Assessment of Risk Factors for Acute Kidney Injury with Machine Learning Tools in Children Undergoing Hematopoietic Stem Cell Transplantation.

Background: Although acute kidney injury (AKI) is a common complication in patients undergoing hematopoietic stem cell transplantation (HSCT), its prophylaxis remains a clinical challenge. Attempts at prevention or early diagnosis focus on various methods for the identification of factors influencing the incidence of AKI. Our aim was to test the artificial intelligence (AI) potential in the construction of a model defining parameters predicting AKI development. Methods: The analysis covered the clinical data of children followed up for 6 months after HSCT. Kidney function was assessed before conditioning therapy, 24 h after HSCT, 1, 2, 3, 4, and 8 weeks after transplantation, and, finally, 3 and 6 months post-transplant. The type of donor, conditioning protocol, and complications were incorporated into the model. Results: A random forest classifier (RFC) labeled the 93 patients according to presence or absence of AKI. The RFC model revealed that the values of the estimated glomerular filtration rate (eGFR) before and just after HSCT, as well as methotrexate use, acute graft versus host disease (GvHD), and viral infection occurrence, were the major determinants of AKI incidence within the 6-month post-transplant observation period. Conclusions: Artificial intelligence seems a promising tool in predicting the potential risk of developing AKI, even before HSCT or just after the procedure.

KIM-1, IL-18, and NGAL, in the Machine Learning Prediction of Kidney Injury among Children Undergoing Hematopoietic Stem Cell Transplantation-A Pilot Study.

Children undergoing allogeneic hematopoietic stem cell transplantation (HSCT) are prone to developing acute kidney injury (AKI). Markers of kidney damage: kidney injury molecule (KIM)-1, interleukin (IL)-18, and neutrophil gelatinase-associated lipocalin (NGAL) may ease early diagnosis of AKI. The aim of this study was to assess serum concentrations of KIM-1, IL-18, and NGAL in children undergoing HSCT in relation to classical markers of kidney function (creatinine, cystatin C, estimated glomerular filtration rate (eGFR)) and to analyze their usefulness as predictors of kidney damage with the use of artificial intelligence tools. Serum concentrations of KIM-1, IL-18, NGAL, and cystatin C were assessed by ELISA in 27 children undergoing HSCT before transplantation and up to 4 weeks after the procedure. The data was used to build a Random Forest Classifier (RFC) model of renal injury prediction. The RFC model established on the basis of 3 input variables, KIM-1, IL-18, and NGAL concentrations in the serum of children before HSCT, was able to effectively assess the rate of patients with hyperfiltration, a surrogate marker of kidney injury 4 weeks after the procedure. With the use of the RFC model, serum KIM-1, IL-18, and NGAL may serve as markers of incipient renal dysfunction in children after HSCT.

Systemic Immune Inflammation Index as a Key Predictor of Dialysis in Pediatric Chronic Kidney Disease with the Use of Random Forest Classifier.

BACKGROUND: Low-grade inflammation is a significant component of chronic kidney disease (CKD). Systemic immune inflammation index (SII), a newly defined ratio combining neutrophil, lymphocyte, and platelet counts, has not yet been evaluated in the pediatric CKD population nor in the context of CKD progression or dialysis. Thus, this study aimed to analyze the complete blood cell count (CBC)-driven parameters, including SII, in children with CKD and to assess their potential usefulness in the prediction of the need for chronic dialysis. METHODS: A single-center, retrospective study was conducted on 27 predialysis children with CKD stages 4-5 and 39 children on chronic dialysis. The data were analyzed with the artificial intelligence tools. RESULTS: The Random Forest Classifier (RFC) model with the input variables of neutrophil count, mean platelet volume (MPV), and SII turned out to be the best predictor of the progression of pediatric CKD into end-stage kidney disease (ESKD) requiring dialysis. Out of these variables, SII showed the largest share in the prediction of the need for renal replacement therapy. CONCLUSIONS: Chronic inflammation plays a pivotal role in the progression of CKD into ESKD. Among CBC-driven ratios, SII seems to be the most useful predictor of the need for chronic dialysis in CKD children.

Lymphocyte to monocyte ratio and blood pressure variability in childhood hypertension-a pilot study.

