Cinacalcet as rescue therapy for refractory hyperparathyroidism in young children with advanced chronic kidney disease.

BACKGROUND: Studies in the use of the calcimimetic, cinacalcet, in pediatric chronic kidney disease (CKD) are few and limited to older children with secondary hyperparathyroidism (sHPT), a major morbid complication contributing to poor growth, bone deformities, and cardiovascular disease. Our objectives were to determine a safe and effective dosing regimen of cinacalcet in the treatment of infants and young children with sHPT that was refractory to standard care and to examine their growth during treatment. METHODS: Ten young pediatric patients with advanced CKD were studied retrospectively during 11 courses of treatment with cinacalcet. All had severe sHPT with intact parathyroid hormone (iPTH) levels ≥ 500 pg/ml and were refractory to standard therapy with phosphate binders and active vitamin D analogs at high doses for > 30 days. The cinacalcet dose was advanced by 50% every 2-4 weeks to achieve a decline in the iPTH to a goal of 150-300 pg/ml. Linear growth was assessed at 6-month intervals by change in z-scores (△SDS) for length before and during cinacalcet therapy. RESULTS: Median age at initiation of cinacalcet was 18 months (IQR 6, 36) with an average starting dose of 0.7 ± 0.2 mg/kg/day. Median effective dose required to reach iPTH goal of 150-300 pg/ml was 2.8 mg/kg/day (IQR 2.0, 3.1), and time to goal was 112 days (IQR 56, 259) with a median overall decline in iPTH of 82% from baseline by 6 months (p < 0.0001). No subject experienced a clinical adverse event, although 4 had biochemical asymptomatic hypocalcemia. Linear growth improved significantly during cinacalcet therapy (△SDS - 0.62 ± 1.2 versus + 0.91 ± 1.4; p < 0.005). By multiple regression analysis, the primary determinants of growth were concurrent treatment with growth hormone and age < 2 years (R2 = 89.6%; p < 0.001). A shorter treatment time required to achieve iPTH goals also was associated with improved growth (r = - 0.75; p < 0.01). CONCLUSIONS: Cinacalcet may be used effectively and safely in infants and small children with refractory sHPT in advanced CKD using a cautious dosing regimen. Cinacalcet successfully brings iPTH to target level and supports growth when other treatments have been ineffective.

Fibroblast growth factor-23 and renin-angiotensin system levels in vitamin-D-dependent rickets type I.

BACKGROUND: As 1,25(OH)2D3 vitamin D3 induces fibroblast growth factor-23 (FGF-23) production and suppresses the renin-angiotensin-aldosterone system (RAAS), its absence in vitamin-D-dependent rickets type I (VDDR-I) may have adverse health consequences. CASE DESCRIPTION: An infant presented at age 8 months with hypocalcemia and rickets and very low 1,25(OH)2D3 levels. Genetic analysis confirmed VDRR-I, and calcitriol therapy was initiated. During periods of nonadherence to therapy, chemical measurements revealed detectable FGF-23 levels, with undetectable 1,25(OH)2D3, hypophosphatemia, low tubular reabsorption of phosphate, hypocalcemia, and very elevated parathyroid hormone (PTH) levels. These changes, in addition to elevated RAAS levels, normalized during calcitriol therapy despite elevated FGF-23 levels. At age 12 years, all rachitic manifestations were absent, and bone mineral density (BMD) and the echocardiogram were normal. CONCLUSIONS: Whereas 1,25(OH)2D3 is not indispensable for FGF-23 production, PTH in the absence of vitamin D may maintain FGF-23 secretion despite hypocalcemia. Normalization of urinary phosphate losses despite elevated FGF-23 during calcitriol-mediated suppression of secondary hyperparathyroidism points to a cardinal role of PTH as a cause of the phosphaturia in VDRR-I. Normalization of RAAS by calcitriol may conceivably prevent adverse cardiovascular outcomes.

Longitudinal patterns of urine biomarkers in infants across gestational ages.

