Hypertension in children with congenital anomalies of the kidney and urinary tract.

BACKGROUND: Congenital anomalies of the kidney and urinary tract (CAKUT) are the most common cause of childhood chronic kidney disease (CKD). We hypothesized that hypertension varies across CAKUT categories and increases the risk of CKD. METHODS: This was a retrospective cohort study and included cases with a multicystic dysplastic kidney (MCDK, n = 81), unilateral kidney agenesis (UKA, n = 47), kidney hypoplasia (KH, n = 130), and posterior urethral valves (PUV, n = 75). Hypertension was defined as systolic or diastolic blood pressure ≥ 95th percentile for age, sex and height, and CKD as an estimated glomerular filtration rate < 60 ml/min/1.73 m2, both at 2 consecutive clinic visits at least 3 months apart. RESULTS: Sixty-two (19%) out of 333 cases developed hypertension, with significant difference according to CAKUT type. Patients with smaller kidney size (7.7 vs. 8.3, p = 0.045), kidney anomalies in addition to the primary diagnosis (aCAKUT) (53 vs. 38%, p = 0.03), proteinuria (46 vs. 12%, p < 0.001), and CKD (51 vs. 23%, p < 0.001) were more likely to develop hypertension. When adjusted for kidney size, the diagnoses of PUV (OR 10.9, 95%CI 3.0, 40.5), UKA (OR 6.4, 95%CI 1.6, 24.9) and KH (OR 4.2, 95%CI 1.1, 16.1), and aCAKUT (OR 2.1, 95%CI 1.2, 3.9) were independent risk factors for hypertension. Hypertension increased the risk of developing CKD by twofold (HR 1.9, 95%CI 1.19, 2.94). CONCLUSION: Hypertension is common in children with CAKUT and increases the risk of CKD. These findings will aid in the development of a standardized clinical pathway for the care of hypertensive children with CAKUT.

Congenital anomalies of the kidney and urinary tract: defining risk factors of disease progression and determinants of outcomes.

Congenital anomalies of the kidney and urinary tract (CAKUT) result from disruptions in normal kidney and urinary tract development during fetal life and collectively represent the most common cause of kidney failure in children worldwide. The antenatal determinants of CAKUT are diverse and include mutations in genes responsible for normal nephrogenesis, alterations in maternal and fetal environments, and obstruction within the normal developing urinary tract. The resultant clinical phenotypes are complex and depend on the timing of the insult, the penetrance of underlying gene mutations, and the severity and timing of obstruction related to the sequence of normal kidney development. Consequently, there is a broad spectrum of outcomes for children born with CAKUT. In this review, we explore the most common forms of CAKUT and those most likely to develop long-term complications of their associated kidney malformations. We discuss the relevant outcomes for the different forms of CAKUT and what is known about clinical characteristics across the CAKUT spectrum that are risk factors of long-term kidney injury and disease progression.

Predicting outcomes in children with congenital anomalies of the kidney and urinary tract.

BACKGROUND: Congenital anomalies of the kidney and urinary tract (CAKUT) are the most frequent causes of childhood chronic kidney disease (CKD). Using a large CAKUT cohort, we sought to identify the predictors of CKD and to develop a prediction model that informs a risk-stratified clinical pathway. METHODS: This was a retrospective cohort study including cases with multicystic dysplastic kidneys (MCDK), unilateral kidney agenesis (UKA), kidney hypoplasia (KH), and posterior urethral valves (PUV). We identified risk factors for CKD (estimated glomerular filtration rate [eGFR] <60 ml/min/1.73 m2) and tested their performance in an adjusted multivariate binary regression model. Prediction probability scores for CKD were used to separate cases likely to develop complications from those not needing specialist follow-up. RESULTS: We identified 452 eligible cases of CAKUT with 22% developing CKD. Strongest associations with CKD included primary diagnosis (OR 3.5, 95% CI 2.6-4.6), preterm delivery (OR 2.3, 95% CI 1.2-4.4), non-kidney anomalies (OR 1.8, 95% CI 1.1-3), first eGFR<90 (OR 8.9, 95% CI 4.4-18.1), small kidney size (OR 9, 95% CI 4.9-16.6), and additional kidney anomalies (OR 1.6, 95% CI 1.2-2.8). PUV (OR 4.7, 95% CI 1.5-15.3), first eGFR <90 (OR 4.4, 95% CI 2-9.7), and kidney length to body length ratio <7.9 (OR 4.2, 95% CI 1.9-9.2) were independent predictors of CKD. The regression model had a prediction accuracy of 80% and a prediction probability c-statistic of 0.81. CONCLUSION: Using a large combined CAKUT cohort we identified risk factors for CKD. Our prediction model provides the first steps towards a risk-stratified clinical pathway. A higher resolution version of the Graphical abstract is available as Supplementary information.

