Recurrence Of Nephrotic Syndrome Research Articles

Clinical characteristics and favorable treatment responses of recurrent focal segmental glomerulosclerosis orsteroid-resistant nephrotic syndrome in children after kidney transplantation.

Recurrence of focal segmental glomerulosclerosis (FSGS) or steroid-resistant nephrotic syndrome (SRNS) after kidney transplant leads to significant morbidity and potentially earlier allograft loss. To date however, reported rates, risk factors and treatment outcomes have varied widely. We applied computational phenotypes to a multicenter aggregation of electronic health records data from 7 large pediatric health systems in the USA, to identify recurrence rates, risk factors, and treatment outcomes. We refined the data collection by chart review. From > 7 million patients, we compared children with primary FSGS/SRNS who received a kidney transplant between 2009 and 2020 and who either developed recurrence (n = 67/165; 40.6%) or did not (n = 98/165). Serum albumin level at time of transplant was significantly lower and recipient HLA DR7 presence was significantly higher in the recurrence group. By 36months post-transplant, complete remission occurred in 58.2% and partial remission in 17.9%. Through 6years post-transplant, no remission after recurrence was associated with an increased risk of allograft loss over time (p < 0.0001), but any remission showed similar allograft survival and function decline to those with no recurrence. Since treatments were used in non-random fashion, using spline curves and multivariable non-linear analyses, complete + partial remission chance was significantly higher with greater plasmapheresis sessions, CTLA4-Ig doses or LDL-apheresis sessions. Only treatment with anti-CD20, CTLA4-Ig agents, or LDL-apheresis sessions were associated with complete remission. Excluding 25 patients with mutations did not significantly change our results. Our contemporary high-risk cohort had higher favorable response rates than most prior reports, from combinations of agents.

Secondary Membranous Nephropathy and Immunodeficiency due to a Novel Biallelic Variant in CARMIL2

The cytosolic capping protein, Arp2/3 and myosin-I linker protein 2 or CARMIL2 plays an important role in T/B/NK cell function. Biallelic disease causing variants in CARMIL2 are known to cause immunodeficiency 58. We report a 13-year-old girl with recurrent infections, dermatitis and nephrotic syndrome since childhood. Her renal biopsy was suggestive of membranous nephropathy. Exome sequencing showed a homozygous novel stopgain variant, c.520C&gt;T in CARMIL2 (NM_001013838.3). We expand the phenotypic spectrum of CARMIL2 related immunodeficiency to include membranous nephropathy secondary to probable immune dysregulation.

Relapse during and after regular single-dose rituximab treatment in adult patients with steroid-dependent nephrotic syndrome.

Rituximab is widely used in patients with steroid-dependent nephrotic syndrome. However, information on the effect of long-term rituximab treatment is limited. This study examined the efficacy of rituximab during and after treatment in adult patients with steroid-dependent nephrotic syndrome. This retrospective cohort study included 30 patients with steroid-dependent nephrotic syndrome. Patients received regular single-dose rituximab (500mg) intravenously every 6months. Discontinuation of rituximab was considered after four to six doses if there was no recurrence of nephrotic syndrome. Glucocorticoid discontinuation with remission, first relapse after rituximab initiation, and relapse after regular rituximab treatment discontinuation were evaluated. The median age was 38 (range 18-67) years. Of 30 patients, 13 and 17 were men and women, respectively. Prior to rituximab treatment, the median number of nephrotic syndrome relapses in the patients was 5 (range 2- > 20). The 1year discontinuation rate of glucocorticoids with remission was 83%. All patients discontinued glucocorticoid treatment at least once until 3years and 7months. The 1 and 2year relapse rates after initiation of rituximab treatment were 0% and 3%, respectively. 25 patients discontinued regular rituximab treatment after a median number of six (4-12) doses. Six patients relapsed after discontinuing rituximab, and the 1 and 2year relapse rates after the last regular rituximab treatment were 9% and 25%, respectively. All patients with steroid-dependent nephrotic syndrome who received rituximab could discontinue glucocorticoid treatment with remission, and three-fourths of the patients remained in remission for > 2years after discontinuing rituximab treatment.

