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.

[Do we successfully treat anemia and calcium-phosphate disorders in children with chronic kidney disease at the beginning of the twenty-first century?]. / Czy na poczatku XXI wieku skutecznie leczymy niedokrwistosc i zaburzenia wapniowo-fosforanowe u dzieci z przewlekla choroba nerek?

UNLABELLED: In children with chronic kidney disease (CKD) anemia and calcium-phosphate disturbances are already present at early stages of the disease and require a comprehensive treatment. The aim of this study was to evaluate the efficacy of the treatment of biochemical disturbances, depending on the severity of CKD in children. MATERIAL AND METHODS: The study included 71 children (44 boys, 27 girls) with CKD stage 1-5. Mean age was 11 ± 5 years, mean height: 135.7 ± 28 cm and mean eGFR 32 ml/min/1.73 m2. The serum hemoglobin, urea, creatinine, cystatin C, calcium, phosphorus and parathyroid hormone (PTH) levels were measured. eGFR was calculated according to Schwartz and Filler formulas, employing creatinine and cystatin C as markers. Patients were divided into groups depending on the stage of CKD [group 1: CKD stage 1+2 (GFR > 60), group 2: CKD stage 3 (GFR = 30-59) Group 3: CKD stage 4 (GFR = 15-29 ml/min/1.73 m2), group 4 - dialyzed children]. RESULTS: The concentration of he- moglobin depending on the stage of CKD (group 1 vs. group 2 vs. group 3 vs group 4) was 12.95 vs. 12.68 vs. 12.47 vs. 11.3 g/dI, respectively. The concentration of total and ionized calcium was significantly lower in children on dialysis compared to patients treated conservatively. With the progression of CKD the concentration of phosphorus (1.39 vs. 1.4 vs. 1.49 vs. 1.82 mmolI) and PTH (21.7 vs 48.6 vs 99.9 vs. 219 pg/ml) significantly increased. Treatment with erythropoietin was used in 48% of children, calcium carbonate in 55% and alphacalcidol in 56% of patients. CONCLUSIONS: Despite the use of regular treatment, with the progression of CKD a progression of anemia, increased serum phosphate and parathyroid hormone and a decrease in calcium levels in studied children was observed. The severity of metabolic disorders in dialyzed children indicates the need for administration of new and more effective drugs, to prevent early enough complications of CKD in the form of mineral bone disease and cardiovascular complications.

Clinical validity of urinary interleukin 18 and interleukin 6 determinations in preterm newborns.

INTRODUCTION: Preterm newborns are at a particular risk of acute kidney injury (AKI) and sepsis. PURPOSE: Assessment of urinary interleukin 18 (ulL-18) and urinary interleukin 6 (ulL-6) concentrations in association with AKI and sepsis respectively in newborns hospitalized in Neonatal Intensive Care Unit (NICU). MATERIAL AND METHODS: An evaluation was carried out of the dependence of ulL-18 on neonatal birth weight (BW) and AKI as well as ulL6 on sepsis. In prospective study, the evaluation included 58 children with BW up to 2000 g. Clinical observations spanned the period between the 1st and 28th day of life. RESULTS: The mean gestational age was 30.3 Hbd, mean BW was 1361.9 g. AKI was diagnosed in 35 (60.3%), sepsis in 22 (39.7%) neonates. For median values of uIL-18 and ulL-18/mgCr, as well as for mean logarithmically transformed values of ulL-18 and ulL-18/mgCr, negative, statistically significant linear correlations were demonstrated for BW. In population, median value of ulL-18 and ulL-18/mgCr decreased respectively by 8.21 pg/ml and 84.8 pg/mgCr per each 100 g increment of BW. A negative, statistically significant linear correlation with an average strength was noted for the dependency of the duration of AKI and BW. No significant differences were observed in uIL-18 and ulL-181 mgCr values between the investigated days of AKI and reference group. There was noted a significant increase of the values of uIL-6 and uIL-6/ mgCr on day 0 of sepsis confirmed by the ROC analysis with AUROC 78% and 74%, respectively. CONCLUSIONS: ulL-18 and ulL-18/mgCr values might be a reliable marker of renal tubules maturation in newborns; ulL-18 is not a reliable marker in diagnosing AKI in neonatal population; ulL-6 and uIL-6/ mgCr concentration values measured on actual days may be regarded an early marker of sepsis; AKI duration in preterm neonates is negatively correlated with BW.

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.

[Familial case of oral-facial-digital syndrome type 1 (OFD 1)]. / Rodzinny przypadek zespolu ustno-twarzowo-palcowego typu 1 (OFD 1).

