Assessment of Interleukin-15 (IL-15) Concentration in Children with Idiopathic Nephrotic Syndrome.

Idiopathic nephrotic syndrome (INS) is a chronic glomerular disease in children, characterized by severe proteinuria, hypoalbuminemia, and/or presence of edema and hyperlipidemia. The pathogenesis, however, has not been yet established. The clinical course of the disease is characterized by frequent relapses. Interleukin-15 (IL-15) is a pro-inflammatory cytokine, that apart from its involvement in the immune system, was found to be playing a vital role in various cells' functioning, including renal tissue. It is desirable to look for new predictors of INS. Our study aimed to evaluate IL-15 as a potential marker in the early diagnosis of the disease. The cohort participating in the study consisted of patients hospitalized in Clinical Hospital No. 1 in Zabrze, from December 2019 to December 2021, including study group with INS (n = 30) and control group (n = 44). Results: The concentration of IL-15 in both serum and urine was significantly elevated in patients with INS, compared to healthy controls. The cytokine might serve as a marker of the disease, however, further research on larger study groups is needed.

Diagnosis of bacterial infection in children with relapse of nephrotic syndrome: a personalized decision-analytic nomogram and decision curve analysis.

BACKGROUND: Infections associated with nephrotic relapses (NR) are often managed according to physician preferences. A validated prediction tool will aid clinical decision-making and help in rationalizing antibiotic prescriptions. Our objective was to develop a biomarker-based prediction model and a regression nomogram for the prediction of the probability of infection in children with NR. We also aimed to perform a decision curve analysis (DCA). METHODS: This cross-sectional study included children (1-18 years) with NR. The outcome of interest was the presence of bacterial infection as diagnosed using standard clinical definitions. Total leucocyte count (TLC), absolute neutrophil count (ANC), quantitative C-reactive protein (qCRP), and procalcitonin (PCT) were the biomarker predictors. Logistic regression was used to identify the best biomarker model, followed by discrimination and calibration testing. Subsequently, a probability nomogram was constructed and DCA was done to determine the clinical utility and net benefits. RESULTS: We included 150 relapse episodes. A bacterial infection was diagnosed in 35%. Multivariate analysis showed the ANC + qCRP model to be the best predictive model. This model displayed excellent discrimination (AUC: 0.83), and calibration (optimism-adjusted intercept: 0.015, slope: 0.926). A prediction nomogram and web-application was developed. The superiority of the model was also confirmed by DCA in the probability threshold range of 15-60%. CONCLUSIONS: An ANC-based and qCRP-based internally validated nomogram can be used for the prediction of probability of infection in non-critically ill children with NR. Decision curves from this study will aid in the decision-making of empirical antibiotic therapy, incorporating threshold probabilities as a surrogate of physician preference. A higher resolution version of the Graphical abstract is available as Supplementary information.

Utility of muscle ultrasound in nutritional assessment of children with nephrotic syndrome.

BACKGROUND: Nutritional status assessment in children with nephrotic syndrome (NS) is critical for identifying patients who are at risk of protein-energy wasting (PEW) and for determining their nutritional needs and monitoring nutritional intervention outcomes. METHODS: In a case-control study, we enrolled 40 children (age range: 2-16 years) with NS and 40 apparently healthy children (age and sex-matched) as a control group. Anthropometric data, as well as demographic, clinical, and laboratory data, were collected. A dietary intake assessment using a 3-day food intake record was done, and the quadriceps rectus femoris thickness (QRFT) and quadriceps vastus intermedius thickness (QVIT) were assessed using B-mode ultrasound and compared between both groups. RESULTS: Children with NS had lower QRFT and QVIT measurements than control groups (p < 0.001). Inadequacy in protein intake occurred in 62.5% and 27.5% of the NS and control groups, respectively (p = 0.002). The thickness of the rectus and vastus muscles by ultrasound was significantly associated with the percentage of protein intake (p < 0.001). The ROC curve revealed that the best cutoff value of QRFT for the prediction of the patient at risk of malnutrition was ≤ 1.195 with an area under curve of 0.907, with p < 0.001. CONCLUSION: In children with NS, skeletal muscle ultrasound is a simple and easy-to-use bedside technique for the identification of patients at risk of malnutrition. A higher resolution version of the Graphical abstract is available as Supplementary information.

