SARS-CoV-2 Infection as a Possible Trigger for IgA-Associated Vasculitis: A Case Report.

BACKGROUND: IgA-associated vasculitis (IgAV), formerly known as Henoch-Schönlein purpura (HSP) disease, is the most common type of systemic vasculitis observed during developmental age. Available published studies associate the outbreak of the disease with streptococci, adenovirus, parvovirus, mycoplasma, respiratory syncytial virus (RSV), and influenza infection in approximately 50% of patients with HSP, while some emerging reports have described a few cases of COVID-19 infection being associated with HSP in both adults and children. CASE PRESENTATION: a 7-year-old girl was diagnosed with HSP, fulfilling the four required clinical criteria (palpable purpura and abdominal pain, arthralgia and edema, and periodic renal involvement). Infection with SARS-CoV-2 was confirmed via the presence of IgM and IgG antibodies. The disclosure of the Henoch-Schönlein purpura (HSP) disease was preceded by a mild, symptomatically treated infection of the upper respiratory tract. High levels of inflammatory markers were observed during hospitalization, including leukocytosis, an increased neutrophil count and a high neutrophil-to-lymphocyte ratio (NLR). All of these markers are associated with IgAV gastrointestinal bleeding, which was also associated with rotavirus diarrhea observed in the patient. CONCLUSIONS: This case presented by us and similar cases presented by other authors indicate the possible role of SARS-CoV-2 in the development of HSP, but this assumption requires further research and evidence-based verification.

X-linked variations in SHROOM4 are implicated in congenital anomalies of the urinary tract and the anorectal, cardiovascular and central nervous systems.

BACKGROUND: SHROOM4 is thought to play an important role in cytoskeletal modification and development of the early nervous system. Previously, single-nucleotide variants (SNVs) or copy number variations (CNVs) in SHROOM4 have been associated with the neurodevelopmental disorder Stocco dos Santos syndrome, but not with congenital anomalies of the urinary tract and the visceral or the cardiovascular system. METHODS: Here, exome sequencing and CNV analyses besides expression studies in zebrafish and mouse and knockdown (KD) experiments using a splice blocking morpholino in zebrafish were performed to study the role of SHROOM4 during embryonic development. RESULTS: In this study, we identified putative disease-causing SNVs and CNVs in SHROOM4 in six individuals from four families with congenital anomalies of the urinary tract and the anorectal, cardiovascular and central nervous systems (CNS). Embryonic mouse and zebrafish expression studies showed Shroom4 expression in the upper and lower urinary tract, the developing cloaca, the heart and the cerebral CNS. KD studies in zebrafish larvae revealed pronephric cysts, anomalies of the cloaca and the heart, decreased eye-to-head ratio and higher mortality compared with controls. These phenotypes could be rescued by co-injection of human wild-type SHROOM4 mRNA and morpholino. CONCLUSION: The identified SNVs and CNVs in affected individuals with congenital anomalies of the urinary tract, the anorectal, the cardiovascular and the central nervous systems, and subsequent embryonic mouse and zebrafish studies suggest SHROOM4 as a developmental gene for different organ systems.

Relationship between Gd-IgA1 and TNFR1 in IgA nephropathy and IgA vasculitis nephritis in children - multicenter study.

AIM OF THE STUDY: To evaluate the relationship between serum Gd-IgA1 (sGd-IgA1) and serum and urine TNFR1 (sTNFR1, uTNFR1) levels as possible prognostic factors in IgA nephropathy (IgAN) and IgA vasculitis nephritis (IgAVN). MATERIAL AND METHODS: From 299 patients from the Polish Registry of Pediatric IgAN and IgAVN, 60 children (24 IgAN and 36 IgAVN) were included in the study. The control group consisted of 20 healthy children. Proteinuria, haematuria, serum creatinine as well as IgA and C3 levels were measured and glomerular filtration rate (GFR) was calculated at onset and at the end of the follow-up. Kidney biopsy findings were evaluated using the Oxford classification. Serum Gd-IgA1 and serum and urine TNFR1 levels were measured at the end of follow-up. RESULTS: Serum Gd-IgA1 level was significantly higher in IgAN and IgAVN patients in comparison to the control group. Urine TNFR1 was significantly higher in IgAN than in IgAVN and the control group. We did not observe any differences in sTNFR1 level between IgAN, IgAVN and control groups. We found a positive correlation between Gd-IgA1 and creatinine (r = 0.34), and negative between Gd-IgA1 and GFR (r = -0.35) at the end of follow-up. We observed a negative correlation between uTNFR1/creatinine log and albumin level and protein/creatinine ratio. We did not find any correlations between Gd-IgA1 and TNFR1. CONCLUSIONS: The prognostic value of sGd-IgA1 in children with IgAN and IgAVN has been confirmed. TNFR1 is not associated with Gd-IgA1 and is not a useful prognostic marker in children with IgAN/IgAVN and normal kidney function.

