Minimal Change Nephrotic Syndrome Research Articles

Implication of acute tubular injury in minimal change nephrotic syndrome.

While acute tubular injury (ATI) is known to occur in a significant number of minimal change disease (MCD) nephrotic syndrome cases with acute kidney injury (AKI), the clinical significance is not certain, and AKI may also occur without ATI. This study aimed to evaluate whether the severity of AKI defined by Kidney Disease Improving Global Outcomes (KDIGO) criteria correlated with the presence or severity of ATI in a series of adult patients with MCD. We also looked at whether time to remission of nephrotic syndrome (NS) with treatment correlated with the presence of ATI in those with and without AKI. We excluded patients with secondary MCD. Of 61 patients, 20 had AKI (33%). ATI was significantly more likely to occur in those with AKI than in those without AKI (60 vs. 24%). Overall, the severity of AKI did not clearly correspond with the severity of ATI. Remission rates at 4 weeks were lowest (25%) in those with both AKI and ATI, while they were highest (100%) in those with neither AKI nor ATI. Patients with AKI but no ATI and those with no AKI but having ATI were intermediate in remission rates and similar to each other (60 and 62%, respectively). The time to remission in the group of those without AKI was significantly longer in those with ATI than in those without (p=0.0027), but the numerical difference in remission did not reach statistical significance in the smaller group of AKI patients. Patients with ATI were older and more often male than those without ATI. It appears that having ATI may predict a slower remission rate in MCD though the reason for this is unclear. The different demographics of those with ATI may also play a role.

Patients with infusion-related reactions on fixed-dose rituximab treatment have higher body surface area than those without infusion-related reactions in adults with frequently relapsing minimal change nephrotic syndrome: a retrospective study

BackgroundInfusion-related reactions (IRRs) are major side effects of rituximab administration. Male sex, high body weight, body surface area (BSA), and body mass index are predictive markers of rituximab-induced IRRs. However, as rituximab was not administered at a fixed dosage in a previous study, whether a higher dosage or factors associated with a larger physique are more strongly associated with rituximab-induced IRRs is unknown.Main bodyThirteen adults with frequently relapsing minimal change nephrotic syndrome (MCNS) who received an initial rituximab dose of 500 mg between September 2015 and November 2022 were retrospectively evaluated. Data on IRRs were collected from medical records. The incidence of rituximab-induced IRRs was 38.5% (5/13). The IRR group had a significantly higher BSA than the non-IRR group (median, 1.86 vs. 1.48 m2; p = 0.045). Additionally, rituximab dosage normalized by BSA in the IRR group was significantly lower than that in the non-IRR group (median, 268.8 vs. 337.9 mg/m2; p = 0.045).ConclusionsOur study revealed that adults with frequently relapsing MCNS who experienced IRRs tend to have a higher BSA, even with fixed-dose rituximab treatment. Therefore, when patients with higher BSA receive rituximab treatment, clinicians should be careful about monitoring patient condition whether the dosage is fixed or not.

Steroid-resistant minimal change nephrotic syndrome associated with thymoma treated effectively with rituximab following thymectomy and cyclosporine: a case report

BackgroundMinimal change nephrotic syndrome (MCNS) can be complicated by thymoma; however, no standard therapy for thymoma-associated MCNS has yet been established. We herein describe a case of steroid-resistant MCNS associated with thymoma, treated effectively with rituximab.Case presentationA 71-year-old Japanese man was referred to our department with severe proteinuria (20 g/gCr). Renal biopsy showed minimal change disease and computed tomography revealed an anterior mediastinal mass. Based on these findings, he was diagnosed with thymoma-associated MCNS. He was treated with oral prednisolone (50 mg/day) and cyclosporine, and underwent thymectomy and plasma exchange. However, no improvement in proteinuria was observed. He therefore received intravenous rituximab 500 mg, resulting in a marked decrease in proteinuria from 5328 to 336 mg/day after 1 week.ConclusionsThis case suggests that rituximab might be an effective therapy in patients with steroid-resistant MCNS associated with thymoma.

