Relapse Of Minimal Change Nephrotic Syndrome Research Articles

Circulating plasmablasts and high level of BAFF are hallmarks of minimal change nephrotic syndrome in adults.

The recent success achieved with the use of B cell-depleting agents in some patients with minimal change nephrotic syndrome (MCNS) suggests an unexpected role for B lymphocytes in the pathogenesis of this immune-mediated glomerular disease. Nevertheless, no extensive B-cell phenotyping analysis has ever been performed in untreated adult patients soon after MCNS diagnosis. We investigated the distribution of the different B-cell subpopulations in 22 untreated adult patients with biopsy-proven MCNS [MCNS relapse (MCNS-Rel)]. We compared these data with those for 24 healthy controls, 13 MCNS patients in remission (with no specific treatment) and 19 patients with idiopathic membranous nephropathy (IMN). Patients with MCNS-Rel or IMN had higher proteinuria and lower serum albumin and gammaglobulin levels (P < 0.0001 for all comparisons) than MCNS patients in remission. Plasmablasts were the only B-cell subsets present at significantly higher levels in MCNS-Rel patients than in the patients of the other three groups (P < 0.05 for all comparisons). The lower albumin levels and higher proteinuria levels were positively correlated with the percentage of circulating plasmablasts (Spearman test's ρ = -0.54, P = 0.01 and ρ = 0.65, P = 0.002, respectively). Similarly, the increase of immunoglobulin M (IgM) and the decrease of IgG levels were significantly associated with the percentage of plasmablasts in MCNS-Rel patients (Spearman's ρ = 0.36, P = 0.01 and Spearman's ρ = -0.60, P = 0.01, respectively). Increased production of interleukin (IL)-21, IL-6 and B-cell activating factor (BAFF) in the serum of MCNS-Rel patients was found significantly correlated with the percentage of plasmablasts (ρ = 0.72, P = 0.0002, ρ = 0.49, P = 0.04 and ρ = 0.62, P = 0.009, respectively). An increase in the proportion of circulating plasmablasts seems to be a hallmark of untreated MCNS in adult patients. Further studies are required to more precisely determine the phenotype and functions of these cells.

MON-034 A case of frequent relapse minimal change nephrotic syndrome with steroid-induced psychiatric syndromes treated by a low-dose and short-term steroid therapy in combination with cyclosporine

Oral prednisolone (PSL) alone in an initial dosage of 1.0 mg/kg/day is generally administered for a minimum of 4 weeks in adult patients with minimal change nephrotic syndrome (MCNS), and 80% of patients with MCNS achieve clinical remission. However, relapses frequently occur in manyMCNS patients,rendering repeathigh-dosePSLtreatment necessary. Long-term treatment with high-dose steroids increasesthe risk of steroid toxicity, such as diabetes mellitus, gastric complications, infections, osteoporosis, and steroid-induced psychiatric syndrome, which may compromise the patient’s quality of life. Therefore, useful strategies are necessary to reduce the dosage and duration of steroid therapy for frequent relapse MCNS (FRNS) troubled by steroid toxicity.Here we suggest a new combination therapy of low-dose and short-term steroid with cyclosporine (CyA). A 51-year-old man with FRNS with a history of recurrent steroid-induced psychiatric syndrome was admitted to our department in April 2018. Immunosuppressive therapy with both PSL and CyA (initial dose0.3 mg/kg/day and 1.5 mg/kg/day, respectively)was started. Complete remission was obtained just 2 weeks later;the dose of PSL was promptly reduced and tapered. Clinical course and Results A 51-year-old man was admitted to our hospital for biopsy-proven recurrence of FRNS. MCNS initially occurred at the age of 15, and he was basically treated withPSL(initial dosage 1.0 mg/kg/day at onset and at relapses). The steroid therapy had finished at the age of 42, after which complete remission was maintained. At the age of 16 he had developed steroid-induced depression ;hispsychiatric symptoms were maintained in stable condition with psychiatrist visits andfluvoxamine maleate acid (300 mg/day). After admission we started an immunosuppressive therapy with PSL in combination with CyA (initial dosage of 0.3 mg/kg/day and 1.5 mg/kg/day, respectively), based on his history of depression and in attempt to reduce the dosage and duration of steroid therapy. Complete remission was obtained after 2 weeks of treatment, but steroid-induced psychiatric syndrome recurred the day after remission. Thus, we promptly reduced the dosage of PSL (weekly by 2.5-5 mg/day), which rapidly improvedpsychiatric syndrome. The dosage of PSL was 5 mg/day at 5 weeks after the start of treatment, and complete remission wasmaintained without relapse of MCNS. We successfully treated a recurrent case of FRNS with steroid-induced psychiatric syndrome by alow-dose,short-term steroid therapy andCyA, which induced early complete remission,allowed promptPSL dose reductionwithout relapse,and quickly resolved psychiatric symptoms. This treatment protocol is very useful and can be a future treatment strategy for FRNS with steroid-induced psychiatric syndrome.