ОСОБЕННОСТИ ИММУННОГО СТАТУСА У БОЛЬНЫХ ГЛОМЕРУЛОНЕФРИТАМИ С РЕФРАКТЕРНЫМ НЕФРОТИЧЕСКИМ СИНДРОМОМ

Abstract. Introduction. Research in the issues related to glomerulonephritis with nephrotic syndrome is an important problem of modern medicine due to their prevalence among the global population and mainly in the younger age group, with a significant proportion of patients with refractory nephrotic syndrome (frequent relapses, persistent course). Currently, there are no ways to predict the development of glomerulonephrites with refractory nephrotic syndrome. Due to the immunological nature of glomerulonephrites, it seems advisable to search for predictors of refractory nephrotic syndrome among the indicators characterizing the patient’s immune status. Aim of the study was to study the characteristic features of the immune status and their prognostic value in glomerulonephritis with refractory nephrotic syndrome. Materials and Methods. We examined 136 glomerulonephritis patients with active nephrotic syndrome, hospitalized in the nephrology department in 2015-2021. Along with conventional examinations, humoral and T-cell immunity indicators were tested in the patients. The end point of the study was in 2022 where the the clinical course of the disease was assessed in patients, and patients with nephrotic syndrome who showed refractory to steroid therapy were placed into one group, while those with non–refractory nephrotic syndrome were placed into another one. Within the selected groups of patients, we performed the comparative study of demographic, clinical and laboratory parameters, the indicators of humoral and T-cell immunity, and the ROC analysis of indicators correlating with the nephrotic syndrome recurrence frequency. Results and Discussion. In the group of patients with a refractory course of the disease, an increase was detected in the number of T helper phenotype cells and of the activated T cells carrying activation markers, HLA-DR and CD38, on their surfaces. At the same time, the relative content of regulatory T cells (Treg) among T helper cells decreased. The B system was characterized by an increase in the number of B lymphocytes, an increase in the levels of circulating immune complexes and IgM, and a decrease in IgG levels. The changes detected in the parameters of humoral and T-cell immunity may be essential to the development of refractory nephrotic syndrome. In the refractory nephrotic syndrome pathogenesis, the most important is the decrease in the number of Tregs, which correlated most closely with the nephrotic syndrome recurrence frequency. Conclusions. An association was found between refractory nephrotic syndrome and the pronounced activation of humoral immunity, and a significant imbalance was detected between various immunoregulatory and activated T-lymphocyte subpopulations. The Treg content in the blood can be a prognostic indicator: Treg content values of under 1.9% indicate a high probability of developing refractory nephrotic syndrome.

Comparison of Serum IgE Level between Initial Attack and Relapse Cases of Idiopathic Nephrotic Syndrome in Children

Background: Nephrotic Syndrome (NS) is a common and recurrent glomerular disease in childhood. Although the exact etiology of NS is not fully known, it is believed that immune system plays a pivotal role in its pathogenesis. Studies have been reported a strong association between NS and increased level of serum immunoglobulin E (IgE). In addition, children with recurrent NS, the IgE level significantly increases, and there is a higher relapse rate.&#x0D; Objective: The aim of the study was to determine the difference of Serum IgE level between initial attack and relapse cases of idiopathic Nephrotic Syndrome in children.&#x0D; Methodology: A cross sectional analytical study has been conducted on 35 initial attack and 35 relapse cases of idiopathic Nephrotic Syndrome children admitted in the Department of paediatrics, Sir Salimullah Medical College Mitford Hospital (SSMCMH), Dhaka from May 2021 to April 2022. Study subjects were enrolled by purposive sampling after confirming the diagnosis and fulfilling the inclusion and exclusion criteria. Informed written consent was taken from each patient's legal guardian before enrollment. A detailed history and thorough physical examination was done in each patient on admission. With all aseptic precaution five ml of venous blood was collected and sent for serum albumin, serum cholesterol and serum IgE level measurement. Data were analyzed using the statistical package for social sciences (SPSS) version 23.0. Independent sample t test or Mann-whitney test was used to compare data between groups. P value of less than 0.05 was considered as significant.&#x0D; Results: The mean age of the studied samples was 3.86 (ranging from 2 to 6 years). Moreover, among the studied sample male was a little bit greater than female. A significant prevalence of relapse cases were found among the children with middle income family status (P&lt;0.05).Spot urine protein and creatinine ratio and serum cholesterol level was significantly higher in patients experience relapse attack (P&lt;0.05). However, serum albumin level was quite similar in both cases. The mean serum IgE of patients experiencing relapse attack was 985.11+433.65 which was significantly higher than patients experiencing initial attack 470.48+227.35 (P&lt;0.001). &#x0D; Conclusion: This study showed that serum IgE levels are higher in relapse cases of Nephrotic Syndrome than that of initial attack. Furthermore, serum IgE is more in frequent relapse as compared to infrequent relapse. Serum IgE levels have a positive correlation with disease activity and relapse of Nephrotic Syndrome.