BACKGROUND: Urinary biomarkers may be indicators of acute kidney injury (AKI), although little is known of their developmental characteristics in healthy neonates across a full range of gestational age (GA). The purpose of this study was to examine patterns of urinary biomarkers across GA groups from birth to 3 months of age. METHODS: Fifty-two infants ranging from 24 to 41 weeks' GA had urine assayed from birth through 3 months of age for 7 biomarkers including albumin (ALB), beta-2-microglobulin (B2M), cystatin-C (CysC), epidermal growth factor (EGF), neutrophil-gelatinase-associated lipocalin (NGAL), osteopontin (OPN), and uromodulin (UMOD). RESULTS: Of the seven urinary biomarkers, EGF and UMOD increased while others decreased with advancing GA. By 3 months of age, EGF and UMOD had increased in preterm infants to levels similar to those of term infants. UMOD/ml and EGF/ml appeared to be predominantly developmental biomarkers distinguishing estimated glomerular filtration rate (GFR) <30 ml/min/1.73 m(2) with receiver operator characteristic area under the curve (ROC-AUC) of 0.82; p = 0.002. When factored by urine creatinine CysC/cr + ALB/cr were the most significant functional markers with AUC = 0.79; p = 0.004; sensitivity 96 %; specificity 58 %. CONCLUSIONS: Among healthy neonates, urinary biomarkers vary with GA. These data support the use of urinary biomarkers in the assessment of normal kidney development in the absence of injury.

Predictors of resolution and persistence of renal laboratory abnormalities in pediatric HIV infection.

BACKGROUND: Among human immunodeficiency virus (HIV)-infected youth, the role of renal disease (RD) and its management has become increasingly important as these children/adolescents mature into young adults. The identification of predictors of abnormal renal laboratory events (RLE) may be helpful in the management of their HIV infection and its associated renal complications. METHODS: Data collected from HIV-infected youth followed for ≥ 48 months were analyzed to identify predictors of resolution versus persistence of RLE and determine the utility of RLE to predict the onset of RD. Analysis included descriptive and inferential methods using a multivariable extended Cox proportional hazards model. RESULTS: Of the 1,874 at-risk children enrolled in the study, 428 (23 %) developed RLE, which persisted in 229 of these (54 %). CD4 percentages of <25 % [hazard ratio (HR) 0.63, p < 0.002) and an HIV viral load of >100,000 copies/ml (HR 0.31, p < 0.01) were associated with reduced rates of resolution, while in most cases exposure to highly active antiretroviral therapy (HAART)/nephrotoxic HAART prior to or subsequent to RLE were not. Persistence of RLE was 88 % sensitive for identifying new RD. Negative predictive values for RD were >95 % for both the at-risk cohort and those with RLE. CONCLUSIONS: Advanced HIV disease predicted persistence of RLE in HIV-infected youth. Persistent RLE were useful for identifying RD.

Neonatal kidney size and function in preterm infants: what is a true estimate of glomerular filtration rate?

OBJECTIVES: To distinguish between cystatin C (CysC) and creatinine (Cr) as markers of estimated glomerular filtration rate (eGFR) in preterm infants and to correlate eGFR with total kidney volume (TKV) as a surrogate of nephron mass. STUDY DESIGN: Sixty preterm (<37 weeks' gestational age [GA]) and 40 term infants were enrolled at birth. Serum Cr and CysC levels were assessed during the first week of life. Renal ultrasounds were performed to assess kidney dimensions with calculation of the TKV as a surrogate of nephron mass. Six equations derived from reference inulin, iohexol, and iothalamate clearance studies were used to calculate eGFR. Multiple regression analysis was applied to assess the relative impact of neonatal measures on eGFR, including TKV, GA, and mean arterial pressure (MAP). RESULTS: Renal lengths correlated with GA and were within the reference values for intrauterine measurements. Estimation equations for glomerular filtration rate (GFR) based on Cr, CysC, and combined CysC + Cr demonstrated that Cr-based equations consistently underestimated GFR, whereas CysC and combined equations were more consistent with referenced inulin clearance studies. Term infants demonstrated significantly better eGFR than preterm infants. TKV, GA, and MAP correlated positively with eGFR, although only MAP and GA remained significant when adjusted for other covariates. CONCLUSIONS: Primary determinants of eGFR in preterm infants are GA and MAP. The CysC level is a superior biomarker to serum Cr in the assessment of GFR in premature infants.

Abnormalities in renal tubular phosphate handling in children with sickle cell disease.