BACKGROUND AND AIMS: The investigation of inflammatory background of hypertension (HTN) concentrates mainly on patients with primary HTN. The aim of the study was to analyze the role of new parameters of inflammation-lymphocyte to monocyte ratio (LMR), neutrophil to lymphocyte ratio (NLR), and platelet to lymphocyte ratio (PLR), in the population of children with primary (pHTN) and secondary renal hypertension (rHTN). MATERIAL AND METHODS: The study group consisted of 70 children with pHTN, 46 patients with rHTN, and 30 age-matched normotensive controls. The retrospective analysis focused on the evaluation of LMR, NLR, and PLR values in relation to blood pressure (BP) parameters from in-office and ambulatory BP monitoring measurements. Twenty-four hours, daytime, and nighttime periods were evaluated. Blood pressure variability (BPV) was defined by standard deviation and coefficient of variation of analyzed values. RESULTS: LMR and NLR values in HTN patients differed significantly vs. controls. Dippers with pHTN demonstrated significant correlations between LMR, NLR, PLR, and markers of BPV, in 24 h and daytime diastolic BP and mean arterial pressure. In dippers with rHTN such correlations concerned only LMR. CONCLUSIONS: LMR may become a promising marker of BPV, useful in children with primary and secondary hypertension. IMPACT: Lymphocyte to monocyte ratio is a novel marker of blood pressure variability, connected to target-organ damage, in children with primary and secondary renal hypertension. Our study analyzes for the first time the connections between blood cell count-driven inflammatory markers (lymphocyte to monocyte, neutrophil to lymphocyte, and platelet to lymphocyte ratios) and parameters of blood pressure variability, and compares those ratios in children with primary and secondary hypertension. The increasing incidence of hypertension among children urges the search for simple methods of assessment of its complications. LMR may be of added value in the analysis of the inflammatory background of hypertension.

Biomarkers in Pediatric Nephrology-From Bedside to Bench and Back Again.

The progress in biomarker research is characterized by the perpetual quest for parameters that fulfill the strict criteria of sensitivity, specificity, ease and speed in performance and cost-effectiveness [...].

Update on Innate Immunity in Acute Kidney Injury-Lessons Taken from COVID-19.

The serious clinical course of SARS-CoV-2 infection is usually accompanied by acute kidney injury (AKI), worsening prognosis and increasing mortality. AKI in COVID-19 is above all a consequence of systemic dysregulations leading to inflammation, thrombosis, vascular endothelial damage and necrosis. All these processes rely on the interactions between innate immunity elements, including circulating blood cells, resident renal cells, their cytokine products, complement systems, coagulation cascades and contact systems. Numerous simultaneous pathways of innate immunity should secure an effective host defense. Since they all form a network of cross-linked auto-amplification loops, uncontrolled activation is possible. When the actions of selected pathways amplify, cascade activation evades control and the propagation of inflammation and necrosis worsens, accompanied by complement overactivity and immunothrombosis. The systemic activation of innate immunity reaches the kidney, where the damage affecting single tubular cells spreads through tissue collateral damage and triggers AKI. This review is an attempt to synthetize the connections between innate immunity components engaged in COVID-19-related AKI and to summarize the knowledge on the pathophysiological background of processes responsible for renal damage.

Bone Morphogenetic Proteins (BMPs), Extracellular Matrix Metalloproteinases Inducer (EMMPRIN), and Macrophage Migration Inhibitory Factor (MIF): Usefulness in the Assessment of Tubular Dysfunction Related to Chronic Kidney Disease (CKD).

Bone morphogenetic proteins (BMP), extracellular matrix metalloproteinases inducer (EMMPRIN), and macrophage migration inhibitory factor (MIF) are known to be closely connected to renal tubule damage by experimental data; however, this has not been analyzed in children with chronic kidney disease (CKD). The aim of this study was to determine their usefulness in the assessment of CKD-related tubular dysfunction. The study group consisted of 61 children with CKD stages 1-5 and 23 controls. The serum and urine concentrations of BMP-2, BMP-6, EMMPRIN, and MIF were assessed by ELISA and their fractional excretion (FE) was calculated. The serum and urine concentrations of BMP-2, BMP-6, EMMPRIN, and MIF were significantly elevated in children with CKD vs. controls. The FE of BMP-2, FE BMP-6, and EMMPRIN increased significantly in CKD stages 1-2, but exceeded 1% in CKD stages 3-5. FE MIF became higher than in controls no sooner than in CKD 3-5, but remained below 1%. The FE values for BMP-2, BMP-6, and EMMPRIN of <1% may result from the tubular adaptive mechanisms, whereas those surpassing 1% suggest irreversible tubular damage. The analysis of serum/urinary concentrations and fractional excretion of examined parameters may allow the assessment of CKD-related tubular dysfunction.

