Chronic Renal Insufficiency In Children Research Articles

Pediatric febrile urinary tract infections: the current state of play

Studies undertaken in recent years have improved our understanding regarding the consequences and management of febrile urinary tract infections (UTIs), which are amongst the most common serious bacterial infections in childhood, with renal scarring a frequent outcome.In the past pyelonephritic scarring of the kidney, often associated with vesico-ureteral reflux (reflux nephropathy) was considered a frequent cause of chronic renal insufficiency in children. Increasing recognition as a consequence of improved antenatal ultrasound, that the majority of these children had congenital renal hypo-dysplasia, has resulted in a number of studies examining treatment strategies and outcomes following UTI.In recent years there is a developing consensus regarding the need for a less aggressive therapeutic approach with oral as opposed to intravenous antibiotics, and less invasive investigations, cystourethrography in particular, following an uncomplicated first febrile UTI. There does remain a concern that with this newer approach we may be missing a small subgroup of children more prone to develop severe kidney damage as a consequence of pyelonephritis, and in whom some form of intervention may prove beneficial. These concerns have meant that development of a universally accepted diagnostic protocol remains elusive.

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ABSTRACT. Hypertension frequently complicates the course of chronic renal insufficiency (CRI) in children. This study sought to define the role of hypertension in progression of CRI in children by using the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) CRI database. The study cohort consisted of 3834 patients aged 2 to 17 yr with an estimated GFR (eGFR) ≤75 ml/min·1.73 m² enrolled onto NAPRTCS. The time to end point was defined as the time between registry enrollment and progression to renal substitution therapy or a 10 ml/min·1.73 m² drop in GFR from baseline, whichever was first. Forty-eight percent of the study patients had hypertension at baseline. There was a significant difference in reaching end points between hypertensive and normotensive children (58% <i>versus</i> 49%, respectively, <i>P</i> &lt; 0.001). Significant difference in outcome between hypertensive and nonhypertensive patients was seen in children with eGFR 50 to 75 ml/min·1.73 m² (<i>P</i> &lt; 0.001). Multivariate Cox regression modeling demonstrated that systolic hypertension was a significant independent predictor of progression of CRI (<i>P</i> = 0.003). Other significant predictors of CRI progression in this model included older age (<i>P</i> = 0.0001), African American ethnicity (<i>P</i> = 0.03), acquired cause of renal disease (<i>P</i> = 0.0001), and baseline eGFR &lt;50 ml/min·1.73 m² (<i>P</i> = 0.0001). Hypertension is a highly significant and independent predictor for progression of CRI in children. E-mail: Mark.Mitsnefes@cchmc.org

Leukocytes Induce Epithelial to Mesenchymal Transition after Unilateral Ureteral Obstruction in Neonatal Mice

Urinary tract obstruction during renal development leads to tubular apoptosis, tubular atrophy, and interstitial fibrosis. Epithelial to mesenchymal transition (EMT) has been proposed as a key mechanism of myofibroblast accumulation in renal fibrosis. We studied the interplay of leukocyte infiltration, tubular apoptosis, and EMT in renal fibrosis induced by unilateral ureteral obstruction (UUO) in neonatal mice. We show that leukocytes mediate tubular apoptosis and EMT in the developing kidney with obstructive nephropathy. Blocking leukocyte recruitment by using the chemokine receptor-1 antagonist BX471 protected against tubular apoptosis and interstitial fibrosis, as evidenced by reduced monocyte influx, a decrease in EMT, and attenuated collagen deposition. EMT was rapidly induced within 24 hours after UUO along with up-regulation of the transcription factors Snail1 and Snail2/Slug, preceding the induction of alpha-smooth muscle actin and vimentin. In the presence of BX471, the expression of chemokines, as well as of Snail1 and Snail2/Slug, in the obstructed kidney was completely attenuated. This was associated with reduced macrophage and T-cell infiltration, tubular apoptosis, and interstitial fibrosis in the developing kidney. Our findings provide evidence that leukocytes induce EMT and renal fibrosis after UUO and suggest that chemokine receptor-1 antagonism may prove beneficial in obstructive nephropathy.

