Course Of Nephrotic Syndrome Research Articles

#1246 The impact of severe nephrotic syndrome on thyroid function

Abstract Background and Aims Nephrotic syndrome (NS) is a clinical condition characterized by massive urinary loss of proteins, mostly albumin, but also hormones and their carrier proteins among others. The most frequently reported hormonal complication is thyroid dysfunction. The study aimed to assess the frequency of thyroid dysfunction in NS and its association with carrier protein levels and indicators of disease severity. Method A case-control study was conducted involving patients with newly diagnosed or relapsed severe NS, defined as proteinuria > 3.5 g/day and serum albumin ≤ 2.5 g/dL (NS group), and patients without proteinuria (control group). The evaluation included thyroid hormone profiles, serum levels of carrier proteins (prealbumin – PAB, and thyroid-binding globulin – TBG), and markers reflecting the course of NS. Results Forty-two nephrotic and 40 matched non-proteinuric patients were enrolled. The NS group comprised 67% males with a mean age of 49 years and an average proteinuria of 8.9 g/day (Table 1). The leading cause of NS was minimal change disease (22 patients), followed by membranous nephropathy (11 patients). The other causes included: amyloidosis (3 patients: AL – 2 cases, A – 1 case), focal segmental glomerulosclerosis (2 patients) and lupus nephritis (1 case). In 5 cases, no histological diagnosis was made. Thyroid dysfunction secondary to NS was observed in the majority of patients, occurring 18-times more frequently than in the control group (67% vs 10%, OR = 18, 95% CI: 5.3-60.7). Euthyroid sick syndrome was the most commonly seen in NS (15 cases, 36%), followed by overt (8 cases, 19%) and subclinical hypothyroidism (5 cases, 12%). According to the current guidelines, levothyroxine supplementation was required in 11 patients (26% of the NS group, 36% of those with thyroid dysfunction). Serum TSH correlated inversely with PAB (R = −0.63, p < 0.001), and positively with TBG (R = 0.39, p = 0.010), while no relationships were found between carrier proteins and free hormones (fT3 or fT4). The only indicator of NS severity related to thyroid function was serum albumin. It correlated, however, only with TSH (R = −0.41, p = 0.007), not with free hormones. Additionally, neither histological type, nor clinical course of NS distinguished between euthyroidism, euthyroid sick syndrome, or hypothyroidism (Table 2). Conclusion Thyroid dysfunction is a common complication of severe NS. Although euthyroid sick syndrome predominates, the proportion of patients with hypothyroidism who may potentially require levothyroxine replacement therapy remains substantial.

#2358 Impact of COVID-19 on the clinical course of nephrotic syndrome in children: a single-center study

Abstract Background and Aims Children with nephrotic syndrome may experience disease relapse or aggravation triggered by various viral infections. Limited studies on the clinical implications of the coronavirus disease 2019 (COVID-19) pandemic in children with nephrotic syndrome have been published worldwide. Therefore, this study aimed to investigate the effects of COVID-19 on the clinical course of nephrotic syndrome in children. Method The medical records of pediatric patients with idiopathic nephrotic syndrome who visited our hospital between February and June 2022 were retrospectively analyzed. Patients aged <1 year and >19 years and those with inadequate medical records were excluded. Finally, total 59 patients (20 pediatric patients diagnosed with COVID-19 and 39 pediatric patients who did not have COVID-19) were included in the study. Results Twenty of the total 59 patients with nephrotic syndrome were diagnosed with COVID-19 during the study period. The mean age at the time of the diagnosis of nephrotic syndrome and COVID-19 in all 20 patients was 4.6 ± 3.5 and 8.9 ± 3.9 years, respectively. Three patients (15%) were diagnosed with nephrotic syndrome relapse during COVID-19 and the relapse rate was similar to them without COVID-19 (20.5%, 8/39 patients). At the time of the COVID-19 diagnosis, fever (85%) and cough (40%) were the most common symptoms. After the diagnosis of COVID-19, all patients showed improvement with symptomatic treatment, including antipyretic analgesics and cold medicine. None of the critical patients required hospitalization or oral antiviral medications. Conclusion Despite the use of immunosuppressants, the clinical manifestations of COVID-19 in children with nephrotic syndrome were not severe and are expected to be similar to that in the general population. The relapse rate of nephrotic syndrome in children with COVID-19 was also not different from them without COVID-19.