Current Concepts of Pediatric Acute Kidney Injury-Are We Ready to Translate Them into Everyday Practice?

Pediatric acute kidney injury (AKI) is a major cause of morbidity and mortality in children undergoing interventional procedures. The review summarizes current classifications of AKI and acute kidney disease (AKD), as well as systematizes the knowledge on pathophysiology of kidney injury, with a special focus on renal functional reserve and tubuloglomerular feedback. The aim of this review is also to show the state-of-the-art in methods assessing risk and prognosis by discussing the potential role of risk stratification strategies, taking into account both glomerular function and clinical settings conditioned by fluid overload, urine output, or drug nephrotoxicity. The last task is to suggest careful assessment of eGFR as a surrogate marker of renal functional reserve and implementation of point-of-care testing, available in the case of biomarkers like NGAL and [IGFBP-7] × [TIMP-2] product, into everyday practice in patients at risk of AKI due to planned invasive procedures or treatment.

The Impact of Allogeneic Hematopoietic Stem Cell Transplantation on Kidney Function in Children-A Single Center Experience.

BACKGROUND: Knowledge about the impact of allogeneic hematopoietic stem cell transplantation (alloHSCT) on renal function in children is still limited. OBJECTIVES: The aim of the study was to evaluate kidney function in children undergoing alloHSCT, with special focus on differences between patients transplanted due to oncological and non-oncological indications. MATERIALS AND METHODS: The data of 135 children undergoing alloHSCT were analyzed retrospectively. The serum creatinine and estimated glomerular filtration rate (eGFR) values were estimated before transplantation at 24 h; 1, 2, 3, 4 and 8 weeks; and 3 and 6 months after alloHSCT. Then, acute kidney injury (AKI) incidence was assessed. RESULTS: Oncological children presented with higher eGFR values and more frequent hyperfiltration rates than non-oncological children before alloHSCT and until the 4th week after transplantation. The eGFR levels rose significantly after alloHSCT, returned to pre-transplant records after 2-3 weeks, and decreased gradually until the 6th month. AKI incidence was comparable in oncological and non-oncological patients. CONCLUSIONS: Children undergoing alloHSCT due to oncological and non-oncological reasons demonstrate the same risk of AKI, but oncological patients may be more prone to sustained renal injury. Serum creatinine and eGFR seem to be insufficient tools to assess kidney function in the early post-alloHSCT period, when hyperfiltration prevails, yet they reveal significant differences in long-term observation.

The incidence of acute kidney injury in children undergoing allogenic hematopoietic stem cell transplantation: A pilot study.

BACKGROUND: Acute kidney injury (AKI) is a common feature in adults undergoing allogeneic hematopoietic stem cell transplantation (alloHSCT). However, accurate assessment of AKI incidence in the pediatric population still seems a challenge. OBJECTIVES: To evaluate the incidence of AKI according to the pRIFLE criteria in children undergoing alloHSCT, with special focus on differences between patients transplanted due to oncological and non-oncological indications. MATERIAL AND METHODS: A retrospective analysis of data, concerning 135 children undergoing alloHSCT due to oncological (89 patients) or other (46 patients) reasons, was performed. The values of estimated glomerular filtration rate (eGFR) were measured before alloHSCT, 24 h after, 1, 2, 3, 4, 8 weeks, 3 and 6 months after alloHSCT, and the AKI incidence was analyzed. RESULTS: Acute kidney injury was diagnosed in 54% of all patients. The Risk stage (R) was noticed at least once in 46% of oncological and 37% of non-oncological children. The Injury stage (I) concerned 12% of oncological and 6% of non-oncological patients undergoing alloHSCT. The incidence of AKI in both groups was comparable. The mean eGFR values in oncological children were higher than those in the non-oncological patients even before transplantation and until the 4th week after alloHSCT. The eGFR increased significantly in all patients 24 h after alloHSCT and returned to pre-transplantation records after 2-3 weeks. Then, oncological patients demonstrated a gradual decrement of eGFR. Six months after transplantation, eGFR values in oncological children were significantly lower compared to pre-transplantation records, whereas in non-oncological children, these values were comparable. CONCLUSIONS: Although the type of indication for alloHSCT has no impact on the AKI incidence, children undergoing alloHSCT due to oncological reasons are at greater risk of renal impairment 6 months after transplantation than non-oncological patients.