UNLABELLED: Ciliopathies are phenotypically and genetically heterogeneous disorders that share ciliary dysfunction as a common pathological mechanism. Ciliary dysfunction results in a broad range of malformations including renal, hepatic and pancreatic cysts, visceral abnormalities, retinal degeneration, anosmia, cerebellar or other brain anomalies, polydactyly, bronchiectasis and infertility. The paper presents a familial case of oral-facial-digital syndrome type 1 in 14 year old girl suspected to polycystic kidney disease. CONCLUSIONS: Molecular testing in daughters of known OFD1 mutation carriers and mothers of affected daughters seems to be reasonable. Not each case of policystic kidney disease which looks like autosomal dominant policystic kiedney disease is actually the above disease. The insight into the pathogenesis of ciliopathies is mandatory for understanding these combined congenital anomaly syndromes of seemingly unrelated symptoms of hepatorenal and pancreatic fibrocystic disease. Close interdisciplinary approach is mandatory in terms of efficient and reliable diagnostic and therapeutic interventions in patients presenting with ciliopathies.

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.

[Early markers of acute kidney injury in newborns]. / Wczesne markery ostrego uszkodzenia nerek w okresie noworodkowym.

The incidence of acute kidney injury (AKI) at neonatal intensive care units (NICU) is estimated as 6-24%. Traditional AKI markers i.e. serum creatinine (SCr) concentration, fractional sodium exertion, urine sodium concentration and renal failure index--are low sensitivity and low specificity markers but beside remain very late ones. Serum creatinine concentration arises 48 hours after renal tissue damage. The paper presents contemporary knowledge concerning concentration reference ranges of some early AKI biomarkers (NGAL, hKIM1, OPN, IL18)--either in term or preterm newborns. The most current reports about chosen AKI biomarkers in newborns with uncomplicated clinical course and in children with AKI within the course of sepsis or after cardiopulmonary bypass surgery--were discussed. Disposing of the reliable clinical data referring to early AKI biomarkers constitutes a valuable aid for clinicians who having got to know about the actual risk possess the time for proper clinical interventions.

The effect of peritoneal dialysis method on residual renal function in children.

We set out to assess the effect of continuous ambulatory peritoneal dialysis (CAPD) and automated peritoneal dialysis (APD) on residual renal function (RRF) in children with end-stage renal disease (ESRD). In 101 children (age: 8.84 +/- 5.25 years; 44 on CAPD, 57 on APD) over 36 months, we evaluated RRF [as daily diuresis (DD) in mL/kg/24 h and mL/m2/24 h], glomerular filtration rate [GFR (in mL/min/1.73 m2)], ESRD cause, presence of arterial hypertension (HTN), biochemical parameters, peritoneal equilibration test (PET), adequacy [as total weekly Kt/V (twKt/V) and creatinine clearance (twCCr)], and infectious complications of PD. Initially, the CAPD and APD groups did not differ significantly in DD, but mean GFR was significantly higher in the APD group (p < 0.05). In the CAPD group, the volume of high osmolarity PD fluid was significantly lower (p < 0.05), and the rates of peritonitis and exit-site infection and of aminoglycoside use were higher (p < 0.001, p < 0.05, and p < 0.005 respectively). Over 36 months, the mean twKt/V and twCCr were within norms in both groups, but were higher in APD, significantly so (p < 0.05) for twKt/V at 24 and 36 months and for twCCr initially. In both groups, RRF decreased systematically, with a significantly lower (p < 0.05) rate of DD (mL/m2/24 h) and GFR decline in the first year in CAPD, but without a difference in the next 2 years. The longest RRF preservation was in children with tubulointerstitial nephropathies, particularly hypoplasia and dysplasia (p < 0.05). Children with hemolytic uremic syndrome (HUS) and hereditary nephropathy were at the highest anuria risk. Compared with the 22 children (7 CAPD, 15 APD) who became anuric, the 20 children (10 CAPD, 10 APD) with RRF preserved for 36 months had a higher DD and GFR before dialysis onset; higher hemoglobin and albumin; and lower HTN prevalence, cholesterol, triglycerides, and proteinuria (p < 0.05). Risk of anuria during 36 months did not differ significantly between the CAPD and APD groups. In children on CAPD or APD, risk factors for RRF loss include HUS, hereditary nephropathy, low diuresis and GFR before dialysis onset, HTN, anemia, hypoalbuminemia, hyperlipidemia, and proteinuria. Compared with children on APD, those on CAPD show better preservation of RRF during year 1, although the risk of anuria seems to be the same for both methods. In children with risk factors for rapid diuresis loss, CAPD might be considered the preferred initial dialysis method.

[Non-structural abnormalities of CNS function resulting in coincidence of endocrinopathies, epilepsy and psychoneurologic disorders in children and adolescents]. / Niestrukturalne zaburzenia czynnosci OUN odpowiedzialne za wspólwystepowanie endokrynopatii, padaczki i zaburzen psychoneurologicznych u dzieci i mlodziezy.