Low Birth Weight is Associated with More Severe Course of Steroid-Sensitive Nephrotic Syndrome in Children, Multicentric Study.

Several previous studies have reported a more severe course of nephrotic syndrome in children with low birth weight. Cohort of 223 children with idiopathic nephrotic syndrome. We aimed to investigate the association between course of nephrotic syndrome and low birth weight. Data from seven paediatric nephrology centres were used. Children with low birth weight had 3.84 times higher odds for a more severe course of steroid-sensitive nephrotic syndrome (95% CI 1.20-17.22, P=0.041), and those with low birth weight and remission after 7 days had much higher odds for a more severe course of disease (OR 8.7). Low birth weight children had a longer time to remission (median 12 vs. 10 days, P=0.03). They had a higher need for steroid-sparing agents (OR for the same sex=3.26 [95% CI 1.17-11.62, P=0.039]), and the odds were even higher in females with low birth weight (OR 6.81). There was no evidence of an association either between low birth weight and focal segmental glomerulosclerosis or between low birth weight and steroid-resistant nephrotic syndrome. We conducted the first multicentric study confirming the worse outcomes of children with NS and LBW and we found additional risk factors. Low birth weight is associated with a more severe course of steroid-sensitive nephrotic syndrome, while being female and achieving remission after 7 days are additional risk factors.

Allergy to Cow’s Milk Proteins and Other Allergens—An Unrecognized Co-Factor of Idiopathic Nephrotic Syndrome in Children or a Factor Interfering with the Treatment of This Disease? A Case Report

Idiopathic nephrotic syndrome (INS) is one of the chronic kidney diseases that occurs in childhood. Starting from a few case reports in the 1950s–1970s and up to the present, the relationship between idiopathic nephrotic syndrome (INS) and the occurrence of atopic disorders in these patients has been discussed in many medical publications. These publications show that in certain patients, mainly children and adolescents, but also in adults with INS, various clinical symptoms and laboratory indicators of an atopic allergic process may be present. This process has been shown to involve Th2 lymphocytes, to have an excessive production of interleukins (IL-4, IL-5, IL-13), and to have an increased serum level of immunoglobulin E (IgE). This leads to the development of a systemic allergic inflammatory process, of which the kidneys can also become the effector organ. The coexistence of an allergic process which may adversely affect the course of nephrotic syndrome may be confirmed by the increased serum IgE level and the hypersensitivity reaction of the patient’s body to various environmental allergens (through the presence of allergen-specific IgE /asIgE/ antibodies to food, pollen, mould, dust, or other allergens in the blood serum). High concentrations of IL-13 and other plasma mediators of this inflammation (e.g., histamine, bradykinin) structurally and functionally damage the renal filtration barrier, and in particular, the function of podocytes in the glomeruli. Podocyte dysfunction disturbs the physiological process of plasma filtration in the glomeruli, leading to excessive protein loss in the urine. These disorders initiate the development of idiopathic nephrotic syndrome in these patients. This publication presents the coexistence of an allergic process caused by allergy to cow’s milk proteins and hypersensitivity to other allergens in a child with idiopathic nephrotic syndrome. This publication also assesses whether treatment of the allergic process coexisting with INS with an elimination diet (milk-free, hypoallergenic) and anti-allergic drugs affected the course and treatment of INS in this child.

Clinical Course of Adult FSGS and Minimal Change Disease in North American and Japanese Cohorts.