Minimal change nephrotic syndrome associated with non-Hodgkin lymphoid disorders: a retrospective study of 18 cases.

Few studies have examined the occurrence of minimal change nephrotic syndrome (MCNS) in patients with non-Hodgkin lymphoma (NHL). We report here a series of 18 patients with MCNS occurring among 13,992 new cases of NHL. We analyzed the clinical and pathologic characteristics of this association, along with the response of patients to treatment, to determine if this association relies on a particular disorder. The most frequent NHLs associated with MCNS were Waldenström macroglobulinemia (33.3%), marginal zone B-cell lymphoma (27.8%), and chronic lymphocytic leukemia (22.2%). Other lymphoproliferative disorders included multiple myeloma, mantle cell lymphoma, and peripheral T-cell lymphoma. In 4 patients MCNS occurred before NHL (mean delay, 15 mo), in 10 patients the disorders occurred simultaneously, and in 4 patients MCNS was diagnosed after NHL (mean delay, 25 mo). Circulating monoclonal immunoglobulins were present in 11 patients. A nontumoral interstitial infiltrate was present in renal biopsy specimens from 3 patients without significant renal impairment. Acute kidney injury resulting from tubular lesions or renal hypoperfusion was present in 6 patients. MCNS relapse occurred more frequently in patients treated exclusively by steroid therapy (77.8%) than in those receiving steroids associated with chemotherapy (25%). In conclusion, MCNS occurs preferentially in NHL originating from B cells and requires an aggressive therapeutic approach to reduce the risk of MCNS relapse.

Patients with adult minimal change nephrotic syndrome treated with long-term cyclosporine did not experience a reduction in their eGFR

The long-term efficacy and safety of cyclosporine (CyA) in the treatment of adult minimal change nephrotic syndrome (MCNS) was examined. The medical record of 15 patients diagnosed with MCNS by renal biopsy and treated with CyA for at least 2 years were reviewed. The mean administration period of CyA was 78.3 months. The mean CyA dose for the induction period was 2.1 ± 0.9 mg/kg and 1.7 ± 1.0 mg/kg for the maintenance period. The mean dose of prednisolone used during the induction period was 20.3 mg and 2.7 mg during the maintenance. The frequency of MCNS relapse was decreased to 0.5 times/year in patients treated with CyA, compared to treatment without CyA (2.4 times/y). Two cases of mild liver damage and 3 cases of elevated blood pressure were observed during the administration of CyA. These adverse effects improved after reducing the CyA dose or treatment with an antihypertensive agent. A decrease in the estimated glomerular filtraion rate (eGFR) was not associated with long-term CyA use. At our institution, patients who were treated for MCNS with CyA for at least 2 years experienced no deterioration in renal function.

20年後に再発し,副腎皮質ステロイド,シクロスポリン併用療法が著効した高齢者微小変化型ネフローゼ症候群の1例

20年後に再発し,副腎皮質ステロイド,シクロスポリン併用療法が著効した高齢者微小変化型ネフローゼ症候群の1例

Combined cyclosporine and prednisolone therapy in adult patients with the first relapse of minimal-change nephrotic syndrome

Although minimal-change nephrotic syndrome (MCNS) is highly steroid-responsive, some patients show frequent relapses, necessitating administration of repeated courses of prednisolone (PSL) at high doses. The adverse effects of long-term PSL treatment include osteoporosis, infection, diabetes, cataract, etc., most of which are serious. It is therefore necessary to establish useful strategies to reduce the PSL dose. Patients with the first relapse of MCNS were randomly assigned to two groups, namely, the CyA (AUC 1700-2000 ng/ml) + PSL (0.8 mg/kg/day) group (n = 26) and the PSL alone (PSL) (1.0 mg/kg/day) group (n = 26), and the clinical characteristics were compared between the two groups. All patients used C2 for CyA monitoring. A significant decrease of the urinary protein excretion (P = 0.02) and serum total cholesterol (P = 0.003) was observed at 2 weeks from the first relapse in the CyA + PSL group. The increase in the serum total protein (P = 0.03) and serum albumin (P = 0.007) as compared with that in the PSL group was also observed in the CyA + PSL group at this time-point. The time to remission in the CyA + PSL group was shorter than that in the PSL group (P = 0.006). It was possible to obtain early remission and reduce the PSL dose with combined CyA and PSL therapy in patients with MCNS.