Assessment of hearing levels in children with nephrotic syndrome.

OBJECTIVE: Due to the similarities in the physiological mechanisms and antigenicity of the kidney and cochlea, they are simultaneously affected by certain diseases and drugs. Therefore, the purpose of this study was to investigate whether the hearing functions of patients with nephrotic syndrome (NS) were affected by the severity of the disease and the cyclosporine treatment. METHODS: The sample of this study consisted of 87 participants, including 65 patients (130 ears) with NS and 22 age- and sex-matched normal hearing children (44 ears). Based on the severity of the disease, the patients were divided into two groups: infrequently relapsing nephrotic syndrome (IRNS) and steroid-dependent or frequently relapsing nephrotic syndrome (SD/FRNS). Their audiologic tests, including Pure-tone Audiometry and Distortion-Product Otoacoustic Emission (DPOAE), were compared with the tests of the control group. In addition, the audiologic tests of the NS patients who received cyclosporine were compared with those who did not. RESULTS: In the pure-tone audiometry, there were statistically significant differences between the IRNS, SD/FRNS, and control groups at 2000, 4000 Hz, and pure-tone average (PTA). Hearing levels of the SD/FRNS group at 2000, 4000 Hz, and PTA were higher than those of the control group. At 6000 Hz in pure-tone audiometry, there was a very weak positive correlation between the hearing level and the number of relapses. At 250 Hz and PTA, hearing levels of the group that received cyclosporine were higher compared to the group that did not receive it. In DPOAE, there was no significant difference between the groups according to the severity of the disease and the use of cyclosporine. CONCLUSION: During the follow-up of the patients with NS, their hearing functions should be questioned, especially in patients with SD/FRNS and receiving cyclosporine treatment.

Assessment of Carotid Intima Media Thickness and Left Ventricular Mass Index in Children with Idiopathic Nephrotic Syndrome.

BACKGROUND: Children with nephrotic syndrome (NS) are at a greater risk of atherosclerosis due to recurrent exposures to hyperlipidemia, hypertension, and immunosuppressive medications. CIMT (carotid intima media thickness) is a reliable marker for assessment of atherosclerosis of large and medium-sized blood vessels; endothelial dysfunction and increased CIMT usually precede the development of cardiovascular diseases. Some manifestations of NS, like proteinuria and hyperlipidemia, are associated with an increased risk of cardiac morbidity and mortality. The aim of the current study was to evaluate the carotid intima media thickness and LVM (left ventricular mass) thickness in children with nephrotic syndrome. SUBJECTS AND METHODS: Eighty-one children with nephrotic syndrome and 100 healthy children as controls were enrolled in the study. The inclusion criteria were: disease duration of minimum of 12 months, glomerular filtration rate >60mL/min/1.73m 2 and children aged two years or more at the time of study. CIMT and left ventricular mass index, lipid profile, protein/creatinine ratio in urine and kidney function tests were done for cases and controls after approval of internal ethical committee. RESULTS: The mean CIMT (mm) was significantly higher in NS (0.51± 0.12) compared to controls (0.42± 0.09) (P <0.001). LVM and LVM Index were significantly higher in NS than controls (p< 0.001, for both). Subsequently, CIMT was significantly correlated to duration of the disease (p< 0.001), LVM index was significantly correlated with duration of the disease, body mass index (BMI), blood pressures and triglycerides level (p< 0.05). CONCLUSION: Children with NS are at increasing risk to develop atherosclerosis as measured by CIMT. LVM was significantly higher in NS and positively correlated to BP, disease duration, triglyceride levels and BMI.

Long term tapering versus standard prednisolone treatment for first episode of childhood nephrotic syndrome: phase III randomised controlled trial and economic evaluation.

