Progression Of Chronic Kidney Disease In Children Research Articles

Plasma and Urinary Platelet Factor 4 as Biomarkers for Cardiovascular Risk in Children with Chronic Kidney Disease.

Children suffering from chronic kidney disease (CKD) have a high risk of cardiovascular disease (CVD). The early detection and diagnosis of subclinical CVD in pediatric CKD can reduce mortality later in life. Plasma factor 4 (PF4) is a chemokine released by activated platelets. We examined whether or not PF4 in the plasma and urine, its kidney function normalized ratio, and fractional excretion have differential associations with CVD risk markers in 139 youths aged 3 to 18 years old with CKD stages G1-G4. Significant negative correlations were observed between plasma PF4 and cardiovascular surrogate markers, such as the left ventricular mass index (LVMI), carotid intima-media thickness (cIMT), and pulse wave velocity (PWV). The plasma PF4/creatinine (Cr) ratio was lower in CKD children with a high daytime BP and 24 h BP, high BP load, and nocturnal non-dipping status. After adjusting for confounders, the plasma PF4 and plasma PF4/Cr ratio still independently predicted an abnormal ABPM profile. In addition, both the plasma PF4 and plasma PF4/Cr ratio presented a negative correlation with the L-arginine and asymmetric dimethylarginine ratio. These findings provide convincing evidence supporting the link between PF4 and CVD markers in pediatric CKD. Our study highlights the importance of further research to assess the performance of PF4-related biomarkers in predicting CVD events and CKD progression in children with CKD.

Association between serum total cholesterol and chronic kidney disease progression in children: results from the KNOW-PedCKD.

Dyslipidemia can cause cardiovascular disease and increase the fatality rate among children with chronic kidney disease (CKD); this makes early screening and treatment of dyslipidemia crucial. This study aimed to assess the association between the changes in serum total cholesterol levels over time and the degree of CKD progression in children. From April 2011 to August 2021, 379 of the 432 participants enrolled in the KoreaN cohort study for Outcomes in patients With Pediatric CKD (KNOW-PedCKD) were included and divided into 4 categories based on total cholesterol levels (< 170mg/dL, acceptable; 170-199, borderline; 200-239, high; and ≥ 240, very high). Survival analysis using conventional and time-dependent Cox proportional hazards model were performed for a composite event of CKD progression (≥ 50% decrease in estimated glomerular filtration rate from baseline, a twofold increase in creatinine, or the occurrence of dialysis or kidney transplantation). The incidence of composite event of CKD progression was 96.3, 90.4, 87.3, and 270.6 cases per 1000 person-years in the acceptable, borderline, high, and very high categories, respectively. On using the time-dependent Cox proportional hazards model, the hazard ratio of the very high category was significantly higher than that of the acceptable category by 3.13 times as per univariate analysis and 2.37 times as per multivariate analysis. Very high serum total cholesterol is a significant risk factor for CKD progression in children. Lowering total cholesterol levels below the very high category in children with CKD may delay the progression of CKD. A higher resolution version of the Graphical abstract is available as Supplementary information.

Protein Biomarkers in Chronic Kidney Disease in Children-What Do We Know So Far?

Chronic kidney disease (CKD) in children is a major concern of medical care and public health as it is related to high morbidity and mortality due to progression to end-stage kidney disease (ESKD). It is essential to identify patients with a risk of developing CKD to implement therapeutic interventions. Unfortunately, conventional markers of CKD, such as serum creatinine, glomerular filtration rate (GFR) and proteinuria, have many limitations in serving as an early and specific diagnostic tool for this condition. Despite the above, they are still the most frequently utilized as we do not have better. Studies from the last decade identified multiple CKD blood and urine protein biomarkers but mostly assessed the adult population. This article outlines some recent achievements and new perspectives in finding a set of protein biomarkers that might improve our ability to prognose CKD progression in children, monitor the response to treatment, or even become a potential therapeutic target.

Dietary acid load in children with chronic kidney disease: its association with nutritional status and health-related quality of life.