Reduced Systolic Myocardial Function in Children with Chronic Renal Insufficiency

Increased left ventricular (LV) mass in children with chronic renal insufficiency (CRI) might be adaptive to sustain myocardial performance in the presence of increased loading conditions. It was hypothesized that in children with CRI, LV systolic function is impaired despite increased LV mass (LVM). Standard echocardiograms were obtained in 130 predialysis children who were aged 3 to 18 yr (59% boys) and had stages II through IV chronic kidney disease and in 130 healthy children of similar age, gender distribution, and body build. Systolic function was assessed by measurement of fractional shortening at the endocardial (eS) and midwall (mS) levels and computation of end-systolic stress (myocardial afterload). The patients with CRI exhibited a 6% lower eS (33.1 +/- 5.5 versus 35.3 +/- 6.1%; P < 0.05) and 10% lower mS (17.8 +/- 3.1 versus 19.7 +/- 2.7%; P < 0.001) than control subjects in the presence of significantly elevated BP, increased LVM, and more concentric LV geometry. Whereas the decreased eS was explained entirely by augmented end-systolic stress, mS remained reduced after correction for myocardial afterload. The prevalence of subclinical systolic dysfunction as defined by impaired mS was more than five-fold higher in patients with CRI compared with control subjects (24.6 versus 4.5%; P < 0.001). Systolic dysfunction was most common (48%) in patients with concentric hypertrophy and associated with lower hemoglobin levels. CRI in children is associated with impaired intrinsic LV contractility, which parallels increased LVM.

Tu-P9:342 Endothelial dysfunction precedes arterial wall stiffening in chronic renal insufficiency in children

Tu-P9:342 Endothelial dysfunction precedes arterial wall stiffening in chronic renal insufficiency in children

Left Ventricular Geometry in Children with Mild to Moderate Chronic Renal Insufficiency

Left ventricular hypertrophy (LVH) is the most important independent marker of cardiovascular risk in adults with chronic kidney disease. Cardiovascular morbidity seems increased even in children with chronic renal insufficiency (CRI), but the age and stage of CRI when cardiac alterations become manifest are unknown. For assessing the prevalence and factors associated with abnormal LV geometry in children with CRI, echocardiograms, ambulatory BP monitoring, and biochemical profiles were obtained in 156 children aged 3 to 18 yr with stages 2 through 4 chronic kidney disease (GFR 49 +/- 19 ml/min per 1.73 m2) and compared with echocardiograms obtained in 133 healthy children of comparable age and gender. LV mass was indexed to height2.7. Concentric LV remodeling was observed in 10.2%, concentric LVH in 12.1%, and eccentric LVH in 21% of patients. LVH was more common in boys (43.3 versus 19.4%; P < 0.005). Probability of LVH independently increased with male gender (odds ratio [OR] 2.62; P < 0.05) and standardized body mass index (OR 1.56; P = 0.01). Low hemoglobin, low GFR, young age, and high body mass index were independent correlates of LV mass index (0.005 < P < 0.05). LV concentricity (relative wall thickness) was positively associated with serum albumin (P < 0.05). Probability of abnormal LV geometry increased with C-reactive protein >10 mg/dl (OR 26; P < 0.001). In conclusion, substantial cardiac remodeling of both concentric and eccentric type is present at young age and early stages of CRI in children. Prevalence of LVH is related to male gender, anemia, and ponderosity but not to BP. Additional effects of volume status and inflammation on cardiac geometry are also evident.

Cardiovascular Disease in Children with Chronic Kidney Disease

In children with end-stage renal disease (ESRD), cardiovascular disease (CVD) mortality has not changed for the past 3 decades. Cardiac disease remains the second most common cause of death. Recent data demonstrate a high incidence and prevalence of traditional and chronic kidney disease (CKD)-related CVD risk factors in children. Early markers of cardiomyopathy, such as left ventricular hypertrophy (LVH) and left ventricular dysfunction (LV dysfunction), and early markers of atherosclerosis, such as increased carotid artery intima-media thickness (IMT) and carotid arterial wall stiffness, are frequently found in this patient population. Early identification of modifiable risk factors and treatment of asymptomatic CVD might lead to decrease of cardiovascular morbidity and mortality in young adults who developed CKD during childhood.

Referral to the pediatric dialysis unit – The earlier the better?

