Mild X-linked Alport syndrome due to the COL4A5 G624D variant originating in the Middle Ages is predominant in Central/East Europe and causes kidney failure in midlife.

A study of 269 children enrolled into a National Registry for children with persistent glomerular hematuria identified 131 individuals with genetically confirmed X-linked Alport Syndrome. A single variant c.1871G>A p.Gly624Asp (G624D) in COL4A5 was predominant and accounted for 39% of X-linked Alport Syndrome in unrelated Polish families (44 of 113). To evaluate its origins, the genetic variation in a 2.79 Mb segment encompassing the COL4A5 locus on chromosome X was assessed. All G624D alleles were found on the same rare haplotype background, indicating a founder effect dating back to the 12-13th century. The phenotypic data of 131 children with X-linked Alport Syndrome and their 195 affected adult relatives revealed that the G624D variant was associated with a significantly milder clinical course in comparison to other pathogenic COL4A5 variants. Furthermore the clinical course of this genetically uniform cohort was milder than that observed in individuals with other COL4A5 missense mutations. In spite of the benign clinical manifestation throughout childhood and early adulthood, the G624D variant confers significant risk for both kidney failure and deafness in males, albeit 20-30 years later than that observed in individuals with other COL4A5 pathogenic variants (50% cumulative risk of starting dialysis at 54 years (95% confidence interval: 50-62) v. 26 years (95% confidence interval: 22-30)). Thus, males with G624D are candidates for existing and emerging therapies for Alport Syndrome.

Multicenter analysis of the efficacy and safety of a non-standard immunosuppressive therapy with rituximab in children with steroid-resistant nephrotic syndrome.

The aim of the study was a multicenter analysis of the efficacy and safety of a non-standard immunosuppressive therapy with rituximab (Rtx) in children with steroid-resistant nephrotic syndrome (SRNS) with particular emphasis on the possibility of permanent discontinuation or dose reduction of other immunosuppressive drugs such as glucocorticoids and cyclosporine A after 6 months of observation. The study group consisted of 30 children with idiopathic nephrotic syndrome, who were unresponsive to standard immunosuppressive treatment, and hospitalized in the years 2010-2017 in eight paediatric nephrology centres in Poland. The children were administered a single initial infusion of rituximab at the dose of 375 mg/m2 of the body surface area. Proteinuria, the daily supply of glucocorticoids, and cyclosporine were assessed at the moment of the start of the treatment and after 6 months since its commencement. Before Rtx therapy, complete remission was found in 13 patients (43%) and partial remission was found in 8 patients (26%). These numbers increased to 16 (53%) and 12 (40%), respectively. At the start of the treatment 23 patients (76.6%) were treated with cyclosporine A. After 6 months, this number decreased to 15 patients (35%). At the start of the treatment, 18 patients (60%) were treated with prednisone. After 6 months, this number decreased to 8 patients (44%). Children with SRNS may potentially benefit from Rtx treatment despite relative risk of side effects. The benefits may include reduction of proteinuria or reduction of other immunosuppressants.

[Mycophenolate mofetil (MMF) as the first choice immunosuppressive drug in treatment of steroid-dependent nephrotic syndrome in children]. / Mykofenolan mofetilu (MMF) jako lek immunosupresyjny pierwszego wyboru w leczeniu steroidozaleznego zespolu nerczycowego (SZZN) u dzieci.