OBJECTIVE: To determine whether extending initial prednisolone treatment from eight to 16 weeks in children with idiopathic steroid sensitive nephrotic syndrome improves the pattern of disease relapse. DESIGN: Double blind, parallel group, phase III randomised placebo controlled trial, including a cost effectiveness analysis. SETTING: 125 UK National Health Service district general hospitals and tertiary paediatric nephrology centres. PARTICIPANTS: 237 children aged 1-14 years with a first episode of steroid sensitive nephrotic syndrome. INTERVENTIONS: Children were randomised to receive an extended 16 week course of prednisolone (total dose 3150 mg/m2) or a standard eight week course of prednisolone (total dose 2240 mg/m2). The drug was supplied as 5 mg tablets alongside matching placebo so that participants in both groups received the same number of tablets at any time point in the study. A minimisation algorithm ensured balanced treatment allocation by ethnicity (South Asian, white, or other) and age (5 years or less, 6 years or more). MAIN OUTCOME MEASURES: The primary outcome measure was time to first relapse over a minimum follow-up of 24 months. Secondary outcome measures were relapse rate, incidence of frequently relapsing nephrotic syndrome and steroid dependent nephrotic syndrome, use of alternative immunosuppressive treatment, rates of adverse events, behavioural change using the Achenbach child behaviour checklist, quality adjusted life years, and cost effectiveness from a healthcare perspective. Analysis was by intention to treat. RESULTS: No significant difference was found in time to first relapse (hazard ratio 0.87, 95% confidence interval 0.65 to 1.17, log rank P=0.28) or in the incidence of frequently relapsing nephrotic syndrome (extended course 60/114 (53%) v standard course 55/109 (50%), P=0.75), steroid dependent nephrotic syndrome (48/114 (42%) v 48/109 (44%), P=0.77), or requirement for alternative immunosuppressive treatment (62/114 (54%) v 61/109 (56%), P=0.81). Total prednisolone dose after completion of the trial drug was 6674 mg for the extended course versus 5475 mg for the standard course (P=0.07). There were no statistically significant differences in serious adverse event rates (extended course 19/114 (17%) v standard course 27/109 (25%), P=0.13) or adverse event rates, with the exception of behaviour, which was poorer in the standard course group. Scores on the Achenbach child behaviour checklist did not, however, differ. Extended course treatment was associated with a mean increase in generic quality of life (0.0162 additional quality adjusted life years, 95% confidence interval -0.005 to 0.037) and cost savings (difference -£1673 ($2160; €1930), 95% confidence interval -£3455 to £109). CONCLUSIONS: Clinical outcomes did not improve when the initial course of prednisolone treatment was extended from eight to 16 weeks in UK children with steroid sensitive nephrotic syndrome. However, evidence was found of a short term health economic benefit through reduced resource use and increased quality of life. TRIAL REGISTRATION: ISRCTN16645249; EudraCT 2010-022489-29.

Assessment of factors associated with mizoribine responsiveness in children with steroid-dependent nephrotic syndrome.

BACKGROUND: Several immunosuppressants have been used to treat children with steroid-dependent nephrotic syndrome (SDNS). Mizoribine (MZR) is an immunosuppressant used to maintain remission in children with SDNS, although its effectiveness for treating SDNS remains controversial. Therefore, in this study, we assessed the clinical factors associated with children having SDNS who were successfully treated with MZR. METHODS: A total of 47 children with SDNS who underwent MZR treatment were retrospectively evaluated. Clinical features including pharmacokinetics after MZR administration were compared between MZR responders and non-responders. RESULTS: The comparison of the two groups revealed no significant differences in age, body weight (BW), daily dose of MZR per BW, serum concentration 2 h after administration (C2), peak serum concentration (Cmax), and area under the concentration curve 0-4 h after administration (AUC0-4). C2/(single dose/BW), Cmax/(single dose/BW), and AUC0-4/(single dose/BW) were significantly higher in the MZR responders than in the non-responders (all p < 0.01). Receiver operating characteristic analysis revealed that the cutoff values of C2 (single dose/kg), Cmax/(single dose/BW), and AUC0-4/(single dose/BW) were 0.55, 0.58, and 1.37, respectively. CONCLUSIONS: MZR is a useful immunosuppressant for treating frequent-relapse NS in children who are susceptible to the drug. The efficacy of MZR may be associated with not only serum concentrations defined by the dosage or absorption efficiency through MZR transporters, but also the susceptibility defined by the expression level and performance of MZR transporters on the target cells.

Familial Chylomicronemia Syndrome: A Clinical Guide For Endocrinologists.