A new approach to immunosuppressive therapy in patients with glomerulonephritis with nephrotic syndrome

Glomerulonephritis (GN) is a group of immuno-inflammatory kidney diseases with predominant glomerular lesions that are difficult to treat. The greatest problems are caused by the treatment of GN with nephrotic syndrome, which often has a recurrent course. The aim of the research was to study the effectiveness of recombinant interleukin-2 (rIL-2) therapy in the GN patients with nephrotic syndrome. 62 patients with a nephrotic form of primary GN with frequent relapses admitted to the Nephrology Department have been recruited into the study. The age of patients was from 18 to 65 years. The patients underwent standard examinations, as well as immunological studies, before administration of the anti-relapse treatment, and 12 months after the treatment was started. Immunological testing included immunophenotyping of lymphocytes with counting of T and B lymphocytes, immunoregulatory and activated subpopulations of T lymphocytes, determination of urinary immunoglobulins (IgM, IgG, IgA) by immunoturbidimetric assays, proinflammatory cytokines – IL-1β, IL-8, IL-17A and anti-inflammatory cytokine IL-10 by ELISA tests. As a result of studies, the examined patients showed an increased contents of T helper cells, activated T lymphocytes (CD8+HLA-DR+CD45+, CD3+CD8brightCD38+) along with decreased numbers of Treg cells and an increased contents of proinflammatory cytokines IL-1β, IL-8, IL-17A and immunoglobulins of all three classes in urinary samples.The cohort of patients with GN selected for the study was divided in two groups (the main group and the comparison group). In addition to nephroprotective and steroid therapy, the treatment regimen of patients included rIL-2 in the main group, or cyclophosphamide in the comparison group. Regardless of the method used, the levels of protein, IgG and IL-17A in the urine proved to be decreased relative to the initial values; the contents of B cells and HLA-DR+ cytotoxic T lymphocytes in peripheral blood were found to be decreased. The revealed changes were more pronounced in the main group of patients. By 12 months after starting the treatment, the mentioned indexes began to differ significantly in the main group from those in the comparison group. Serum creatinine levels, numbers of T helper cells and Treg cells, IL-1β levels in urine did not undergo significant changes in the comparison group, whereas a decrease in serum creatinine and urinary IL-1β was registered in the main group of patients, along with decreased number of T helpers and increased numbers of Treg cells. In the main group of patients treated with rIL-2, the average number of relapses per year decreased by 4 times, showing only a 1.2-fold decrease in the comparison group. Hence, the low-dose therapy with rIL-2 may be considered an effective and safe alternative to conventional immunosuppressive therapy and a new option of the targeted treatment of glomerulonephritis with frequent recurrence of nephrotic syndrome.

Iliofemoral thrombosis in a patient with recurrent nephrotic syndrome

Nephrotic syndrome is one of the most common glomerulopathies in children, accompanied by a high risk of thrombosis due to hypoalbuminemia, hypovolemia, hyperlipidemia, hyperfibrinogenemia, and antithrombin III deficiency. The article describes a clinical case of iliofemoral thrombosis in a 16-year-old boy with recurrent nephrotic syndrome and primary thrombophilia (heterozygote F5 — Leiden mutation) was diagnosed. The presented clinical observation indicates the multifactorial origin of thrombotic complications in nephrotic syndrome, caused by a combination of an imbalance between the proand anticoagulant components of the blood coagulation system and individual risk factors (severity of proteinuria, hypoalbuminemia, comorbidity, hereditary thrombophilia), and therefore further study is needed to determine the tactics of prevention and treatment.

Dent disease manifesting as nephrotic syndrome.