Tumour necrosis factor alpha (TNFα) and alpha-Klotho (αKL) in children and adolescents with chronic kidney disease (CKD).

INTRODUCTION: Chronic kidney disease (CKD) in children, despite the progress in science and technology, is still a serious challenge. Early CKD detection gives a chance of early therapeutic intervention and lowering the progression of the disease. According to several publications indicating the possible use of alpha-Klotho (αKL) and tumour necrosis factor alpha (TNFα) for the early detection of the disease in adults, an attempt was made to evaluate their usefulness in the paediatric population. MATERIAL AND METHODS: The study group consisted of 42 patients with CKD with a mean age of 10.7 years (18 girls and 24 boys). The control group involved 21 healthy children with a mean age of 8.4 years (11 girls and 10 boys). Anthropometrical parameters and blood pressure were taken and routine biochemical tests were performed in the whole group. The concentrations of TNFα and αKL in serum and urine were determined by enzyme immunoassay. RESULTS: Children from the CKD group showed a statistically significant difference in serum TNFα and αKL in comparison to the control group. There was no significant relationship between the evaluated markers and sex, presence of hypertension, or proteinuria in the children. The mean αKL serum concentration was higher in patients on dialysis compared to the group of conservatively treated children, whereas the values of TNFα in serum and urine, as well as the αKL in urine, did not differ significantly in these groups. A significant positive correlation was found between serum αKL concentration and serum creatinine, but there was no other correlation between serum αKL or TNFα concentration and any of the measured anthropometric and laboratory parameters. CONCLUSIONS: Serum TNFα and αKL levels in children with chronic kidney disease, although being statistically different compared to the group of healthy children, except for the correlation of serum aKL and creatinine, showed no other correlations to the most parameters used for chronic kidney disease evaluation including, eGFR. Their usefulness in the early detection of kidney dysfunction in children was not proven.

The Role of Complement Component C3 Activation in the Clinical Presentation and Prognosis of IgA Nephropathy-A National Study in Children.

The aim of the study was to evaluate the influence of the intensity of mesangial C3 deposits in kidney biopsy and the serum C3 level on the clinical course and outcomes of IgAN in children. The study included 148 children from the Polish Pediatric IgAN Registry, diagnosed based on kidney biopsy. Proteinuria, creatinine, IgA, C3 were evaluated twice in the study group, at baseline and the end of follow-up. Kidney biopsy was categorized using the Oxford classification, with a calculation of the MEST-C score. The intensity of IgA and C3 deposits were rated from 0 to +4 in immunofluorescence microscopy. The intensity of mesangial C3 > +1 deposits in kidney biopsy has an effect on renal survival with normal GFR in children with IgAN. A reduced serum C3 level has not been a prognostic factor in children but perhaps this finding should be confirmed in a larger group of children.

IgA vasculitis nephritis clinical course and kidney biopsy - national study in children.