Clinical profile of a Polish cohort of children and young adults with cystinuria.

BACKGROUND: Cystinuria is an inherited disorder that results in increased excretion of cystine in the urine. It accounts for about 1-2% of pediatric kidney stones. In this study, we sought to identify the clinical characteristics of patients with cystinuria in a national cohort. METHODS: This was a retrospective study involving 30 patients from the Polish Registry of Inherited Tubulopathies. Initial data and that from a 6-month follow-up were analyzed. Mutational analysis was performed by targeted Sanger sequencing and, if applicable, MLPA analysis was used to detect large rearrangements. RESULTS: SLC7A9 mutations were detected in 15 children (50%; 10 males, 5 females), SLC3A1 mutations in 14 children (47%; 5 males, 9 females), and bigenic mutations in one male patient. The first clinical symptoms of the disease were detected at a median of 48 months of age (range 3-233 months). When individuals with different mutations were compared, there were no differences identified in gender, age of diagnosis, presence of UTI or urolithiasis, eGFR, calcium, or cystine excretion. The most common initial symptoms were urolithiasis in 26 patients (88%) and urinary tract infections in 4 patients (13%). Urological procedures were performed in 18 out of 30 (60%). CONCLUSIONS: The clinical course of cystinuria is similar among patients, regardless of the type of genetic mutation. Most patients require surgery before diagnosis or soon after it. Patients require combined urological and pharmacological treatment for prevention of stone recurrence and renal function preservation.

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.

New methods of differentiation between primary and secondary hypertension in a pediatric population: A single-center experience.

BACKGROUND: Kidney diseases are the main causative factors of secondary hypertension (HTN) in children. Although primary HTN is less common in the pediatric population, its increasing prevalence, especially among teenagers, makes early diagnosis an emerging issue. OBJECTIVES: To analyze the potential differences between primary HTN and HTN secondary to renal diseases, in order to tailor diagnostic procedures to pediatric patients with suspicion of HTN. MATERIAL AND METHODS: A retrospective evaluation was performed of medical records of 168 children (aged from 1 month to 18 years) diagnosed with arterial HTN in the Pediatric Nephrology Department of Wroclaw Medical University (Poland). The comparative analysis concerned demographics, causes of HTN, clinical picture, laboratory tests, and parameters of ambulatory blood pressure monitoring (ABPM). RESULTS: Out of 168 children, 47% were diagnosed with primary HTN and 53% with secondary renal HTN. The patients with primary HTN were significantly older than those with HTN secondary to renal disease. Among the children with primary HTN, 26% were overweight and 42% were obese; among those with renal HTN, the proportions were 16% and 19%, respectively. The patients with primary HTN had significantly higher body mass index (BMI) percentiles and z-scores, and tended toward higher pulse pressure (PP) values. In the group with secondary HTN, ABPM parameters of diastolic blood pressure (DBP) and total cholesterol were significantly elevated. The BMI z-scores correlated positively with PP in the whole group. CONCLUSIONS: As expected, HTN secondary to renal disease prevails in younger children, but primary HTN has become an emerging issue in teenagers. The diagnostics of HTN secondary to kidney disease have revealed risk factors worsening the prognosis, including higher values of cholesterol or of parameters connected with DBP. Primary HTN risk factors include obesity and a tendency towards higher PP values.

Monocyte chemoattractant protein-1, macrophage colony stimulating factor, survivin, and tissue inhibitor of matrix metalloproteinases-2 in analysis of damage and repair related to pediatric chronic kidney injury.