OBJECTIVE: Familial chylomicronemia syndrome (FCS) is a rare autosomal recessive disorder caused by mutations in lipoprotein lipase, resulting in accumulation of chylomicrons in plasma and hypertriglyceridemia. Elevated triglycerides cause several complications in patients, the most serious being episodes of acute pancreatitis. This review focuses on expert guidance and opinion from an experienced lipidologist and endocrinologist as well as a current review of the literature, as there are no specific guidelines on FCS. METHODS: Discussion of expert guidance and opinion review of current literature. RESULTS: To date, there is no pharmacologic treatment for affected patients, and management options primarily include adoption of an extremely restricted, very-low-fat diet, along with avoidance of certain medications and alcohol. Endocrinologists often diagnose and manage patients with metabolic disorders, including patients with high triglyceride levels, but rare diseases like FCS can be missed or poorly evaluated due to knowledge gaps about disease state. Given endocrinologists' role in the treatment of lipid disorders, it is important that they understand the clinical signs and symptoms of FCS to correctly diagnose patients. Patients with FCS can be identified based on a defined clinical criteria and a thorough review of medical history, after excluding differential diagnoses and secondary factors. Typical manifestations include hypertriglyceridemia characterized by lipemic serum, history of abdominal pain, and acute/recurrent pancreatitis. Secondary factors to be excluded are pregnancy, alcohol abuse, uncontrolled diabetes, and use of certain medications. CONCLUSION: FCS is a rare, inherited lipid disorder disease that often goes underdiagnosed and unmanaged. This review provides a summary of clinical characteristics of FCS that can be potentially used to screen patients in an endocrinologist's office and direct them to the appropriate standard of care. ABBREVIATIONS: apoB = apolipoprotein B; apoC-III = apolipoprotein CIII; ASO = antisense oligonucleotide; FCS = familial chylomicronemia syndrome; HTG = hypertriglyceridemia; LPL = lipoprotein lipase; LPLD = lipoprotein lipase deficiency.

Apolipoprotein A-1-related amyloidosis 2 case reports and review of the literature.

RATIONALE: Apolipoprotein A-1 (ApoA-1)-related amyloidosis is characterized by the deposition of ApoA-1 in various organs and can be either hereditary or nonhereditary. It is rare and easily misdiagnosed. Renal involvement is common in hereditary ApoA-1 amyloidosis, but rare in the nonhereditary form. PATIENT CONCERNS: We reported two cases with ApoA-1 amyloidosis, a 64-year-old man suffering from nephrotic syndrome and a 40-year-old man with nephrotic syndrome and splenomegaly. Renal biopsies revealed glomerular, interstitial and vascular amyloid deposits and positive phospholipase A2 receptor staining in the glomerular capillary loop in case 1, and mesangial amyloid deposits in case 2. DIAGNOSES: After immunostaining failed to determine the specific amyloid protein, proteomic analysis of amyloid deposits by mass spectrometry was performed and demonstrated the ApoA-1 origin of the amyloid. Genetic testing revealed no mutation of the APOA1 gene in case 1 but a heterozygous mutation, Trp74Arg, in case 2. Case 1 was thus diagnosed as nonhereditary ApoA-1 associated renal amyloidosis with membranous nephropathy, and case 2 as hereditary ApoA-1 amyloidosis with multiorgan injuries (kidney and spleen) and a positive family history. INTERVENTIONS: Case 1 was treated with glucocorticoid combined with cyclosporine. Case 2 was treated with calcitriol and angiotensin converting enzyme inhibitors. OUTCOMES: Two cases were followed up for 5 months and 2 years, respectively; and case 1 was found to have attenuated proteinuria while case 2 had an elevation of cholestasis indices along with renal insufficiency. LESSONS: Proteomic analysis by mass spectrometry of the amyloid deposits combined with genetic analysis can provide accurate diagnosis of ApoA-1 amyloidosis. Besides, these 2 cases expand our knowledge of ApoA-1-related renal amyloidosis.

Assessment of quality of life in children with nephrotic syndrome at a teaching hospital in South India.