This study aimed to determine the dietary acid load of children with chronic kidney disease (CKD) and to evaluate the relationship between dietary acid load, nutritional status, and health-related quality of life (HRQOL). A total of 67 children aged 3-18 years with a diagnosis of CKD stages II-V were included in the study. Anthropometric measurements (body weight, height, mid-upper arm circumference, waist, and neck circumference) and 3-day food consumption records were taken to evaluate the nutritional status. The net endogenous acid production (NEAP) score was calculated to determine the dietary acid load. "Pediatric Inventory of Quality of Life (PedsQL)" was used to assess the participants' HRQOL. The mean NEAP was 59.2 ± 18.96 mEq/day. Stunted and malnourished children had significantly higher NEAP than those who were not (p < 0.05). There were no significant differences in terms of HRQOL scores according to NEAP groups. The multivariate logistic regression analysis showed that waist circumference (OR: 0.890, 95% CI: 0.794-0.997), serum albumin (OR: 0.252, 95% CI: 0.068-0.929), and glomerular filtration rate (GFR) (OR: 0.985, 95% CI: 0.970-1.000) were negatively associated with high NEAP. This study shows that a diet shifted in an acidic direction in children with CKD and a higher dietary acid load are associated with lower serum albumin, GFR, and waist circumference, but not HRQOL. These results suggest that dietary acid load might affect nutritional status and CKD progression in children with CKD. Future studies with larger samples are needed to confirm these results and to understand underlying mechanisms. A higher resolution version of the Graphical abstract is available as Supplementary information.

Role of hypertension in progression of pediatric CKD.

Hypertension is frequent in children with chronic kidney disease (CKD). Its prevalence varies according to CKD stage and cause. It is relatively uncommon in children with congenital kidney disease, while acquired kidney disease is associated with a higher prevalence of hypertension. Studies in children with CKD utilizing ambulatory blood pressure monitoring also showed a high prevalence of masked hypertension. Uncontrolled and longstanding hypertension in children is associated with progression of CKD. Aggressive treatment of high blood pressure should be an essential part of care to delay CKD progression in children.

Blood levels of pro- and anti-inflammatory cytokines in children after acute kidney injury at different stages of observation

Identifying the factors for progression of kidney pathology after acute kidney injury (AKI) in children is important for making clinical decisions and creating strategies for the prevention and treatment of chronic kidney disease (CKD).&#x0D; The present study aimed to investigate the value of serum levels of tumor necrosis factor α (TNF-α) and transforming growth factor (TGF-β) as markers of CKD progression in children after AKI.&#x0D; Methods. In this cross-sectional cohort study, the levels of serum cytokines were studied in 63 children from 6 months to 18 years old who had undergone AKI and 10 healthy children (reference group) using ELISA. The peculiarities of those who recovered (n=14) and those who were subsequently diagnosed with CKD stage 1 ​ (n=22) or CKD stages 2-3 (n=27) were determined. An analysis was also carried out taking into account the duration from the episode of AKI: early recovery period up to 3 months (n=21), 3-12 months (n=9), 1-3 years (n=22), and more than 3 years (n=11). “SPSS for Windows. Version 11" - Student's test or Mann-Whitney Rank Sum Test was used. The correlation analysis was determined using the Pearson (r) or Kendall/Spearman method (ρ).&#x0D; Results. An increase in serum levels of the anti-inflammatory but pro-sclerotic TGF-β was observed in all children convalescing with AKI regardless of disease progression, with mean levels of the indicator increasing in the delayed phase. An increase in TGF-β levels ≥40.5 pg/mL in the first 3 months after AKI was documented in patients with an unfavorable disease course, such that these patients could be classified as a risk group for the development of fibrotic complications.&#x0D; No peculiarities in mean serum levels of proinflammatory TNF-α were observed in children who had suffered AKI, and there was no significant difference when comparing the groups according to the consequences of the disease. In the individual analysis, it was found that after the 12th month of observation, a high TNF-α level (≥8.0 pg/ml) was associated with an increase in the proportion of patients with CKD 2-3 (p &lt; 0.001), which can be used to predict disease progression.&#x0D; Conclusions. This study demonstrates the feasibility of determining serum levels of TNF-α and TGF-β in children with AKI, which could be used as potential predictors of CKD risk to optimize treatment and prevention.

Reduced Blood Pressure Dipping Is A Risk Factor for the Progression of Chronic Kidney Disease in Children.

