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.

[B-type natriuretic peptide as a marker of cardiac dysfunction in children with chronic kidney disease]. / Peptyd natriuretyczny typu B jako marker uszkodzenia serca u dzieci z przewlekla choroba nerek.

Left ventricular hypertrophy is the most common organ damage in children with chronic kidney disease (CKD). AIM: The aim of the study was to assess the usefulness of B-type natriuretic peptide (BNP) as a marker of heart injury in children with CKD. MATERIALS AND METHODS: We included 66 children (41 boys and 25 girls) aged 0.7 to 18.6 (median 11.6) years with CKD stage 1-5. The concentrations of urea, creatinine, cystatin C and BNP in blood serum were assessed, and the estimated glomerular filtration rate (eGFR) was calculated from the Schwartz and Filler formulas. Patients were divided into groups depending on the CKD stage [group 1: CKD stages 1 + 2 (GFR> 60 ml/min/1.73 m2), group 2: stage 3 (GFR = 30-59 ml/min/1.73 m2), group 3: CKD stage 4 (GFR 15-29 ml/min/ 1.73 m2), group 4 - stage 5 (dialyzed children)]. On the basis of echocardiography, the left ventricular mass (LVM) was calculated, which was indexed for height (left ventricular mass index, LVMI). Left ventricular hypertrophy (LVH) was diagnosed if the LVMI value was > 95th percentile for sex and age. RESULTS: Depending on the CKD stage the median BNP concentrations for group 1, group 2, group 3, and group 4 were 2.5 pg/ml, 6.0 pg/ml, 9.3 pg/ml and 18.0 pg/ml, and the LVH prevalence 27.3%, 33.3%, 60.0% and 63.6% , respectively. Significant correlations between BNP concentration and LVH expressed by LVMI (R=0.256, p=0.038), creatinine (R=0.453, p<0.001), cystatin (R=0.494, p<0.001) and eGFR (R=-0.473, p<0.001) were found. CONCLUSIONS: In children with chronic kidney disease, BNP is an indicator of heart failure correlating with renal function parameters and left ventricular mass index.

Blood concentration of aminothiols in children with relapse of nephrotic syndrome.

BACKGROUND: The role of idiopathic nephrotic syndrome (INS) in the pathogenesis of atherosclerosis in childhood has not been clearly elucidated. However, antioxidative defense in INS is thought to be imbalanced. This study aimed to assess the changes of plasma concentration of selected aminothiols in the blood of children with INS at various stages of the disease. METHODS: This cross-sectional study was conducted in 125 children aged 2-18 years. The children were divided into 4 groups: group A, early relapse (n=37); group B, early remission for 4-6 weeks from the onset (n=37); group C, late steroid-free remission (n=31); and group D, long-term remission for 2-5 years (n=20). Control group (E) consisted of 30 age- and gender-matched healthy children. The study protocol comprised an analysis of plasma concentrations of glutathione, homocysteine, cysteine and cysteinylglycine by high-performance liquid chromatography. Fractions of protein-bound and free aminothiols were measured. Endothelial injury was assessed by thrombomodulin, PAI-1 concentration, and von Willebrand factor activity. RESULTS: The children with INS had unbalanced aminothiol metabolism only in relapse and early remission, that shifted towards increased oxidative processes. Administration of cyclosporine A caused a significant increase in homocysteine and cysteine concentration. Changes in aminothiol metabolism were significantly related to endothelial injury. CONCLUSIONS: The findings of this study may be helpful in elucidating the pathogenesis of premature atherosclerosis in patients with INS refractory to the treatment or in the case of frequent relapse.

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.

Oxidative Stress Biomarkers and Left Ventricular Hypertrophy in Children with Chronic Kidney Disease.

Cardiovascular diseases remain the most frequent cause of morbidity and mortality in patients with chronic kidney disease (CKD). The aim of the study was to assess the association between oxidative stress biomarkers and cardiovascular risk factors and left ventricular hypertrophy in children with CKD. Material and Methods. The studied group consisted of 65 patients aged 1.4-18.6 (mean 11.2) years with stages 1 to 5 CKD. Serum oxidized low-density lipoprotein (oxLDL), protein carbonyl group, creatinine, cystatin C, albumin, lipids, high-sensitivity C-reactive protein, intercellular adhesion molecule-1, insulin, plasma renin activity, and aldosterone levels were measured. Patients were divided into groups depending on CKD stage. Anthropometric measurements, ambulatory blood pressure (BP) measurements, and echocardiography with left ventricular mass (LVM) calculation were performed. Results. Serum oxLDL strongly correlated with creatinine (R = 0.246; p = 0.048), cystatin C (R = 0.346; p = 0.006), total cholesterol (R = 0.500; p < 0.001), triglycerides (R = 0.524; p < 0.001), low-density lipoprotein concentrations (R = 0.456; p < 0.001), and 24 hour BP values of systolic (R = 0.492; p = 0.002), diastolic (R = 0.515; p < 0.001), and mean arterial pressure (R = 0.537; p < 0.001). A significant correlation between oxLDL levels and LVM z-scores (R = 0.299; p = 0.016) was found. Conclusions. Hypertension and dyslipidemia correlated with lipid oxidation in children with CKD. oxLDLs seem to be valuable markers of oxidative stress in CKD patients, correlating with left ventricular hypertrophy.