Complete remission of minimal-change nephrotic syndrome induced by apheresis monotherapy

We report a case of a 17-year-old male with relapse of minimal-change nephrotic syndrome (MCNS), in whom apheresis monotherapy without steroids or immunosuppressants resulted in complete remission. The patient initially developed nephrotic syndrome in February 1998. The first renal biopsy confirmed the diagnosis of MCNS. The patient was also found to be a carrier of hepatitis B virus. Steroid therapy was started with oral prednisolone 60 mg/day. Complete remission was achieved in 3 months, and the steroid treatment was tapered off in May 2001. During the steroid tapering, temporal exacerbation of liver function was noted. In July 2002, the patient was admitted to our hospital again due to relapse of nephrotic syndrome. Second biopsy reconfirmed the diagnosis of MCNS. Since the serum titer of HBV was elevated, apheresis monotherapy was selected to avoid the risk of steroid-induced fulminant hepatitis. Four sessions of low-density lipoprotein apheresis (LDL-A) and 5 sessions of double-filtration plasmapheresis (DFPP) reduced the proteinuria from 9.2 g/day to 0.2 g/day over 38 days without any additional medication. Proteinuria remained suppressed below 0.2 g/day for more than 12 months and no exacerbation of liver function was observed up to the final follow-up in September 2003. The present case suggested the potential of apheresis monotherapy to induce and maintain complete remission of MCNS and an important role of circulating factors in the pathogenesis of MCNS.

Up-regulation of interleukin-4 and CD23/FcepsilonRII in minimal change nephrotic syndrome.

Although the pathogenesis of childhood minimal change nephrotic syndrome (MCNS) has not been clearly defined, the current hypothesis favors an involvement of T cell dysfunction. The symptom onset and the relapse of MCNS are frequently associated with allergy and increased IgE levels in sera. Since a T cell-derived cytokine interleukin-4 (IL-4) plays a key role in the regulation of IgE production and allergic response, we investigated the role of IL-4 in the pathophysiology of MCNS. Using fluorescence-activated cell scanning we observed a significantly higher expression of CD23, the type II IgE receptor (FcepsilonRII), on fresh B cells from active MCNS patients (n=22) compared with age-matched healthy normal controls (n=12). The upregulation of CD23 correlates with greater IL-4 activity in the culture supernatant of MCNS peripheral blood lymphocytes (PBLs) than normal PBLs stimulated by mitogens, as assessed by the CD23-inducing effect of the PBL supernatant on tonsillar B cells. Furthermore, Northern blot and reverse transcription-based polymerase chain reaction analysis have revealed significantly elevated levels of IL-4 mRNAs both in mitogen-stimulated and unstimulated MCNS PBLs, compared with healthy normals or disease controls with other renal disorders. Together these results strongly suggest that the upregulation of IL-4 in T cells may be part of the T cell dysfunction involved in MCNS.

Glomerular hypertrophy in relapsing minimal change nephropathy.

Clincopathological and morphometric analysis of glomerular hypertrophy was conducted using biopsies from 89 patients with minimal change nephrotic syndrome (MCNS). Of the 80 patients, in 69 with complete remission and in 20 with one or more relapses, various clinical and morphometric parameters were compared to 15 normal controls. Proteinuria was more severe and serum creatinine (Cr) concentration significantly higher in patients with relapse of proteinuria. The morphometric analysis showed that the sizes of (1) glomerular tufts and (2) glomerular capillaries were significantly larger in patients in the relapse group than in the remission or control groups, but no difference in the size of Bowman's capsule was found between the two MCNS subgroups. The intertubular capillaries were narrower in patients who failed to reach prompt complete remission. A negative correlation between intra- and extraglomerular capillary size was evident (r = -0.83, p < 0.001). A definitive correlation was detected between the circumference of glomerular capillary loops and the degree of proteinuria (r = 0.89, p < 0.001). The mean tubulocapillary diffusion distance was significantly longer in biopsies of the patients in relapse and showed a close significant correlation with serum Cr level (r = -0.87, p < 0.001) and intertubular capillary size (r = -0.87, p < 0.001). These data suggest that extra- and intraglomerular hemodynamic alterations in MCNS lead to glomerular hypertrophy, and dilatation of the glomerular capillary loop plays a key role in the relapse of MCNS.

Cerebral venous sinus thrombosis in minimal change nephrotic syndrome

Three cases of cerebral venous sinus thrombosis (CVST) occurring in patients with minimal change nephrotic syndrome (MCNS) are described. Personality change in two of these patients was wrongly attributed to steroid therapy prior to the discovery of the CVST. In addition, von Willebrand factor (vWF) levels were grossly elevated in one patient, during a previous relapse of MCNS, prior to developing CVST, and may be a useful prognostic tool in predicting thrombotic events in nephrotic patients.

Cerebral venous sinus thrombosis in minimal change nephrotic syndrome

Three cases of cerebral venous sinus thrombosis (CVST) occurring in patients with minimal change nephrotic syndrome (MCNS) are described. Personality change in two of these patients was wrongly attributed to steroid therapy prior to the discovery of the CVST. In addition, von Willebrand factor (vWF) levels were grossly elevated in one patient, during a previous relapse of MCNS, prior to developing CVST, and may be a useful prognostic tool in predicting thrombotic events in nephrotic patients.