Complete Remission Of Nephrotic Syndrome Research Articles

#1162 Paraneoplastic podocytopathy in patients with solid cancer: clinical characteristics and new insights into pathophysiological processes about 21 cases

Abstract Background and Aims Minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) may occur in patients with solid cancer but this rare association has never been extensively investigated. Here, we report the first series of patients presenting this association, also named paraneoplastic podocytopathy with nephrotic syndrome (PPNS) . Previous study has demonstrated the specific induction in both podocytes and Reed-Sternberg cells of C-Maf Inducing Protein (CMIP) in patients with MCD and Hodgkin lymphoma. Here, we examined whether this molecular relationship was also relevant in patients developing PPNS in the setting of solid cancer. We have investigated the potential CMIP expression in kidney biopsies and in tumor tissues. Method We collected data from patients who presented with histologically proven cancer and concomitantly developed a nephrotic syndrome (± 3 months) related to MCD or FSGS Follow-up data were collected after 3, 6, 12 months and at last visit. We identified a control group of idiopathic nephrotic syndromes (INS) matched on sex, age and histological type, in order to compare the characteristics of these controls with patients with PPNS. Expression of CMIP was studied by immunohistochemistry and by immunofluorescence confocal microscopy on kidney biopsy and tumor samples. We used kidney biopsies from INS and tumors from patients without associated nephrotic syndrome as controls. Results Twenty-one PPNS patients and 21 controls with INS without cancer were identified. The median age of PPNS patients was higher (68 years) than usually observed in INS. Most of them (76%) had a MCD. A broad spectrum of cancers was found (bronchopulmonary, prostatic, colorectal…) . Baseline characteristics were similar between PPNS patients and INS controls, with a median urinary protein creatinine ratio of 865 and 900 mg/mmol, blood albumin t 15 and 15.3 g/L. Estimated glomerular filtration rate were 48 and 60 ml/min/1.73 m² respectively (no significant difference) . At presentation, PPNS patients were more likely to have hematuria (p = 0.031) , a lower median hemoglobin level than controls (p = 0.039) . Moreover, PPNS patients were less often treated with immunosuppressive drugs (p = 0.004) . After 12 months of follow-up, PPNS patients had a less favorable outcome than INS controls, with a mortality rate three times higher (30% vs 9.5%, p = 0.098) and a much lower rate of complete remission of nephrotic syndrome (25% vs 73.7%, p = 0.008, Table 1). CMIP labeling was performed on 13 tumor samples and 16 kidney biopsies in PPNS patients, and on 5 kidney biopsies with INS, and on 5 control tumor samples. Podocyte labeling of CMIP is observed on all but one kidney biopsy. CMIP labeling was positive on all case tumors, but only a scarce staining was detected in control patients with solid cancer without nephrotic syndrome (Fig. 1). In PPNS patients, confocal microscopy analysis on tumoral tissue showed high expression of CMIP in some epithelial cells and in immune infiltrating cells.. In addition, we found that CMIP was specifically express in CD4 T lymphocyte subset (Fig. 2), but not in CD20, FOXP3 or PD1 lymphocytes, defining a novel FOXP3−/PD1− CMIP high CD4+T lymphocyte subpopulation, within immune cell infiltrates. Conclusion We report the first series of patients with PPNS, who have a more severe renal and overall prognosis than controls. We show that patients with PPNS display higher induction of CMIP, both in the tumor and in podocytes. Strikingly, we identified within immune infiltrates a new subset of T-cell harboring a particular phenotype (CD4+, CMIPhigh, FOXP3−, PD1−) , which is not detected in patients with solid tumor without nephrotic syndrome and which could play a key role in the pathophysiology of PPNS.

A Case of Imatinib Induced Nephrotic Syndrome in a Child with Chronic Myeloid Leukaemia

Background:Tyrosin kinase inhibitors (TKI) are used as a targeted therapy for the treatment of chronic myeloid leukaemia and Philadelphia chromosome positive acute lymphoblastic leukaemia. Increasing use of TKI has been associated with hypertension, proteinuria and acute kidney injury. There are only afew reports of adults with TK -inhibitor associated nephrotic syndrome.But TK inhibitor associated Nephrotic syndrome is very rare in paediatric age group. Case:A -6- year old boy presented with fever, anaemia, splenomegaly, leucocytosis and finally diagnosed as accelerated phase of chronic myeloid leukaemia (CML) by bone marrow study.He achieved clinical and haematological remission with Imatinib. But developed generalized oedema and was found to have massive proteinuria and microscopic haematuria after three and half months. Renal biopsy revealed focal segmental glomerulosclerosis. Imatinib along with Prednisolone, 60 mg/m2/ day was added to treat nephrotic syndrome. Imatinib discontinued as the patient did not achieve complete remission. After one week of Imatinib withdrawal and five weeks of daily prednisolone the boy attained complete remission of nephrotic syndrome. Conclusion:Tyrosine Kinase inhibitors are important therapies in paediatric cancer and their use is expanding. Timely recognition of renal adverse effectsfor TK inhibitors can aid in the proper management of cancer patients. J Bangladesh Coll Phys Surg 2023; 41: 170-172

MO174: Proliferative Glomerulonephritis with Monoclonal Immunoglobulin Deposits: Rare Disease with Poor Prognosis?