Regional differences in presentation and clinical course of nephrotic syndrome (NS) have not been studied well because few studies directly compared the data from different intercontinental regions. We included adult nephrotic patients with Focal Segmental Glomerulosclerosis (FSGS) and Minimal Change Disease (MCD) who received immunosuppressive therapy (IST) in a North American (NEPTUNE, n=89) or Japanese (N-KDR, n=288) cohort. Baseline characteristics and rates of complete remission (CR) were compared. Factors associated with time to CR were evaluated by Cox regression models. NEPTUNE cases had more FSGS (53.9 vs. 17.0%) and family history of kidney disease (35.2 vs. 3.2%). N-KDR cases were older (median 56 vs. 43 years) and demonstrated greater levels of UPCR (7.73 vs. 6.65) and hypoalbuminemia (1.6 vs. 2.2 mg/dL). N-KDR cases showed higher proportion of CR (overall: 89.2 vs. 62.9%; FSGS: 67.3 vs. 43.7%; MCD: 93.7 vs. 85.4%). A multivariable model showed that FSGS (vs. MCD: HR=0.28, 95%CI 0.20-0.41), systolic blood pressure (per 10 mmHg: HR=0.93, 95%CI 0.86-0.99) and eGFR (per 10 mL/min/1.73m2: HR=1.16, 95%CI 1.09-1.24) were associated with time to CR. There were significant interactions in patient age (p=0.004) and eGFR (p=0.001) between the cohorts. The North American cohort had more FSGS and more frequent family history. Japanese patients showed more severe NS with better response to IST. FSGS, hypertension and lower eGFR were shared predictors of poor treatment response. Identifying shared and unique features across geographically diverse populations may help uncover biologically relevant subgroups, improve prediction of disease course and better design future multi-national clinical trials.

The problem of focal-segmental glomerulosclerosis in primary glomerulonephritis

The concept of focal segmental glomerulosclerosis in clinical practice is used to describe both a separate disease and morphological characteristics of secondary kidney damage. Most often, focal segmental glomerulosclerosis occurs as a result of the course of primary glomerulonephritis and is the cause of the development of nephrotic syndrome. A feature of the course of nephrotic syndrome in focal segmental glomerulosclerosis is a longer response to steroid therapy, or the formation of dependence/resistance to glucocorticosteroids. Despite the development of scientific progress, the problem of focal segmental glomerulosclerosis in primary glomerulonephritis is still relevant. Understanding the mechanisms of podocyte damage and disease progression is important not only for basic research, but also for everyday clinical practice.

Effectiveness of a Low Dose Prednisolone Regimen for Treatment of Relapses in Children with Steroid Sensitive Nephrotic Syndrome.

Dear Editor, We read with interest the original article by Mantan et al.[1] titled “Effectiveness of a low dose prednisolone regimen for treatment of relapses in children with steroid sensitive nephrotic syndrome” and would like to compliment the authors for their elegant study on a very relevant issue in pediatricnephrology, which has been attempted by very few investigators earlier.[2] We, however, have a few observations which we would like to highlight through your journal. The study was conducted on children who had infrequently relapsing course of nephrotic syndrome (IFRNS) with median relapse rate of one per year before enrollment in both intervention and control groups, with both groups requiring very low cumulative dose of steroids per kilogram body weight in previous 6 months, making its results extrapolatable to only children with very mild disease. It would have been more clinically relevant if the study could have included patients with frequently relapsing course and steroid dependence. Secondly, the authors have accepted short follow-up as a limitation but hypothesize that the enrolled children were likely to have similar course on prolongation of follow-up period, which is conjectural at best, and at least 6 months to 1-year of follow-up would be required to comment on noninferiority of reduced dose of steroids on the number of relapses in the patients. Attention of the authors is drawn to a study by our group which we had to terminate prematurely in accordance with stoppage rules decided a priori, when 30% of the children showed treatment failure while on reduced dose therapy, which included children with infrequently relapsing course while on additional immunosuppression.[3] Finally, the primary outcome of the study was taken to be proportion of patients with remission in each group at the end of therapy, which appears to be confusing as all patients in the control group are expected to achieve remission by virtue of only children with steroid-sensitive nephrotic syndrome included in the study. Financial support or sponsorship Nil. Conflicts of interest There are no conflicts of interest.