Whereas recent research has demonstrated clear evidence for beneficial effects of early referral to the nephrologist in chronic renal insufficiency in adults, no such data exist for the pediatric population. In this study, we therefore correlated patient age and residual renal function at first presentation to a specialized pediatric nephrologist with the extent of secondary uremic complications and the further course of renal function. From March 2003 until March 2004, 43 children (34 boys, aged 10.1 +/- 6.3 yrs) with congenital-urologic (n = 26), congenital-nephrologic (n = 13) or acquired (n = 4) renal diseases had been followed for 3.9 yrs (14 days to 17.5 yrs) at the Kinderdialyse Wien, with a residual renal function of 35 +/- 20.5 ml/min/1.73 m(2) at first presentation. With regards to uremic secondary complications, the majority of children exhibited involvement of at least two systems at first presentation. Thereafter, children with congenital diseases who were referred to the specialized pediatric nephrology unit within the first year of live demonstrated a significantly better course of residual renal function (1.8% vs -0.7%, p = 0.034) than children who were referred later. These data confirm recent registry reports on chronic renal insufficiency in children. Only about a third of the children of our population were presented to a specialized pediatric nephrology center within their first year of life (despite a congenital disease in 90% of them). Thus, therapeutic interventions might be currently offered at a delayed time point in the majority of children.

Hypertension and progression of chronic renal insufficiency in children: a report of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS).

Hypertension frequently complicates the course of chronic renal insufficiency (CRI) in children. This study sought to define the role of hypertension in progression of CRI in children by using the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) CRI database. The study cohort consisted of 3834 patients aged 2 to 17 yr with an estimated GFR (eGFR) </=75 ml/min.1.73 m2 enrolled onto NAPRTCS. The time to end point was defined as the time between registry enrollment and progression to renal substitution therapy or a 10 ml/min.1.73 m2 drop in GFR from baseline, whichever was first. Forty-eight percent of the study patients had hypertension at baseline. There was a significant difference in reaching end points between hypertensive and normotensive children (58% versus 49%, respectively, P < 0.001). Significant difference in outcome between hypertensive and nonhypertensive patients was seen in children with eGFR 50 to 75 ml/min.1.73 m2 (P < 0.001). Multivariate Cox regression modeling demonstrated that systolic hypertension was a significant independent predictor of progression of CRI (P = 0.003). Other significant predictors of CRI progression in this model included older age (P = 0.0001), African American ethnicity (P = 0.03), acquired cause of renal disease (P = 0.0001), and baseline eGFR <50 ml/min.1.73 m2 (P = 0.0001). Hypertension is a highly significant and independent predictor for progression of CRI in children.

Chronic renal insufficiency in children: the 2001 Annual Report of the NAPRTCS.

End-stage renal disease (ESRD) is a major cause of morbidity in children. Besides its high cost to society, ESRD carries significant mortality. Chronic renal insufficiency (CRI) often precedes ESRD. Identifying factors that correlate with the rate of progression to ESRD is beneficial in the management of children with CRI. Since 1994 the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) has extended its registry to include children with CRI, defined as creatinine clearance ( C(Cr)) <75 ml/min per 1.73 m(2). As of January 2001, our database registered 4,666 children (<20 years of age) with CRI. Data analysis showed that at least 40% of patients entered had congenital urological anomalies; 39% of patients were followed for at least 3 years. Follow-up data showed that 31% of all registered patients progressed to ESRD by the end of the reporting period. There was a correlation between CRI and several co-morbid clinical factors: low hematocrit, hypoalbuminemia, hypocalcemia, hyperphosphatemia, and hyperparathyroidism, and the rate of progression to ESRD. Primary clinical diagnosis and the age at entry into registry were additional factors that correlated with the rate of progression to ESRD. The main cause of hospitalization in this registry was infection, which accounted for 45% of hospital admissions. Growth delay measured by standard deviation score at baseline was -1.40 at the time of registration. Our data suggest potential areas of improved care that could impact the onset of ESRD.

Prognostic factors in prenatally-detected posterior urethral valves: a multivariate analysis.

To identify prognostic factors associated with chronic renal insufficiency in children with posterior urethral valves (PUV), 22 children with PUV were submitted to a systematic protocol and prospectively followed. Prognostic factors associated with fetal echography and clinical and laboratory findings were studied on admission. Median follow-up was 76 months. The analysis was conducted in two steps: in univariate analysis, variables associated with adverse outcome were identified by the Kaplan-Meier method. The variables that were significantly associated with adverse outcome were then included in a multivariate analysis using the Cox model. Eleven patients (50%) developed chronic renal failure (CRF) during follow-up. After adjustment by the multivariate model, four factors were identified as independent predictors of adverse outcome: oligohydramnios (relative risk [RR] = 10.6, 95% CI = 2.7 - 77, P = 0.02), ventilatory support (RR = 6, 95% CI = 2 - 24, P = 0.01), urea higher than 40 mg/dl (RR = 3.7, 95% CI = 0.92 - 15.0, P = 0.06), and bilateral vesicoureteral reflux (VUR) (RR = 6.1, 95% CI = 1.25 - 30, P = 0.02). On the other hand, the presence of unilateral VUR was a protective factor against the development of CRF or death during follow-up (RR = 0.92, 95% CI = 0.87 - 0.98, P = 0.05).