Abstract BACKGROUND AND AIMS Proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMIDs) is a recently described disease among the spectrum of monoclonal gammopathy of renal significance (MGRS). The disease is renal limited and manifests with chronic glomerular disease, altered renal function and albuminuria, sometimes in the nephrotic range. Kidney injury results from direct glomerular deposition of the monoclonal immunoglobulin. Of note, in approximately 70% of the cases of PGNMID, a clone cannot be detected. METHOD Clinical case of PGNMID. RESULTS A 36-year-old woman, with a past history of acute glomerulonephritis, was treated with mycophenolate mofetil 2 g and concomitant methylprednisolone 2 mg from January 2020 to September 2021 (kidney biopsy was not performed). After 3 months, she showed recurrence of nephrotic syndrome: peripheral edema, severe weakness, shortness of breath, decreased diuresis up to oliguria and increased blood pressure. Blood analysis has shown: GFR 127 mL/min/1.73 m2, total protein 44.4 g/L, albumin 16.2 g/L; autoimmune markers—negative; kappa free light chains 182 mg/L (3.3–19.4 mg/L); lambda free light chains 112 mg/L (5.71–26.3 mg/L), ratio of kappa/lambda 1.63 (0.26 to 1.65). Urine analysis has shown: total protein excretion rate 3.5 g/24 h; albuminuria 1000 mg/g; urine microscopy—normal; kappa free light chains ++++; lambda free light chains +++. A kidney biopsy has shown up to 12 glomerulies, which have different sizes, some are enlarged, as due to diffuse proliferation of mesangial cells, oedema and segmental proliferation of endothelial cells, as fibrinoid changes; some of the capillary loops are infiltrated with monocytes, an uneven increase in the mesangial matrix, there are small areas of segmental sclerosis that tend to be nodular in some glomerulies. Degenerative changes (granular, vacuolar, in some areas hyaline-droplet dystrophy), necrosis of epithelial cell groups, areas of epithelial atrophy with thickening of the tubular basement membrane (up to 10% of the biopsy volume) are sharply expressed in the tubules. In the tubules—protein masses, exfoliated epithelium, the lumen of the tubules is sharply reduced and/or absent due to pronounced degenerative changes in the epithelium. In the stroma—edema, areas of interstitial fibrosis, including perivascular (up to 10% of the biopsy volume), focal lymphohistiocytic cell infiltrates. By definition, there is evidence of monoclonal deposits by immunofluorescence: IgA (predominantly), IgG, IgM, С3 deposits; С1q, CD20 (В- lymphocytes), AA amyloidosis -negative expression; kappa free light chains (predominantly) +++; lambda free light chains ++ (Figure 1). Finally, we reached a clinical diagnosis of CKD G1, A3: PGNMIDs (IgM, IgA, IgG; LC Ķ˃λ). Nephrotic syndrome. Light Chain Deposition Disease. At that point (January 2021), we have started clone-targeted chemotherapy following the data sheet, with urinary and haematological response after 2 weeks, and normal kidney function with complete remission of nephrotic syndrome after 4 weeks, as well as a negativization of kappa and lambda free light chains deposits (Table 1). Three months after admission, the patient maintained haematological and kidney remission up to now. CONCLUSION MGRS is not an independent kidney disease, not ‘chronic glomerulonephritis’, but a condition in which kidney damage is secondary to clonal B-cell proliferation. In other words, MGRS is a precancerous disease combined with chronic kidney disease that requires immediate treatment. Renal prognosis is poor, with progression to ESKD in 25% of patients within 30 months and frequent early recurrence on the renal allograft. However, recent studies indicate that clone-targeted chemotherapy may significantly improve renal outcomes, opening future perspectives for the management of this rare disease.

Interventions for focal segmental glomerulosclerosis in adults.