Bicellular Localization of Tricellular Junctional Protein Angulin-3/ILDR2 Allows Detection of Podocyte Injury

Podocytes serve as part of the renal filtration unit with slit diaphragms. Although the structure of slit diaphragms between two cells is well characterized, it has remained unknown how the tricellular contact of podocytes is organized and how it changes in injured podocytes. This study focused on a tricellular junction protein, angulin-3, and its localization was analyzed in healthy podocytes as well as in developmental stage and in pathologic conditions, using a newly established monoclonal antibody. Angulin-3 was confined at tricellular junctions of primordial podocytes, then transiently localized at bicellular junctions as foot process interdigitation developed and the intercellular junctions rearranged into slit diaphragm, and eventually distributed in a sparse punctate pattern on the foot processes of adult podocytes. In the rodent podocyte injury models, angulin-3 showed bicellular localization between the foot processes, and the localization turned from punctate to dashed linear pattern along the effaced foot processes as podocyte injury progressed. Angulin-3 also accumulated between foot processes in a linear pattern in kidney biopsy samples of human nephrotic syndrome. Furthermore, it was discovered that the line length of angulin-3 staining signal correlated with risk of relapse under glucocorticoid therapy in patients with minimal change nephrotic syndrome. In this article, an image program was proposed to score the linearity of the accumulation pattern of angulin-3 to evaluate the relapse risk of patients with minimal change nephrotic syndrome.

A Case of Minimal Change Nephrotic Syndrome Secondary to Methotrexate-associated Hodgkin Lymphoma.

The patient was a 64-year-old man who had been receiving methotrexate (MTX) for rheumatoid arthritis for 8 years. Computed tomography (CT) obtained one month prior to admission revealed numerous enlarged lymph nodes. Lower leg edema appeared two weeks prior to admission. Severe proteinuria was confirmed, and the patient was admitted. A renal biopsy revealed minimal changes in glomeruli. CT on day 14 revealed shrinking lymph nodes, and the patient was diagnosed with Hodgkin lymphoma by a neck lymph node biopsy. This is the first report of secondary minimal change nephrotic syndrome caused by an MTX-associated lymphoproliferative disorder.

"Idiopathic" minimal change nephrotic syndrome: a podocyte mystery nears the end.

The discovery of zinc fingers and homeoboxes (ZHX) transcriptional factors and the upregulation of hyposialylated angiopoietin-like 4 (ANGPTL4) in podocytes have been crucial in explaining the cardinal manifestations of human minimal change nephrotic syndrome (MCNS). Recently, uncovered genomic defects upstream of ZHX2 induce a ZHX2 hypomorph state that makes podocytes inherently susceptible to mild cytokine storms resulting from a common cold. In ZHX2 hypomorph podocytes, ZHX proteins are redistributed away from normal transmembrane partners like aminopeptidase A (APA) toward alternative binding partners like IL-4Rα. During disease relapse, high plasma soluble IL-4Rα (sIL-4Rα) associated with chronic atopy complements the cytokine milieu of a common cold to displace ZHX1 from podocyte transmembrane IL-4Rα toward the podocyte nucleus. Nuclear ZHX1 induces severe upregulation of ANGPTL4, resulting in incomplete sialylation of part of the ANGPTL4 protein, secretion of hyposialylated ANGPTL4, and hyposialylation-related injury in the glomerulus. This pattern of injury induces many of the classic manifestations of human minimal change disease (MCD), including massive and selective proteinuria, podocyte foot process effacement, and loss of glomerular basement membrane charge. Administration of glucocorticoids reduces ANGPTL4 upregulation, which reduces hyposialylation injury to improve the clinical phenotype. Improving sialylation of podocyte-secreted ANGPTL4 also reduces proteinuria and improves experimental MCD. Neutralizing circulating TNF-α, IL-6, or sIL-4Rα after the induction of the cytokine storm in Zhx2 hypomorph mice reduces albuminuria, suggesting potential new therapeutic targets for clinical trials to prevent MCD relapse. These studies collectively lay to rest prior suggestions of a role of single cytokines or soluble proteins in triggering MCD relapse.