The aim of the study was to investigate the relationship between the severity of typical clinical symptoms, severity of histopathological lesions in kidney biopsies in IgA vasculitis nephritis (IgAVN) and to propose indications for kidney biopsy in children. MATERIAL AND METHODS: This retrospective study enrolled 106 patients, included in the IgAVN registry of Polish children, diagnosed by kidney biopsy. Renal and extrarenal symptoms at onset of the disease were analyzed. Biopsy results were assessed using Oxford classifications (MEST-C). The patients were divided into 3 groups depending on the severity of proteinuria: A-nephrotic proteinuria with hematuria; B-non-nephrotic proteinuria with hematuria; C-isolated hematuria. RESULTS: The first symptoms of nephropathy were observed at the 0.7 (1-128.4) months from the onset of extrarenal symptoms. Kidney biopsy was performed on 39 (6-782) days after the onset of nephropathy symptoms. MEST-C score 4 or 5 was significantly more frequent in children from group A than in groups B and C. Significantly higher mean MEST-C score was found in patients with abdominal symptoms than without. In group A: S0 and T0 we found in significantly shorter time to kidney biopsy than in S1, T1-2 p < 0.05) and in group B the significantly shorter time in T0 compare to T1-2 p < 0.05). The ROC analysis shows that S1 changes appear in kidney biopsies in group A with cut off 21 days (AUC 0,702, p = 0.004, sensitivity 0.895 specificity 0.444) T1-2 changes after 35 days (AUC 0.685, p = 0.022, sensitivity 0.750, specificity 0.615), and in goupn B T1-2 cut off is 74 days (AUC 0,738, p = 0.002, sensitivity 0.667, specificity 0.833). CONCLUSIONS: In childhood IgAVN, the severity of changes in the urine is clearly reflected in the result of a kidney biopsy. The biopsy should be performed in patients with nephrotic proteinuria no later than 3 weeks after the onset of this symptom in order to promptly apply appropriate treatment and prevent disease progression. Accompanying abdominal symptoms predispose to higher MESTC score.

Atypical Hemolytic Uremic Syndrome (aHUS) and Adenosine Deaminase (ADA)-Deficient Severe Combined Immunodeficiency (SCID)-Two Diseases That Exacerbate Each Other: Case Report.

Hemolytic uremic syndrome (HUS) is defined by the triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury (AKI). Atypical HUS (aHUS), distinguished by its etiology, is caused by uncontrolled overactivation of the alternative complement pathway. The correct diagnosis of aHUS is complex and involves various gene mutations. Severe combined immunodeficiency (SCID), characterized by severe T-cell lymphocytopenia and a lack of antigen-specific T-cell and B-cell immune responses, is of seldom occurrence. In 10-15% of pediatric patients, SCID is caused by adenosine deaminase (ADA) deficiency. The authors describe the case of a boy who suffered from both aHUS and ADA-deficient SCID. At the age of 9 months, the patient presented acute kidney injury with anuria and coagulopathy. The diagnosis of aHUS was established on the basis of alternative complement pathway deregulation and disease-associated gene mutations. Further examination revealed immune system failure and, at the age of 13 months, the ADA deficiency was confirmed by genetic tests and the boy was diagnosed with ADA-SCID. ADA SCID has recently been described as a possible triggering factor of aHUS development and progression. However, more research is required in this field. Nevertheless, it is crucial in clinical practice to be aware of these two co-existing life-threatening diseases.

Evaluation of the frequency of RETN c.62G>A and RETN c.-180C>G polymorphisms in the resistin coding gene in girls with anorexia nervosa.

INTRODUCTION: Anorexia nervosa (AN) is a serious psychosomatic syndrome, classified as an eating disorder. AN patients strive to lose weight below the normal limits defined for a specific age and height, achieving their goal even at the expense of extreme emaciation. AN has a multifactorial aetiology. Genetic factors are believed to be significant in the predisposition to the development of AN. In girls suffering from AN significantly lower levels of resistin (RES) in blood serum are observed as compared to healthy girls. These differences may lead to a thesis that functional genetic polymorphisms in RES coding genes can be responsible for this phenomenon. In our pilot study we demonstrated significant differences in the distribution of genotypes in the locus RETN c.-180C>G of the RES gene in 67 girls with AN and 38 healthy girls. It seems reasonable to compare the frequency of polymorphisms of RETN c.62G>A and RETN c.-180C>G in the RES gene in girls with AN and in healthy subjects in a bigger cohort and to analyse correlations between individual variants of the polymorphisms referred to above and the RES levels in blood plasma. MATERIAL AND METHODS: The study covered 308 girls with the restrictive form of AN (AN) and 164 healthy girls (C) (aged 11-19 years). The RES levels in blood serum were determined by means of the ELISA method on a Bio-Vendor machine from LLC (Asheville, North Carolina, USA). The DNA isolation was carried out by means of Genomic Mini AX BLOOD (SPIN). The PCR reaction was carried out on a ThermoCycle T100 thermocycler. 80-150 ng of the studied DNA and relevant F and R starters were added to the reaction mixture. The reaction products were subjected to digestion by restriction enzymes and separated on agarose gels (RFLP). RESULTS: The average RES level in blood serum in the AN group was significantly lower (p < 0.0001) than in the C group. The distribution of genotypes in the locus RETN c.62 of the RES gene was similar in both groups. A significant difference was demonstrated in the distribution of genotypes in the polymorphic site RETN c.-180 of the RES gene between AN and C (p = 0.0145) and in the distribution of the C and G alleles in the locus RETN c.-180 (p < 0.0001). The C allele occurred significantly more frequently than the G allele in the C group as compared to the AN group. In all the study subjects jointly (AN and C) a significant positive correlation between the blood RES levels on one hand and the body mass (r = 0.42; p < 0.0001) and BMI (r = 0.61; p< 0.0001) on the other was observed. There was no correlation between the concentration of RES in blood serum and the distribution of genotypes in the loci of the resistin gene referred to above. CONCLUSIONS: The CG genotype in the locus RETN c.-180 C>G of the RES gene may constitute one of the factors predisposing to the development of AN in girls. The genotype in the loci RETN c.62 G>A and RETN c.-180 C>G of the resistin gene has no influence on the levels of this hormone in blood in AN patients.