Focal segmental glomerulosclerosis (FSGS) can be separated into primary, genetic or secondary causes. Primary disease results in nephrotic syndrome while genetic and secondary forms may be associated with asymptomatic proteinuria or with nephrotic syndrome. Overall only about 20% of patients with FSGS experience a partial or complete remission of nephrotic syndrome with treatment. FSGS progresses to kidney failure in about half of the cases. This is an update of a review first published in 2008. To assess the benefits and harms of immunosuppressive and non-immunosuppressive treatment regimens in adults with FSGS. We searched the Cochrane Kidney and Transplant Register of Studies to 21 June 2021 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. Randomised controlled trials (RCTs) and quasi-RCTs of any intervention for FSGS in adults were included. Studies comparing different types, routes, frequencies, and duration of immunosuppressive agents and non-immunosuppressive agents were assessed. At least two authors independently assessed study quality and extracted data. Statistical analyses were performed using the random-effects model and results were expressed as a risk ratio (RR) for dichotomous outcomes, or mean difference (MD) for continuous data with 95% confidence intervals (CI). Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Fifteen studies (560 participants) were included. No studies specifically evaluating corticosteroids compared with placebo or supportive therapy were identified. Studies evaluated participants with steroid-resistant FSGS. Five studies (240 participants) compared cyclosporin with or without prednisone with different comparators (no specific treatment, prednisone, methylprednisolone, mycophenolate mofetil (MMF), dexamethasone). Three small studies compared monoclonal antibodies (adalimumab, fresolimumab) with other agents or placebo. Six single small studies compared rituximab with tacrolimus, cyclosporin plus valsartan with cyclosporin alone, MMF with prednisone, chlorambucil plus methylprednisolone and prednisone with no specific treatment, different regimens of dexamethasone and CCX140-B (an antagonist of the chemokine receptor CCR2) with placebo. The final study (109 participants) compared sparsentan, a dual inhibitor of endothelin Type A receptor and of the angiotensin II Type 1 receptor, with irbesartan. In the risk of bias assessment, seven and five studies were at low risk of bias for sequence generation and allocation concealment, respectively. Four studies were at low risk of performance bias and 14 studies were at low risk of detection bias. Thirteen, six and five studies were at low risk of attrition bias, reporting bias and other bias, respectively. Of five studies evaluating cyclosporin, four could be included in our meta-analyses (231 participants). Cyclosporin with or without prednisone compared with different comparators may increase the likelihood of complete remission (RR 2.31, 95% CI 1.13 to 4.73; I² = 1%; low certainty evidence) and of complete or partial remission (RR 1.64, 95% CI 1.10 to 2.44; I² = 19%) but not of partial remission (RR 1.36, 95% CI 0.78 to 2.39, I² = 22%). In Individual studies, cyclosporin with prednisone versus prednisone may increase the likelihood of partial (49 participants: RR 7.96, 95% CI 1.09 to 58.15) or complete or partial remission (49 participants: RR 8.85, 95% CI 1.22 to 63.92) but not of complete remission. The remaining individual comparisons may make little or no difference to the likelihood of complete remission, partial remission or complete or partial remission compared with no treatment, methylprednisolone, MMF, or dexamethasone. Individual study data and combined data showed that cyclosporin may make little or no difference to the outcomes of chronic kidney disease or kidney failure. It is uncertain whether cyclosporin compared with these comparators in individual or combined analyses makes any difference to the outcomes of hypertension or infection. MMF compared with prednisone may make little or no difference to the likelihood of complete remission (33 participants: RR 1.05, 95% CI 0.58 to 1.88; low certainty evidence), partial remission, complete or partial remission, glomerular filtration rate, or infection. It is uncertain whether other interventions make any difference to outcomes as the certainty of the evidence is very low. It is uncertain whether sparsentan reduces proteinuria to a greater extent than irbesartan. No RCTs, which evaluated corticosteroids, were identified although the KDIGO guidelines recommend corticosteroids as the first treatment for adults with FSGS. The studies identified included participants with steroid-resistant FSGS. Treatment with cyclosporin for at least six months was more likely to achieve complete remission of proteinuria compared with other treatments but there was considerable imprecision due to few studies and small participant numbers. In future studies of existing or new interventions, the investigators must clearly define the populations included in the study to provide appropriate recommendations for patients with primary, genetic or secondary FSGS.