Is Helminthiasis a Precipitating Factor for Frequently Relapsing Nephrotic Syndrome?

Nephrotic Syndrome (NS) is a common childhood illness. It is a disease of relapse and remission with major concern to manage the cases with relapse. Helminthiasis also a common problem in our subcontinent. So, it is very important to find out any relation with helminthiasis and relapse in children. In our study, 88 patients, clinically diagnosed as minimal change nephrotic syndrome, were studied to find out any relationship with helminthiasis and frequent relapse. 36 patients (40.9%) had no helminthic infection, 34 patients (38.6%) had helminthiasis and 18 patients (20.5%) had atopic disorders. 62 patients were successfully followed up for 6 months. Relapses occurred 47.8% (11/23) patients in non-helminthiasis group. 88.5% (23/26) in helminthiasis group and 84.6% (11/13) in atopic group, patients who completed follow up. Thirteen percent (3) patients in non-helminthiasis group, 50% (13) in helminthiasis group and 38.5% (5) in atopic group were found to be frequent relapser. The differences were statistically significant.
 Pulse Volume 12-14 2020-2022 p.10-12
  

Japanese clinical practice patterns of primary nephrotic syndrome 2021: a web-based questionnaire survey of certified nephrologists.

With the publication of the "Evidence-Based Clinical Practice Guideline for Nephrotic Syndrome 2020," we examined nephrologists' adherence to the recommendations of four of its clinical questions (CQs). This was a cross-sectional web-based survey conducted between November and December 2021. The target population comprised nephrologists certified by the Japanese Society of Nephrology who were recruited using convenience sampling. The participants answered six items regarding the four CQs about adult patients with nephrotic syndrome and their characteristics. In total, 434 respondents worked in at least 306 facilities, of whom 386 (88.9%) provided outpatient care for primary nephrotic syndrome. Of these patients, 179 (41.2%) answered that they would not measure anti- phospholipase A2 receptor antibody levels in cases of suspected primary membranous nephropathy (MN) in which kidney biopsy was not possible (CQ1). Regarding immunosuppressants as maintenance therapy after relapse of minimal change nephrotic syndrome (CQ2), cyclosporine was the most common choice (290 [72.5%] and 300 [75.0%] of 400 respondents after the first and second relapses, respectively). The most common treatment for steroid-resistant cases of primary focal segmental glomerulosclerosis (CQ3) was cyclosporine (323 of 387, 83.5%). For the initial treatment of primary MN with nephrotic-range proteinuria (CQ4), corticosteroid monotherapy was the most common choice (240 of 403, 59.6%), followed by corticosteroid and cyclosporine (114, 28.3%). Gaps in recommendations and practices regarding serodiagnosis and treatment of MN (i.e., CQ1 and 4) are observed, suggesting the need to address the barriers to their insurance reimbursement and the lack of evidence behind them.