Mortality in Children Treated With Maintenance Peritoneal Dialysis: Findings From the International Pediatric Peritoneal Dialysis Network Registry.

RATIONALE & OBJECTIVE: Research on pediatric kidney replacement therapy (KRT) has primarily focused on Europe and North America. In this study, we describe the mortality risk of children treated with maintenance peritoneal dialysis (MPD) in different parts of the world and characterize the associated demographic and macroeconomic factors. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: Patients younger than 19 years at inclusion into the International Pediatric Peritoneal Dialysis Network registry, who initiated MPD between 1996 and 2017. EXPOSURE: Region as primary exposure (Asia, Western Europe, Eastern Europe, Latin America, North America, and Oceania). Other demographic, clinical, and macroeconomic (4 income groups based on gross national income) factors also were studied. OUTCOME: All-cause MPD mortality. ANALYTICAL APPROACH: Patients were observed for 3 years, and the mortality rates in different regions and income groups were calculated. Cause-specific hazards models with random effects were fit to calculate the proportional change in variance for factors that could explain variation in mortality rates. RESULTS: A total of 2,956 patients with a median age of 7.8 years at the start of KRT were included. After 3 years, the overall probability of death was 5%, ranging from 2% in North America to 9% in Eastern Europe. Mortality rates were higher in low-income countries than in high-income countries. Income category explained 50.1% of the variance in mortality risk between regions. Other explanatory factors included peritoneal dialysis modality at start (22.5%) and body mass index (11.1%). LIMITATIONS: The interpretation of interregional survival differences as found in this study may be hampered by selection bias. CONCLUSIONS: This study shows that the overall 3-year patient survival on pediatric MPD is high, and that country income is associated with patient survival.

Analysis of the association between kidney injury biomarkers concentration and nephritis in immunoglobulin A vasculitis: A pediatric cohort study.

OBJECTIVE: The aim of this study was to investigate the clinical course, selected biochemical parameters and concentrations of renal injury biomarkers such as neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1) and liver-fatty acid binding protein (L-FABP) in patients with immunoglobulin A vasculitis (IgAV) to identify the markers associated with nephritis in the course of the disease (IgAVN). METHODS: The study involved 29 children with IgAV and 34 healthy controls. Eleven (38%) patients had renal involvement (IgAV-N) and 18 (62%) did not exhibit nephritis (IgAV-noN). Initial laboratory tests, determining the concentrations of NGAL, KIM-1 and L-FABP in serum and urine, were conducted on children from the study group in an acute phase of IgAV as well as after an average of 6 months, during a follow-up visit. The interconnection between renal involvement, anthropometric measurements, epidemiological data, laboratory parameters and levels of examined biomarkers have been thoroughly evaluated. RESULTS: The serum and urine levels of NGAL, KIM-1 and L-FABP were significantly higher in children with an acute phase of IgAV as compared to the control group (P < .001) and markedly lower during follow-up retesting in comparison with the values obtained at inclusion (P < .001). However, the concentration of none of the evaluated biomarkers correlated with nephrological indices. Among all examined parameters, only male subjects were associated with nephritis (P = .017). CONCLUSIONS: We have established no evident association between the concentrations of NGAL, KIM-1 and L-FABP and nephritis in the course of IgAV in children. Additionally, we confirmed a significant male predominance in patients with nephritis.