MO301RITUXIMAB FOR RELAPSING MEMBRANOUS NEPHROPATHY: A SPANISH HOSPITAL EXPERIENCE

Abstract Background and Aims B cell targeting agent Rituximab has been proven to be effective and safe for the treatment of idiopathic membranous nephropathy (iMN) in previous studies with nearly 75% achievement of partial or complete remission of nephrotic syndrome. The aim of this study was to evaluate this treatment in a cohort of patients at Complejo Hospitalario de Navarra with relapsing disease. Method This is a retrospective, cross sectional study including 12 patients with membranous nephropathy diagnosed by means of a kidney biopsy. All of them were treated before with different immunosuppressive regimens and had a relapse at the time of the inclusion. All of them were treated with two iv infusions of Rituximab. In this study we report patient clinical and immunological baseline characteristics and treatment response at 12 months of follow up. Results Between 2015-20 a total of 12 patients (41,6% women and 58,3% men) were treated with two iv infusions of Rituximab with a total mean dose of 2gr. All of them diagnosed previously of iMN, and 10/12 were PLA2r positive. Baseline laboratory data showed serum creatinine levels 1,3±0,9 mg/dl, serum albumin 29±9 g/L, 24 hour- urinary protein excretion of 6,8±3,2 and serum PLA2R levels of 50,54±63,2 RU/ml. Either complete or partial response (CR and PR) were achieved in 83,3% of the cases, however only 3/12 (25%) patients had a complete response at 12 months follow up. All patients who responded had also a significative decrease PLA2r antibodies. Three of the patients who did a PR were treated with an incomplete dose of iv Rituximab (two infusions of 500mg). Conclusion Rituximab was effective in our cohort of patients with iMN with achievement of 83,3% response at 12 months of follow up, however only 25% of patients had complete response maybe due to incomplete dosing. Immunological response was seen in all patients. Still, a longer follow up of these patients is needed in order to evaluate Rituximab response.

Spontaneous Bacterial Peritonitis in an Adult Patient with Minimal Change Disease

Patient: Male, 60-year-oldFinal Diagnosis: PeritonitisSymptoms: Abdominal pain • edema of lower extermitiesMedication: —Clinical Procedure: —Specialty: NephrologyObjective:Rare diseaseBackground:Pediatric patients with nephrotic syndrome have a high risk of developing spontaneous bacterial peritonitis (SBP). However, SBP in adults with nephrotic syndrome is very rare. We report a case of SBP induced by Escherichia coli in a 60-year-old male patient on immunosuppressive therapy for the treatment of minimal change disease (MCD).Case Report:The patient was hospitalized with abdominal pain and generalized edema that had lasted for 2 weeks. The patient first started treatment with high-dose oral prednisolone after being diagnosed with MCD 6 months ago. Complete remission of nephrotic syndrome was not achieved even after 5 months of treatment. Thus, the treatment was changed to combination therapy with cyclosporine and low-dose prednisolone. At the time of admission, leukocytosis, hypoalbuminemia, decreased serum immunoglobulin G (IgG), azotemia, and nephrotic-range proteinuria were observed. Ascitic fluid analysis showed a leukocyte count of 4960/μL (neutrophils 90%). On the suspicion of SBP associated with MCD, intravenous administration of empirical cefotaxime and supportive therapy were initiated; however, symptoms of peritonitis persisted. Extended-spectrum beta-lactamase-negative E. coli was found in ascites cultures. Laparoscopy-assisted peritoneal biopsy revealed no evidence of fungal infection; however, chronic inflammation without granuloma formation was noted. Afterward, cefotaxime was changed to piperacillin-tazobactam. After 4 weeks of antibacterial therapy, the peritonitis was cured and renal function was improved.Conclusions:Adult patients with steroid-resistant MCD accompanied by refractory ascites, severe hypoalbuminemia, and marked reduction in serum IgG are at a high risk of subsequent SBP and require careful monitoring.

Complete remission of nephrotic syndrome in a young woman with anti-LRP2 nephropathy after immunosuppressive therapy

BackgroundAnti-low density lipoprotein receptor-related protein 2 (LRP2) nephropathy/anti-brush border antibody (ABBA) disease is a disorder characterized by acute tubulointerstitial injury associated with circulating antibodies to kidney proximal tubular brush border protein LRP2/megalin. Patients are typically elderly and present with acute kidney injury and subnephrotic proteinuria. They progress to end-stage renal disease with poor response to immunosuppressive therapies.Case presentationWe report a case of a 29-year-old Chinese woman, who presented with nephrotic syndrome with normal kidney function. Kidney biopsy showed no obvious tubular injury or interstitial inflammation. Positive immunoglobulin G (IgG) staining was revealed along the brush border of proximal tubular cells. Anti-LRP2 antibody was identified in serum, consistent with a diagnosis of anti-LRP2 nephropathy. The patient achieved complete remission after receiving prednisone and cyclophosphamide.ConclusionsAnti-LRP2 nephropathy can also present as nephrotic syndrome in young patients and complete remission from nephrotic syndrome may be achieved after immunosuppressive therapy.

Circulating anti-phospholipase A2 receptor antibodies as a diagnostic and prognostic marker in Greek patients with idiopathic membranous nephropathy - a retrospective cohort study.