Favorable four-yr outcome after renal transplantation in a patient with complement factor H antibody and CFHR1/CFHR3 gene mutation-associated HUS.

UNLABELLED: aHUS is a clinical challenge for successful renal transplantation. CASE REPORT: A 14-yr-old girl lost her kidneys at the age of 7, due to CFH antibodies and CFH-related protein (CFHR1/CFHR3) homozygous deletion-associated aHUS. CFH, CFI, and MCP gene mutations were excluded. The patient was a candidate for renal transplantation despite persistent presence of CFH antibodies (up to 539 AU/mL). Treatment with MMF, IVIG, and repeated PF (n = 8) was introduced while being placed on urgent waiting list. Three years after aHUS onset, the patient underwent the deceased donor renal transplantation "under cover" of PF, as PF was performed directly prior to surgery and, then, PFs were repeated up to overall 14 sessions. Quadruple immunosuppression (basiliximab + tacrolimus + MMF + prednisolone) was used. Moderate symptoms of aHUS (hemolysis, low platelets, and low C3) were present within first seven days post-transplant and then normalized with PF therapy. The patient remained stable during four yr of further follow-up after transplantation. CONCLUSION: Specific pre- and post-transplant management allowed successful renal transplantation in a CFH antibody-positive patient.

Relationship between serum IgA/C3 ratio and severity of histological lesions using the Oxford classification in children with IgA nephropathy.

BACKGROUND: The aim of this study was to evaluate the usefulness of serum immunoglobulin A/complement factor 3 (IgA/C3) ratio for predicting histological severity of kidney lesions in children with IgA nephropathy (IgAN) based on World Health Organization (WHO) and the Oxford classification (OC). METHODS: We studied 89 children with IgAN with a mean age of 11.38 ± 4.1 years (range 2-18 years). Based on available medical records, we retrospectively evaluated clinical data, IgA/C3 ratio, and kidney biopsy findings using the five-grade WHO classification and the OC The mesangial hypercellularity (M), endocapillary hypercellularity (E), segmental sclerosis (S), tubular atrophy/interstitial fibrosis (T) (MEST) score (absent = 0, present = 1) calculated as the sum of M+E+S+T ranging from 0 to 4. RESULTS: Mean IgA/C3 ratio values were significantly higher (P < 0.05) in patients with M1, S1, and T1 compared with M0, S0, and T0, respectively (P < 0.05); there were no differences in the WHO classification. We found a significant positive correlation between the IgA/C3 ratio and proteinuria (r = 0.24) and determined optimal cutoff values of the IgA/C3 ratio, with a corresponding confidence interval for specific MEST scores. CONCLUSIONS: The IgA/C3 ratio in children with IgAN may be a useful marker of the severity of lesions found in kidney biopsy as evaluated using the OC.

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.

[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.

[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.

Anaemia treatment in chronically dialysed children: a multicentre nationwide observational study.

OBJECTIVE: Erythropoiesis-stimulating agents (ESAs) are applied as a standard therapy in children with anaemia in chronic kidney disease. The aim of this study was to describe the efficacy and details of ESA treatment in a population of dialysed children in Poland. MATERIAL AND METHODS: The study had a prospective observational design and was performed in 12 dialysis centres. The study group comprised 117 dialysed children with a mean age at enrolment of 165.33 (97.18-196.45) months. RESULTS: Dialysed children were treated mostly with epoietin beta and darbepoietin. The mean dose of ESA was 99 (68-147) U/kg/week with a significant difference between patients on peritoneal dialysis [83 (54-115)] and haemodialysis [134 (103-186)] (p < 0.0001). The mean haemoglobin of all the time-point tests during 6 months was 10.91 ± 1.18 g/dl. The efficacy of anaemia treatment was unsatisfactory in 52% of subjects. In multivariate analysis, initial haemoglobin level <10 g/l, any infection, younger age at first dialysis, malnutrition and inadequate ESA dosage remained significant predictors of anaemia. CONCLUSIONS: The study revealed that anaemia treatment in Polish children is unsatisfactory. Late commencement of the treatment, inadequate dosing, malnutrition and infections could constitute risk factors for therapy failure.

[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.