A rare complication of systemic lupus erythematosus in a 9-year-old girl: Questions.

Serious renal involvement in systemic diseases is common and generally constitutes a pivotal prognostic factor, making those pathology frequently seen in nephrology departments. Authors describe the case of a nine-year-old girl with lupus nephritis. After admission the patient's state deteriorated over a period of a few days, with an unremitting high-grade fever, significant weakness and drowsiness, generalized erythema, and decrease of the kidney function to eGFR nadir of 56 ml/min/1,73m 2. Treatment with pulsed methylprednisolone was started. After the first pulse the general state of the patient improved slightly, although laboratory tests showed an alarming evolution, with the exacerbation of anemia, leukopenia, neutropenia, increase of serum CRP concentration, extremely high D-dimer concentration and increase in activity of lactate dehydrogenase. The concentration of ferritin rose reaching the level of 540 µg/l, triglicerydes level was also high. Intravenous cyclophosphamide pulse therapy was added to the ongoing steroid treatment, and resulted in a radical patient improvement. Authors underline that it seems important to be aware of rare, non-renal, but potentially devastating complications of systemic diseases, like in this clinical case: the secondary hemophagocytic lymphohistiocytosis (HLH). When HLH complicates a rheumatic disease, it is also referred to as macrophage activation syndrome (MAS). Unfortunately treatment of MAS is still based on reports provided by individual centres and gathered own experiences so drawing up unambiguous diagnostic criteria will be valuable in future. The treatment should be individually tailored, and more specific evidence-based recommendations are needed.

Evaluation of liver-type fatty acid binding protein (L-FABP) and interleukin 6 in children with renal cysts.

BACKGROUND: Renal cysts, according to their etiology, can be divided into genetic and acquired cysts. This is of great importance in patients with cystic kidney disease with a possible poor prognosis to identify markers of early kidney damage. OBJECTIVES: The objective of this study was to evaluate the concentration of serum and urine liver-type fatty acid binding protein (L-FABP) and interleukin 6 (IL-6) in children with kidney cysts. MATERIAL AND METHODS: The study was conducted on a group of 39 children with kidney cysts including 20 subjects with autosomal dominant polycystic kidney disease (ADPKD). RESULTS: Serum and urine L-FABP concentration in children with renal cysts was significantly higher compared to the controls, regardless of the underlying type of cystic degeneration, number of cysts and gender. Also, serum and urinary IL-6 concentration was significantly higher than in the control group. There was a significant negative correlation between serum L-FABP concentration and standard deviation score (SDS) for diastolic blood pressure (DBP). A significant negative correlation was found between serum IL-6 concentration and systolic blood pressure (SBP), DBP and mean arterial pressure (MAP) values as well as SDS for SBP and DBP. In addition, a significant positive correlation was found between urinary IL-6 concentration and estimated glomerular filtration rate (eGFR). CONCLUSIONS: Higher concentration of L-FABP in serum and urine in children with kidney cysts indicates the early damage to the renal parenchyma, detectable before the onset of hypertension and other organ damage. Significantly higher serum and urinary IL-6 levels in children with cystic kidney disease compared to healthy children may suggest the role of this cytokine in chronic kidney disease development.

Angiotensinogen and interleukin 18 in serum and urine of children with kidney cysts.

BACKGROUND: The most common disease associated with the presence of kidney cysts in the population is autosomal dominant polycystic kidney disease (ADPKD), which finally leads to end-stage renal disease. METHOD: The study evaluated serum and urinary concentration of angiotensinogen (AGT) and interleukin 18 (IL-18) in a group of 39 children with renal cysts of different aetiology. RESULTS: Serum and urinary AGT concentration in children with renal cysts was higher compared to controls, regardless of the underlying background and gender. Serum IL-18 concentration was lower, in contrast, and the concentration of IL-18 in the urine did not differ between affected and healthy children. Negative correlation between urinary IL-18 concentration and systolic and mean arterial blood pressure was noted. CONCLUSIONS: Higher AGT levels in serum and urine in children with renal cysts may indicate the activation of the renin-angiotensin-aldosterone system, including its intrarenal part, even before the onset of hypertension. Lower serum concentration of IL-18 in children with kidney cysts may indicate the loss of the protective role of this cytokine with the occurrence of hypertension.