Circulating autoantibodies against phospholipase A2 receptor (anti-PLA2R) are recognized as key elements in the pathogenesis of idiopathic membranous nephropathy. In current clinical practice, they are increasingly gaining attention as novel tools for diagnosis and disease monitoring. We investigated the diagnostic and prognostic utility of anti-PLA2R antibody measurements in Greek patients with biopsy-proven membranous nephropathy. Anti-PLA2R levels were measured in serum samples from 33 patients at diagnosis using ELISA and were associated with treatment outcome. Moreover, serial anti-PLA2R measurements were performed in 15 patients under different clinical conditions and level alterations were correlated with disease activity. Positive anti-PLA2R antibodies at diagnosis were found in 16 of 33 patients (48.5%). Anti-PLA2R levels were independently associated with the achievement of complete remission of nephrotic syndrome after immunosuppressive treatment compared to partial remission (p = 0.02, R2 = 0.265, 95%CI -0.019 to -0.0003). Higher detectable antibody levels at diagnosis were correlated with higher proteinuria levels (r = 0.813, p = 0.0001, 95%CI 0.532 to 0.933) and lower eGFR at the end of follow-up (r = -0.634, p = 0.0083, 95%CI -0.86 to -0.202). Serial antibody measurements during follow-up showed that anti-PLA2R titers were significantly reduced at the end of treatment after complete remission was achieved, remained low under sustained clinical remission, and increased during relapse. Our findings confirm the usefulness of anti-PLA2R measurements in the diagnosis of idiopathic membranous nephropathy. Low levels of anti-PLA2R antibodies at diagnosis are predictive of complete remission of nephrotic syndrome following immunosuppressive treatment. Serial anti-PLA2R measurements correlate well with clinical status throughout the follow-up period and could be used routinely for monitoring of disease activity and treatment planning.

Membranous nephropathy succeeding autologous hematopoietic stem cell transplant: a case report

BackgroundMembranous nephropathy (MN), the leading cause of nephrotic syndrome in adults, is characterized by the deposition of subepithelial immune deposits. Most of the cases are primary, while only approximately 25% of the cases are secondary to some known diseases. Recently, MN has been considered to be a possible presentation of chronic graft-versus-host disease (GVHD) of the kidney in allogeneic hematopoietic stem cell transplantation (HSCT) patients. In autologous HSCT populations, there have been scarce reports of associated MN, as a result of immune dysregulation leading to systemic autoimmunity and miming chronic GVHD.Case presentationWe report an exceptional case of MN associated to an acute renal failure occurring within days following an autologous HSCT indicated by multiple myeloma. There was no evidence of GVHD or myeloma relapse. A complete remission of nephrotic syndrome with normalization of renal function were rapidly obtained by corticosteroid therapy.ConclusionThis is the first published case of acute renal failure due to MN occurring in the acute phase of an autologous HSCT. These findings support the antibodymediated autoimmune glomerular disease.

Tip lesion variant of primary focal and segmental glomerulosclerosis: clinicopathological analysis of 20 cases

The glomerular tip lesion (GTL) is a distinctive histopathologic lesion which is regarded as a variant of focal and segmental glomerulosclerosis (FSGS). The prognostic significance of GTL among other FSGS variants has been disputed. In order to define the clinical features and outcome of GTL, we retrospectively reviewed the presenting clinical features, laboratory and biopsy findings and surveillance in our cohort of GTL, which consisted of 20 adults with native kidneys (mean age 46 years) with follow-up data ranging from 3 to 137 months. At presentation, mean urine protein, serum albumin and cholesterol levels were 5.17 g/d, 2.6 g/dL and 312.9 mg/dL, respectively, and none had renal insufficiency. Microscopic hematuria was detected in five patients. At biopsy, glomerular segmental lesions consisted of GTL without perihilar or collapsing lesions. GTL was observed in a variable proportion of glomeruli from 2.6% to 100%. Mesangial proliferation was seen in nine cases, at a moderate degree in two and mild in the rest. Three biopsies showed mild, two showed moderate interstitial fibrosis/tubular atrophy. Eleven patients received steroids alone and eight received sequential therapy with steroids and a cytotoxic agent. At a mean follow-up of 40.6 months, 17 patients (85%) achieved complete remission of nephrotic syndrome, 15% had partial remission. Four of 17 suffered from recurrences. No patient progressed to end-stage renal disease. Serum albumin at diagnosis was the only predictor of a recurrence (p = 0.037). Microscopic hematuria correlated with incomplete remission (p = 0.045). Our study demonstrates a clearly favorable prognosis in patients with FSGS-GTL variant.