Background: Elevated blood pressure and proteinuria are well-established risk factors for chronic kidney disease (CKD) progression in children. This study aimed to analyze risk factors for CKD progress, emphasizing detailed ambulatory blood pressure (ABPM) data. Methods: In 55 children with CKD II–V, observed for ≥1 year or until initiation of kidney replacement therapy, we analyzed ABPM, clinical, and biochemical parameters. Results: At the beginning, the glomerular filtration rate (eGFR) was 66 (interquartile range—IQR: 42.8–75.3) mL/min/1.73 m2, and the observation period was 27 (16–36) months. The mean eGFR decline was 2.9 ± 5.7 mL/min/1.73 m2/year. eGFR decline correlated (p < 0.05) with age (r = 0.30), initial proteinuria (r = 0.31), nighttime systolic and mean blood pressure (r = 0.27, r = 0.29), and systolic and diastolic blood pressure dipping (r = −0.37, r = −0.29). There was no relation between mean arterial pressure during 24 h (MAP 24 h Z-score) and eGFR decline and no difference in eGFR decline between those with MAP 24 h < and ≥50 th percentile. In multivariate analysis, systolic blood pressure dipping (beta = −0.43), presence of proteinuria (beta = −0.35), and age (beta = 0.25) were predictors of eGFR decline. Conclusions: Systolic blood pressure dipping may be a valuable indicator of CKD progression in children.

Efficacy and Safety of Dapagliflozin in Children With Inherited Proteinuric Kidney Disease: A Pilot Study

Efficacy and Safety of Dapagliflozin in Children With Inherited Proteinuric Kidney Disease: A Pilot Study

Association of GSTM1 Deletion With Progression of CKD in Children: Findings From the Chronic Kidney Disease in Children (CKiD) Study

Loss of function of the product of the GSTM1 gene has been implicated in rapid progression of adult chronic kidney disease (CKD). Its role in pediatric CKD has not been previously described. Secondary analysis of a prospective observational cohort examining the association between deletions in GSTM1 and progression of CKD. We used data and samples from the prospective Chronic Kidney Disease in Children (CKiD) cohort aged 1-16 years at enrollment with CKD. We defined the exposure as fewer than 2 GSTM1 alleles on real-time polymerase chain reaction amplification. The primary outcome was a composite of 50% decrease in estimated glomerular filtration rate (eGFR) or start of kidney replacement therapy. Secondary outcomes included remission of proteinuria in children with glomerular disease and cardiovascular complications. The primary analysis was by Cox proportional hazards model. Analysis was adjusted for age, sex, race, ethnicity, body mass index category, diagnosis category, and eGFR. The analysis included 674 children. Their mean age at most recent visit was 11.9 years; 61% were male, and 20% were Black. There were 241 occurrences of the primary outcome at the time of analysis. After adjustment for baseline characteristics, the risk of progression of CKD for exposed children was 1.94 (95% CI, 1.27-2.97). The effect size was similar with either 1 or 2 deletions (autosomal dominant inheritance). The relationships between number of functional GSTM1 alleles and prespecified secondary outcomes were not statistically significant after adjustment. Missing data, especially for secondary outcomes, and relatively small sample size compared to genetic studies in adults. GSTM1 deletion is associated with more rapid progression of pediatric CKD after adjustment in this large prospective cohort. No statistically significant associations were seen with secondary outcomes. If replicated, these findings may inform development of interventions for CKD in children.

Variability in CKD Biomarker Studies: Soluble Urokinase Plasminogen Activator Receptor (suPAR) and Kidney Disease Progression in the Chronic Kidney Disease in Children (CKiD) Study