Dent disease is an X-linked recessive renal tubular disorder, which is mainly caused by mutations of the CLCN5 gene and OCRL gene. It is characterized by low molecular weight proteinuria, hypercalciuria, nephrocalcinosis or nephrolithiasis, and progressive renal failure. Nephrotic syndrome is a glomerular disorder characterized by massive proteinuria, hypoalbuminemia, edema, and hyperlipidemia. In this study, we report two cases of Dent disease manifesting as nephrotic syndrome. Two patients were initially diagnosed with nephrotic syndrome due to edema, nephrotic range proteinuria, hypoalbuminemia, and hyperlipidemia, and responded to prednisone and tacrolimus therapy. Genetic testing revealed mutations in the OCRL and CLCN5 genes. They were eventually diagnosed with Dent disease. Nephrotic syndrome is a rare and insidious phenotype of Dent disease, and its pathogenesis is not fully understood. Patients with nephrotic syndrome are recommended to routinely undergo urinary protein classification and urinary calcium testing, especially those with frequently recurrent nephrotic syndrome and poor response to steroid and immunosuppressive therapy. To date, there is no effective drug treatment for Dent disease. About 30% to 80% of patients progress to end-stage renal disease at the age of 30-50.

Cellular and Humoral Responses to Recombinant and Inactivated SARS-CoV-2 Vaccines in CKD Patients: An Observational Study.

It remains unclear what B cell and humoral responses are mounted by chronic kidney disease (CKD) patients in response to recombinant and inactivated SARS-CoV-2 vaccines. In this study, we aimed to explore the cellular and humoral responses, and the safety of recombinant and inactivated SARS-CoV-2 vaccines in CKD patients. 79 CKD and 420 non-CKD individuals, who completed a full course of vaccination, were enrolled in the study. Adverse events (AEs) were collected via a questionnaire. Cellular and humoral responses were detected at 1, 3, and 6 months, including IgG antibody against the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein (anti-RBD-IgG), neutralizing antibodies (NAbs), the positive rate of NAbs and anti-RBD-IgG, RBD-atypical memory B cells (MBCs) (CD3 - CD19 + RBD + CD21 - CD27-), RBD-activated MBCs (CD3 - CD19 + RBD + CD21 - CD27+), RBD-resting MBCs (CD3 - CD19 + RBD + CD21 + CD27+), and RBD-intermediate MBCs (CD3 - CD19 + RBD + CD21 + CD27-). We found no differences in the positivity rates of NAbs (70.89% vs. 79.49%, p = 0.212) and anti-RBD IgG (72.15% vs. 83.33%, p = 0.092) between the CKD and control groups. A total of 22 CKD individuals completed the full follow-up (1, 3, and 6 months). Significant and sustained declines were found at 3 months in anti-RBD IgG (26.64 BAU/mL vs. 9.08 BAU/mL, p < 0.001) and NAbs (161.60 IU/mL vs. 68.45 IU/mL p < 0.001), and at 6 months in anti-RBD IgG (9.08 BAU/mL vs. 5.40 BAU/mL, p = 0.064) and NAbs (68.45 IU/mL vs. 51.03 IU/mL, p = 0.001). Significant differences were identified in MBC subgroups between CKD patients and healthy controls, including RBD-specific atypical MBCs (60.5% vs. 17.9%, p < 0.001), RBD-specific activated MBCs (36.3% vs. 14.8%, p < 0.001), RBD-specific intermediate MBCs (1.24% vs. 42.6%, p < 0.001), and resting MBCs (1.34% vs. 22.4%, p < 0.001). Most AEs in CKD patients were mild (grade 1 and 2) and self-limiting. One patient with CKD presented with a recurrence of nephrotic syndrome after vaccination. The recombinant and inactivated SARS-CoV-2 vaccine was well-tolerated and showed a good response in the CKD cohort. Our study also revealed differences in MBC subtypes after SARS-CoV-2 vaccination between CKD patients and healthy controls.