BACKGROUND: Kidney injury in the course of chronic kidney disease (CKD) is a consequence of aggravated cell migration, inflammation, apoptosis, and fibrosis. However, the sequence of these phenomena, as well as of the reparatory mechanisms, are not fully known. Monocyte chemoattractant protein 1 (MCP-1) and macrophage colony-stimulating factor (MCSF) trigger monocyte migration to the sites of inflammation and their transition into macrophages. Tissue inhibitor of matrix metalloproteinases-2 (TIMP-2) plays a protective role against excessive matrix remodeling, whereas survivin is known for its anti-apoptotic activity. OBJECTIVES: To analyze the serum, urine and fractional excretion (FE) values of MCP1, MCSF, TIMP-2, and survivin in children at subsequent stages of CKD being treated conservatively, and to analyze the potential applicability of these markers in the evaluation of CKD-related renal damage and protective mechanisms against it. MATERIAL AND METHODS: The study group consisted of 70 children with conservatively treated CKD, stages 1-5, and 12 controls. The serum and urine concentrations of MCP1, MCSF, TIMP-2, and survivin were assessed using enzyme-linked immunosorbent assay (ELISA). The FE of these parameters in the urine was also assessed. RESULTS: The serum values of all parameters were significantly elevated at CKD stage 1 compared to the controls. The urinary concentrations of MCP-1 and MCSF (stages 1-2) rose earlier than TIMP-2 and survivin (stage 4) concentrations. The FE values started increasing at CKD stage 3 (MCP-1) or stage 4 (other parameters). CONCLUSIONS: The complex analysis of serum/urinary/FE values of the selected parameters revealed a sequence of multifaceted CKD-related phenomena, when the migration of cells and inflammation were followed by delayed and insufficient anti-fibrotic and anti-apoptotic activity.

Clusterin as a New Marker of Kidney Injury in Children Undergoing Allogeneic Hematopoietic Stem Cell Transplantation-A Pilot Study.

BACKGROUND AND AIMS: The markers of renal damage defining subclinical AKI are not widely used in children undergoing allogeneic hematopoietic stem cell transplantation (alloHSCT). The aim of the study was to evaluate serum and urinary clusterin as indices of kidney injury after alloHSCT in relation to damage (kidney injury molecule (KIM)-1) and functional (cystatin C) markers. MATERIAL AND METHODS: Serum and urinary clusterin, KIM-1 and cystatin C concentrations were assessed by ELISA in 27 children before alloHSCT, 24 h, 1, 2, 3 and 4 weeks after alloHSCT and in controls. RESULTS: All parameters were significantly higher in HSCT patients compared to controls even before the transplantation. The serum concentrations increased after HSCT and this rising trend was kept until the third (clusterin) or 4th (KIM-1, cystatin C) week. Urinary clusterin and KIM-1 were elevated until the third week and then decreased yet remained higher than before HSCT. Urinary cystatin C has risen from the second week after HSCT and decreased after the third week but was still higher than before alloHSCT. CONCLUSIONS: The features of kidney injury are present even before alloHSCT. Clusterin seems useful in the assessment of subclinical AKI and may become a new early marker of sublethal kidney injury in children.

Markers of acute kidney injury in children undergoing hematopoietic stem cell transplantation.

Acute kidney injury (AKI), one of the major complications in children undergoing hematopoietic stem cell transplantation (HSCT), is an independent predictor of the patient's survival and a prognostic factor of progression to chronic kidney disease (CKD). Despite the multifaceted role of AKI, its early diagnosis in the course of HSCT remains a challenge. These difficulties may result from the inefficiency of traditional methods used to assess kidney function, like serum creatinine or estimated glomerular filtration rate. Moreover, the list of potential AKI markers tested in HSCT conditions is limited and does not involve indexes evaluated in the pediatric population. This review summarizes current knowledge on the pathophysiology of AKI developing in the course of HSCT; presents well-known markers of AKI that are potentially applicable in children who have undergone HSCT; discusses the role of new markers in diagnosing AKI and predicting the renal outcome in children undergoing HSCT; and analyzes the prospects for the use of new tools for assessing kidney injury in everyday clinical practice.

New markers of cell migration and inflammation in children with chronic kidney disease.

Context: Chronic kidney disease (CKD) is characterized by immunocompetent cell migration and inflammation. Monocyte chemoattractant protein (MCP)-1 and macrophage colony-stimulating factor (MCSF) stimulate monocyte migration and transition into macrophages with subsequent release of neopterin. Objective: The aim of the study was to analyze these parameters in children with various stages of CKD. Material and methods: The study group consisted of 41 CKD children, 19 patients on haemodialysis (HD), 22 children on automated peritoneal dialysis (APD) and 23 controls. Serum concentrations of MCP-1, MCSF and neopterin were assessed by ELISA. Correlations to matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) were analyzed. Results: MCP-1, MCSF and neopterin were significantly elevated in all patients versus controls and the highest values concerned HD children. A single HD session lessened the concentrations of all parameters, yet they rose back before the next HD session. All markers correlated with MMPs and TIMPs in different combinations. Conclusions: Systemic inflammation and cell migration are triggered by CKD and additionally aggravated by chronic dialysis, with the more evident negative impact of HD than APD. Discrepancies in MCP1, MCSF and neopterin serum concentrations suggest they may serve as new markers of cellular and inflammatory responses in children with CKD.