This study was conducted to assess the quality of life (QOL) in children between 2 and 18 years of age with primary idiopathic nephrotic syndrome (NS) using Pediatric Quality of Life Inventory (PedsQL 4.0 Generic Core Scales). This cross-sectional comparative study was conducted at a tertiary care hospital in South India between December 2014 and February 2015. In this questionnaire-based study, 50 children with primary idiopathic NS and an equal number of age-matched controls with other chronic ailments were recruited. Their clinical and demographic details were recorded, and QOL was assessed using PedsQL 4.0 Generic Core Scales. The median (interquartile range) total QOL score in children with NS [65 (59-68.75)] was found to be higher compared to controls [62.19 (58.05-65.78)] (P = 0.012). Children with NS had significantly higher QOL scores in physical (P = 0.004), emotional (0.029), and social functioning (0.010) domains as compared to controls; however, the school performance was not different from controls. The QOL scores did not significantly differ between the various clinical pheno- types of NS. Demographic details such as age, gender, duration of illness, and steroid resistance did not significantly influence the total QOL scores among the nephrotic children. The present study shows that the overall QOL in children with NS was better than in children with other chronic illnesses. Further studies are needed to confirm these findings and explore the underlying cause of poor school performance.

[Significance of the determination of urinary excretion of kidney injury molecule-1 (KIM-1) in the assessment of the activity and prognosis of chronic glomerulonephritis].

AIM: To estimate the urinary excretion of KIM-1 in groups of patients with varying clinical activity of chronic glomerulonephritis (CGN) and to determine the possibility of using the urinary KIM-1 concentration as a criterion for predicting the course of CGN. SUBJECTS AND METHODS: A total of 47 patients with CGN were examined. Group 1 included 10 patients with nephrotic syndrome (NS) and decreased glomerular filtration rate (GFR); Group 2 consisted of 16 patients with NS and normal GFR; Group 3 comprised 10 patients with partial remission of NS; Group 4 included 11 patients with CGN, hematuria, moderate proteinuria, and normal GFR. A control group consisted of 9 healthy individuals. In the examined groups, urinary KIM-1 concentrations were estimated using an indirect immunoassay. RESULTS: The urinary KIM-1 excretion in the patients with CGN was higher than that in the healthy individuals (p <0.0001), at the same time, in the average the KIM-1 excretion was statistically significantly higher in the patients with proteinuria than in those with hematuria (p=0.01). The highest levels were registered in Group 1; Group 2 was intermediate in the level of KIM-1 excretion and the difference between Groups 3 and 4 proved to be statistically insignificant. The lowest levels were noted in Group 4 and in the controls; the differences between the groups were statistically insignificant. In the patients with CGN, the level of KIM-1 excretion was established to correlate with all indicators of NS severity. The value of the determination of KIM-1 as a risk factor of persistent/refractory NS was estimated. The results of constructing the ROC-curve indicate that KIM-1 levels higher than 2.34 ng/ml could predict NS persistence in CGN patients with a high sensitivity and specificity. CONCLUSION: Urinary KIM-1 levels may be used to estimate the activity of CGN with NS and to evaluate the efficiency of treatment. The results of the study substantiate the search for ways of pharmacological blockade of KIM-1 production in the kidney in order to optimize the methods that impact on the pathogenesis of CGN progression.

Matching the Genotype in Resolution: Innovative Ways of Phenotype Capture.

Social and spatial context are important determinants of morbidity and mortality. However, there is little clarity about the role of context for kidney disease specifically, particularly before the end stage. Meanwhile, research clarifying the clinical, cellular, molecular, and genetic causes of kidney disease is accelerating considerably. We postulate that without contextual information, even the most detailed biomedical information cannot fully capture the factors that ultimately drive the development and progression of kidney disease. The Nephrotic Syndrome Study Network is integrating detailed, state-of-the-art information on a social and spatial context to enable the exploration of the associations between the social environment and kidney disease. Here, we discuss the extant literature on social context and kidney disease, present information on sources of contextual information, and provide recommended further reading to facilitate future research on the contribution of the social context to kidney disease.

The impact of pediatric nephrotic syndrome on parents' health-related quality of life and family functioning: an assessment made by the PedsQL 4.0 family impact module.