Most children diagnosed with nephrotic syndrome show favourable response to corticosteroid therapy, nonetheless 30% of patients have frequent relapses or a steroid-dependent course of disease. Cyclophosphamide, cyclosporin A or MMF are being used in treatment of steroid-dependent nephrotic syndrome in search of a drug with highest long-term effectiveness and least amount of side effects. AIM: The aim of study was to assess of the efficacy of MMF as the first choice immunosuppressive drug in children with nephrotic syndrome after determining a steroid-dependency. MATERIALS AND METHODS: 23 children with steroid-dependent nephrotic syndrome were enrolled in the study. Mean age at disease onset was 3.8 years. Mean disease duration time before introducing MMF was 21.3 months. Mean treatment time with MMF was 23.6 months. Patients previously treated with immunosuppressive drug, except for prednisone were excluded from the study. RESULTS: Per year of treatment with MMF 56,5% of patients had not more than 1 relapse of the disease, 5 patients had more than 1, but less than 2 relapses. After the mean time of 23.6 months MMF treatment was discontinued in 15 patients (62,5%). 11 patients (48%) from that group significantly benefited from treatment in the form of no further relapses, defer of steroid-dependence or the possibility to reduce the dose of corticosteroids to minimal. CONCLUSIONS: MMF has advantage over cyclophosphamide and calcineurin inhibitors in reference to side effect profile, especially glomerular filtration markers, hypertension and frequent drug dependency. Treatment with MMF is effective in maintaining long-term remission and enables the reduction of cumulative steroid dose. Regarding nearly 50% of patients with benefits after MMF treatment and good treatment tolerance, it seems justified to introduce MMF as the first choice immunosuppressive drug in patients with steroiddependent nephrotic syndrome.

Modification of the Schwartz equations for children increases their accuracy at eGFR > 60 mL/min/1.73 m(2).

AIM: Estimation of eGFR in children with normal kidney function using the Schwartz equations results in underestimating real GFR. MATERIALS AND METHODS: We propose modification of three Schwartz equations - two based on creatinine concentration (eGFRScrBS bedside) and (eGFRScr) and one 3-marker based on creatinine, urea and cystatin C concentrations (eGFRS3M). The iohexol test (reference method) was performed 417 times in 353 children >2 years with mean GFR: 98 ± 31.6 ml/min/1.73m(2). The assessment included also the Filler and Zappitelli equations. The modification was performed using methods: (1) based on equation, eGFRcor = a [eGFR - T] + T, where T = 50, if eGFR > T, and a equals for: eGFRScrBS 1.4043, for eGFRScr 2.0048, for eGFRS3M 1.2951, and (2) based on correction of all coefficients of the original equation. RESULTS: For comparison of all the results and for children with GFR< 60, 60-90, 90-135 and > 135 ml/min/1.73m(2) the correlation coefficient, relative error (RE) and root mean square relative error (RMSRE) was employed and revealed improvement of RE from 25.9 to 6.8 and 3.9% (depending on the correction method) for eGFRScr; from 19 to 8.1 and 3.9% for eGFRScrBS and: from 11.6% to 2.0 and 2.3% for eGFRS3M (respectively). The RMSRE values changed from 30 to 21.3 and 19.8% for eGFRScr, from 25.1 to 21.6 and 19.8% for eGFRScrBS and from 19.1 to 15.8 and 15.3 % for eGFRS3M. CONCLUSIONS: Modifications of Schwartz equations at GFR > 60 ml/min/1.73m(2) significantly improves the accuracy of calculating eGFR. The 3-markers equation is more accurate and should be employed frequently.

Retrospective cohort study of familial hypomagnesaemia with hypercalciuria and nephrocalcinosis due to CLDN16 mutations.

BACKGROUND: Familial hypomagnesaemia with hypercalciuria and nephrocalcinosis (FHHNC) is a rare autosomal recessive tubular disorder exhibiting a high risk for progressive chronic kidney disease (CKD). METHODS: This is a retrospective multicentre study of 25 paediatric cases with FHHNC in Poland. Median age at diagnosis was 4 years and median follow-up time was 4.8 years. RESULTS: All cases of FHHNC carried recessive mutations in CLDN16. The founder mutation in CLDN16, Leu151Phe, was the most frequent cause of FHHNC in Polish patients, with 13 (52%) cases being homozygous and 5 (20%) carrying Leu151Phe allele in compound heterozygosity. All cases showed nephrocalcinosis, increased urinary fractional excretion of magnesium and hypercalciuria. Other disease features included hypomagnesaemia (76%), hyperparathyroidism (76%), hyperuricaemia (56%) and hypocitraturia (60%). Treatment with thiazides effectively reduced hypercalciuria in most cases. During follow-up, renal function declined in 60% of patients; 12% of patients reached CKD stage 3 or 4 and one patient developed end-stage renal failure. CONCLUSIONS: We report one of the largest cohorts of FHHNC cases caused by CLDN16 mutations. A missense variant of CLDN16, Leu151Phe, is the most common mutation responsible for FHHNC in Poland. Additionally, we found that normomagnesaemia does not exclude FHHNC and the calculation of fractional excretion of Mg can be diagnostic in the setting of normomagnesaemia. We also demonstrate the efficacy of a treatment with thiazides in terms of hypercalciuria in the majority of patients.