Impact of COVID-19 on the clinical course of nephrotic syndrome in children: a single-center study

Purpose: Children with nephrotic syndrome may experience disease relapse or aggravation triggered by various viral infections. Limited studies on the clinical implications of the coronavirus disease 2019 (COVID-19) pandemic in children with nephrotic syndrome have been published worldwide. Therefore, this study aimed to investigate the effects of COVID-19 on the clinical course of nephrotic syndrome in children.Methods: The medical records of 59 patients with idiopathic nephrotic syndrome who visited our hospital between February and June 2022 were retrospectively analyzed. Results: Twenty of the total 59 patients with nephrotic syndrome were diagnosed with COVID-19 during the study period. The mean age at the time of the diagnosis of nephrotic syndrome and COVID-19 in all 20 patients was 4.6±3.5 and 8.9±3.9 years, respectively. Three patients (15%) were diagnosed with nephrotic syndrome relapse during COVID-19 and the relapse rate was similar to them without COVID-19 (20.5%, 8/39 patients). At the time of the COVID-19 diagnosis, fever (85%) and cough (40%) were the most common symptoms. After the diagnosis of COVID-19, all patients showed improvement with symptomatic treatment, including antipyretic analgesics and cold medicine. None of the critical patients required hospitalization or oral antiviral medications.Conclusions: Despite the use of immunosuppressants, the clinical manifestations of COVID-19 in children with nephrotic syndrome were not severe and are expected to be similar to that in the general population. The relapse rate of nephrotic syndrome in children with COVID-19 was also not different from them without COVID-19.

Urine protein electrophoresis as a prognostic factor in childhood nephrotic syndrome relapse – An observational study in govt. medical college, Mulankunnathukavu, Thrissur

Childhood nephrotic syndrome (NS) is a chronic illness characterized by relapses and remissions. In many there will be disability, caused by the disease and from the treatment in the form of immunosuppression or end stage renal disease. Progression to renal failure will require anticipation for dialysis and/or renal transplant. A noninvasive biomarker such as urine protein profile that accurately predicts responsiveness to steroid therapy would be valuable in predicting the course of nephrotic syndrome. Our study tries to correlate between the selectivity of proteinuria and the outcome of relapses and thus prognosticate the course of the disease. Few similar studies have been done in India.Our study is a cross-sectional hospital based study, comprised of a population of 43 children with nephrotic syndrome relapse, between 1 and 14 years of age. Blood and urine samples were collected, to look for selective or nonselective proteinuria using the Agarose gel electrophoresis (Age) method. The treatment for relapse was started with steroid and, outcome was then related to the selectivity of proteinuria.Majority of our patients had non selective proteinuria (NSP) 60.5%, the rest had selective proteinuria (SP) 39.5%.There was a significant relation between nonselective proteinuria and- 1: Hypertension (p =0.049); 2: Low GFR p<0.001(p =0.0005); 3: Steroid dependent nephrotic syndrome. (p =0.0199).Non selective proteinuria was more in children, above the age of 6 years (p=0.001).The nonselective proteinuria group took more time for remission pointing to the lesser degree of steroid sensitivity.Non selective proteinuria can be used as a biomarker to predict the course in childhood nephrotic syndrome. The higher prevalence of non-selective proteinuria could be due to severe forms of nephrotic syndrome in our study. Selective proteinuria had a better outcome.

Acute abdominal pain and nephrotic syndrome: pediatric case reports and review of the literature

BackgroundAcute abdominal pain in nephrotic syndrome (NS) is a well-known clinical symptom and is mainly related to peritonitis. The presence, although rare, of red umbilicus may guide the diagnosis as a suggestive sign of peritonitis also in the non-neonatal period. Instead, the association between intussusception and NS is quite limited. We reviewed all published cases in the literature, and to our knowledge, this is one of the few pediatric cases of spontaneous resolution of intussusception in the setting of NS. Finally, a review of the causes of abdominal pain during the course of NS was made.Cases presentationWe report two pediatric patient cases who complained of acute abdominal pain during a relapse episode of their NS. The first case is a 4-year-old boy with NS (fourth relapse) who presented with acute abdominal pain, ascites, and red umbilicus. Our suspect of primary peritonitis was clinically confirmed because of the subsequent appearance of the classical peritoneal signs. The second case is a 4-year-old boy who developed an ileo-ileal intussusception during the treatment of his first NS relapse, with spontaneous reduction.ConclusionsGastrointestinal disorders are frequently encountered in the course of NS. The appearance of acute abdominal pain in children with NS requires quick management, both clinical and instrumental. A multidisciplinary team approach needs to be encouraged to lead to an accurate diagnosis and a correct treatment.