Plasmapheresis combined with rituximab for refractory idiopathic membranous nephropathy

Idiopathic membranous nephropathy (IMN) is known to be one of the most common causes of nephrotic syndrome in adults [1]. Severe therapy-refractory IMN is a life-threatening disease and demands new treatment options. We report the first successful treatment for severe therapy-refractory INM with a combination of plasmapheresis and rituximab. A 34-year-old male Caucasian was admitted to the hospital with newly developed peripheral edema. Kidney function was normal, whereas proteinuria exceeded 6.2 g protein/g creatinine (normal value: \0.15 g protein/g creatinine) and the serum albumin level was decreased (2.6 g/ dl, normal value: 3.5–5.4 g/dl). Kidney biopsy showed typical membranous glomerulopathy with subepithelial immunoglobulin-containing deposits along the glomerular basement membrane. The causes of secondary membranous nephropathy (MN) such as hepatitis, HIV, autoimmune disease and cancer were excluded. A high titer of anti-phospholipase A2 receptor antibody was detected in serum (1:640) by indirect immunofluorescence. Initially, the patient was treated with an angiotensinconverting enzyme (ACE) inhibitor, an angiotensin II receptor blocker (ARB), an anticoagulant and prednisolone (60 mg/day, progressively tapered to 5 mg/day). Six months later, his condition deteriorated. Serum creatinine level increased to 1.5 mg/dl (135 lmol/l) while serum albumin declined to 1.5 g/dl (15 g/l). The patient was still heavily proteinuric (4.6 g protein/g creatinine). The treatment was then complemented by cyclosporine (CsA) and switched later to tacrolimus (Tac) due to side effects. However, his condition further deteriorated rapidly with increased protein excretion (8.8 g protein/g creatinine). He gained 20 kg in 3 weeks and showed increased peripheral edema and dyspnea. We decided to perform a combined treatment with plasmapheresis (d1-3, d5, d7) followed by two infusions of rituximab (d8 ? d28). Each plasmapheresis was performed over 2–3 h, using 5,000 ml of fresh frozen plasma (FFP), approximately 1.2 times the circulating plasma volume, as a replacement fluid. Subsequently, the patient received intravenous infusions of rituximab (375 mg/m, d8 ? d28). Complete remission of nephrotic syndrome was achieved 8 weeks later. The concentration of anti-PLA2R antibodies in the serum was continuously reduced during the treatment and eventually disappeared during remission (Fig. 1). Protein excretion was below 0.3 g/day in eight consecutive visits under ACE inhibitor/ARB treatment. Despite numerous studies, the optimal treatment for IMN remains disputable. Remuzzi et al. [2] reported the therapeutic benefit of rituximab in high-risk patients with IMN. However, remission was achieved in a relatively long time frame, between 3.2 and 12.0 months. As our patient was non-responsive to conservative treatment and immunosuppression including steroids, CsA and Tac, his condition was too critical to allow time for exclusive rituximab treatment to take effect. Therefore, the patient received plasmapheresis treatments in order to rapidly eliminate all possible antibodies and immune M. Wen C. Kuchle O. Sarkar L. Renders U. Heemann C. Schmaderer (&) Department of Nephrology, Klinikum rechts der Isar, Technische Universitat Munchen, Ismaninger Strase 22, 81675 Munich, Germany e-mail: christoph.schmaderer@lrz.tu-muenchen.de

Nephrotic syndrome associated with tyrosine kinase inhibitors for pediatric malignancy: case series and review of the literature

Tyrosine kinase (TK) inhibitors are increasingly being used to treat a variety of pediatric malignancies. Reports in adult patients describe a range of effects of TK inhibitors on the kidney, including hypertension, proteinuria, acute kidney injury, and thrombotic microangiopathy (TMA); however, there are only a few reports of TK-inhibitor-associated nephrotic syndrome. We report four pediatric patients with various malignancies (chronic myelogenous leukemia, acute lymphoblastic leukemia, and glioma/renal cell carcinoma) who developed nephrotic syndrome during treatment with TK inhibitors (imatinib, sunitinib, dasatinib, and quizartinib). One of the four patients also had clinical features of TMA. Three of the four patients achieved complete remission of nephrotic syndrome with discontinuation of the TK inhibitor and have had no additional nephrotic syndrome relapses to date. The temporal relationship of nephrotic syndrome onset to TK-inhibitor therapy and resolution of nephrotic syndrome with cessation of therapy strongly imply an association in these patients. TK inhibitors are important therapies in pediatric cancer, and their use is expanding. Nephrotic syndrome with or without features of TMA is a potential complication of these therapies in children.

Long-term prognosis of 4 children with steroid-sensitive nephrotic syndrome and relapse after 30years of age.