Characterization of 28 novel patients expands the mutational and phenotypic spectrum of Lowe syndrome.

BACKGROUND: The oculocerebrorenal syndrome of Lowe (OCRL) is a rare X-linked multi-systemic disorder, almost always characterized by the triad of congenital cataract, cognitive and behavioral impairment and a proximal tubulopathy. METHODS: Twenty-eight novel patients with suspected Lowe syndrome were studied. RESULTS: All patients carried OCRL gene defects with mutational hot spots at CpG dinucleotides. Mutations previously unknown in Lowe syndrome were observed in ten of the 28 patients, and carriership was identified in 30.4 % of the mothers investigated. Mapping the exact breakpoints of a complete OCRL gene deletion revealed involvement of several flanking repeat elements. We noted a similar pattern of documented clinically relevant symptoms, and even though the patient cohort comprised relatively young patients, 32 % of these patients already showed advanced chronic kidney disease. Thrombocytopenia was seen in several patients, and hyperosmia and/or hyperacusis were reported recurrently. A p.Asp523Asn mutation in a Polish patient, associated with the typical cerebrorenal spectrum but with late cataract (10 year), was also evident in two milder affected Italian brothers with ocular involvement of similar progression. CONCLUSIONS: We have identified clinical features in 28 patients with suspected Lowe syndrome that had not been recognized in Lowe syndrome prior to our study. We also provide further evidence that OCRL mutations cause a phenotypic continuum with selective and/or time-dependent organ involvement. At least some of these mutants might exhibit a genotype-phenotype correlation.

Genotype-phenotype associations in WT1 glomerulopathy.

WT1 mutations cause a wide spectrum of renal and extrarenal manifestations. Here we evaluated disease prevalence, phenotype spectrum, and genotype-phenotype correlations of 61 patients with WT1-related steroid-resistant nephrotic syndrome relative to 700 WT1-negative patients, all with steroid-resistant nephrotic syndrome. WT1 patients more frequently presented with chronic kidney disease and hypertension at diagnosis and exhibited more rapid disease progression. Focal segmental glomerulosclerosis was equally prevalent in both cohorts, but diffuse mesangial sclerosis was largely specific for WT1 disease and was present in 34% of cases. Sex reversal and/or urogenital abnormalities (52%), Wilms tumor (38%), and gonadoblastoma (5%) were almost exclusive to WT1 disease. Missense substitutions affecting DNA-binding residues were associated with diffuse mesangial sclerosis (74%), early steroid-resistant nephrotic syndrome onset, and rapid progression to ESRD. Truncating mutations conferred the highest Wilms tumor risk (78%) but typically late-onset steroid-resistant nephrotic syndrome. Intronic (KTS) mutations were most likely to present as isolated steroid-resistant nephrotic syndrome (37%) with a median onset at an age of 4.5 years, focal segmental glomerulosclerosis on biopsy, and slow progression (median ESRD age 13.6 years). Thus, there is a wide range of expressivity, solid genotype-phenotype associations, and a high risk and significance of extrarenal complications in WT1-associated nephropathy. We suggest that all children with steroid-resistant nephrotic syndrome undergo WT1 gene screening.

Dosimetry during iodine-131 therapy - a technical point of view from a single centre's own experience.