BACKGROUND: In the population of children and adolescents, epilepsy affects approximately 1% of cases, nonepileptic seizures are seen in approximately 3%, and endocrine disorders are several times more common. For this reason, coincidence of endocrine disorders and epilepsy and psychoneurologic disorders is frequent. Much less common are structural abnormalities (tumors, developmental abnormalities), and especially non-structural CNS abnormalities, resulting in coincidence of both disorders. There are no reports available in the literature that would address the problem. AIM OF THE STUDY: 1) Assessment of the frequency of coincidental epilepsy and endocrine disorders in patients without structural CSN abnormalities treated as outpatients and inpatients of Department of Endocrinology University Children's Hospital of Krakow. 2) Presentation of diagnostic and therapeutic difficulties in these patients, and 3) An attempt at defining the common etiology of both disorders. MATERIAL AND METHODS: On the basis of ICD code patients with coincidance of endocrine disorders, epilepsy and psychoneurologic disorders were selected from several thousands of children treated between 2000 and 2009 in Pediatric Endocrinology Department. The neurologic disorders were diagnosed and treated in Chair and Department of Children's and Adolescents Neurology or in another pediatric neurology center. RESULTS: Various forms of epilepsy (symptomatic or idiopathic) and other psychoneurological disorders (disorders of behavior and emotions, obsession-compulsion syndromes, stereotypias, aggression, autoaggression, or hypothalamic obesity) coincident with one or more endocrine disorders, such as growth disorders, disorders of pubertal development, obesity, thyroid diseases, adrenal diseases, hyperprolactinemia, hypoparathyroidism and ion metabolism disorders were diagnosed in 49 patients. The group included: i) children after cranial irradiation and chemotherapy due to medulloblastoma (3 patients), oligodenroglioma (1 patient), ependymoma (1 patient), optic chiasm glioma (2 patients), suprasellar germinal tumor (1 patient), ii) children with Hashimoto encephalopathy (2 patients), iii) children with Prader-Willi syndrome (20 patients), with Klinefelter syndrome (10 patients), with Albright syndrome (9 patients). Of the 49 patients, a group of 6 children representative for individual disorders was selected. In those patients, the etiology of both endocrine disorders, epilepsy and neuropsychiatric disorders was suspected to be common, and the diagnosis was usually delayed. CONCLUSIONS: 1. Cranial irradiation and chemotherapy, encephalopathy associated with Hashimoto disease and some of the syndromes with the chromosomal and genetic background are the causes of non-structural CNS abnormalities and coincidence of endocrinopathies, epilepsy and psychoneurologic disorders. 2. MR/CT CNS imaging should be performed in any case of central neurological disorders, disorders of behavior, epilepsy or seizures, but also in patients with delayed psycho-motor development, delayed or accelerated growth and pubertal development. All of the above-mentioned manifestations may be symptoms of structural CNS abnormalities and their early treatment determines the child's future. 3. Excluding structural CNS abnormalities allows for forming suspicions associated with diseases resulting in non-structural disorders of the CNS function, predisposing to coincidence of endocrine and neurological disorders. 4. In the diagnosis of Hashimoto's encephalopathy, a decisive factor is exclusion of structural, infectious, traumatic and metabolic causes, intoxications, epilepsy and presence of neuropsychiatric symptoms in patients with high level of against TPO antibodies. In cases of steroids resistance, a good therapeutic effect may be achieved by plasmapheresis, Rituximab therapy and progestagene inhibition of the menstrual cycle.

[Effectiveness of plasmapheresis in adolescent myasthenia gravis treatment]. / Skutecznosc plazmaferezy w leczeniu lekoopornej miastenia gravis u mlodocianej.

BACKGROUND: Myasthenia gravis (MG) is a disease with autoimmune background. Impaired neuromuscular transmission is caused by blockage of acetylcholine receptors on postsynaptic membrane by circulating specific antibodies. Recognition of myasthenia gravis in children, especially its ocular type, may be difficult due to occurrence of similar clinical symptoms in other diseases like ecephalomyopathies. MG is characterized by variety of clinical symptoms and their alternations during excercise and rest. AIM OF THE STUDY: Case report of nearly 18-year-old girl with generalized type of MG. MATERIAL AND METHODS: Before hospitalization the girl had been treated psychiatrically for 6 months due to suspicion of conversion disorders. After performance of clinical test and electro-neurophysiological examinations mysathenia gravis was diagnosed and conservative treatment was instituted. Additionally, on the ground of low effectiveness of the treatment, sterydotherapy and immunosuppressive treatment were instituted without marked clinical improvement. Thymectomy was also low effective. Thymic inflammation was recognised histopathologically. Only after performance of 5 plasmapheresis was significant clinical improvement achieved. CONCLUSION: Plasmapheresis may be used not only in the treatment of myasthenic crisis but also in the treatment of drug-resistant mysthenia gravis.