Quality of Life in Children with Minimal Change Nephrotic Syndrome

Introduction: Nephrotic syndrome (NS) in children is a common, yet challenging, relapsing, and remitting renal disorder and exhibits a heterogeneous clinical phenotype ranging from a single episode, infrequently relapsing, frequently relapsing to steroid-resistant disease. Although 80% of these children are corticosteroid responsive, nearly half of them demonstrate a frequently relapsing or steroid-dependent course, often resulting in multiple complications, hospitalizations, or even chronic renal failure. Objective: To assess the quality of life in patients with minimal change nephrotic syndrome. Methods: This cross-sectional, comparative, questionnaire-based study was conducted in Dhaka Shishu Hospital, Dhaka, Bangladesh July to December 2022. The cases included children with MCD, attending the pediatric nephrology unit and outpatient clinic of nephrology unit. 100 children were selected then they were randomly subdivided into 2 groups, group 1 included 50 known cases of MCD aged 2–18 years and group 2 included 50 age matched children attending the general pediatric outpatient clinic and other pediatric subspecialty clinics. We distributed two questionnaires to 32 outpatients with MCNS. We also used the Self-Care Behavior Scale for patients with chronic kidney disease (CKD), which consists of 31 questions with 4 subscales. Results: Total of one hundred studied nephrotic patients with MCD and an equal number of controls with other chronic diseases aged 2.2–15 year and 3.5–13 years, respectively, were included in the study. Table 1 illustrated the demographic details of the studied cases and controls. Among children with MCD, 32% had first attack or infrequently relapsing variant while 68% had difficult to treat clinical phenotypes (frequently relapsing, steroid– dependent and steroid-resistant varieties). The SF-36v2 social functioning subscale was most impaired and bodily pain was least affected in patients with MCNS. The self-care subscales of information/communication and positive behavior had positive correlations with the QOL subscales of mental health (𝑃 < 0.05) and vitality (p<0.05). The correlation between social functioning and information/communication was close to significant (𝑃 = 0.051). Conclusion: In conclusion, our findings suggest that patients with MCNS have lower QOL based on low social functioning and that QOL is related to the positive behavior and thoughts of the patients. These results also show that healthcare professionals should be conscious of the QOL of children with MCNS.

Angiopoietin-like protein 3: a novel potential biomarker for nephrotic syndrome in children.

Angiopoietin-like 3 (ANGPTL3) is a secretory glycoprotein. It has been demonstrated that ANGPTL3 level was upregulated in minimal change nephrotic syndrome (MCNS) kidney tissues. Subsequently, our group found that ANGPTL3 level was closely correlated with nephropathy in vivo and in vitro. Hence, whether ANGPTL3 level could be correlated with the proteinuria level, and assessment of disease severity of nephrotic syndrome (NS) remained to be investigated. This study aimed to analyzed the correlation between the levels of ANGPTL3 in serum and urine of patients with nephrotic syndrome and proteinuria, and assessed the severity of the patients' disease. In future clinical translation, the level of ANGPTL3 in serum, urine will be used as a biomarker to better predict the development of nephrotic syndrome. A total of 200 NS patients and 80 healthy controls (age, 1-18 years) were admitted to our institution between 2021 and 2022. The etiology of NS included primary nephrotic syndrome (PNS, n = 144) and NS with other causes (n = 56). A total of 280 serum samples and 244 urinary samples were collected to determine ANGPTL3 level using enzyme-linked immunosorbent assay (ELISA). Serum ANGPTL3 and urinary ANGPTL3/Cre were remarkably elevated in NS patients compared with those in healthy controls. Furthermore, serum ANGPTL3 and urinary ANGPTL3/Cre were significantly correlated with proteinuria level. Additionally, multivariate linear regression analysis demonstrated that serum ALB was independently correlated with serum ANGPTL3 and PRO/CR was independently correlated with urinary ANGPTL3/Cre in NS patients. Serum ANGPTL3 and urinary ANGPTL3/Cre showed a promising performance in the diagnosis of NS, and served as novel potential noninvasive biomarkers to assess disease severity of NS. Further exploration of the role of ANGPTL3 level may shed a new light on the treatment of NS.

Immunoglobulin G deposition on proximal tubules and the tubular basement membrane in acute tubular injury complicated with focal segmental glomerulosclerosis (FSGS): A possible prediction tool for subclinical FSGS