BACKGROUND: Nuclear medicine uses radionuclides in medicine for diagnosis, staging, therapy, and monitoring the response to therapy. The application of radiopharmaceutical therapy for the treatment of certain diseases is well-established, and the field is expanding. Internal dosimetry is multifaceted and includes different workflows, as well as various calculations based on patient- specific dosimetry. AIM: The objective of this study was to introduce the technical issues which might occur during iodine-131 (¹³¹I) dosimetry performed in nuclear medicine departments. MATERIAL AND METHODS: Retrospective analysis was performed on a group of 44 patients with papillary thyroid cancer who between May 2021 and October 2021 underwent a 131I treatment: 80-100 mCi (2200-3700 MBq, based on the previous medical history and stage of the disease). Patients underwent a series of ¹³¹I therapy scans using gamma camera Discovery NM 670 CT. Whole body scan (WBS) was performed 2, 4, 24 and 48 hours after ¹³¹I administration. Additionally, after 24 hours of single photon emission computed tomography/ computed tomography, two fields of view (SPECT/CT 2-FOV) were performed from the mid-head to the bladder. RESULTS: During the dosimetry procedure, several issues arise. Firstly, after receiving therapeutic doses of ¹³¹I, patients should remain in their rooms until the appropriate activity is achieved before being transported to the diagnostic room. Secondly, the walls between examination rooms meet the requirements for accurate diagnosis but not for therapy, leading to the occurrence of artefacts in patients examined behind the wall, potentially influencing the examination results. Thirdly, personnel in the control room also experience additional exposure (10 times greater than in the case of standard diagnostic procedure). CONCLUSIONS: The dosimetry in patients in whom therapeutic procedures are performed with the use of isotopes is mandatory according to Polish and European law, technical issues which occur during the dosimetry procedures might influence the organization of the work in departments.

Metabolic syndrome as risk factor for left ventricular hypertrophy in children with chronic kidney disease.

Background: The metabolic syndrome (MS), a cluster of clinical and biochemical abnormalities including insulin resistance, dyslipidemia and hypertension, is often diagnosed in chronic kidney disease (CKD) children. Left ventricular hypertrophy (LVH) is a major target organ damage in hypertension and an important cardiovascular risk factor in CKD patients. We aimed to identify the most significant risk factors of LVH in children with CKD. Methods: Children with CKD stage 1-5 were enrolled in the study. MS was diagnosed according to De Ferranti (DF) as ≥3 from 5 criteria. Ambulatory blood pressure measurements (ABPM) and echocardiographic evaluation were performed. LVH was defined as ≥95th percentile of LV mass index related to height and age. Clinical and laboratory parameters included: serum albumin, Ca, HCT, cystatin C, creatinine, estimated glomerular filtration rate (eGFR) based on Schwartz formula, triglycerides, high-density lipoprotein (HDL), proteinuria, BMI standard deviation score (SDS), height SDS, waist circumference, ABPM data. Results: 71 children (28 girls/43 boys) with median age 14.05 (25%-75%:10.03-16.30) years and median eGFR 66.75 (32.76-92.32) ml/min/1.73m2 were evaluated. CKD stage 5 was diagnosed in 11 pts (15.5%). MS (DF) was diagnosed in 20 pts (28.2%). Glucose ≥ 110 mg/dL was present in 3 pts (4.2%); waist circumference ≥75th pc in 16 pts (22.5%); triglycerides ≥ 100 mg/dL in 35 pts (49.3%); HDL < 50mg/dL in 31 pts (43.7%) and BP ≥ 90th pc in 29 pts (40.8%), respectively. LVH was detected in 21 (29.6%) children. In univariate regression the strongest risk factor for LVH was CKD stage 5 (OR 4.9, p=0.0019) and low height SDS (OR 0.43,p=0.0009). In stepwise multiple logistic regression analysis (logit model) of the most important risk factors for LVH in CKD children, only three were statistically significant predictors: 1)MS diagnosis based on DF criteria (OR=24.11; 95%CI 1.1-528.7; p=0.043; Chi2 = 8.38,p=0.0038); 2), high mean arterial pressure (MAP SDS) in ABPM (OR=2.812; 95%CI 1.057-7.48; p=0.038;Chi2 = 5.91, p=0.015) and 3) low height SDS (OR=0.078; 95%CI 0.013-0.486;p=0.006; Chi2 = 25.01, p<0.001). Conclusions: In children with chronic kidney disease LVH is associated with the cluster of multiple factors, among them the components of MS, hypertension, stage 5 CKD and growth deficit were the most significant.

Polish 2010 growth references for school-aged children and adolescents.