P8.108: Therapeutic Plasma Exchange, Rituximab and Steroids in Pediatric Kidney Transplant Recipients With Early Recurrence of FSGS: A Single Large Pediatric Hospital Experience

Focal segmental glomerular sclerosis (FSGS) is the most common glomerular disease leading to end-stage renal disease (ESRD) in children. FSGS frequently recurs after kidney transplant and may cause graft failure. Therapeutic plasma exchange (TPE), rituximab and steroids have been used to treat post-transplant FSGS recurrence, but limited data is available to support their combined efficacy. We conducted a retrospective cohort study of all kidney transplant recipients at a single pediatric center between 2007 and 2018 to determine frequency of FSGS and early recurrence of nephrotic syndrome within 4 days of transplant. Primary outcome was graft survival and secondary outcome was remission of nephrotic syndrome. FSGS was the indication for renal transplant in 11% of cases(n=29). Of these, 24% of patients had early FSGS recurrence after transplant(n=7). Treatment was at the discretion of the treating physician, but generally included TPE, rituximab and steroids. Five responded; the other two returned to chronic dialysis. 22 patients without recurrence experienced 100% 1-year graft survival. For all FSGS recipients, including those with recurrence, 3-year graft survival was 94.4%. 5/7(71%) of recipients with recurrence achieved partial or full remission of nephrotic syndrome following treatment. This study, the largest to uniformly employ the combination of TPE, rituximab and high-dose steroids, supports the efficacy of this treatment for pediatric patients with FSGS recurrence.

Rituximab use in the treatment of children with nephrotic syndrome

Background. High recurrence rates of nephrotic syndrome in children and consequences in the form of steroid dependence and a high risk of side effects from corticosteroids as a result involve immunosuppressive steroid-preserving agents that would increase long-term remission. Rituximab, a chimeric anti-CD20 monoclonal antibody that inhibits CD20-mediated B-cell proliferation and differentiation, has been identified as a possible alternative treatment. The purpose of the study — to estimate the efficacy and safety of treatment recurrence of nephrotic syndrome in children using rituximab like we did it on three clinical cases. Materials and methods. The experience of rituximab in children was analyzed according to the databases of Scopus, Web of Science, MedLine, The Cochrane Library, EMBASE, Global Health and our own study of the treatment of three children with steroid-sensitive nephrotic syndrome was presented. Results. Treatment of nephrotic syndrome in three children who are 5 to 7 years with rituximab was conducted. One child had a second recurrence, two children had a first recurrence. The previous episode of nephrotic syndrome in all children was treated according to the recommendations of KDIGO 2021. All patients received rituximab (two intravenous injections two weeks apart) at a dose of 15 mg/kg for 5–6 hours with prior administration of methylprednisolone at a dose of 7–10 mg/kg. One child had side effects to the first administration of rituximab in the form of hypotension 70/40 and tachycardia 116–118. Reducing the speed of administration helped to eliminate side effects. The next injection in two weeks the child endured well. The other two children had no side effects to both rituximab injections. Moreover after 1 month of rituximab administration was without side effects or hematological changes. The next administration of rituximab is scheduled in 6 months after the last administration with prior control of CD20 level. Conclusions. In general a review of studies of rituximab confirms the high efficacy of the medication in nephrotic syndrome in children and the requirement for long-term evaluation. Rituximab can be considered as a first-line treatment for recurrence of nephrotic syndrome, including in resource-limited settings. Our own experience with rituximab in recurrent nephrotic syndrome has revealed slight short-term side effects.

FC065: Combined Proteomic Analyses of Recurrent Idiopathic Nephrotic Syndrome Plasma and Plasma-Treated Human Podocytes