Immunofluorescent deposition of immunoglobulin G (IgG) in the tubular basement membrane (TBM) has been evaluated in the diagnosis of various diseases; however, few studies have investigated the immunofluorescence of acute tubular injury (ATI). Herein, we attempted to clarify IgG expression in the proximal tubular epithelium and TBM in ATI due to various causes. Patients with ATI with nephrotic-range proteinuria, including focal segmental glomerulosclerosis (FSGS, n = 18) and minimal change nephrotic syndrome (MCNS, n = 8), ATI with ischemia (n = 6), and drug-induced ATI (n = 7), were enrolled. ATI was evaluated by light microscopy. CD15 and IgG double staining and IgG subclass staining were performed to evaluate immunoglobulin deposition in the proximal tubular epithelium and TBM. IgG deposition was identified in the proximal tubules only in the FSGS group. Furthermore, IgG deposition in the TBM was observed in the FSGS group showing severe ATI. IgG3 was predominantly deposited by the IgG subclass study. Our results indicate that IgG deposition in the proximal tubular epithelium and TBM suggests the leaking of IgG from the glomerular filtration barrier and its reabsorption by proximal tubules, which may predict disruption of the glomerular size barrier, including subclinical FSGS. FSGS with ATI should be included as a differential diagnosis when IgG deposition in TBM is observed.

High Albumin Clearance Predicts the Minimal Change Nephrotic Syndrome Relapse.

Although albuminuria leakage that occurs in minimal change nephrotic syndrome (MCNS) may be related to the disease state, albumin kinetics in MCNS has never been evaluated. In this study, we investigated albumin kinetics in adult Japanese patients with MCNS by the estimated 24-h albumin clearance (eCALB) and examined the association between eCALB and relapse. We retrospectively identified 103 adult patients with a histological diagnosis of MCNS from four hospitals in Japan (2010-2020). The primary outcome is the first relapse in 2 years after complete remission (CR) following corticosteroid therapy. The estimated 24-h albumin clearance (eCALB) [µL/min] was defined as (2.71828log(0.0445 + 0.9488*log(urinary protein) [g/24h]/(serum albumin [g/dL] × 1440 [min/24 h]) for women and (2.71828log(-0.1522 + 0.9742*log(urinary protein) [g/24h]/(serum albumin [g/dL] × 1440 [min/24 h]) for men. Relapse was observed in 44 patients (103 kidney biopsy samples; 42.7%). The mean patient age was 41.0 years. Patients had an estimated glomerular filtration rate (eGFR) of 71.0 mL/min/1.73 m2, urinary protein excretion (UPE) of 6.8 g/day, serum albumin of 1.4 g/dL, and eCALB of 2.27 μL/min. eCALB was strongly associated with hypoalbuminemia, severe proteinuria, lipid abnormalities, and coagulopathy. In the multivariable analysis, a high eCALB was significantly associated with relapse after adjusting for age, eGFR, time to CR, and UPE (adjusted hazard ratio = 5.027, 95% confidence interval 1.88-13.47, P = 0.001). This study revealed that eCALB, which could substitute albumin kinetics, reflected the severity of MCNS, and a high eCALB was associated with recurrence.

Seasonal variations in renal biopsy numbers and primary glomerular disease features based on the Japan renal biopsy registry

We analyzed the seasonal variations in the number of renal biopsies and clinical characteristics of primary glomerular disease in Japan using the Japan Renal Biopsy Registry (J-RBR). We retrospectively collected clinical and pathological data of patients with primary glomerular disease who were registered in the J-RBR between 2007 and 2018. Immunoglobulin A nephropathy (IgAN), minimal change nephrotic syndrome (MCNS), membranous nephropathy (MN), and postinfectious acute glomerulonephritis (PIAGN) constituted the four major glomerular disorders included in this study (total, 13,989; IgAN, 9121; MCNS, 2298; MN, 2447; and PIAGN, 123). The number of patients with IgAN or MCNS was higher during summer. However, no overt seasonal variations were observed in patients with MN or PIAGN. Subgroup analyses suggested that in the patients with IgAN, more renal biopsies of severe cases were performed during winter, probably owing to age and blood pressure. Furthermore, more renal biopsies of severe cases were performed during spring and winter in patients with MCNS even after adjusting for the abovementioned host factors. This study suggests that seasonal factors influence the decision to perform renal biopsy as well as the pathogenesis of primary glomerular disease. Thus, our findings may provide important insights regarding the pathophysiology of primary glomerular disease.