Growth references are useful in monitoring a child's growth, which is an essential part of child care. The aim of this paper was to provide updated growth references for Polish school-aged children and adolescents and show the prevalence of overweight and obesity among them. Growth references for height, weight, and body mass index (BMI) were constructed with the lambda, mu, sigma (LMS) method using data from a recent, large, population-representative sample of school-aged children and adolescents in Poland (n = 17,573). The prevalence of overweight and obesity according to the International Obesity Taskforce definition was determined with the use of LMSGrowth software. Updated growth references for Polish school-aged children and adolescents were compared with Polish growth references from the 1980s, the Warsaw 1996-1999 reference, German, and 2000 CDC references. A positive secular trend in height was observed in children and adolescents from 7 to 15 years of age. A significant shift of the upper tail of the BMI distribution occurred, especially in Polish boys at younger ages. The prevalence of overweight or obesity was 18.7% and 14.1% in school-aged boys and girls, respectively. The presented height, weight, and BMI references are based on a current, nationally representative sample of Polish children and adolescents without known disorders affecting growth. Changes in the body size of children and adolescents over the last three decades suggest an influence of the changing economical situation on anthropometric indices.

Urinary procollagen III aminoterminal propeptide and ß-catenin - New diagnostic biomarkers in solitary functioning kidney?

PURPOSE: We aimed at evaluating urinary levels of procollagen III aminoterminal propeptide (PIIINP) and ß-catenin and the relationship between these markers and clinical and laboratory variables in children with a solitary functioning kidney (SFK). PATIENTS AND METHODS: The study group consisted of 98 (M/F: 62/36) children with an SFK with a median age of 8 years. An age-matched control group contained 54 healthy peers. Urinary levels of procollagen III aminoterminal propeptide and ß-catenin were measured using a commercially available immunoassay kit. RESULTS: The urinary values of PIIINP (UPIIINP) were significantly increased in patients with SFK versus controls (p < 0.01). Our analysis revealed no significant differences in urinary ß-catenin levels between the SFK patients and control subjects (p > 0.05). Only urinary PIIINP levels were correlated to renal function tests, such as serum creatinine, urea, uric acid, and estimated glomerular filtration rate (p<0.05). CONCLUSIONS: An increased urinary level of PIIINP may indicate early kidney impairment in children with SFK. Urinary ß-catenin does not seem to play any important role as a marker of renal function in children with SFK. Further long-term studies are required in order to evaluate the clinical usefulness of these markers and their predictive value of chronic kidney disease (CKD) progression.

eGFR values and selected renal urine biomarkers in preterm neonates with uncomplicated clinical course.

BACKGROUND: Diagnosing acute kidney injury (AKI) in preterm newborns, who are particularly susceptible to renal damage, is a serious challenge as there is no definite consensus about the diagnostic criteria. OBJECTIVES: The objective of this study was to measure the values for selected urinary biomarkers and estimated glomerular filtration rate (eGFR) among a population of preterm infants with uncomplicated clinical course as well as to determine whether these markers depend on birth weight (BW), gestational age (GA), postnatal age (PNA), or gender. MATERIAL AND METHODS: The prospective study was carried out in neonatal intensive care unit (NICU). The evaluation included 57 children that were divided into 3 categories according to BW: low birth weight (LBW) - 1501-2500 g (22 infants); very low birth weight (VLBW) - 1000-1500 g (25 infants); and extremely low birth weight (ELBW) - 750-999 g (10 infants). Urine samples were collected daily between the 4th and 28th day of life for measurements of creatinine (Cr), neutrophil gelatinase-associated lipocalin (NGAL), osteopontin (OPN), and human kidney injury molecule 1 (hKIM1). RESULTS: The values of the 3 urine tubular biomarkers, serum creatinine and eGFR were taken in substantially healthy preterm infants with normal kidney function at 4 time intervals during the neonatal period. Their correlations were determined and a multivariable regression analysis was carried out with respect to BW, GA, PNA, and gender. Trends of the studied markers in terms of PNA and BW were also assessed with the Jonckheere-Terpstra test. CONCLUSIONS: Glomerular and tubular function in preterm neonates during the 1st month of life is significantly influenced by BW, GA, PNA, and gender.