Risk factors associated with short- and long-term kidney injury in children with post infectious glomerulonephritis.

BACKGROUND: Post infectious glomerulonephritis (PIGN) is the most common form of acute glomerulonephritis in children. The objective of this study was to evaluate the risk factors for kidney injury in children with PIGN referred to a tertiary care center. METHODS: This was a retrospective cohort study. The primary outcome was acute kidney injury (AKI) at initial presentation; secondary outcome was composite kidney injury, defined as reduced estimated glomerular filtration rate (eGFR), proteinuria, or hypertension at last follow-up. Binary logistic regression defined risk factors associated with the primary and secondary outcomes. RESULTS: We identified 125 PIGN cases with a mean age of 8.3±3.5 years at presentation and 252 ± 501 days of follow-up. Sixty-six percent (79/119) presented with AKI and 57% (71/125) were admitted to hospital. Shorter time to seeing a nephrologist (OR 6.7, 95%CI 1.8-24.6), nadir C3 < 0.12 g/L (OR 10.2, 95%CI 1.9-53.7), starting an antihypertensive medication (OR 7.6, 95%CI 1.8-31.3), and nephrotic range proteinuria (OR 3.8, 95%CI 1.2-12.4) were independent risk factors for AKI when adjusted for each other. At last follow-up 35% (44/125) of the cohort had the composite outcome, with older age at presentation (OR 1.2, 95%CI 1.04-1.4) and nadir C3 < 0.17 g/L (OR 2.6, 95%CI 1.04-6.7) being independent risk factors when adjusted for AKI. CONCLUSION: PIGN is an important cause of AKI in children and adolescents. The severity of initial illness is associated with the extent of kidney injury in both the short- and longer-term. Findings will help identify cases requiring lengthier surveillance. A higher resolution version of the Graphical abstract is available as Supplementary information.

Kidney length standardized to body length predicts outcome in infants with a solitary functioning kidney.

BACKGROUND: Infants with a solitary functioning kidney (SFK) are at risk for chronic kidney injury (CKI). Lack of compensatory kidney growth (CKG) is associated with CKI, but measuring CKG is challenging since it is typically reported relative to normal kidneys. This study aims to (1) standardize SFK growth in infants, (2) investigate the relationship between standardized kidney length and clinical outcomes, and (3) use these results to develop a risk-based prediction model and local clinical pathway for SFK care. METHODS: This was a quality improvement study of 166 infants with an SFK. Linear regression was used to assess kidney growth from 0 to 180 days of life. Univariate binary regression analysis was used to identify kidney length to body length thresholds associated with the development of CKI, defined as the composite outcome of chronic kidney disease (eGFR < 60 mL/min/1.73 m2), hypertension, or proteinuria. RESULTS: Kidneys grew in length from 0 to 180 days, and growth was constant when standardized to body length. Over follow-up, infants with a baseline kidney length to body length ≤ 0.088 were more likely to experience CKI than the rest of the cohort (27 vs. 8%, p = 0.04). Kidney length to body length ≤ 0.088 was also significantly associated with CKI development (OR 4.17, 95% CI 1.14-15.28, p = 0.04). CONCLUSIONS: In this study, kidney length to body length ratio was a stable CKG metric over 0-180 days, and a baseline ratio ≤ 0.088 was a risk factor for CKI. Results will aid in developing a practical, point-of-care risk assessment tool, and overarching risk-stratified clinical pathway for infants with an SFK. A higher resolution version of the Graphical abstract is available as Supplementary information.