Nephrolithiasis and/or nephrocalcinosis is significantly related to renal dysfunction in patients with primary Sjögren's syndrome.

The present study compared the clinical features of patients with primary Sjögren's syndrome (pSS) with and without nephrolithiasis and/or nephrocalcinosis to determine factors related to renal dysfunction. The clinical features of 68 patients with anti-Sjogren's syndrome antigen A (SSA)/Ro-antibody-positive pSS with and without nephrolithiasis and/or nephrocalcinosis who underwent abdominal computed tomography and/or ultrasonography were retrospectively analysed. Of the 68 patients with anti-SSA-antibody-positive pSS, 23 (33%) had renal nephrolithiasis and/or nephrocalcinosis, whereas 45 (67%) did not. Fourteen (20%) patients had renal dysfunction at diagnostic imaging. Among five patients who underwent renal biopsy, four patients with renal nephrolithiasis and/or nephrocalcinosis were diagnosed with tubulointerstitial nephritis, and one without nephrolithiasis and/or nephrocalcinosis was diagnosed with minimal change nephrotic syndrome. Estimated glomerular filtration rate at diagnostic imaging was significantly lower in patients with than without nephrolithiasis and/or nephrocalcinosis group (P = 0.010). In addition to nephrolithiasis and/or nephrocalcinosis (odds ratio [OR], 3.467; P = 0.045), the gap between serum sodium and chloride concentrations (OR, 10.400; P = 0.012) and increased urinary β2-microglobulin (OR, 5.444; P = 0.033) were associated with renal dysfunction at the time of diagnostic imaging. Nephrolithiasis and/or nephrocalcinosis, normal anion gap metabolic acidosis, and tubulointerstitial damage are associated with renal dysfunction in patients with pSS.

Minimal change nephrotic syndrome diagnosed with acute femoral thromboembolism and successfully salvaged limb: a case report.

A 64-year-old man visited the outpatient department of our hospital for the first time due to bilateral lower limb edema, which he noticed 1week before the visit. Pain suddenly developed in the left lower limb while the patient was in the waiting room. Nephrotic syndrome was suspected based on blood and urine test results. Acute arterial thromboembolism in the left lower limb associated with hypercoagulation due to nephrotic syndrome was suspected, and a diagnosis was made using computed tomography angiography. Arterial thrombectomy was urgently performed, and the limb was salvaged without sequelae. Based on renal biopsy, minimal change nephrotic syndrome was diagnosed, and the patient underwent remission induction with steroid therapy. Heparin was drip infused and apixaban was orally administered to prevent recurrent thrombosis. Nephrotic syndrome in the acute phase is often complicated by thrombosis. Particularly, arterial thromboembolism requires prompt treatment, and prophylactic anticoagulation therapy needs to be considered.

Glomerular parietal epithelial expression of CD44 in minimal change nephrotic syndrome and primary focal segmental glomerulosclerosis: A clinico-pathological study.

Minimal change nephrotic syndrome (MCNS) and focal segmental glomerulosclerosis (FSGS) are the two common causes of nephrotic syndrome (NS) in both children and adults with overlapping clinical features, but with distinct prognostic and therapeutic implications. The distinction between these relies entirely on histopathology, which can sometimes be difficult. CD44 is expressed by activated parietal epithelial cells, plays a role in matrix deposition and thus in the pathogenesis of FSGS. To assess the expression of CD44 in MCNS and FSGS and to evaluate its association with the known clinical and histopathological prognostic factors. Thirty cases each of MCNS and FSGS were studied. The clinical, laboratory, histopathological, and CD 44 immunohistochemical data were recorded. The findings were analyzed and correlated. A P value of < 0.05 was considered statistically significant. Statistical association was noted between CD44 positivity and serum creatinine (p = 0.031), estimated glomerular filtration rate (p = 0.040), segmental sclerosis (p < 0.001), tubular atrophy (p = 0.027), interstitial fibrosis (p = 0.027), and histological diagnosis (p < 0.001). The sensitivity, specificity, positive predictive, and negative predictive values were 90%, 76.67%, 79.41% and 88.46%, respectively. CD44 immunostain can effectively distinguish MCNS from FSGS. The congruent results of CD44 positivity with known prognostic factors support the possibility of using the CD44 marker as a predictive tool in selecting high-risk patients and offering appropriate therapeutic measures.