EXTRAPERITONEAL ACCESS FOR KIDNEY TRANSPLANTATION IN CHILDREN WEIGHING 20 KG. OR LESS

We present our experience with kidney transplantation in children weighing 20 kg. or less. Surgery was done via extraperitoneal access while preserving the peritoneal cavity intact with special attention given to technical feasibility and the complication rate. Included in our study were 46 children with a median age of 7 years weighing 20 kg. or less (mean 16.6), of whom 16 weighed less than 15 kg. (median 13.2). The 25 boys and 21 girls underwent a total of 49 kidney transplants, including 2 in 3 during the study. Donors were living related in 44 cases and cadaveric in 5. Surgical access was obtained by making a J-shaped pararectal incision in a curvilinear fashion from the symphysis pubis to near the costal border. Mean hospital stay was 22.9 days (range 6 to 83) and mean followup was 55.8 months (range 12 to 131). All patients received water on day 1 and food on day 2 postoperatively. In 6 patients 7 surgical complications developed, including urinary fistula in 2, superficial wound infection in 2 and vascular complications in 3 (renal vein thrombosis, stenosis and renal artery kinking in 1 each). Only 1 graft was lost due to a surgical complication. There are many advantages to using extraperitoneal access without an increase in surgical complications or technical difficulty. Absent gastrointestinal complications, an easier way to perform percutaneous biopsy, treatment of any surgical complication with no need for repeat laparotomy and the possibility of using the peritoneal cavity when dialysis is needed postoperatively are attractive justifications for extraperitoneal access.

Chronic renal insufficiency in children and adolescents: the 1996 annual report of NAPRTCS. North American Pediatric Renal Transplant Cooperative Study.

The 1996 annual report of the Chronic Renal Insufficiency Arm of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) summarizes descriptive data and highlights important features on 1,725 patients from 130 centers. This database contains information on patients with an estimated glomerular filtration rate (GFR) < or = 75 ml/min per 1.73 m2 as calculated by the Schwartz formula, who were treated on or after 1 January 1994. Thus this report reflects 2 years of data entry. Analysis of the data revealed that nearly two-thirds of patients registered had a structural anomaly. On average, patients were 1.5 standard deviations below age- and sex-specific norms for height, and 0.6 standard deviations below weight norms. Mean serum creatinine for the entire group was 2.4 mg/dl and 68% of patients had a baseline GFR of at least 25 ml/min per 1.73 m2. The mean hematocrit for all children at registration was 33.3 +/- 6.3%, and did not vary among age groups. Overall, 30.9% of patients had a hematocrit < 30%. Only 12.8% of patients were receiving Epoetin therapy. Although still in infancy, the Chronic Renal Insufficiency Arm of the NAPRTCS database in providing important insights into this disorder.

Évaluation critique du traitement par l'hormone de croissance chez l'enfant atteint d'insuffisance rénale chronique

Growth failure remains a major complication of chronic renal insufficiency in children, which greatly affects their quality of life. Based upon the data published in the literature it appears that growth hormone therapy improves growth in these children, with little secondary effects. However, some uncertainties persist concerning the safety and efficacy of this therapy, so that careful evaluations must continue.

Renal transplantation, chronic dialysis, and chronic renal insufficiency in children and adolescents. The 1995 Annual Report of the North American Pediatric Renal Transplant Cooperative Study.