Rationale & ObjectiveBiomarker studies are important for generating mechanistic insight and providing clinically useful predictors of chronic kidney disease (CKD) progression. However, variability across studies can often muddy the evidence waters. Here we evaluated real-world variability in biomarker studies using two published studies, independently conducted, of the novel plasma marker soluble urokinase-type plasminogen activator receptor (suPAR) for predicting CKD progression in children with CKD.Study DesignA comparison of 2 prospective cohort studies.Setting & Participants541 children from the Chronic Kidney Disease in Children (CKiD) study, median age 12 years, median glomerular filtration rate (GFR) of 54 mL/min/1.73m2.OutcomeThe first occurrence of either a 50% decline in GFR from baseline or incident end-stage kidney disease.Analytical ApproachThe suPAR plasma marker was measured using the Quantikine ELISA immunoassay in the first study and Meso Scale Discovery (MSD) platform in the second. The analytical approaches varied. We used suPAR data from the 2 assays and mimicked each analytical approach in an overlapping subset.ResultsWe found that switching assays had the greatest impact on inferences, resulting in a 38% to 66% change in the magnitude of the effect estimates. Covariate and modeling choices resulted in an additional 8% to 40% variability in the effect estimate. The cumulative variability led to different inferences despite using a similar sample of CKiD participants and addressing the same question.LimitationsThe estimated variability does not represent optimal repeatability but instead illustrates real-world variability that may be present in the CKD biomarker literature.ConclusionsOur results highlight the importance of validation, avoiding conclusions based on P value thresholds, and providing comparable metrics. Further transparency of data and equal weighting of negative and positive findings in explorations of novel biomarkers will allow investigators to more quickly weed out less promising biomarkers.

Risk Factors for Renal Function Impairment in Childen with Meningomyelocele; a Single Center Study

Introduction: Chronic kidney disease and its complications are among the most frequent cause of morbidity and mortality in patients with meningomyelocele. Objective: In this study, we aimed to determine the risk factors leading to chronic kidney disease progression in these patients. Material and Method: Fifty patients with meningomyelocele were analyzed retrospectively. Age, gender, followup period, serum creatinine, glomerular filtration rate, vesicoureteral reflux (VUR), initial urodynamic findings and initiation time of clean intermittent catheterization (CIC) were noted. The progression of Chronic kidney disease (CKD) was evaluated by DMSA renal scintigraphy, changes in serum creatinine (Screa), and glomerular filtration rate (GFR). Results: 30 of the 50 patients were included in the study. VUR was detected in 63% of the patients, and scar was detected in 83% by renal scintigraphy. The median value of Screa was 0.5 mg/dl in admission, while the median Screa was 1.02 mg/dl (min-max: 0.27-5) at the last visit and the difference was statistically significant (p=0.001). A statistically significant was found between CKD progression and GFR in admission (p=0.001), CIC onset age (p=0.03), degree of VUR (p=0.046), presence of renal scar (p=0.002). It was shown that delay in admission (p=0.011; OR 1.36; CI 1.07-1.73) and low GFR in admission (p=0.036 OR 0.915 CI 0.842-0.994) were the most important risk factors. Conclusion: In our study, it was shown that delay in neurogenic bladder treatment, delay in the initiation of CIC, and low GFR at admission were important risk factors for the progression of CKD in children with meningomyelocele. Therefore, we aimed to emphasize the importance of regular follow-up of these children in Pediatric Nephrology Clinics from the neonatal period.

Achieved clinic blood pressure level and chronic kidney disease progression in children: a report from the Chronic Kidney Disease in Children cohort.

Control of hypertension delays progression of pediatric chronic kidney disease (CKD), yet few data are available regarding what clinic blood pressure (BP) levels may slow progression. Longitudinal BP data from children in the Chronic Kidney Disease in Children cohort study who had hypertension or an auscultatory BP ≥ 90th percentile were studied. BP categories were defined as the maximum systolic or diastolic BP percentile (< 50th, 50th to 75th, 75th to 90th, and ≥ 90th percentile) with time-updated classifications corresponding to annual study visits. The primary outcome was time to kidney replacement therapy or a 30% decline in estimated glomerular filtration rate. Cox proportional hazard models described the effect of each BP category compared to BP ≥ 90th percentile. Seven hundred fifty-four participants (median age 9.9 years at study entry) met inclusion criteria; 65% were male and 26% had glomerular CKD. Any BP < 90th percentile was associated with a decreased risk of progression for those with glomerular CKD (hazard ratio (HR), 0.63; 95% CI, 0.28-1.39 (< 50th); HR, 0.59; 95% CI, 0.28-1.26 (50th-75th); HR, 0.40; 95% CI, 0.18-0.93 (75th-90th)). Similar results were found for those with non-glomerular CKD: any BP < 90th percentile was associated with decreased risk of progression (HR, 0.78; 90% CI, 0.49-1.25 (< 50th); HR, 0.53; 95% CI, 0.33-0.84 (50th-75th); HR, 0.71; 95% CI, 0.46-1.08 (75th-90th)). Achieved clinicBP < 90th percentile was associated with slower CKD progression in children with glomerular or non-glomerular CKD. These data provide guidance for management of children with CKD in the office setting. Graphical abstract.