[Chronic kidney disease in children up to 2 years of age - a single center data analysis]. / Przewlekla choroba nerek u dzieci do 2. roku zycia ­ analiza danych z jednego osrodka.

Although anomalies in the urinary tract are the leading cause of chronic kidney disease (CKD) in the pediatric population, there are few studies focusing on etiological discrepancies between younger and older children. AIM: The aim of the study was to perform a comparative analysis of etiology of CKD in children hospitalized in the Department of Pediatric Nephrology at the Wroclaw Medical University, with reference to the patients' age and gender. MATERIALS AND METHODS: The retrospective analysis considered medical records of 174 patients aged 0-18 years, diagnosed with CKD, hospitalized in our Department in the years 2011-2017. The analyzed population was divided regarding the patients' age. Group A contained children up to 2 years of age (45 patients), group B - children aged 2-18 years (129 patients). RESULTS: In younger children, boys prevailed, in older children gender distribution was equal. The most common causative factors of CKD in group A were: urinary tract anomalies (66,7%), perinatal acute kidney injury (17,8%) and hereditary renal disorders (8,9%). In children over 2 years of age, urinary tract anomalies were also the leading cause of CKD (48,8%), followed by glomerulopathies (16,3%) and hereditary renal disorders (15,5%). CONCLUSIONS: Anomalies within the urinary tract are the predominant cause of CKD in children, irrespective of age. Male predominance concerned only children up to 2 years of age. The second causative factor for CKD in the youngest children is acute kidney injury, mainly in the perinatal period. Glomerulopathies and hereditary renal disorders are significant etiological factors for CKD in older children.

Fractional excretion as a new marker of tubular damage in children with chronic kidney disease.

OBJECTIVES: Vitamin D-binding protein (VDBP), retinol-binding protein (RBP)4, and heat shock proteins (hsp) are markers of tubular function and apoptosis, accompanying chronic kidney disease (CKD) from its earliest stages. Fractional excretion of proteins with urine is a marker of tubular damage. The aim of study was to assess the usefulness of fractional excretion (FE) of VDBP, RBP4, HSF1 and Hsp27 as markers of tubular damage in the course of CKD. METHODS: The study group consisted of 70 children with CKD stages 1-5, treated conservatively, and 12 age-matched controls with normal kidney function. The serum and urine concentrations of VDBP, RBP4, HSF1 and Hsp27 were assessed by ELISA. The fractional excretion of analyzed parameters was calculated according to the formula: ([parameter urine concentration] × [creatinine serum concentration]) / ([parameter serum concentration] × [creatinine urine concentration])×100%. RESULTS: The FE values of all parameters exceeded 1% in CKD stage 2. However, the values of FE have raised significantly versus control group no sooner than CKD stage 2 (RBP4 and HSF1), stage 3 (VDBP) or stage 4 (Hsp27). CONCLUSION: Fractional excretion of RBP4 and HSF1 with urine may become a valuable marker, assessing the damage of tubular cells in children with CKD.

New Markers of Inflammation and Tubular Damage in Children with Chronic Kidney Disease.

INTRODUCTION AND AIMS: Monocyte chemoattractant protein- (MCP-) 1, macrophage colony-stimulating factor (MCSF), and neopterin are connected with monocyte migration and transition into macrophages, leading to fibrosis and tubular damage in the course of CKD. The aim of the study was to analyze the applicability of urinary fractional excretion (FE) of MCP1, MCSF, and neopterin, as markers of inflammation and tubular damage, in children with CKD. METHODS: The study group consisted of 61 children with CKD stages 1-5 and 23 age-matched controls. The serum and urine concentrations of MCP1, MCSF, and neopterin were assessed by ELISA and then the fractional excretion (FE) was calculated. RESULTS: FE MCSF and neopterin values exceeded 1% already in controls. FE MCSF rose significantly since CKD stages 1-2, FE neopterin since CKD stages 3-5. FE MCP1 was below 1% in healthy controls and in CKD stages 1-2, then increased significantly in CKD stages 3-5. CONCLUSIONS: The FE MCP-1 values show that inflammation precedes the tubular dysfunction. FE MCSF and FE neopterin may be considered new markers of the renal parenchyma progressive damage. Fractional excretion may become a useful tool in the assessment of inflammation and tubular damage in children with CKD.