Fluid overload and acute kidney injury in children with tumor lysis syndrome.

AIM: Tumor lysis syndrome (TLS) is a common oncologic emergency among patients with pediatric hematologic malignancies. The mainstay of TLS management is aggressive intravenous hydration. However, the epidemiology of fluid overload (FO) and acute kidney injury (AKI) in this population is understudied. In this study, we aimed to describe the incidence, severity, and complications of FO and AKI among pediatric patients with TLS. METHODS: We completed a single-center retrospective cohort study of pediatric patients with a new diagnosis of hematologic malignancy over a 10-year period. Patients with TLS were analyzed in two groups based on the severity of AKI and FO. Charts were reviewed for complications associated with AKI and FO including hypoxemia, mechanical ventilation, hyponatremia, pulmonary edema, pediatric intensive care (PICU) admission, and need for renal replacement therapy (RRT). RESULTS: We analyzed 56 patients with TLS for FO and AKI. We found severe FO (≥10%) occurred in 35.7% (n = 20). PICU admission occurred in 35% of patients with severe FO compared to 8.3% in those with mild/moderate FO <10% (p = .013). Complications of hypoxemia (30% vs. 5.6%, p = .012) and pulmonary edema (25% vs. 2.8%, p = .010) were more common among those with severe FO. AKI occurred in 37.5% (n = 21) patients and resulted in a significant increase in PICU admission and requirement for RRT (p = .001 and <.001, respectively). CONCLUSION: Our results show FO and AKI are common, and often unrecognized complications of TLS associated with increased morbidity. Prospective, multicenter studies are needed to further dissect the burden of FO and AKI within this vulnerable population.

Dietary intakes of children with nephrotic syndrome.

BACKGROUND: Our multidisciplinary clinical pathway for treatment of childhood nephrotic syndrome (NS) was established with the goal of standardizing local clinical practice. This descriptive study aimed to assess nutrient intakes of children with newly diagnosed NS compared with nutrition goals defined by our pathway. METHODS: Our pathway includes evidence-based recommendations that target daily intakes during corticosteroid induction therapy: energy (Estimated Energy Requirements (EER) × Sedentary Physical Activity (PA)), sodium (1 mg/kcal), calcium (Dietary Reference Intake (DRI) + 500 mg elemental calcium), and vitamin D (DRI +800-1000 IU). After dietitian-led education at initial diagnosis, 3-day food records were completed at 4 weeks post-diagnosis. Daily nutrient intakes were compared to pathway targets and DRIs. RESULTS: Thirty-six children (median age 4.8 years, 44% female) with newly diagnosed NS submitted food records. Mean energy and sodium intakes were 103±22% and 99±53% of pathway targets, respectively. Fourteen (39%) children exceeded pathway sodium recommendations, with four (11%) exceeding them by greater than 50%. Seven (19%) children met DRI for calcium, while six (17 %) met pathway targets for calcium. No children met DRI for vitamin D from diet alone; and only one met the target with supplementation. CONCLUSIONS: This is the first study to describe dietary intakes of children with newly diagnosed NS. Our clinical pathway targets for energy and sodium were achievable; however, calcium and vitamin D intakes fell short of pathway guidelines and DRIs. Prescription of supplemental calcium and vitamin D may be needed to achieve target intakes of calcium and vitamin D.

Outcomes of solitary functioning kidneys-renal agenesis is different than multicystic dysplastic kidney disease.