The importance of fetuin-A in vascular calcification in children with chronic kidney disease.

BACKGROUND: The status of the cardiovascular (CV) system in children with chronic kidney disease (CKD) is significantly influenced by increasing stiffness of the arterial wall. This largely depends on the shortage of local and systemic inhibitors of soft tissue calcification. OBJECTIVES: The aim of the study was to evaluate the role of fetuin-A in conjunction with other factors in the progressive hardening of the vascular wall in these children. We examined serum fetuin-A concentrations in relation to renal function, dialysis modality, and other clinical and biochemical markers promoting vascular calcification. MATERIAL AND METHODS: Twenty children on peritoneal dialysis (PD), 20 on hemodialysis (HD), 36 treated conservatively, and 26 healthy subjects were enrolled into a cross-sectional study. In all children, fetuin-A and numerous clinical and biochemical parameters were measured. RESULTS: The fetuin-A concentration was significantly lower in children on hemodialysis (HD) vs children on peritoneal dialysis (PD), conservatively treated subjects, and the control group. In sick children, fetuinA concentration negatively correlated with dialysis vintage, PWV/ht, phosphate concentration, calcium phosphate product (CaxP), cumulative doses of calcium, and vitamin D3. In the whole study population, fetuin-A negatively correlated with blood pressure (BP), pulse wave velocity indexed to height (PWV/ht), intact parathyroid hormone (iPTH), high sensitivity C-reactive protein (hsCRP), and cholesterol concentrations. CONCLUSIONS: In children with CKD, the decreased concentration of fetuin-A is related to other vascular calcification risk factors. Serum fetuin-A concentration may play a role in the identification of vascular disease risk factors in this population.

Serum GDIgA1 levels in children with IgA nephropathy and Henoch-Schönlein nephritis.

INTRODUCTION: GDIgA1 (galactose deficient IgA1) plays a significant role in the pathogenesis of IgA nephropathy (IgAN) and Henoch-Schönlein nephritis (HSN). AIM OF THE STUDY: The aim of this study was to assess the relevance of serum GDIgA1 level as a prognostic marker in children with IgAN and HSN. MATERIAL AND METHODS: 41 children were included to the study group (15 IgAN, 26 HSN) and 22 to the control group. The following parameters were evaluated at baseline and endpoint: proteinuria, erythrocyturia, serum creatinine, serum IgA, GFR. A kidney biopsy was performed in all patients and evaluated according to the Oxford Classification (1 - present, 0 - absent: M - mesangial hypercellularity; E- endocapillary hypercellularity; S - segmental sclerosis/adhesion; T - tubular atrophy/interstitial fibrosis), and was calculated as the total score (sum of M, E, S, T). At the end of follow-up, the serum GDIgA1 concentration was measured. RESULTS: The serum GDIgA1 concentration in patients with IgAN and HSN was significantly higher than in the control group. No significant differences in mean proteinuria, erythrocyturia, GFR, MEST score, or GDIgA1 in serum, as well as the duration of follow-up between IgAN and HSN were observed. Baseline serum IgA concentration and time to kidney biopsy were significantly higher in children with IgAN than in children with HSN. We observed a positive correlation between GDIgA1 and IgA levels (r = 0.53), and GDIgA1 and serum creatinine levels (r = 0.5), as well as negative correlation between GDIgA1 and GFR (r = -0.37). CONCLUSIONS: Serum GDIgA1 level may have a prognostic value in children with IgAN and HSN; however, to fully elucidate its clinical potential further studies performed in larger patient cohorts are required.

L-FABP and IL-6 as markers of chronic kidney damage in children after hemolytic uremic syndrome.