Serum indoxyl sulfate concentrations associate with progression of chronic kidney disease in children.

The uremic toxins indoxyl sulfate (IS) and p-cresyl sulfate (pCS) accumulate in patients with chronic kidney disease (CKD) as a consequence of altered gut microbiota metabolism and a decline in renal excretion. Despite of solid experimental evidence for nephrotoxic effects, the impact of uremic toxins on the progression of CKD has not been investigated in representative patient cohorts. In this analysis, IS and pCS serum concentrations were measured in 604 pediatric participants (mean eGFR of 27 ± 11 ml/min/1.73m2) at enrolment into the prospective Cardiovascular Comorbidity in Children with CKD study. Associations with progression of CKD were analyzed by Kaplan-Meier analyses and Cox proportional hazard models. During a median follow up time of 2.2 years (IQR 4.3–0.8 years), the composite renal survival endpoint, defined as 50% loss of eGFR, or eGFR <10ml/min/1.73m2 or start of renal replacement therapy, was reached by 360 patients (60%). Median survival time was shorter in patients with IS and pCS levels in the highest versus lowest quartile for both IS (1.5 years, 95%CI [1.1,2.0] versus 6.0 years, 95%CI [5.0,8.4]) and pCS (1.8 years, 95%CI [1.5,2.8] versus 4.4 years, 95%CI [3.4,6.0]). Multivariable Cox regression disclosed a significant association of IS, but not pCS, with renal survival, which was independent of other risk factors including baseline eGFR, proteinuria and blood pressure. In this exploratory analysis we provide the first data showing a significant association of IS, but not pCS serum concentrations with the progression of CKD in children, independent of other known risk factors. In the absence of comorbidities, which interfere with serum levels of uremic toxins, such as diabetes, obesity and metabolic syndrome, these results highlight the important role of uremic toxins and accentuate the unmet need of effective elimination strategies to lower the uremic toxin burden and abate progression of CKD.

P0599THE LYSOSOMAL URINE ENZYMES ACTIVITY IN CHILDREN AFTER ACUTE KIDNEY INJURI

Abstract Background and Aims The urgency of the problem of acute kidney injury (AKI) in children is due to the high risk of chronic kidney disease (CKD) as an outcome. Lysosomal enzymes in urine are considered to be informative markers of renal parenchyma damage. The aim of study was to determine the activity of lysosomal enzymes β-galactosidase (GAL) and N-acetyl-β-D-glucosamynidase (NAG) in urine as markers of CKD progression in children after AKI. Method 41 children were examined after AKI with achieving self-diuresis and clinical improvement. The functional state of the kidneys was evaluated by the glomerular filtration rate (Schwartz GFR), the level of albuminuria. Urine enzyme activity was determined and cross-linked to mmol urinary creatinine. The control (reference) group consisted of 28 children who were conditionally healthy, without kidney disease. Results The NAG activity was 8 times higher level than in the reference group of healthy children (87/46;193 vs. 15/11;18, p&amp;lt;0.001), and GAL was elevated in 3 times either (34/22;45 vs. 10/6;13, p&amp;lt;0.001) in patients with a disease period of up to 2 years after AKI. In patients with follow-up period 2 or more years enzyme activity levels decreased, but remained 4 times higher (NAG: 49/31;109, p &amp;lt;0.001 compared to control; GAL: 35/25;44, p &amp;lt;0.001 compared to control). The high levels of enzyme activity was documented in 73.2% of patients after one year of follow up, but the GFR decrease was found in 22.0%, and albuminuria - only in 34.1%. Conclusion The urine activity of NAG and GAL in children is an informative marker for diagnosing recovery after AKI or CKD progression with renal function decline. This method is non-invasive, inexpensive, and simple to conduct.

Reduction in urinary angiotensinogen levels and improvement of proteinuria by renin-angiotensin system blockade in pediatric chronic kidney disease patients with very low birth weight.