Some children with steroid-sensitive nephrotic syndrome (SSNS) have been reported to suffer relapses in adulthood, but the clinical course of such adults is unclear. Four children with SSNS suffered relapses after 30 years of age. Those 4 patients developed frequently relapsing nephrotic syndrome (NS) between 2 and 10 years of age. They were treated with prednisolone (PSL) combined with cyclophosphamide in 3 patients, mizoribine in 2, and cyclosporine in 1 during childhood, and with cyclosporine in 2 during adulthood. After 20 years of age, the frequency of relapses gradually decreased. The last relapse occurred between 33 and 39 years of age, and proteinuria disappeared within 1 month after the start of treatment with PSL. At the last follow-up, all 4 patients continued to receive PSL, had normal renal function, and were in complete remission of NS when they were between 33 and 41 years of age. Although the long-term outcome of SSNS is usually considered to be favorable, pediatricians should be aware that some children with SSNS may require long-term treatment during adulthood.

Development of minimal-change glomerular disease and Hashimoto's thyroiditis during the treatment of sarcoidosis.

Minimal-change glomerular disease, sarcoidosis and autoimmune thyroid disease rarely occur in the same patient. We herein report a patient in which minimal-change glomerular disease and Hashimoto's thyroiditis developed during the treatment of sarcoidosis with steroids. A 66-year-old female was admitted to our hospital with symptoms of nephrotic syndrome. Nine months before admission, she was diagnosed as having ocular and pulmonary sarcoidosis, for which prednisolone at an initial dose of 40mg/day was started. When the dose of prednisolone was tapered to 20mg/day, she noticed swelling of the lower extremities. Examination confirmed the simultaneous occurrence of minimal-change glomerular disease and Hashimoto's thyroiditis, which were diagnosed based on kidney histology, ultrasonography of the thyroid gland and positive antithyroglobulin antibodies. We used intravenous methylprednisolone pulse therapy followed by 40mg/day oral prednisolone. The patient achieved complete remission of nephrotic syndrome and steroids were tapered without relapse.

Cure of relapsing nephrosis by an allogeneic marrow graft for chronic myelogenous leukemia

Minimal-change nephrotic syndrome has recently been attributed to an immature, dysfunctional T-cell population. A woman, now 23 years old, developed nephrotic syndrome when she was 6 years old. Despite treatment with steroids and immunosuppressants such as cyclosporine, mizoribine, mycophenolate mofetil, and tacrolimus, the patient relapsed 14 times. At the age of 19 years, she developed chronic myelogenous leukemia, against which imatinib achieved cytogenetic remission. The patient received an allogeneic bone marrow graft transplantation from an unrelated marrow bank donor, with an uncomplicated recovery and molecular genetic remission. Immunosuppressants were withdrawn within 6 months. The patient is now without drug treatment. Complete remission of nephrotic syndrome has also been maintained for over 4 years without any drug administration. The patient's course supports suggestions that immunological dysfunction in nephrosis is associated with abnormality of immature, relatively unclassified T cells (CD34(+)) representing hematopoietic stem cells, as opposed to mature T cells (CD34(-)).

Successful management of factor IX inhibitor-associated nephrotic syndrome in a hemophilia B patient

Nephrotic syndrome (NS) is a recognized complication of immune tolerance induction (ITI) therapy, a treatment strategy used to treat inhibitors in patients with hemophilia B receiving factor IX concentrate. We present a 4-year-old boy with hemophilia B and an inhibitor who underwent ITI, and developed NS 19months into this therapy. A percutaneous renal biopsy was safely performed with factor IX (FIX) concentrate administration both preceding and following the procedure. The patient's inhibitor level had increased to 1.4-1.6 Bethesda Units just prior to the onset of proteinuria. Histology confirmed segmental membranous nephropathy (MGN). The patient was continued on FIX concentrate as ITI and also received 4 weekly doses of rituximab and ongoing immunosuppression with mycophenolate mofetil. This resulted in the complete resolution of his inhibitor and his NS. He continues with a modified ITI regimen and remains inhibitor-free without proteinuria >12months post-biopsy. Hemophilia B patients undergoing ITI should be regularly screened for NS. At first detection of proteinuria, with proper precautions, a percutaneous kidney biopsy can be performed safely in patients with low levels of inhibitor. Our patient had segmental MGN with complete remission of NS.

Type III membranoproliferative glomerulonephritis in a patient with primary Sjögren’s syndrome

Renal involvement in the form of glomerulonephritis in Sjögren's syndrome (SS) is less common and usually a latent sequel in the course of the disease. We report a patient with Type III membarnoproliferative glomerulonephritis (MPGN) with hypothyroidism, which precedes the onset of the clinical manifestation of SS. She received immunosuppressions consisting of i.v. cyclophosphamide and high-dose corticosteroid and subsequently oral corticosteroid resulting in complete remission of nephrotic syndrome. To our knowledge, this is the first report of successfully treated Type III MPGN associated with SS.