[Mycophenolate mofetil in treatment of childhood nephrotic syndrome--preliminary report]. / Mykofenolan mofetilu w leczeniu dzieci z zespolem nerczycowym--doniesienie wstepne.

The management of nephrotic syndrome (NS) in children remains a clinical challenge for pediatricians and pediatric nephrologists. Especially, the treatment of patients with steroid-resistant (SR) and steroid-dependent (SD) nephrotic syndrome, because they are at risk for developing complications from prolonged exposure to steroids, CsA and alkylating agents. Mycophenolate mofetil (MMF) is a selective and reversible inhibitor of inosine monophosphate dehydrogenase used above all in transplantology and recently also in patients with nephrotic syndrome. The aim of this study was to tentatively assess the usefulness and the safety of MMF as an immunosuppressive agent in children with steroid-resistant NS, in whom remission was not obtained with previous treatment regimens, and those with steroid-dependent NS, in whom severe adverse reactions were observed in steroid and cyclosporine therapy. The study included 19 children with NS (11 girls, 8 boys) aged 7 to 19.5 years (a mean of 13.5), treated at the Deptartment of Pediatric Nephrology. The duration of disease was from 1 to 16 years (a mean of 9.3). The patients were divided into 3 groups: I--9 children with steroid-dependent NS; II--6 children with steroid-dependent NS and episodes of steroid-resistance; III--4 children with steroid-resistant NS. All patients in groups II and III required multi-drug therapy (prednisone, cyclosporine A, methylprednisolone, chlorambucil, cyclophosphamide) before MMF was introduced. MMF was administered orally: 180-600 mg/m2 body surface/dose, twice daily. The follow-up period lasted for 4 to 16 months (a mean of 7.7). The clinical outcome analysis included decrease or disappearance of proteinuria, clinical improvement and/or possibility of tapering therapy intensity, especially the dosage of steroids and/or CsA. Also, renal function was monitored with serum cystatine C concentration. Particular attention was paid to adverse effects of MMF upon the gastro- intestinal tract and/or opportunistic infections. All medication (apart from MMF) could be discontinued in 4 patients; in 15 cases, prednizone dose was reduced and in 9 cases CsA dose was reduced or discontinued. In group I (SD) steroid treatment could be reduced from a mean prednisone dose of 22.8 to 3.6 mg/m2/48 hours (p=0.018), in groups II and III, in spite of 50 % reduction of a mean prednisone dose, the difference did not reach statistical significance. During MMF therapy Csa treatment could be reduced from a mean CsA dose 4.3 to 2.9 mg/kg/24 hours (p=0.008). Improvement or preservation of stable renal function was observed in all patients--cystatin C levels decreased significantly from a mean 1.35 to 0.96 mg/l (p=0.007). Adverse reaction to MMF (abdominal pain) was observed in 2 patients (nausea, vomiting, diarrhoea in 1, CMV infection in 1). The initial clinical observation of MMF treatment in nephrotic patients shows its best effect in the group of patients with steroid-dependent NS. MMF can safely be used in children with NS. The introduction of MMF allows for reduction of other chronically used medications, especially CsA and steroids.

Which equations should and which should not be employed in calculating eGFR in children?

PURPOSE: We assessed the reliability of calculating eGFR in children as compared to the iohexol disappearance test (GFR-I), which was performed 417 times in 353 children aged 2 and more. MATERIAL/METHODS: eGFR was estimated with equations based on serum creatinine: Schwartz (1: eGFR-Scr), Cockroft-Gault (2: eGFR-CG) and MDRD (3: eGFR-MDRD), and on creatinine clearance (4: eGFR-U), or relying on serum cystatin C: Hoeck (5: eGFR-H), Bokenkamp (6: eGFR-B) and Filler (7: eGFR-F), and on the three Schwartz markers (8: eGFR-S3M). Mean relative error (RE), correlation (R), Bland-Altman analysis and accuracy of GFR-I were studied in all patients and in subgroups: at GFR<60ml/min/1.73m(2); in children aged ≤12 and >12. RESULTS: The results by eGFR-Scr, eGFR-S3M demonstrated no statistical difference to GFR-I at GFR<60ml/min/1.73m(2), but underestimated eGFR at higher filtration values by 11.6±15.1% and 19.1±16.4, respectively (p<0.0000). The eGFR-B, eGFR-F and eGFR-MDRD equations illustrated important overestimation of reference GFR results (RE: 84±44.2%; 29.5±27.9%, 35.6±62%; p<0.0000 for all). The MDRD and C-G formulas showed statistically better consistency in children aged >12. A good agreement was achieved by the eGFR-H equation (5.1±21.9%; p<0.0000; R=0.78). CONCLUSIONS: (1) Schwartz equations show a good conformity at GFR<60ml/min/1.73m(2), but underestimate the results at higher GFR values. (2) The Bokenkamp equation with original coefficient should not be employed in children. (3) The use of the Hoeck formula in all children and C-G and MDRD formula in children aged >12 is possible. (4) The error of eGFR calculations increases at higher GFR values.