The multi-dimensional impact on the quality of life (QOL) of families of children with the nephrotic syndrome (NS) has not been studied sufficiently in the literature. We aimed to study this aspect and the predictors of poor QOL among Indian families having children with NS. A cross-sectional study was conducted to compare the parents of children with chronic NS on treatment for at least one year with parents of a matched healthy control group. The parents of both groups were asked to complete the standard self-administered multi-dimensional questionnaire of Pediatric Quality of Life Inventory 4 (PedsQL TM ) Family Impact Module (FIM). Descriptive and analytical statistics were performed to compare scores between the two groups. Possible predictors of poor outcome in each of the summary scales among the cases were assessed by both univariate and multivariate analysis. The parents of 61 cases and 72 controls completed the PedsQL TM FIM questionnaire. The scores in each of the categories, namely FIM Total Scale Score, Parent HRQOL Summary Score, Family Functioning Summary Score and eight individual domains, were found to be significantly higher among controls. Female gender of the affected child was an independent risk factor for poor Family Functioning Summary Score. Also, presence of serious complications during the course of the disease independently predicted poor Total FIM and Parent HRQOL Summary Scores. Even a relatively benign and potentially curable chronic disorder in children, like the NS, can disturb the QOL of parents in multiple domains of functioning.

Short course daily prednisolone therapy during an upper respiratory tract infection in children with relapsing steroid-sensitive nephrotic syndrome (PREDNOS 2): protocol for a randomised controlled trial.

BACKGROUND: Relapses of childhood steroid-sensitive nephrotic syndrome (SSNS) are treated with a 4- to 8-week course of high-dose oral prednisolone, which may be associated with significant adverse effects. There is a clear association between upper respiratory tract infection (URTI) and relapse development. Previous studies in developing nations have suggested that introducing a 5- to 7-day course of daily prednisolone during an URTI may prevent a relapse developing and the need for a treatment course of high-dose prednisolone. The aim of PREDNOS 2 is to evaluate the effectiveness of a 6-day course of daily prednisolone therapy during an URTI in reducing the development of a subsequent relapse in a developed nation. METHODS/DESIGN: The subjects will be 300 children with relapsing SSNS (≥2 relapses in preceding year), who will be randomised to receive either a 6-day course of daily prednisolone or no change to their current therapy (with the use of placebo to double blind) each time they develop an URTI over 12 months. A strict definition for URTI will be used. Subjects will be reviewed at 3, 6, 9 and 12 months to capture data regarding relapse history, ongoing therapy and adverse effect profile, including behavioural problems and quality of life. A formal health economic analysis will also be performed. The primary end point of the study will be the incidence of URTI-related relapse (3 days of Albustix +++) following the first infection during the 12-month follow-up period. DNA and RNA samples will be collected to identify a potential genetic cause for the disease. Subjects will be recruited from over 100 UK centres with the assistance of the Medicines for Children Research Network.PREDNOS 2 is funded by the National Institute for Health Research Health Technology Assessment Programme (11/129/261). DISCUSSION: We propose that PREDNOS 2 will be a pivotal study that will inform the future standard of care for children with SSNS. If it is possible to reduce the disease relapse rate effectively and safely, this will reduce the morbidity and cost associated with drug treatment, notwithstanding hospital admission and parental absence from employment. TRIAL REGISTRATION: Current Controlled Trials (ISRCTN10900733).

Long-term outcomes in idiopathic nephrotic syndrome: from childhood to adulthood.