Steroid-resistant minimal change nephrotic syndrome in Waldenström macroglobulinemia

Dear Editor, Renal complications of IgM-secreting monoclonal proliferations are rare. Kidney lesions associated with Waldenstrom macroglobulinemia (WM) include mainly intracapillary deposits of IgM with or without cryoglobulinemia, ALamyloidosis and interstitial lymphoplasmatic cell infiltration [1, 2]. Minimal change nephrotic syndrome is a rare complication of WM and has been described, best to our knowledge, only twice in the literature [3, 4]. We herein report a case of WM-associated steroid-resistant nephrotic syndrome due to minimal change lesions. A 67-year-old female was admitted to our department for generalised oedema. Past medical history included WM and anxio-depressive syndrome. WM was diagnosed 2 years ago and necessitated only regular follow-up without any specific treatment; capillary electrophoresis was showing a stable serum monoclonal IgM at 17 g/L. Physical examination on admission confirmed the generalised oedema, weight gain of 6 kg, blood pressure 130/80 mmHg, no hepatosplenomegaly nor lymphadenopathy. Biological tests showed mild acute renal failure with serum creatinine 105 μmol/L (reference 50–90) and severe nephrotic syndrome with hypoalbuminaemia of <10 g/L (35–52) and proteinuria 15 g/day. Her haemoglobin was 11.4 g/dL (12.5–15.5 g/dL); leucocytes, 9.4×10/ L (4–10×10/L), and platelet count, 599×10/L (150–400× 10/L). Capillary electrophoresis showed an increase of serum monoclonal IgM from 17 to 26 g/L, indicating tumour progress. Treatment with high doses of IV furosemide was initiated promptly. Our primary hypothesis was amyloidosis to explain severe nephrotic syndrome in the context of evolving WM. Surprisingly, the renal biopsy (28 glomeruli) showed only minimal change lesions, without amyloidosis or significant interstitial infiltrate (Fig. 1). The immunofixation study showed very mild mesangial IgM deposits. Electron microscopy was not available. Rapidly, the renal function deteriorated with serum creatinine reaching 400 μmol/L. Renal imaging excluded urologic and vascular causes, and particularly, there was no renal vein thrombosis. Most probably, furosemideinduced relative hypovolemia contributed to the aggravating renal failure that has regressed quickly after furosemide dose reduction. We established the diagnosis of WM-associated minimal change nephrotic syndrome (MCNS), and the patient was treated with three pulses of IV methylprednisolone (500 mg/ day) and, subsequently, oral prednisone (1 mg/kg/day) without any response, leading us to reconsider our treatment. Steroids were then withdrawn, and specific WM chemotherapy was started with five courses of rituximab, cyclophosphamide and dexamethasone (RCD). Complete remission of nephrotic syndrome (albumin 36 g/L, proteinuria 0.2 g/day) and significantly improved renal function (serum creatinine 87 μmol/L) were obtained after the third RCD cycle. The renal function was normalised eventually after furosemide J. Sayegh :V. Boisliveau : C. Savary : F. Beloncle : J.-F. Augusto LUNAM Universite, Angers, France

De novo minimal change disease after ABO‐incompatible kidney transplantation

We report the clinical and pathological findings of a case of de novo minimal change disease (MCD) after ABO-incompatible living kidney transplantation. A 62-yr-old man with end-stage renal disease associated with type I diabetes received ABO-incompatible kidney transplantation from his 58-yr-old wife. Although allograft function was excellent immediately after surgery, massive proteinuria (35 g/d) appeared on post-transplantation day 5. After the allograft biopsy taken on post-transplantation day 6, he was treated with 12 cycles of plasma exchange, but the nephrotic-range proteinuria showed no remission. The biopsy specimen showed no significant pathological findings on light microscopy, but electron microscopy showed diffuse effacement of podocyte foot processes. Based on the diagnosis of de novo MCD, the patient received intravenous methylprednisolone pulse therapy, followed by high-dose steroid maintenance therapy. The steroid therapy induced complete remission of nephrotic syndrome and stable allograft function immediately, which was also maintained at one yr after the transplantation.

Treatment of Hepatitis B Virus-Associated Membranous Nephropathy: Lamivudine Era versus Post-Lamivudine Era

Treatment of Hepatitis B Virus-Associated Membranous Nephropathy: Lamivudine Era versus Post-Lamivudine Era