Children with low birth weight (LBW) have an increased risk of developing chronic kidney disease (CKD), and no effective strategies have been established to prevent the progression of CKD in these patients. Urinary angiotensinogen (UAGT) may represent a useful marker of intrarenal renin-angiotensin system (RAS) activation, which has been suggested to play a critical role in the development of hypertension and CKD. Herein, we conducted a prospective study to determine whether RAS blockade is beneficial for suppressing the progression of CKD in children with LBW, using UAGT as a surrogate marker of renal impairment. Nine children with CKD (stages: 1-2) who had very low birth weight (VLBW; < 1500g) were started on RAS blockade with candesartan. We measured blood pressure and laboratory parameters, including urinary concentrations of angiotensinogen, protein, albumin, creatinine (Cr), and estimated glomerular filtration rate (eGFR), before and after candesartan treatment. Birth weight was 712g (range, 536-800g). Age at evaluation was 11.6years (range, 10.3-15.6years). After candesartan treatment for 47.6 ± 25.0months, the UAGT to urinary Cr ratio decreased from 61.9 ± 44.7 to 16.8 ± 14.4μg/g (p= 0.015). The urinary protein to Cr and albumin to Cr ratios also decreased (p= 0.008 and p= 0.012, respectively), whereas there was no significant change in eGFR. RAS blockade reduced UAGT levels and improved proteinuria/albuminuria in children with CKD who had VLBW. Suppression of intrarenal RAS activity may slow the progression of CKD in children with LBW.

Oxidant stress and renal function among children with chronic kidney disease: a repeated measures study

It is hypothesized that chronic kidney disease (CKD) induces oxidant stress which contributes to the decline in kidney function. However, few studies have incorporated longitudinal designs and no studies have investigated this association among children. Using data from the Chronic Kidney Disease in Children (CKiD) study, we examined longitudinal associations between urinary biomarkers of oxidant stress, 8-OH deoxyguanosine (8-OHdG) and F2-isoprostane, and measures of renal function and blood pressure among children with CKD. Baseline levels of 8-OHdG were positively associated with estimated glomerular filtration rate (eGFR) over time and a log-unit increase in baseline 8-OHdG predicted a 5.68 ml/min/1.73 m2 increase in eGFR (95% Confidence Interval (CI): 3.75, 7.61). This association was attenuated when longitudinal measures of 8-OHdG were analyzed in relation to longitudinal eGFR (per log-unit increase in 8-OHdG, β = 0.81, 95% CI: 0.22, 1.39). Baseline 8-OHdG concentrations were also associated with decreased proteinuria over time, as measured by urinary protein:creatinine ratio. In addition, F2-isoprostane concentrations were associated with increases in eGFR, but only when baseline levels (vs. longitudinal levels) were considered in relation to longitudinal eGFR. There were no significant associations between either 8-OHdG or F2-isoprostane and blood pressure over time. Urinary measures of oxidant stress are not associated with worsening GFR over time. Our findings suggest that excretion of these biomarkers may be influenced by changes in glomerular and tubular function in varying patterns, which would limit their value in evaluating the impact of oxidant stress on CKD progression in children.

The CKiD study: overview and summary of findings related to kidney disease progression.

The Chronic Kidney Disease in Children (CKiD) cohort study is a North American (USA and Canada) multicenter, prospective study of children with chronic kidney disease (CKD). The original aims of the study were (1) to identify novel risk factors for CKD progression; (2) to measure the impact of kidney function decline on growth, cognition, and behavior; and (3) to characterize the evolution of cardiovascular disease risk factors. CKiD has developed into a national and international resource for the investigation of a variety of factors related to CKD in children. This review highlights notable findings in the area of CKD progression and outlines ongoing opportunities to enhance understanding of CKD progression in children. CKiD's contributions to the clinical care of children with CKD include updated and more accurate glomerular filtration rate estimating equations for children and young adults, and resources designed to help estimate the CKD progression timeline. In addition, results from CKiD have strengthened the evidence that treatment of hypertension and proteinuria should continue as a primary strategy for slowing the rate of disease progression in children.