BACKGROUND: Multicystic dysplastic kidney (MCDK) disease and unilateral renal agenesis (URA) are well-known causes of a solitary functioning kidney (SFK) and are associated with long-term kidney injury. The aims of this study were to characterize the natural history of SFK at our center, define the risk factors associated with chronic kidney injury, and identify distinguishing features between URA and MCDK that predict outcome. METHODS: This was a retrospective cohort study of 230 SFK patients. We compared MCDK (n=160) and URA (n=70) according to clinical features at diagnosis and kidney outcomes over follow-up. Univariate and multivariate binary regression analysis was used to determine independent risk factors for chronic kidney injury, defined as the composite outcome of hypertension, proteinuria, or chronic kidney disease (eGFR <60 mL/min/1.73m2). RESULTS: URA had a higher prevalence of comorbid genetic syndromes (15 vs. 6%, p=0.04), non-renal anomalies (39 vs. 11%, p<0.001), and congenital anomalies of the kidney and urinary tract (CAKUT) (51 vs. 26%, p<0.001) than MCDK. Over follow-up, URA experienced more hypertension (19 vs. 3%, p=0.002), proteinuria (12 vs. 3%, p=0.03), and the composite outcome (19 vs. 6%, p=0.003) than MCDK. Independent risk factors for chronic kidney injury included CAKUT (OR 5.01, p=0.002) and URA (OR 2.71, p=0.04). CONCLUSIONS: In our population, URA was more likely to have associated syndromes or anomalies, and to have worse outcomes over time than MCDK. URA diagnosis was an independent risk factor for chronic kidney injury. Our results will be used to develop a standardized clinical pathway for SFK management. A higher resolution version of the Graphical abstract is available as Supplementary information.

Henoch-Schönlein purpura in children: Use of corticosteroids for prevention and treatment of renal disease.

QUESTION: A few patients have previously presented to my clinic with palpable purpura, joint inflammation, and severe abdominal pain characteristic of Henoch-Schönlein purpura (HSP). Considering that renal injury is the primary long-term complication of HSP, are corticosteroids effective in preventing or treating renal disease in children with HSP? ANSWER: Henoch-Schönlein purpura is self-limiting in 94% of children, but permanent renal injury is reported in one-fifth of children with nephritic or nephrotic features. Corticosteroids have been considered as candidates for preventing and treating renal involvement in HSP. There is a moderate level of evidence to suggest corticosteroids are not effective in preventing renal involvement in HSP. However, based on low-level evidence and similarities with primary immunoglobulin A nephropathy, experts recommend corticosteroids in treating renal involvement in HSP to prevent long-term kidney injury. Dose and duration of therapy should be carefully considered in consultation with a pediatric nephrologist.

Induction prednisone dosing for childhood nephrotic syndrome: how low should we go?

BACKGROUND: Historically, children with nephrotic syndrome (NS) across British Columbia (BC), Canada have been cared for without formal standardization of induction prednisone dosing. We hypothesized that local historical practice variation in induction dosing was wide and that children treated with lower doses had worse relapsing outcomes. METHODS: This retrospective cohort study included 92 NS patients from BC Children's Hospital (1990-2010). We excluded secondary causes of NS, age < 1 year at diagnosis, steroid resistance, and incomplete induction due to early relapse. We explored cumulative induction dose and defined dosing quartiles. Relapsing outcomes above and below each quartile threshold were compared including total relapses in 2 years, time to first relapse, and proportions developing frequently relapsing NS (FRNS) or starting a steroid-sparing agent (SSA). RESULTS: Cumulative prednisone was widely distributed with approximated median, 1st, and 3rd quartile doses of 2500, 2000, and 3000 mg/m2 respectively. Doses ≤ 2000 mg/m2 showed significantly higher relapses (4.2 vs 2.7), shorter time to first relapse (61 vs 175 days), and higher SSA use (36 vs 14%) compared to higher doses. Doses ≤ 2500 mg/m2 also showed significantly more relapses (3.9 vs 2.2), quicker first relapse (79 vs 208 days), and higher FRNS (37 vs 17%) and SSA use (28 vs 11%). Relapsing outcomes lacked statistical difference in ≤ 3000 vs > 3000 mg/m2 doses. CONCLUSIONS: Results strongly justify our development of a standardized, province-wide NS clinical pathway to reduce practice variation and minimize under-treatment. The lowest induction prednisone dosing threshold to minimize future relapsing risks is likely between 2000 and 2500 mg/m2. Further prospective studies are warranted.