P43-6 A case of unresectable colorectal cancer who could continue chemotherapy by hemodialysis for renal failure after FOLFOX

It is reported that 1.0% of membranous nephropathy is associated with malignant disease. We report a case of unresectable colorectal cancer complicated with membranous nephropathy and acute renal failure triggered by the introduction of drug therapy, which required the introduction of hemodialysis. The case was a 53-year-old man. He consulted a former doctor with a chief complaint of abdominal pain and diarrhea, and was referred to our department for detailed examination and treatment. Image search revealed wall thickening in the transverse colon, mass in the rectal bladder fossa, and infiltration into the sigmoid colon, and multiple low-concentration masses in the liver. Diagnosis of transverse colon cancer, multiple liver metastases, and stenosis due to peritoneal dissemination. Laparoscopic tissue biopsy and ileostomy were performed. The pathological result was colorectal cancer, and mFOLFOX6 was started 6 days after the operation. After the start of chemotherapy, urine volume decreased and edema of the lower limbs progressed, and dialysis was introduced with the diagnosis of renal failure due to tumor-related membranous nephropathy. When chemotherapy was continued while continuing hemodialysis, shrinkage of liver metastases and improvement of renal function were observed. After 3 courses of mFOLFOX6, hemodialysis was withdrawn and the patient was discharged from the hospital. After that, he continued chemotherapy at the outpatient department and died of the primary disease 250 days after the start of treatment. In general, the complication of acute renal failure was low during the course of nephrotic syndrome, which was a rare case. Even if organ failure due to paraneoplastic syndrome is observed as in this case, recovery of organ function can be expected due to successful treatment. Therefore, in some cases, continuation of drug therapy can be expected to prolong the prognosis.

POS-169 LEVAMISOLE IS A PROMISING ALTERNATE IMMUNOSUPPRESSIVE THERAPY IN FREQUENT RELAPSING AND STEROID DEPENDENT CHILDHOOD NEPHROTIC SYNDROME

Frequent Relapsing Nephrotic Syndrome (FRNS) and Steroid Dependent Nephrotic Syndrome (SDNS) are often difficult to manage in terms of need of prolonged steroid use, recurrent relapses, frequent infection and hospital admission. Similarly, alternate immunosuppressive therapies have themselves risk of bone marrow suppression and organ toxicities. Levamisole is an anthelminthic with less immunomodulatory action which can be effective in managing FRNS and SDNS This is a retrospective chart review of data from Feb 2018 to Jan 2020 of children with nephrotic syndrome who received levamisole and whose initiation on levamisole was begun before August 2019. The response of levamisole on course of Nephrotic Syndrome and side effect profile among FRNS and SDNS was observed. 45 cases were put on levamisole during the study period, of which 9 cases were SDNS and remaining were FRNS. The mean age of FRNS was 6±2 yrs., among FRNS cases remission for at least 6 months was achieved among 61.1%, while 22.2% had In-Frequent Relapsing course. On the other hand, switch over to other immunosuppressive therapy was required in just 16.6% of the cases. The mean age of SDNS was 4.5±2 yrs., 22.2% among SDNS had sustained remission for at least 6 months and 55.5% had in frequent relapsing course and 22.2% needed switch over to other immunosuppressive therapy. 1 case of FRNS was admitted with pneumonia while 2 cases of SDNS needed admission (1 with pneumonia and 1 with peritonitis). No cases had bone marrow suppression, 2 cases with SDNS had skin manifestation in the form of Tinea cruris and molluscum contagiosum. Levamisole is one of the cheap and effective alternate immunosuppressive agents which can be used in FRNS and SDNS, with better advantage in FRNS and also has minimum side effect profile.