BACKGROUND: The aim of the study was to assess idiopathic nephrotic syndrome (INS) relapse rate, co-morbidities, and social status of adults diagnosed with INS in childhood. MATERIAL AND METHODS: A written questionnaire was sent to 118 adults treated for INS in childhood. In 61 (51.7%) responders (aged 26.0 ± 6.2 years, range 18 - 51.5 years), we used available medical records to evaluate age at the onset of INS, number of INS relapses below 18 years of age, response to corticosteroids (CS), renal biopsy findings, and immunosuppressive treatment as well as questionnaire to evaluate the number and treatment of INS relapses above 18 years of age, co-morbidities, age at menarche, marital status, offspring, educational status, and occupation. RESULTS: In the group of 61 responders, median age at the onset of INS was 3 (range 1.3 - 14.0) years, median number of INS relapses at < 18 years of age was 5 (1 - 20). Steroid-sensitive nephrotic syndrome (SSNS) was diagnosed in 37 (60.7%) patients, steroid-dependent nephrotic syndrome SDNS in 18 (29.5%) patients, and steroid-resistant nephrotic syndrome (SRNS) in 6 (9.8%) patients. Mesangial proliferation was the most common pattern in renal biopsy (35.7%). All patients received CS, 15 were treated with methylprednisolone pulses, 13 with cyclophosphamide, 11 with chlorambucil, 2 with cyclosporine, and 21 with levamisole. All patients achieved remission and had normal renal function at the age of 18. In adulthood, INS relapsed in 10 (16.4%) patients, including 5 (13.5%) patients with SSNS, 4 (22.2%) with SDNS, and 1 (16.7%) with SRNS (p = 0.72). Median number of relapses was 2 (range 1 - 11). Patients with relapses at > 18 years of age had more (p < 0.005) relapses at < 18 years of age. Hypertension was diagnosed in 8 (16.1%), overweight in 14 (23.0%), obesity in 3 (4.9%), and bone fractures in 12 (19.7%) patients. Five patients had height < 3rd percentile, including 4 with INS onset at < 3 years of age. One patient had growth retardation before the treatment. No myocardial infarctions, strokes, severe infections, or malignancies were reported. Mean age at menarche was 12.9 ± 1.4 years, 37 (60.7%) patients were in a steady relationship/ married, 1/18 (5.6%) patients treated with cytostatic agents and 12/43 (24/7%) patients not treated with cytostatic agents had offspring (p < 0.05). Elementary education was reported by 4 (6.6%), secondary education by 32 (52.5%), and higher education by 25 (40.9%) patients, and 34 (55.7%) patients were professionally active. None of the 6 patients with SRNS developed end-stage renal disease. CONCLUSIONS: 1. High number of INS relapses in childhood is a risk factor for recurrences in adulthood. 2. INS relapses in childhood do not preclude active professional life in adulthood.

Assessment of genetic risk factors for thromboembolic complications in adults with idiopathic nephrotic syndrome.

AIMS: Nephrotic syndrome (NS) may occur with acquired hypercoagulability, however, the fact that it is accompanied by an underlying hereditary thrombophilia, especially combined hereditary thrombophilia would lead to thrombotic events. In this study, we aimed to evaluate the contribution of genetic thrombophilia to development of thrombotic events in adult patients with NS. MATERIAL AND METHODS: Factor V Leiden (FVL), prothrombin, and methylenetetrahydrofolate reductase (MTHFR) gene mutation were studied in 51 newly diagnosed idiopathic NS patients and age- and gender-matched 20 healthy control subjects included in the study. Renal vein Doppler ultrasound was conducted in order to investigate the prevalence of subclinical renal vein thrombosis. RESULTS: Of 51 patients, 6 (11.8%) were established to have thromboembolic (TE) complications at the time of diagnosis (4 symptomatic, 2 subclinical), and no recurring thrombotic episode was observed. Genetic mutation was established in all patients that were found to have TE complications. Acquired hypercoagulability factors were similar in patients without and with TE complication. CONCLUSIONS: The coexistence of inherited thrombophilia in NS may facilitate thromboembolic complications. If the cause of thrombosis cannot be explained by the usual factors attributed to the occurrence of thrombosis in NS, screening for the other factors, such as FVL, MTHFR, and prothrombin gene mutation, may be beneficial.

Genetic testing in nephrotic syndrome--challenges and opportunities.

Monogenic nephrotic syndrome (nephrotic syndrome caused by a single gene defect) is responsible for only a small percentage of cases of nephrotic syndrome, but information from studies of the unique cohort of patients with this form of the disease has dramatically improved our understanding of the disease pathogenesis. The use of genetic testing in the management of children and adults with nephrotic syndrome poses unique challenges for clinicians in terms of who to test and how to use the information obtained from testing in the clinical setting. In our view, not enough data exist at present to justify the routine genetic testing of all patients with nephrotic syndrome. Testing is warranted, however, in patients with congenital nephrotic syndrome (onset at 0-3 months), infantile nephrotic syndrome (onset at 3-12 months), a family history of nephrotic syndrome, and those in whom nephrotic syndrome is associated with other congenital malformations. The family and/or the patient should be given complete and unbiased information on the potential benefits and risks associated with therapy, including the reported outcomes of treatment in patients with similar mutations. Based on the data available in the literature so far, intensive immunosuppressive treatment is probably not indicated in monogenic nephrotic syndrome if complete or partial remission has not been achieved within 6 weeks of starting treatment. We advocate that family members of individuals with genetic forms of nephrotic syndrome undergo routine genetic testing prior to living-related kidney transplantation. Prospective, multicentre studies are needed to more completely determine the burden of disease caused by monogenic nephrotic syndrome, and randomized controlled trials are needed to clarify the presence or absence of clinical responses of monogenic nephrotic syndrome to available therapies.