Acute kidney injury in children with sickle cell disease-compounding a chronic problem.

In an article recently published in Pediatric Nephrology, Baddam and colleagues discuss the relatively underreported clinical problem of repeated episodes of acute kidney injury (AKI) in children with sickle cell disease (SCD). Their report is a cautionary note about the importance of repeated kidney injury on the background of underlying chronic kidney injury and its potential implications on long-term kidney outcome. In children and adults with SCD, this includes the effects of repeated vaso-occlusive crises and the management of these painful episodes with non-steroidal anti-inflammatory drugs. Here we review the scope of kidney involvement in SCD in children and discuss the potential short- and long-term consequences of AKI in children with SCD.

Indications for kidney biopsy in idiopathic childhood nephrotic syndrome.

BACKGROUND: Most cases of childhood nephrotic syndrome (NS) are due to minimal change disease (MCD), while a minority of children have focal segmental glomerulosclerosis (FSGS) and an unfavorable clinical course, requiring a kidney biopsy to confirm diagnosis. We hypothesized that clinical characteristics at diagnosis and initial response to corticosteroid treatment accurately predict FSGS and can be used to guide consistent practice in the indications for kidney biopsy. METHODS: This was a case control study (1990-2012). Inclusion criteria included age 1-17 years, meeting the diagnostic criteria for NS, and having biopsy-proven FSGS or MCD. Clinical characteristics at diagnosis included age, kidney function [estimated glomerular filtration rate (eGFR)], hypertension, hematuria, nephritis (reduced eGFR, hematuria, hypertension), and response to steroids. RESULTS: From a total of 169 children who underwent kidney biopsy for NS we included 65 children with MCD and 22 with FSGS for analysis. There were no significant between-group differences in age, sex, or eGFR at the time of diagnosis. The FSGS group had a higher proportion of hypertension (40 vs. 15%; p = 0.02), hematuria (80 vs. 47%; p = 0.01), and nephritis (22 vs. 2%; p = 0.004) and was more likely to be steroid resistant after 6 weeks of treatment than the MCD group (67 vs. 19%; p < 0.001). As predictors of FSGS, hematuria had a high sensitivity of 0.80 [95% confidence interval (CI) 0.56-0.93] and low specificity of 0.53 (95% CI 0.39-0.66), nephritis had a low sensitivity of 0.22 (95% CI 0.07-0.48) and high specificity of 0.98 (95% CI 0.88-0.99), and steroid resistance had a low sensitivity of 0.67 (95% CI 0.43-0.85) and high specificity of 0.81 (95% CI 0.68-0.90). The combination of steroid resistance after 6 weeks of therapy and/or nephritis at diagnosis yielded the optimal sensitivity and specificity at 0.80 (95% CI 0.56-0.93) and 0.75 (95% CI 0.60-0.86), respectively, confirmed by the highest receiver operator characteristic area under the curve of 0.77. CONCLUSION: Steroid resistance after 6 weeks of therapy and/or nephritis at initial presentation is an accurate predictor of FSGS in children with NS and will be used as the indication for kidney biopsy in our newly developed clinical pathway. This approach will maximize the yield of diagnostic FSGS biopsies while minimizing the number of unnecessary MCD biopsies.

Antenatal Determinants of Long-Term Kidney Outcome in Boys with Posterior Urethral Valves.

BACKGROUND: Posterior urethral valves (PUV) are the most important cause of end-stage renal disease (ESRD) in young boys. The objective of this report was to define the antenatal determinants of long-term postnatal renal outcome in this condition. DESIGN: This was a retrospective cohort analysis. The primary outcome was the development of ESRD defined as starting dialysis or receiving a preemptive kidney transplant. RESULTS: Eighty-two cases of PUV were identified, with 17 (21%) developing ESRD at 6.1 ± 7.1 years. Cases developing ESRD were more likely diagnosed antenatally (41 vs. 19%, p = 0.05), had a younger gestational age (35.5 ± 3.4 weeks vs. 37.3 ± 2.1 weeks, p = 0.02), and on antenatal ultrasound scan were more likely to have oligohydramnios (60 vs. 26%, p = 0.02), renal cortical cysts (47 vs. 17%, p = 0.02), and the combination of oligohydramnios, renal cortical cysts, and increased renal echogenicity (47 vs. 9%, p = 0.002). CONCLUSIONS: In boys with PUV, decreased gestational age, oligohydramnios, renal cysts, and the combination of oligohydramnios, cortical cysts, and echogenic kidneys were associated with ESRD, while the combination was an independent predictor of poor long-term postnatal kidney function.