Clinical Pattern and Course of Nephrotic Syndrome in Children: An Observational Study

Introduction: Chronic renal diseases not only affects the personal life of an individual but also results in social and financial burden on their families too. Nephrotic syndrome is most common in the paediatric age group contributing to significant illness related morbidity and even mortality if not identified early and treated promptly. This common disease has shown varying clinical trends with studies attempting to document them. Aim: To study the clinical pattern and course of nephrotic syndrome in children. Materials and Methods: The study was a retrospective analysis of medical records of diagnosed nephrotic syndrome patients in the Paediatrics and Nephrology Departments of a Tertiary Care Medical college hospital. The patients were prospectively followed-up for a period of two years. A total of 90 patients were enrolled into the study and their case records were systematically reviewed to obtain the details regarding age, sex distribution, number of admissions, hospital stay during first admission, complications and interim problems, histopathology finding where indicated, diagnostic classifications based on traditional operational definitions, treatment received, duration of remission after first episode and its relation to future relapses and the final outcome were noted and then statistically analysed. Results: Of the 90 cases of nephrotic syndrome, 14 were lost during follow-up, so remaining 76 patients were included. There were 49 males (64.5%) and 27 females (35.5%). Steroid- Sensitive Nephrotic Syndrome (SSNS) was the most common type (59%). It was found that 67 (88.1%) patients had first episode within 1-5 years of age, 31(40.8%) had only 1st time admission, 35 (46%) had 2-4 times admissions, while the rest (13.2%) required more than 4 times admissions. Majority of the cases {48 (63.2%)} had hospital stay between 7-14 days. Infectious complications were the most common (35.3%) and 48 (63.1%) cases showed frequent relapse, while 16 (21%) never had a relapse. The final outcome showed 64 (84.2%) of the cases were in remission, 12 (15.8%) were still relapsing, and there was no mortality. Conclusion: Age of onset for nephrotic syndrome was 5 years in majority of cases. Males were more affected than females. Majority of the patients had hospital stay for 7-14 days. SSNS was the most common type of nephrotic syndrome and Urinary Tract Infection (UTI) was the most common infectious complication. As respiratory and UTIs account for majority of relapses, prevention of respiratory infections by observing respiratory etiquettes, early and aggressive treatment and respiratory protective vaccines will go a long way in prevention of relapses.

Childhood nephrotic syndrome in Southeast Nigeria: The old story or any change in pattern?

Background: The chronic course of nephrotic syndrome (NS), it is racial/regional variations, and associated risk of end-stage renal disease is of great pediatric importance. This underscores the need to study the characteristics of this cohort of patients in every nephrology setting. Objective: This study was aimed at documenting the characteristics of children presenting with NS in our hospital. Materials and Methods: This was a cross-sectional descriptive study of children aged 29 days–16 years admitted and managed for NS over 5 years at the Pediatric Nephrology Unit of the Abia State University Teaching Hospital, Nigeria. Children diagnosed with NS in our setting were consecutively enrolled in the study. The parameters documented and analyzed for each patient with NS included Biodata, presenting complaints, duration of illness before the presentation, intake of herbal concoctions, results of investigations done, response to the steroids, duration of treatment before remission, and outcome of admission. Steroid sensitive NS was followed up for a median (range) period of 18.2 (12.0–24.0) months to monitor remission and relapse. Results: A total of 6108 children were admitted into the pediatric wards during the study period, of which 104 were renal disorders. NS accounted for 0.8% of all the pediatric admissions and 49 (47.1%) of the admitted renal disorders. Male:female ratio was 2.3:1. The mean age was 8.35±3.99 years, with peak ages between 7 and 9 years. The major clinical features at first presentation were pedal edema (93.9%) and oliguria (87.8%). A total of 19 patients (38.9%) took herbal concoctions before the presentation (p<0.05) and 12 patients had culture-proven urinary tract infections. There were four patients seropositive to human immunodeficiency virus and two had sickle cell anemia. There were 39 patients (90.7%) who were steroid-sensitive, while four (9.3%) were steroid-resistant. A total of 47 patients were discharged. There was one patient who was referred, while one signed against medical advice. Over this period, 76.9% remained in remission, while relapse was noted in 23.1% of patients. The mortality was 2.0%. Conclusion: NS forms a significant part of our pediatric admissions. Herbal concoction intake among our cohort with NS was high. There was an increased response to the steroid, even in older children. A majority maintained their remission while on follow-up. The mortality rate was low. The prognosis of NS in African children is changing for the better, age notwithstanding.