Plasma Soluble Urokinase Plasminogen Activator Receptor (suPAR) and CKD Progression in Children

Soluble urokinase plasminogen activator receptor (suPAR) is a novel biomarker associated with incident chronic kidney disease (CKD) and has been identified as an independent risk factor for CKD progression in children, although these findings remain preliminary, limited to a single point in time, and unreplicated in pediatric cohorts. Prospective longitudinal cohort study. 565 participants aged 1 to 16 years enrolled in the Chronic Kidney Disease in Children (CKiD) Study. Plasma suPAR levels, categorized by quartiles, measured at study entry and a 6-month follow-up interval. CKD progression, defined as the initiation of kidney replacement therapy (dialysis or transplantation) or >50% decline in estimated glomerular filtrate rate (eGFR). Associations between plasma suPAR quartiles and risk for CKD progression were estimated using lognormal survival models, adjusting for potential confounders. Participants in the highest suPAR quartile experienced 54% faster progression compared with the lowest quartile after adjustment for demographic and traditional CKD risk factors (P< 0.001). Addition of eGFR to the model attenuated the risk, although those in the highest quartile experienced 33% faster progression compared with the lowest quartile (P= 0.008). Plasma suPAR levels showed little change over 6 months. Potential for residual confounding, reliance on observational data, relatively fewer patients with higher eGFRs for subgroup analysis. Higher suPAR levels are associated with shorter time to kidney replacement therapy or halving of eGFR in children with CKD. This association is attenuated slightly with inclusion of eGFR in regression modeling but remains a significant association for participants with the highest suPAR levels.

Chronic kidney disease in children: problems of arterial hypertension

The review contains materials on the course of chronic kidney disease (CKD) in children with arterial hypertension (AH). The relationship between CKD and AH was shown, where hastening of CKD progression to end-stage renal failure in the presence of AH was established. The regulation of AH in children is necessary for the treatment of CKD, because AH is not established on time, is not well controlled and is often masked. Impaired vascular regulation, fluid overload, increased cardiac output, and peripheral vascular resistance, alone or in combination, can lead to hypertension in CKD. The use of modern methods for monitoring and controlling blood pressure is crucial to improve the management of AH and prevent damage to target organs in children. 24-hour blood pressure measurements are an important tool in determining the prognosis and treatment of children with CKD. To identify impaired renal function in CKD, a large number of biomarkers are used. Glomerular filtration rate (GFR), serum creatinine and cystatin C are currently used as biomarkers for renal failure. Recently, biomarkers, including KIM-1, LFABP, NGAL, and IL-18 have been proposed as markers of acute kidney injury, and they may be useful in the future for early detection of CKD progression in children. In newborns and children of early and older age, hypertension occurs due to renovascular and parenchymal diseases.AH is considered a marker of CKD severity and is a risk factor for progressive deterioration of kidney function, as well as thedevelopment of cardiovascular diseases. Sympathetic hyperactivity, excessive formation of free radicals, reduced bioavailability of nitric oxide (NO) and excessive production of angiotensin II leads to an increase in blood pressure. Obesity or an increase in body mass index (BMI) is currently considered as a risk factor not only for cardiovascular diseases and diabetes but also for CKD. Hyperuricemia and CKD are closely related, as the accumulation of uric acid is associated with hypertension, metabolic syndrome and microalbuminuria, which are also risk factors for the progression of CKD. AH has a detrimental effect on target organs, including the kidneys, eyes, and heart. Lifestyle modifications, weight control, healthy eating, reduced sodium intake, maintenance exercises and basic drug therapy using angiotensin-converting enzyme inhibitors (ACE inhibitors), angiotensin receptor blockers can slow the progression of CKD in children.

Widening the lens to childhood: relevance and lifetime risk of kidney failure.

Lifetime risk of outcomes is emerging as a highly relevant health indicator, even in the context of low absolute risk of disease progression in short time frames. Evidence to support this concept for kidney failure is increasing, with growing emphasis on the long-term impact of risk factors occurring early in life. Proteinuria and stage of chronic kidney disease (CKD) are now established predictors of CKD progression in children, and youth with type 2 diabetes are emerging as a group at significant risk. Recent population-based studies have also examined the lifetime risk of end-stage renal disease in individuals with any childhood CKD. A recent study found that even in the absence of biomarkers of renal injury, childhood CKD can increase the lifetime risk of end-stage renal disease four-fold, and up to 10-fold in adults less than 40 years of age. Children with CKD are at high lifetime risk of kidney failure and require follow-up. Identifying children at highest lifetime risk through the use of biomarkers and risk equations, and determining the optimal duration and intensity of follow-up requires further research.