Serum interleukin 6 levels as an early marker of acute kidney injury on children after cardiac surgery.

BACKGROUND: Cardiosurgical operations in cardiopulmonary bypass (CPB) constitute a risk of acute kidney injury (AKI). OBJECTIVES: The aim of the study was an assessment of AKI risk in children within the first 24 hours after CPB cardiac surgery, evaluating serum interleukin 6 (sIL6). MATERIAL AND METHODS: The study included 47 children with congenital heart disease operated in CPB. Blood samples were taken before the procedure (0 hour) as well as at 2, 6, 12, 18 and 24 hours after the operation. RESULTS: AKI was confirmed in 19 children. The mean sIL6 concentration in the AKI compared with non-AKI group was: 180.6 vs. 93.7; p = 0.0017. The maximum sIL6 in the AKI group was obtained at 2 hrs after CPB (350.36 pg/ml). Logistic regression analysis for AKI development depending on the value of sIL6 at 2 hrs after CPB proved that every rise of sIL6 by 100 pg/ml increased the chance of AKI development by 70% (p = 0.0161). With every circulatory arrest time prolongation by 10 minutes for a given sIL6 concentration, the chance of AKI development increased by 47% (p = 0.0407). AKI risk at 2 hrs after CPB, for a sIL6 cut-off point amounting to 185 pg/ml, increased more than 3-fold (AUROC - 68%). CONCLUSIONS: Determining sIL6 in children after cardiosurgical operations at 2 hrs after the procedure constitutes a good, yet not a perfect marker of AKI risk development. Nomograms of the constant risk values of AKI were worked out presenting the ranges of values in relation to serum IL6 concentrations and the child's body mass, age and the time of circulatory arrest.

Idiopathic nephrotic syndrome in Polish children - its variants and associations with HLA.

HLA-DR and HLA-DQ antigens were investigated in 127 Polish children with idiopathic nephrotic syndrome (INS) followed-up for the median time of 11 years (minimum 7 years). HLA typing was performed using the polymerase chain reaction sequence-specific oligonucleotide probing technique and the microlymphocytotoxicity test. Histopathologic INS categories and a response to therapy were analyzed according to particular HLA associations. The results were compared with 330 healthy individuals. In INS children, we observed an increased frequency of HLA-DR7, DR3/7, DQ2 and DQ8, whereas HLA-DR13, DR15, DQ5 and DQ6 were decreased. In minimal change nephrotic syndrome, a relationship with HLA-DR3, DR7, DR3/7 and DQ2 was found. Evolved from minimal changes, focal segmental glomerulosclerosis was associated with HLA-DR7, while primary focal segmental glomerulosclerosis with HLA-DR4 and DQ8. In steroid-dependence and secondary steroid-resistance, an increased frequency of HLA-DR3, DR7, DR3/7 and DQ2 was documented. In contrast, primary steroid-resistant nephrotic syndrome was associated with HLA-DR4 and DQ8. Steroid-dependent patients bearing HLA-DR3 achieved longer remissions after chlorambucil therapy compared with HLA-DR3-negative. In steroid-resistant focal segmental glomerulosclerosis, a reduced response to cyclosporine A was associated with HLA-DR4. Associations with HLA differentiate between pathoanatomic entities of INS and may influence a response to immunosuppressive therapy.