IgG4-RKD is a comprehensive term for renal lesions, including renal parenchymal lesions and renal pelvic lesions, related to IgG4-RD, which is a recently recognized and proposed clinical entity characterized by a dense lymphoplasmacytic infiltrate rich in IgG4+ plasma cells with fibrosis that affects several organs [6], [9]. TIN involving tubules and/or the interstitium of the kidney is the most dominant feature of IgG4-RKD [9]; however, IgG4-RKD in the renal pelvis is rare [7]–[10]. Here, we report a rare case of IgG4-RKD that mimicked renal pelvic carcinoma.

A comprehensive English and non-English search for all articles pertinent to IgG4-RD of the renal pelvis was conducted using PubMed. Since Naoto Kuroda [11] first reported a case of IgG4-RD arising in the renal pelvis in 2009, six cases of IgG4-RD of the renal pelvis have been reported previously in the world literature (Table 1) [12]–[16]. The mean age at diagnosis was 59.8 years (range: 49 to 80 years), with a male: female ratio of 1:1. Most patients presented with renal lesions in the left kidney, with a left-to-right presentation ratio of 2:1. Patients visited the hospital with or without complaints of non-characteristic presentations (i.e., flank pain), and none of the patients had hematuria. Hypocomplementemia and elevated serum IgG are characteristic features of IgG4-RD. Elevated serum IgG and IgG4 were found in all patients, but no hypocomplementemia was found in these seven cases, including our case (Table 1). Although hypocomplementemia is a distinct feature of IgG4-RD, a relatively low proportion of patients actually have it.

Table 1. Previous reports of IgG4-related kidney disease arising in the renal pelvis

Patients with IgG4-RD often have lesions in several organs, either synchronously or metachronously, although others may show the involvement of only a single organ. Renal lesions are recognized as extra-pancreatic manifestations of IgG4-RD; the condition can develop as IgG4-RKD singly or associated with the lesions of other organs. In previous cases, renal and extra-renal (salivary gland) involvements in IgG4-RD have presented simultaneously in two patients [11], [12]. In the current case, a systemic examination showed no other abnormal findings, inclusive of the salivary glands, lacrimal glands, and pancreas. Thus, the condition was diagnosed as IgG4-RD isolated in the renal pelvis without the involvement of other organs.

On the basis of the results of a diagnostic algorithm procedure and with references to several diagnostic criteria for AIP, Mitsuhiro Kawano [6] proposed diagnostic criteria for IgG4-RKD: (1) presence of some kidney damage, as manifested by laboratory examination; (2) kidney imaging studies showing abnormal renal findings, i.e., multiple low-density lesions on enhanced CT; (3) elevated serum IgG4 levels exceeding 135 mg/dL; (4) renal histology showing dense lymphoplasmacytic infiltration with infiltrating IgG4+ plasma cells and fibrosis; and (5) extra-renal histology showing prominent lymphoplasmacytic infiltration with infiltrating IgG4+ plasma cells. The diagnosis is classified into three stages—definite, probable, and possible—according to the combinations of the above conditions. In their diagnostic criteria, abnormal renal imaging findings were essential for making a definitive diagnosis. In the present case, all of these conditions, including imaging studies that identified low-density lesions, pathologic examinations that revealed characteristic changes, and elevated serum IgG4, prompted the definitive diagnosis of IgG4-RKD.

A rapid response to corticosteroid therapy is a characteristic feature of IgG4-RD, and corticosteroids are typically the first line of therapy, although no controlled trial has been performed. Moreover, the protocol used for corticosteroid therapy varies among countries and institutions [1]. Because of the decreased level of serum IgG4 after ureteronephrectomy, our patient received a close follow-up without corticosteroid therapy. In the reported cases, patients with IgG4-RKD arising from the renal pelvis were treated according to different strategies, including surgical treatment alone for two patients, corticosteroid therapy alone for two patients, and surgical and corticosteroid treatment for the remaining two patients. The renal lesions improved or resolved after the corticosteroid treatment in three patients who received corticosteroid treatment (Table 1). Takahashi and colleagues [17] also found that lesions progressed in three IgG4-TIN patients receiving no corticosteroid treatment or surgical resection and that lesions regressed in all IgG4-TIN patients who underwent corticosteroid treatment. These observations indicate that effective interventions should begin as soon as possible for irreversible fibrosis in IgG4-RKD. Because corticosteroid treatment has a remarkable effect in this type of disease, at least in the short term, this treatment is vital to avoid unnecessary surgery. CT-guided biopsy or laparoscopic biopsy of the original tumor might help to rule out malignancy.

Recent studies have revealed several characteristic clinical features of IgG4-RKD, including predominance in middle-aged to older men, frequent association with IgG4-RD in other organs, high levels of serum IgG and IgG4, and a good initial response to corticosteroids. However, longer follow-up data for IgG4-RKD, including relapse information, are still sparse. Takako Saeki and his colleagues [18] retrospectively analyzed the longer-term clinical course of 43 patients with IgG4-TIN in detail in a larger cohort. This analysis included the largest series on the long-term outcomes of corticosteroid treatment of IgG4-RKD. Saeki et al. showed that 1 month after the start of treatment, most of the abnormal serology and radiology parameters had improved, and relapse of IgG4-related lesions occurred in 8 of 40 treated patients. These studies indicate that the response of IgG4-RKD to corticosteroids is rapid and partial, and that irreversible lesions may remain, especially in patients with advanced renal damage. Patients with renal dysfunction should receive corticosteroid therapy, although spontaneous improvement of lesions can also occur in IgG4-TIN and the indications for corticosteroid therapy in IgG4-RKD have not been established. Careful attention should be paid to renal function during follow-up without therapy [18], [19]. A large-scale prospective study is necessary to determine a more useful treatment strategy for IgG4-RKD.

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