The 1995 Annual Report of the North American Pediatric Renal Transplant Cooperative Study summarizes data voluntarily collected from 123 centers on 5,197 children and adolescents grouped into three cohorts: (1) patients who received renal transplants on or after 1 January 1987 (n = 3,066), (2) patients who were maintained on peritoneal dialysis (PD) or hemodialysis (HD) on or after 1 January 1992 (n = 1,488), and (3) patients treated for chronic renal insufficiency (CRI) on or after 1 January 1994 (n = 643). The transplant and dialysis information update previous registry data whereas the CRI information reflects 1st-year registry data. Three-year graft survival rates were 83% and 66% for living donor grafts and cadaver donor (CD) grafts, respectively. Triple drug maintenance therapy with prednisone, cyclosporine, and azathioprine was used by > 70% of all transplant recipients through 5 years of follow-up. The 2-year CD survival has steadily improved from 65% in 1987 to 82% in 1992. Fifty malignancies have been reported, the majority of which are lymphoproliferative disorders. The 2-year patient survival posttransplantation is 95%. Mortality rates for the youngest patients have drastically improved over the past 2 years. Approximately two-thirds of patients in the dialysis cohort are maintained on PD; automated PD remains the preferred modality. Overall, the peritonitis rate is one infection every 13.3 patient months, the frequency of infection being greatest in the youngest patients. Whereas the primary reason for dialysis modality termination is transplantation approximately 40% of the entire dialysis cohort (PD at HD) were not considered active transplant candidate Baseline CRI data revealed the most common primary diagnoses to be obstructive uropathy (24%) and aplastic/hypoplastic/dysplastic kidneys (19%). The standardized height deficit in the CRI cohort was greatest in the younger patients and those with the most impaired renal function.

Long-term treatment of growth retarded children with chronic renal insufficiency, with recombinant human growth hormone

Long-term (5 years) treatment of 20 growth-retarded pre-pubertal children with chronic renal insufficiency (CRI) led to a significant (P < 0.00005) improvement in standardized height from -2.6 at baseline to -0.7 at five years. Eight patients were paused after reaching target height (50th centile midparental height) and 4 (50%) required re-initiation of recombinant human growth hormone (rhGH) because of a substantial decrease in standardized height. Growth potential was not adversely impacted with a delta height age (HA) minus delta bone age (BA) at five years of +0.5 (N = 8). The mean calculated CCr decreased from 32.2 +/- 15.2 ml/min/1.73 m2 at baseline to 24.6 +/- 14.7 ml/min/1.73 m2 at five years (P = 0.04), which would be consistent with the natural history of CRI in children. Despite the absence of clinical consequences, the increase in the mean fasting and two-hour post-prandial plasma insulin levels during treatment compared to baseline requires further investigation. The only clinically significant adverse event potentially related to rhGH was the development of avascular necrosis of the femoral head during the fourth year of treatment in one patient. Long-term rhGH treatment in children with CRI improves the potential of children with CRI achieving target adult height.

Left Atrial Atheromatosis in Childhood Nephrotic Syndrome

Three male children who had onset, at approximately age 2 years, of nephrotic syndrome, which progressed to renal insufficiency had left atrial atheromatosis at autopsy disproportionate to the degree of aortic or vascular atheromatosis found. The atrial atheromatous process was distributed in elongated nodules, which had a ridged or corduroy-like appearance on gross examination. Two of the patients showed renal lesions of advanced focal glomerulosclerosis, but one had membranoproliferative glomerulopathy, suggesting that the "syndrome" of early onset nephrotic syndrome progressing to renal insufficiency, hyperlipidemia, and exaggerated left atrial atheromatosis, of which association we have not found a specific report, is etiologically heterogeneous. The patients reported died in 1943, 1952, and 1963. Whether more recent methods of treatment of nephrotic syndrome, hyperlipidemia, or chronic renal insufficiency in children have altered the incidence of such disproportionate left atrial atheromatosis is not known.

Dosage schedule of gentamicin for chronic renal insufficiency in children.

Gentamicin was given to paediatric patients with chronic renal disease complicated by infections by Gram-negative organisms, in which renal function varied from normal to severely insufficient. Peak serum levels after an intramuscular dose of 1 mg/kg body weight ranged from 3.1 to 9.4 microgram/ml, which appeared adequate for therapy. The peak value was not related to the renal function of the individual patients. The serum half-life of gentamicin correlated inversely with the value for endogenous creatinine clearance. A diagram for the estimation of the serum half-life of gentamicin using the creatinine clearance value is presented. As a practical guide, it is recommended that the dose of gentamicin in children with renal function impairment be 1 mg/kg given intramuscularly and that the interval between doses be almost three times as long as the serum half-life, which can be estimated by means of the diagram for individual patients. The accuracy and safety of this method were confirmed by treating children with this adjusted dosage schedule.