with infiltrating IgG4-positive plasma cells >10/HPF and/or ratio of IgG4-positive plasma cells/IgG-positive plasma cells >40%. The diagnosis is classified into 3 stages of definite, probable and possible according to the combinations of the above conditions. Thirty-nine cases (95.1%) were diagnosed with IgG4-RKD according to the criteria.

Conclusion

The provisional criteria and algorithm appear to be useful for clarifying the entity of IgG4-RKD and seeking underlying IgG4-RKD cases; however, further experience is needed to confirm the validity of these criteria.