Association of low birth weight and prematurity with clinical outcomes of childhood nephrotic syndrome: a prospective cohort study.

Low birth weight (LBW)/prematurity have been proposed as risk factors for the development of kidney disease in adulthood. Whether there is an association between LBW/prematurity and poor renal outcomes in childhood onset nephrotic syndrome remains unknown. Children with nephrotic syndrome diagnosed between 1 and 18years of age were followed prospectively from 1996 to 2016 at The Hospital for Sick Children (N = 377). LBW/prematurity was defined as birth weight < 2500g or gestational age < 36weeks. Normal birth weight (NBW) was defined as birth weight ≥ 2500g. Measures evaluating clinical course of nephrotic syndrome include initial steroid-resistant nephrotic syndrome (SRNS), time to first relapse, and frequently relapsing nephrotic syndrome. Kaplan-Meier survival analysis, logistic regression, and Cox proportional hazards regression were used to determine the association of LBW/prematurity with clinical outcomes. Median birth weights in LBW/premature (n = 46) and NBW (n = 331) children were 2098g (interquartile range [IQR] 1700-2325g) and 3317g (IQR 2977-3685g), respectively. Odds of having SRNS were 3.78 (95% confidence interval [CI] 1.28-11.21) times higher among LBW/premature children than NBW children. An 8% decrease in odds of developing SRNS was observed for every 100g increase in birth weight (adjusted odds ratio [OR] 0.92; 95% CI 0.86-0.98). Median time to first relapse did not differ (hazard ratio [HR] 0.89; 95% CI 0.53-1.16). LBW/premature children were more likely to develop SRNS but did not have a difference in time to first relapse with NBW children. Understanding the impact and mechanism of birth weight and steroid-resistant disease needs further study.

Nephrotic syndrome.

On the basis of observational studies, the most common cause of nephrotic syndrome in school-aged children is minimal change disease. On the basis of research evidence and consensus, corticosteroids are considered first-line therapy for treatment of nephrotic syndrome. On the basis of consensus, prednisone therapy should be initiated at doses of 60 mg/m2 per day (2 mg/kg per day) administered for 4 to 6 weeks, followed by 40 mg/m2 per dose (1.5 mg/kg) every other day for at least 6 to 8 weeks. On the basis of consensus and expert opinion, it is important to recognize and manage the complications that can arise in patients with nephrotic syndrome, such as dyslipidemia, infection, and thrombosis. On the basis of research evidence, consensus, and expert opinion, several alternative therapies have been observed to have variable efficacy in children with both corticosteroid-dependent and corticosteroid-resistant nephrotic syndrome, although caution must be exercised in the administration of these corticosteroid-sparing medications secondary to toxic adverse effects. On the basis of observational studies, the course of nephrotic syndrome in most patients is that of relapse and remission.

Fibronectin glomerulopathy.

Fibronectin glomerulopathy occurs between the second and fifth decades of life in most patients, and it is known to be slowly progressive with mild proteinuria leading to kidney failure. The case of a 78-year-old woman with a rapid course of nephrotic syndrome due to fibronectin glomerulopathy is reported. She had proteinuria that rapidly increased to 6.8 g/day in a month and microscopic haematuria. A renal biopsy specimen showed lobular glomerulopathy and membranoproliferative glomerulonephritis-like lesions on light microscopy. There was scanty staining for immunoglobulins and complement. Electron microscopy revealed granular deposits with fibril formation. Immunohistochemistry of the fibronectin showed intense staining in the mesangium and peripheral loop. Therefore, this case was diagnosed as fibronectin glomerulopathy. The kidney function was rapidly decreasing, necessitating haemodialysis 2 months after renal biopsy. It is important to consider fibronectin glomerulopathy in the differential diagnosis of nephrotic syndrome in older people.