The impact of small kidneys.

BACKGROUND: Small kidneys due to renal hypodysplasia (RHD) result from a decrease in nephron number. The objectives of this study were to identify clinical variables that determine long-term renal outcome in children with RHD and to define the role of kidney size as a predictor of developing end-stage renal disease (ESRD). METHODS: This was a single-center retrospective cohort analysis. The primary outcome was development of ESRD. We identified 202 RHD cases, with 25 (12%) reaching ESRD at mean age of 8.9 (±6.6) years. RESULTS: Children with RHD with a known genetic syndrome had the smallest kidneys while those with posterior urethral valves (PUV) had the largest kidneys at diagnosis. Cases with bilateral RHD were most likely to develop ESRD. Younger gestational age (OR 0.8, CI 0.69-0.99, p = 0.05), smaller kidney size at diagnosis (OR 0.13, CI 0.03-0.47, p = 0.002), lower best-estimated glomerular filtration rate (eGFR) (OR 0.74, CI 0.58-0.93, p = 0.01), proteinuria (OR 1.03, CI 1.01-1.05, p < 0.001) and high blood pressure (OR 1.02, CI 1.01-1.04, p = 0.01) were associated with development of ESRD, while kidney size at diagnosis was independently associated with ESRD (HR 0.03, CI 0.01-0.72, p = 0.043). CONCLUSIONS: In children with RHD, kidney size at diagnosis predicts the likelihood of developing ESRD.

Tacrolimus therapeutic drug monitoring and pediatric renal transplant graft outcomes.

Predose monitoring of tacrolimus levels is standard practice in the care of pediatric renal transplant patients. This is despite a paucity of data investigating the ideal target range in children, and controversy as to whether tacrolimus levels correlate with renal transplant outcomes. We performed a retrospective cohort analysis of 48 renal transplant patients at a single Canadian pediatric transplant center following the initiation of a tacrolimus-mycophenolate-prednisone-based IS protocol. We analyzed the relationship of graft function, as defined by GFR up to five yr post-transplant, to the preceding mean tacrolimus level. There was no significant correlation between absolute GFR and mean tacrolimus levels (r = 0.206, p = 0.38). However, a higher mean tacrolimus level, particularly ≥10 ng/mL in the first three months after transplantation, was associated with a slower rate of decline in GFR with time (r = 0.608, p = 0.004) and with a less likelihood of developing CKD five yr after transplant. We suggest that the optimal target range for tacrolimus levels may be at the upper end of what is currently practiced and that further research to validate these findings would be useful.

The importance of clinical pathways and protocols in pediatric nephrology.

Modern clinical practice is increasingly delivered by teams of individuals working within an environment of rising complexity and daunting patient care loads. Clinical pathways, protocols and checklists offer a way to assure coordination, efficiency, quality and safety in this chaotic environment. In this review, we discuss some of the principal characteristics of these clinical tools, some of the challenges involved with introducing them into clinical practice and the evidence that they can positively affect patient and system outcomes. We believe pediatric nephrology, as a discipline, is ready for the widespread introduction of these important quality tools.

Urinary tract obstruction in the mouse: the kinetics of distal nephron injury.