Clinico-biochemical Profile of Biopsy-proven Minimal Change Disease in Adults from a Tertiary Care Center in South India.

Minimal change disease (MCD) is the most common cause of nephrotic syndrome (NS) in children, and in adults, it contributes to 10%-25% of NS. MCD in adults follows a slightly different course associated with increased incidence of steroid resistance, hematuria, and HTN. This is a prospective-record analysis study aimed to analyze the profile of MCD in adults, response to treatment, and relapse rates. A retrospective observational study was carried out and data were collected retrospectively from all biopsy-proven MCD patients between 2012 and 2018. A total of 86 adults were diagnosed to have biopsy-proven MCD. Of these, 32 were excluded due to insufficient data/lost for follow-up. The IBM SPSS Statistics version 22.0 was used for the statistical analysis. Descriptive analysis includes expression of all the explanatory and outcome variables in terms of frequency and proportions for categorical variables whereas in terms of mean ± standard deviation for continuous variables. Chi-square test was used to compare the age, gender, remission, renal failure and response of different drugs, treatment durations, comorbidity conditions, relapse episodes, and different types of infections based on the degree of proteinuria among study patients. A total of 54 biopsy-proven adult MCD patients were analyzed. The mean age of the patients studied was 36.67 years, with the oldest patient being 76 years. In the study group, 37 (68.5%) patients were male and 14 (31.5%) were female. In the study population, 20 (37%) were hypertensive, 3 (5.6%) were diabetic, and 10 (18.5%) had renal failure at presentation. On treatment, 52 out of 54 patients received steroids, of which 41 (75.9%) were steroid responsive, 6 (11.1%) steroid dependent, and 7 (13%) steroid resistant. The mean time for remission in steroidsensitive patients was 8.8 weeks. Among the steroid-dependent and steroid-resistant patients, 11 patients received calcineurin inhibitors (CNIs), of which 3 were CNI resistant. In the study Group 1 patient received cyclophosphamide and two received rituximab. In the study population, two patients failed to achieve remission and one patient was initiated on hemodialysis and later lost for follow-up. Minimal change NS is a type of NS which is highly responsive to steroids with good prognosis in children. Adult MCD patients require a higher and prolonged course of steroid when compared to children. CNIs and rituximab form a promising second-line drug in patients who are steroid resistant/dependent. However, CNI dependency or relapse after stopping steroids is a concern.

Infectious complications in adult patients with idiopathic minimal change nephrotic syndrome undergoing immunosuppressive therapy.

Patients with idiopathic minimal change nephrotic syndrome (MCNS) undergoing immunosuppressive therapy are susceptible to infectious complications. Study specifically focusing on adult population's infectious complications is lacking. We retrospectively collected 101 adult patients with biopsy-proven idiopathic MCNS and analysed for the infectious complications. Published literatures were also reviewed aiming to evaluate the feasibility of prophylactic antibiotic treatment. Infectious complications developed in 17 of 101 (16.8%) patients, with pneumonia (n=4), cellulitis/fasciitis (n=4) and urinary tract infection (UTI) (n=4) being the dominant diseases, and Gram-negative bacilli the main cause. AKI stage ≥2 (Hazard ratio=6.1; 95% CI: 1.2-31.9, p=0.031) and non-remission by treatment (Hazard ratio=4.4; 95% CI: 1.2-15.6, p=.023) were the two independent risk factors relevant to developing infectious complications. Review of 16 published literatures and our data showed that even no prophylactic antibiotic therapy, only one case of Pneumocystis jirovecii pneumonia developed among the 1787 accumulative cases of MCNS. In contrast, 16 (44%) of acute flare cases were reported among the 36 patients with positive hepatitis B surface antigen that did not receive antiviral prophylactic therapy. Advanced acute kidney injury and non-remission by treatment are the risk factors toward developing infectious complications in adult MCNS undergoing immunosuppressive therapy. It appears unnecessary to use prophylactic antibiotic for Pneumocystis jirovecii pneumonia or other bacterial infections, while screening and prophylactic therapy for hepatitis B and latent tuberculosis are critical for patients in prevalent area.