Thrombosis in Nephrotic Syndrome

Nephrotic syndrome (NS) is characterized by heavy proteinuria, edema, hypoalbuminemia, and hyperlipidemia and the most frequent causes are glomerular diseases. An uncommon presentation is iatrogenic NS, an adverse effect of some drugs administration. In the clinical course of NS, a typical feature is dysregulated coagulation state, promoted by the breakdown of permselectivity barrier of the glomerular capillary wall, resulting in the leakage of high-molecular-mass proteins, at least the size of albumin. This hypercoagulable condition is supported by several factors, such as abnormalities in platelet activation and an imbalance between anticoagulation/antithrombosis and procoagulant/prothrombotic mechanisms. Thus, NS and the risk of developing thromboses are strictly related. Thrombotic events affect the venous system rather than arterial vessels with different features and frequencies. Deep venous system of the lower extremities and renal veins are the most frequent source of pulmonary embolism, the most dangerous NS complication. Prophylactic anticoagulation and thrombosis treatment are not clearly established because large randomized trials and guidelines are lacking. The management of NS and the decision of when and how to anticoagulate the patient represent a teamwork challenge for physicians.

SOCS3 and SOCS5 mRNA expressions may predict initial steroid response in nephrotic syndrome children

Suppressors of Cytokine Signaling (SOCS) inhibit Signal Transducers and Activators of Transcription (STATs) phosphorylation by binding and inhibiting Janus Kinases (JaKs). The aim of the present study was to evaluate the influence of glucocorticosteroids on the JaK/STAT signaling pathway in the leukocytes of nephrotic syndrome (NS) patients. The study group was composed of 34 steroid sensitive NS (SSNS) children and 20 steroid resistant NS (SRNS) subjects. Gene expression was assessed by real-time PCR using pre-designed human JaK/STAT PCR array. Protein expression was evaluated using ELISA assay (plasma concentration) and immunofluorescence (in situ protein expression). In SSNS children, the initial increased expression of JaK1, JaK2, JaK3, STAT1, STAT2, STAT6, TYK2, SOCS1, SOCS2, SOCS3, SOCS4 and SOCS5 was reduced back to the control limits. Similarly, in SRNS patients the increased levels of almost all mRNA expressions for the abovementioned genes were decreased, with the exceptions of SOCS3 and SOCS5 expressions. These mRNA expressions were still significantly increased and correlated with early unfavorable course of nephrotic syndrome in children. Plasma levels of SOCS3, SOCS5, IL-6 and IL-20 were significantly increased in SRNS subjects after six weeks of steroids medication compared to SSNS and control participants. We conclude that SOCS3 and SOCS5 increased mRNA expressions might predict initial resistance to steroids in NS patients.

Comparison of three methods for isolation of urinary microvesicles to identify biomarkers of nephrotic syndrome

Urinary microvesicles, such as 40-100 nm exosomes and 100-1000 nm microparticles, contain many proteins that may serve as biomarkers of renal disease. Microvesicles have been isolated by ultracentrifugation or nanomembrane ultrafiltration from normal urine; however, little is known about the efficiency of these methods in isolating microvesicles from patients with nephrotic-range proteinuria. Here we compared three techniques to isolate microvesicles from nephrotic urine: nanomembrane ultrafiltration, ultracentrifugation, and ultracentrifugation followed by size-exclusion chromatography (UC-SEC). Highly abundant urinary proteins were still present in sufficient quantity after ultrafiltration or ultracentrifugation to blunt detection of less abundant microvesicular proteins by MALDI-TOF-TOF mass spectrometry. The microvesicular markers neprilysin, aquaporin-2, and podocalyxin were highly enriched following UC-SEC compared with preparations by ultrafiltration or ultracentrifugation alone. Electron microscopy of the UC-SEC fractions found microvesicles of varying size, compatible with the presence of both exosomes and microparticles. Thus, UC-SEC following ultracentrifugation to further enrich and purify microparticles facilitates the search for prognostic biomarkers that might be used to predict the clinical course of nephrotic syndrome.