Congenital urinary tract obstruction is the single most important cause of childhood chronic kidney disease. We have previously demonstrated that human and primate fetal obstruction impairs the development, differentiation, and maturation of the kidney. Research using postnatal rodent models has primarily focused upon the role of proximal tubular injury, with few reports of collecting duct system pathology or the suitability of the postnatal models for examining injury to the distal nephron. We have employed the mouse unilateral ureteric obstruction (UUO) model and examined time points ranging from 1 to 14 days of obstruction. Many of the key features of fetal collecting duct injury are replicated in the postnatal mouse model of obstruction. Obstruction causes a sixfold increase in myofibroblast accumulation, two- to threefold dilatation of tubules of the distal nephron, 65% reduction of principal cell aquaporin 2 expression, 75% reduction of collecting duct intercalated cell abundance, and disruption of E-cadherin- and ßcatenin-mediated collecting duct epithelial adhesion. Notably, these features are shared by the distal and connecting tubules. This work confirms that distal nephron pathology is a significant component of postnatal mouse UUO. We have highlighted the utility of this model for investigating collecting duct and distal tubule injury and for identifying the underlying mechanisms of the distal nephron's contribution to the repair and fibrosis.

Long-term risk of CKD in children surviving episodes of acute kidney injury in the intensive care unit: a prospective cohort study.

BACKGROUND: The development of standardized acute kidney injury (AKI) definitions has allowed for a better understanding of AKI epidemiology, but the long-term renal outcomes of AKI in the pediatric critical care setting have not been well established. This study was designed to: (1) determine the incidence of chronic kidney disease (CKD) in children 1-3 years after an episode of AKI at a tertiary-care pediatric intensive care unit (ICU), (2) identify the proportion of patients at risk of CKD, and (3) compare ICU admission characteristics in those with and without CKD. DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: Patients admitted to the British Columbia Children's Hospital pediatric ICU from 2006-2008 with AKI, as defined by AKI Network (AKIN) criteria. Surviving patients, most with short-term recovery from their AKI, were assessed at 1, 2, or 3 years after AKI. PREDICTORS: Severity of AKI as defined by AKIN and several ICU admission characteristics, including demographics, diagnosis, severity of illness, and ventilation data. OUTCOMES & MEASUREMENTS: CKD was defined as the presence of albuminuria and/or glomerular filtration rate (GFR) < 60 mL/min/1.73 m2. Being at risk of CKD was defined as having a mildly decreased GFR (60-90 mL/min/1.73 m2), hypertension, and/or hyperfiltration (GFR ≥ 150 mL/min/1.73 m2). RESULTS: The proportion of patients with AKI stages 1, 2, and 3 were 44 of 126 (35%), 47 of 126 (37%), and 35 of 126 (28%), respectively. The number of patients with CKD 1-3 years after AKI was 13 of 126 (10.3% overall; 2 of 44 [4.5%] with stage 1, 5 of 47 [10.6%] with stage 2, and 6 of 35 [17.1%] with stage 3; P = 0.2). In addition, 59 of 126 (46.8%) patients were identified as being at risk of CKD. LIMITATIONS: Several patients identified with AKI were lost to follow-up, with the potential of underestimating the incidence of CKD. CONCLUSIONS: In tertiary-care pediatric ICU patients, ∼10% develop CKD 1-3 years after AKI. The burden of CKD in this population may be higher with further follow-up because several patients were identified as being at risk of CKD. Regardless of the severity of AKI, all pediatric ICU patients should be monitored regularly for long-term kidney damage.

Congenital urinary tract obstruction: defining markers of developmental kidney injury.

Congenital urinary tract obstruction (diagnosed antenatally by ultrasound screening) is one of the main causes of end-stage kidney disease in children. The extent of kidney injury in early gestation and the resultant abnormality in kidney development determine fetal outcome and postnatal renal function. Unfortunately, the current approach to diagnostic evaluation of the severity of injury has inherently poor diagnostic and prognostic value because it is based on the assessment of fetal tubular function from fetal urine samples rather than on estimates of the dysplastic changes in the injured developing kidney. To improve the outcome in children with congenital urinary tract obstruction, new biomarkers reflecting these structural changes are needed. Genomic and proteomic techniques that have emerged in the past decade can help identify the key genes and proteins from biological fluids, including amniotic fluid, that might reflect the extent of injury to the developing kidney.