Occurrence of infection among children with nephrotic syndrome during hospitalizations.

AIM: The present study was conducted to investigate the trends of childhood nephrotic syndrome (NS) admissions and factors associated with childhood NS admissions with major infections in Taiwan. METHODS: A retrospective analysis was performed using Taiwan National Health Research Insurance Database (NHIRD) to explore the associated factors and health care burden for childhood NS admissions with major infections in 1997 to 2007. RESULTS: Of 133,927 children, a total of 176 children had NS, which incurred 508 hospital admissions. Nineteen percent of admissions were associated with major infections. Pneumonia was the most common infection (49%), followed by urinary tract infection (UTI), bacteraemia/sepsis, peritonitis and cellulitis. Pneumonia was the most common infection among children age younger than 10 years, whereas UTI was more common among children aged greater than 10 years. NS admission with infections had longer periods of hospital length of stay and higher hospital total costs compared to those without infections. Regression analysis reveals that younger age, regional hospitals, admission hospital located in middle and south areas and admission made in spring were associated with increased risk for developing major infections. CONCLUSIONS: While 19% of childhood NS admissions were associated with major infections, young age, admissions made in spring, located in middle and south Taiwan and in regional hospitals were the major associated factors for infection. Age plays an important role in risk and types of infection.

[Protein-creatinine ratio--a simple method for proteinuria assessment in clinical practice]. / Protein-kreatinin-ratio--en enkel metode for vurdering av proteinuri i klinisk praksis.

BACKGROUND: Proteinuria is an indicator of renal disease. Measurement of protein excretion is important for diagnosis and follow-up of renal disease, but measuring 24-hour protein excretion is a cumbersome procedure. MATERIAL AND METHODS: A simplified validated method for measuring excretion is obtained by measuring urine protein/creatinine concentration in a spot urine sample. RESULTS: We have implemented such ratios for clinical routine measurements of proteinuria at Rikshospitalet University Hospital in Oslo. Whenever protein or albumin in urine is requested, the laboratory also measures urine creatinine and reports the ratio in mg protein/mmol creatinine. 24-hour excretion is approximately 10 times the ratio. The rationale for using the ratio is given and proteinuria pathophysiology and potential risks and treatment options are discussed. INTERPRETATION: Our experience is that use of the urine protein/creatinine ratio is a significant improvement. Measurements are now routinely made whereas quantification was rarely performed when 24-hour urine samples were used. We recommend that physicians and laboratories implement the use of this ratio in their daily routines.

Evaluation and management of proteinuria and nephrotic syndrome in children: recommendations from a pediatric nephrology panel established at the National Kidney Foundation conference on proteinuria, albuminuria, risk, assessment, detection, and elimination (PARADE).

OBJECTIVE: The development of this review article evolved from a National Kidney Foundation consensus conference on recent advances in the importance of evaluating and treating proteinuria. From this conference, a series of recommendations for the evaluation of adults with proteinuria was published. Because specific pediatric aspects of the problem were outside the scope of the original National Kidney Foundation publication, an ad hoc committee of 6 pediatric nephrologists who were active participants in the National Kidney Foundation conference was established to provide primary care physicians with a concise, up-to-date reference on this subject. METHODS: The recommendations that are given represent the consensus opinions of the authors. These are based on data from controlled studies in children when available, but many of the opinions are, by necessity, based on uncontrolled series in children or controlled trials performed in adults, because controlled trials in children have not been performed to evaluate many of the treatments described. RESULTS AND CONCLUSIONS: These recommendations are intended to provide primary care physicians with a useful reference when they are faced with a young child or teenager who presents with proteinuria, whether this is mild and asymptomatic or more severe, leading to nephrotic syndrome.