Abstract BACKGROUND AND AIMS Idiopathic nephrotic syndrome (INS) comprises a group of rare glomerulopathies attributed to direct or indirect interaction of putative circulating factors with podocytes. One of the pathological manifestations of INS is the rapid recurrence of focal and segmental glomerulosclerosis (rFSGS) after renal transplant, which occurs in 30–50% of cases. To date, the nature and identity of circulating factors have not been confirmed, while the pathogenic mechanisms in the podocyte are partially understood. Direct analysis of patient plasma proteome has been scarcely addressed, mainly due to methodological difficulties associated with plasma complexity and dynamic range. To better understand the mechanisms involved in FSGS recurrence, the present study had two main objectives: (i) to perform a differential proteomic analysis of soluble plasma proteins and of extracellular vesicles (EV) from rFSGS patients and from controls; and (ii) to study the early proximal signaling events in podocytes in response to plasma from post-transplant rFSGS patients as compared to plasma from controls, by a combination of phosphoproteomics and lipid raft proteomics (raftomics). METHOD We obtained first post-transplant plasma exchange fluid from either rFSGS or non-INS patients (n = 4), the latter used as controls, as well as blood plasma from healthy individuals (n = 4). In a first study, by a combination of immunodepletion and high pH fractionation, we performed in parallel a differential proteomic analysis of soluble plasma proteins and of extracellular vesicles (EV) from the three groups. In a second study, we incubated differentiated human podocytes for 30 min with 10% of plasma exchange fluid from either rFSGS or non-INS patients. Then, we isolated lipid rafts from podocytes by a detergent-free method and performed differential proteomics. In addition, we performed differential phosphoproteomics after phosphopeptide enrichment in a TiO2 column. Proteomics by LC-MS/MS analysis was performed in a TimsTOF Pro mass spectrometer on plasma samples, and in a nanoRSLC-Q Exactive PLUS instrument on podocyte samples. RESULTS The approximate number of proteins identified was 500 in immunodepleted plasma, 1400 in EV, 2500 in podocyte rafts and 4900 podocyte phosphosites. In both soluble and EV protein sets from rFSGS patients, we found a statistically significant increase in a cluster of proteins involved in neutrophil degranulation. A group of lipid binding proteins, generally associated with lipoproteins, was found decreased in the soluble set from rFSGS patients. In addition, several aminoacid transporters involved in mTORC1 activation were found significantly increased in EV from rFSGS individuals. As regards podocyte proteome analyses, the differences found in protein expression and phosphorylation associated with rFSGS plasma incubation suggested alterations in the mTOR pathway, in autophagy, in mitochondrial metabolism and in cytoskeleton organization. In particular, validation experiments indicated an altered phosphorylation pattern of Hsp27. CONCLUSION The technological approaches used in the plasma study show the feasibility of direct proteomic analysis of this material, as well as the potential of some of the identified differential proteins as FSGS biomarkers. The observed changes in podocyte proteome associated with rFSGS plasma incubation highlight some of the potential mechanisms involved in FSGS recurrence and could be used as specific early markers of circulating factor activity on podocytes. Further research will be necessary to confirm and validate these findings.

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.

Comparative assessment of renal complications in children during the COVID-19 pandemic

Although medically children are not at risk, but in the ongoing COVID 19 pandemic has serious implications for children. New evidence do not clearly define renal manifestations. Among the reasons for the lack of efficacy of the ongoing treatment of patients with renal complications, an incomplete understanding of its pathogenesis in children who have had a coronavirus infection plays a special role. Biochemical blood tests revealed the elevated blood and urine MC levels which in 1/5 of the patients with high parameters. Moderate proteinuria and transient macrohaematuria were observed in children in the COVID-19 group with renal complications. Children with moderate to severe ChKD with COVID-19 or with recurrent nephrotic syndrome are at risk of severe complications, including severe AKF or ChKF. This data indicates that the children with COVID-19 infection should be closely monitored for the development and progression of RF and special measures should be taken to prevent it.

Case of recurrent refractory nephrotic syndrome in a Japanese boy with COVID-19.

The authors declare no conflicts of interest.

Role of Zinc Supplementation in Reducing Relapses in Steroid Sensitive Nephrotic Syndrome

Objective: To evaluate and compare the effectiveness of zinc and B-Complex supplementation to prevent the recurrence of nephrotic syndrome in the cases priory responsive to corticosteroid therapy. Methodology It is a randomized controlled trial conducted at OPD Pediatric medicine, Shaheed Zulfiqar Ali Bhutto University, PIMS Children Hospital Islamabad from October 3, 2016 to April 2, 2017. 192 patients (96 in each group) were included in the study after obtaining informed consent from parents or guardians taken before determining the population. Patients were randomly assigned to two groups (Group 1: Zinc and Group 2: B-Complex) to receive oral zinc sulphate (10 mg / day) or B-Complex using a random number table. The patients were followed up after 4 months. All data were collected by the researchers themselves in a structured form. Results: The age of 192 participants of the trial averaged 6.38±3.42 years of age ranging from 1-12 years. There were 88 (45.8%) men and 104 (54.2%) women cases. In group 1, there were 22 (22.9%) and in group 2, there were 47 (49%) cases that had been pardoned. The recurrence of nephrotic syndrome was significantly higher in group 1 than group 2 (p = &lt;0.001). Conclusion: The findings of this study suggest that Zinc supplementation is more preferrable to B-Complex supplementation as the rate of continuous remission was higher in the zinc group, so in the future may be added to the treatment regimen to treat steroid-sensitive nephrotic syndrome.