Pioglitazone enhances proteinuria reduction in complicated pediatric nephrotic syndrome.

Nephrotic syndrome (NS) is a common pediatric kidney disease, yet current treatments for complicated NS are only partially effective and have significant toxicity. There is no Food and Drug Administration (FDA)- or European Medicines Agency (EMA)-approved safe and effective treatment for NS. Thiazolidinediones (TZDs) have been shown to reduce proteinuria in both diabetic and non-diabetic kidney disease and in preclinical studies to directly protect podocytes from injury and reduce proteinuria. Here, we report on the potential utility of the addition of the TZD pioglitazone (PIO) to enhance proteinuria reduction in 8 children and young adults with steroid dependent NS and steroid resistant NS. Clinical data were analyzed in comparable time periods before and after the addition of PIO to their medical regimens. Eight NS patients with minimal change NS (n = 2), focal segmental glomerulosclerosis (FSGS) (n = 4), or collapsing FSGS (n = 2) were evaluated. Prior to PIO initiation, all children and young adults had already received multiple immunosuppressive medications (mean = 3.75). Five of eight patients (63%; "Responders") had notable proteinuria reduction within 1month of PIO initiation (62% reduction; P = 0.04) and normalization within 6months (97% reduction; P = 0.04). PIO-related benefits among the responders included notable increases in serum albumin (2.5 to 3.7g/dl; P = 0.08), dramatic reductions in hospitalizations for IV albumin infusions and diuresis (11 to 0; P < 0.01), and considerable reduction in total immunosuppression (43% reduction; P > 0.1). Importantly, no patients experienced any adverse events attributable to PIO during a total of 136 patient-months of treatment. While confirmatory safety and efficacy studies are needed, these findings suggest pioglitazone (a non-immunosuppressive drug) may be useful to enhance proteinuria reduction in some children and young adults with complicated NS. A higher resolution version of the Graphical abstract is available as Supplementary information.

Upregulation of OASIS/CREB3L1 in podocytes contributes to the disturbance of kidney homeostasis

Podocyte injury is involved in the onset and progression of various kidney diseases. We previously demonstrated that the transcription factor, old astrocyte specifically induced substance (OASIS) in myofibroblasts, contributes to kidney fibrosis, as a novel role of OASIS in the kidneys. Importantly, we found that OASIS is also expressed in podocytes; however, the pathophysiological significance of OASIS in podocytes remains unknown. Upon lipopolysaccharide (LPS) treatment, there is an increase in OASIS in murine podocytes. Enhanced serum creatinine levels and tubular injury, but not albuminuria and podocyte injury, are attenuated upon podocyte-restricted OASIS knockout in LPS-treated mice, as well as diabetic mice. The protective effects of podocyte-specific OASIS deficiency on tubular injury are mediated by protein kinase C iota (PRKCI/PKCι), which is negatively regulated by OASIS in podocytes. Furthermore, podocyte-restricted OASIS transgenic mice show tubular injury and tubulointerstitial fibrosis, with severe albuminuria and podocyte degeneration. Finally, there is an increase in OASIS-positive podocytes in the glomeruli of patients with minimal change nephrotic syndrome and diabetic nephropathy. Taken together, OASIS in podocytes contributes to podocyte and/or tubular injury, in part through decreased PRKCI. The induction of OASIS in podocytes is a critical event for the disturbance of kidney homeostasis.