BACKGROUND: Hemolytic-uremic syndrome (HUS) is a form of thrombotic microangiopathy, in the course of which some patients may develop chronic kidney disease (CKD). From a clinical point of view, it is important to search for markers that allow for early identification of patients at risk of a poor prognosis. OBJECTIVES: The study evaluated the serum and urine levels of liver-type fatty acid binding protein (L-FABP) and interleukin 6 (IL-6). MATERIAL AND METHODS: The study was conducted in 29 children with a history of HUS. The relationship between L-FABP and IL-6 and anthropometric measurements, the value of estimated glomerular filtration rate (eGFR) and albuminuria were additionally evaluated. RESULTS: In children after HUS, L-FABP and IL-6 concentration in both serum and urine was significantly higher in comparison to the control group. No differences in L-FABP and IL-6 concentration in serum and urine depending on the type of HUS and gender were noted. Correlation between L-FABP and IL-6 in serum and urine with eGFR and urine albumin-creatinine ratio (ACR) in the total group of patients after HUS was not detected. In the group of children after 6 month observation after HUS, a negative correlation of L-FABP concentration with eGFR was found. CONCLUSIONS: The results indicate that the higher concentration of L-FABP in serum and urine of children with a history of HUS can be the result of protracted injury initiated during the acute phase of the disease. Lack of correlation of L-FABP concentration with the ACR may be associated with a short (less than 6 months) observation after acute renal failure or merely temporary renal tubular damage in the acute phase of the disease. In contrast, higher levels of IL-6 in serum and urine in children after HUS compared to healthy children and the negative correlation of L-FABP concentration and eGFR in children after 6 month observation after HUS may confirm their participation in CKD. Thus, L-FABP and IL-6 seem to be good biomarkers of chronic kidney damage in survivors of the acute phase of HUS.

Evaluation of adipokines in children with cystic fibrosis.

INTRODUCTION: Patients with CF present numerous pathological conditions such as malnutrition, depletion of fat-free mass, metabolic disturbances (abnormal glucose metabolism, increased insulin resistance, chronic energy deficit, local and chronic inflammation), which could affect or be associated with altered adipokines concentration Material and Methods: We aimed in this study to investigate the levels of selected adipokines such as resistin, apelin, adiponectin to demonstrate their application as possible markers of inflammation. RESULTS: Serum level of resistin was higher (p < 0.001) and adiponectin - lower (p=0.02) in CF children than in healthy children. There was no difference in serum apelin level between two examined groups. However, values of adiponectin/BMI and apelin/BMI ratios in CF did not differ significantly from controls. Higher values of resistin/BMI ratio in CF in comparison to controls were observed Serum resistin/adiponectin ratio was significantly higher in CF patients than in controls (p < 0.0001). Resistin/BMI ratio correlated negatively with FEV1 (R:-48,p < 0.043). Serum resistin/adiponectin ratio correlated negatively with FEV1/FVC (R:-49, p=0.04), Adipokines showed no correlation with BMI and BMI-SDS, glucose, total cholesterol, and LDL-, HDL-cholesterol, triglyceride serum levels. Spirometric parameters FEV1, FVC, VC correlated negatively with serum glucose levels (R: -0.55, p < 0.018; R: -0.65 p < 0.0025; R:-0.76, p < 0.0008 respectively). FEV1 and FVC correlated positively with BMI-SDS (R:0.58, p < 0.01; R:0.5, p < 0.036, respectively). CONCLUSIONS: A significant increase in resistin concentration expressed also as resistin/BMI, and resistin/adiponectin ratios, observed in children with CF may suggests that this adipokine is involved in the inflammatory process underlying the disease and is related to worse spirometric parameters describing airways obstruction.

Low renal but high extrarenal phenotype variability in Schimke immuno-osseous dysplasia.