A Case of Venous Thrombosis at the Time of Recurrence of Nephrotic Syndrome

A Case of Venous Thrombosis at the Time of Recurrence of Nephrotic Syndrome

Trends in pediatric nephrotic syndrome

Nephrotic syndrome (NS) is relatively common in children, with most of its histological types being minimal changed disease. Its etiology has long been attributed to lymphocyte (especially T-cell) dysfunction, while T-cell-mediated vascular hyperpermeability increases protein permeability in glomerular capillaries, leading to proteinuria and hypoproteinemia. Based on this etiology, steroids and immunosuppressive drugs that are effective against this disease have also been considered to correct T-cell dysfunction. However, in recent years, this has been questioned. The primary cause of NS has been considered damage to glomerular epithelial cells and podocyte-related proteins. Therefore, we first describe the changes in expression of molecules involved in NS etiology, and then describe the mechanism by which abnormal expression of these molecules induces proteinuria. Finally, we consider the mechanism by which infection causes the recurrence of NS.

Re-transplantation in pediatric patients with failure of primary transplant due to recurrent focal segmental glomerulosclerosis: A pediatric nephrology research consortium study.

Recurrent focal and segmental glomerulosclerosis (FSGS) in kidney transplant recipients is associated with lower graft survival and increased morbidity. There are limited data to guide the decision to re-transplant patients with transplant failure due to FSGS recurrence. We aimed to evaluate outcomes in patients re-transplanted after having initial graft failure due to recurrent FSGS and to study physician attitudes and practice patterns. Retrospective data from 10 centers were collected on 20 patients transplanted between January 1997 and September 2018. A survey was sent to nephrologist members of the Pediatric Nephrology Research Consortium. Mean patient age (years) was 9.8±4.8 at first transplant and 15.9±4.9 at re-transplantation. Pre-transplant plasmapheresis was used in 1 (5.3%) primary transplant vs. 7 (38.9%) re-transplants (p=.03). Nephrotic syndrome recurred in 14 patients (70%) after re-transplantation and was severe in 21.1% vs. 64.7% after first transplant (p=.04). Graft survival was significantly higher in the second transplant (p .009) with 70% having functioning grafts at a median of 25.2months. Thirty-one physicians from 21 centers completed the survey, 94% indicated they would re-transplant such patients, 44.4% preferred a minimum waiting period before re-transplantation, 36.4% preferred living donors, and 22.2% indicated having protocols for re-transplantation at their centers. Consideration for re-transplantation is high among pediatric nephrologists. Pre-transplant plasmapheresis was more frequent in re-transplanted patients. Nephrotic syndrome recurrence was less severe, with better graft survival. More data and a larger population are necessary to further evaluate outcome determinants and best practices in this special population.

Evaluation of Helicobacter pylori eradication on the course of childhood nephrotic syndrome and its response to treatment.

Background: Idiopathic nephrotic syndrome is one of the most common glomerular diseases, which may be secondary to infections or systemic diseases. The aim of this study was to evaluate the effect of Helicobacter pylori (H. pylori) eradication on childhood nephrotic syndrome. Methods: In this randomized controlled clinical trial study, 38 children with concomitant idiopathic nephrotic syndrome and H. pylori infection were divided into 2 equal groups; the intervention group received a cotreatment for both diseases and the control group received only nephrotic syndrome treatment. Patients were followed for 6 months. Data were analyzed using SPSS 21 software. Chi square test, Fisher exact test, and student t test were used. P value <0.05 was considered statistically significant. Results: The mean interval time from treatment to the recovery of nephrotic syndrome was 48.36±14.48 days in the intervention group and 51.68± 17.32 days in control groups, which was shorter in the intervention group, but not statistically significant. The recurrence of nephrotic syndrome and the mean number of recurrences in the intervention group were lower than the control group, but were not statistically significant. The frequency of diarrhea in the intervention group was significantly higher than the control group (p=0.003). Conclusion: In children with concomitant idiopathic nephrotic syndrome and H. pylori infection, the treatment of both diseases may accelerate the recovery and decrease the recurrence of nephrotic syndrome.