[GFR estimation based upon cystatin C concentration as a substance marker--proposal of a new formula]. / Wyznaczanie GFR na podstawie stezenia cystatyny C jako substancji markerowej--propozycja nowego wzoru.

Glomerular filtration rate (GFR) estimation is very important for evaluation of kidney function. Its calculation is based upon a 24 hour urine collection and serum creatinine concentration values or on the basis of developed for this purpose numerous formulas with special attention dedicated to the abbreviated MDRD formula and Cockcroft-Gault formulas for adults and Schwartz et al. and Counahan et al. formulas for children. Future expectations are related to GFR estimation based on serum cystatin C concentration and formulas specially developed for this cause. The aim of the study was the comparative analysis of GFR results based on Filler's and Lapage's, Grubb's et al. and Schwartz's et al. formulas and reference values obtained in 93 patients after measuring iohexol concentration after its single injection. Significant differences between the results obtained from employed formulas for high, as well as for low values of GFR were shown, respectively. Serial calculations were performed allowing to finding out a new prescription for GFR calculation. A new formula for GFR calculation based on cystatin C concentration: GFR = -7.28+82.29 x C(-1) was proposed.

[Early laboratory markers of acute renal failure]. / Wczesne laboratoryjne markery ostrej niewydolnosci nerek.

Acute renal failure is a sudden clinical condition caused by loss of renal ability to maintain homeostasis. Despite significant advances in renal replacement therapy--the mortality rate in ARF patients is still very high--ranging from 20% to 50%. Differential diagnostics, especially between acute prerenal and intrinsic acute renal failure is an extremly important stage in patient evaluation process. In the article--the authors present a short and concise profile of novel, more and less promising for future diagnostic ARF biomarkers: neutrophil gelatinase associated lipocalin (NGAL), sodium/hydrogen exchanger isoform 3 (NHE3), human kidney injury molecule-1 (hKIM-1), interleukin 6 (IL-6), interleukin 8 (IL-8), interleukin 18 (IL-18), urinary cysteine-rich protein (Cyr 61), urinary glutathione-S-transferase (GST), cystatin C, spermidine/spermine N-acetyl transferase (SSAT) and actin) which are recently either in the animal model research stage or during preliminary clinical studies. Extension of research and wideninig of knowledge about the discussed novel, early markers of ARF--would permit for quicker introduction of specifically guided therapy and might improve the prognosis of ARF patients in the near future.

[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.

[Heterozygotic mutation in NPHS2 gene as a cause of familial steroid resistant nephrotic syndrome in two siblings--case report]. / Mutacja heterozygotyczna w genie NPHS2 jako przyczyna rodzinnego steroidoopornego zespolu nerczycowego u dwojga rodzenstwa--opis przypadku.

Within recent years the number of children with focal segmental glomerulonephritis (FSGS) has increased. A significant progress in defining of molecular basis of the disease has been made. Gene mutations for nephrin, podocin, WT1, alpha-actinin 4 cause the damage of filtration barrier of glomerulus and proteinuria in consequence. A girl (S.G.) became ill at the age of 3.5, suffering form steroid-resistant nephritic syndrome (SRNS) with microscopic hematuria. The renal biopsy showed FSGS accompanied by a complete diffuse effacement of podocyte food processes. Despite intensive and regular immunosuppressive therapy, remission was not achieved. In the control renal biopsy performed a year after cyclosporin A had been applied, 50% of globally sclerosed glomeruli as well as some features of post-cyclosporin damage were found. The girl required renal replacement therapy at the age of 10.5. Dialyzed at the adult dialysis centre she died at the age of 11.5. A boy S.P. was diagnosed with SRNS when he was 11.5 years old. The renal biopsy was performed after one month of treatment and showed mesangial proliferation and diffuse effacement of podocyte food processes. After chlorambucil treatment remission was not achieved, and after methylprednisolon pulse therapy only the reduction of proteinuria was achieved. In a control renal biopsy 10 out of 13 glomeruli were globally sclerosed. At the age of 17 the patient showed chronic renal failure with a fast progression of the disease. In September 2000 the boy started renal replacement therapy, an in June 2001 he received a renal transplant without the recurrence of FGS. In 2001 a heterozygous mutation (A284V) in gene NPHS2 was found in both of the siblings. Within the confines of the clinical project ESCAPE Trial another genetic examination was performed. In the boy one missense mutation on one allele (A284V) and the R229Q polymorphism on the other allele were found. In this family the father is bear. ing the A284V mutation and the mother the R229Q variant. These results prove that this disease is due to alterations of the podocin gene in the described family.