Schimke immuno-osseous dysplasia (SIOD) is a rare multisystem disorder with early mortality and steroid-resistant nephrotic syndrome (SRNS) progressing to end-stage kidney disease. We hypothesized that next-generation gene panel sequencing may unsurface oligosymptomatic cases of SIOD with potentially milder disease courses. We analyzed the renal and extrarenal phenotypic spectrum and genotype-phenotype associations in 34 patients from 28 families, the largest SMARCAL1-associated nephropathy cohort to date. In 11 patients the diagnosis was made unsuspectedly through SRNS gene panel testing. Renal disease first manifested at median age 4.5 yrs, with focal segmental glmerulosclerosis or minimal change nephropathy on biopsy and rapid progression to end-stage kidney disease (ESKD) at median age 8.7 yrs. Whereas patients diagnosed by phenotype more frequently developed severe extrarenal complications (cerebral ischemic events, septicemia) and were more likely to die before age 10 years than patients identified by SRNS-gene panel screening (88 vs. 40%), the subgroups did not differ with respect to age at proteinuria onset and progression to ESKD. Also, 10 of 11 children diagnosed unsuspectedly by Next Generation Sequencing were small at diagnosis and all showed progressive growth failure. Severe phenotypes were usually associated with biallelic truncating mutations and milder phenotypes with biallelic missense mutations. However, no genotype-phenotype correlation was observed for the renal disease course. In conclusion, while short stature is a reliable clue to SIOD in children with SRNS, other systemic features are highly variable. Our findings support routine SMARCAL1 testing also in non-syndromic SRNS.

Dent disease in Poland: what we have learned so far?

PURPOSE: Dent disease (DD) is a rare tubulopathy characterized by proximal tubular dysfunction leading to chronic kidney disease (CKD). The aim of the study was to characterize patients with DD in Poland. METHODS: A retrospective analysis of a national cohort with genetically confirmed diagnosis. RESULTS: Of 24 males, all patients except one carried mutations in the CLCN5 gene; in one patient a mutation in the OCRL gene was disclosed. Molecular diagnosis was delayed 1 year on average (range 0-21 years). The most common features were tubular proteinuria (100%), hypercalciuria (87%), and nephrocalcinosis (56%). CKD (≤stage II) and growth deficiency were found in 45 and 22% of patients, respectively. Over time, a progression of CKD and persistence of growth impairment was noted. Subnephrotic and nephrotic proteinuria (20%) was found in most patients, but tubular proteinuria was assessed in only 67% of patients. In one family steroid-resistant nephrotic syndrome prompted a genetic testing, and reverse phenotyping. Five children (20%) underwent kidney biopsy, and two of them were treated with immunosuppressants. Hydrochlorothiazide and angiotensin-converting enzyme inhibitors were prescribed for a significant proportion of patients (42 and 37.5%, respectively), while supplemental therapy with phosphate, potassium, vitamin D (12.5% each), and alkali (4.2%) was insufficient, when compared to the percentages of patients requiring repletion. CONCLUSIONS: We found CLCN5 mutations in the vast majority of Polish patients with DD. Proteinuria was the most constant finding; however, tubular proteins were not assessed commonly, likely leading to delayed molecular diagnosis and misdiagnosis in some patients. More consideration should be given to optimize the therapy.

Long-Term Outcome of Steroid-Resistant Nephrotic Syndrome in Children.

We investigated the value of genetic, histopathologic, and early treatment response information in prognosing long-term renal outcome in children with primary steroid-resistant nephrotic syndrome. From the PodoNet Registry, we obtained longitudinal clinical information for 1354 patients (disease onset at >3 months and <20 years of age): 612 had documented responsiveness to intensified immunosuppression (IIS), 1155 had kidney biopsy results, and 212 had an established genetic diagnosis. We assessed risk factors for ESRD using multivariate Cox regression models. Complete and partial remission of proteinuria within 12 months of disease onset occurred in 24.5% and 16.5% of children, respectively, with the highest remission rates achieved with calcineurin inhibitor-based protocols. Ten-year ESRD-free survival rates were 43%, 94%, and 72% in children with IIS resistance, complete remission, and partial remission, respectively; 27% in children with a genetic diagnosis; and 79% and 52% in children with histopathologic findings of minimal change glomerulopathy and FSGS, respectively. Five-year ESRD-free survival rate was 21% for diffuse mesangial sclerosis. IIS responsiveness, presence of a genetic diagnosis, and FSGS or diffuse mesangial sclerosis on initial biopsy as well as age, serum albumin concentration, and CKD stage at onset affected ESRD risk. Our findings suggest that responsiveness to initial IIS and detection of a hereditary podocytopathy are prognostic indicators of favorable and poor long-term outcome, respectively, in children with steroid-resistant nephrotic syndrome. Children with multidrug-resistant sporadic disease show better renal survival than those with genetic disease. Furthermore, histopathologic findings may retain prognostic relevance when a genetic diagnosis is established.