BACKGROUND: The mechanisms responsible for the hyperphosphatemia in patients with sickle cell disease (SCD) and preserved glomerular filtration rate (GFR) are not fully understood. The role of fibroblast growth factor 23 (FGF23), a phosphaturic hormone has not been investigated in SCD. Hence, we evaluated parameters of renal tubular phosphorus handling and their relation to prevailing FGF23 levels in a cohort of young SCD patients. METHODS: Renal tubular phosphate handling and circulating levels of various analytes including FGF23 and parathyroid hormone (PTH) were measured in 24 children with SCD and normal estimated GFR in a cross sectional study. Correlation and regression analysis were employed to derive relationships between serum phosphorus and several variables. RESULTS: Most children showed elevated age- adjusted serum phosphorus (5.1 ± 0.7 mg/dl) levels. Tubular re-absorption of phosphorus(TRP) (96.3 ± 2.1%) and tubular maximum re-absorption of phosphorus per unit volume of GFR (TMP/GFR) (4.9 ± 0.6 mg/dl) were both elevated. Plasma intact FGF23 concentrations were elevated (81 ± 38 pg/ml) while the average PTH values were normal in most patients (50 ± 27 pg/ml). Univariate analysis showed significant correlations of serum phosphorus with TMP/GFR, alkaline phosphatase, age, lactate dehydrogenase (LDH), and log intact FGF23. TMP/GFR correlated with log intact FGF23 (r = 0.5, P< or = 0.01) but not with PTH. Multiple regression analysis yielded an independent relationship of serum phosphorus with TMP/GFR. CONCLUSION: The elevated serum phosphorus concentrations with simultaneously increased TMP/GFR and elevated FGF23 levels collectively suggest that patients with SCD display proximal tubular resistance to the action of FGF23 before any decline in GFR.

Albuminuria correlates with hemolysis and NAG and KIM-1 in patients with sickle cell anemia.

BACKGROUND: Although hyperfiltration and albuminuria are common pathological conditions, kidney injury (KI) biomarkers have been seldom studied in individuals with sickle cell anemia (SCA). METHODS: We undertook a cross-sectional assessment of urine KI biomarkers in children and adults with SCA with and without albuminuria and a normal estimated glomerular filtration rate (eGFR). Albumin, KI molecule 1 (KIM-1), N-acetyl-ß-D-glucosaminidase (NAG), endothelin-1 and transforming growth factor-ß1 (TGF-ß1) were measured. Assays were normalized by urine creatinine. Urine intracellular hemosiderin and serum lactate dehydrogenase (LDH) were assessed as markers of hemolysis. Albuminuria was associated to the biomarkers by Pearson and Spearman correlation coefficients. Differences between the albuminuria (yes, no) groups were assessed by the t test. RESULTS: Nineteen patients with albuminuria (mean urine albumin/creatinine 527.14 ± 1070 mg/g, range 38.3--190 mg/g) and 19 patients without albuminuria (mean urine albumin/creatinine 15.93 ± 5.17 mg/g, range 7.9-28.4 mg/g) were studied. The age range for the whole group was 11-48 years, and 47 % were males. Patients with albuminuria were older, had lower hematocrit, were more likely to test positive for urine hemosiderin and had a higher KIM-1 (P = 0.0035) and NAG/ creatinine ratios (P = 0.0062). Urine hemosiderin strongly correlated to a higher LDH level (P < 0.001). CONCLUSIONS: Despite a normal or increased eGFR, KI biomarkers were detected in the urine of individuals with SCA. NAG, KIM-1 and urine hemosiderin correlated with the presence of albuminuria.

Design of the Nephrotic Syndrome Study Network (NEPTUNE) to evaluate primary glomerular nephropathy by a multidisciplinary approach.

The Nephrotic Syndrome Study Network (NEPTUNE) is a North American multicenter collaborative consortium established to develop a translational research infrastructure for nephrotic syndrome. This includes a longitudinal observational cohort study, a pilot and ancillary study program, a training program, and a patient contact registry. NEPTUNE will enroll 450 adults and children with minimal change disease, focal segmental glomerulosclerosis, and membranous nephropathy for detailed clinical, histopathological, and molecular phenotyping at the time of clinically indicated renal biopsy. Initial visits will include an extensive clinical history, physical examination, collection of urine, blood and renal tissue samples, and assessments of quality of life and patient-reported outcomes. Follow-up history, physical measures, urine and blood samples, and questionnaires will be obtained every 4 months in the first year and biannually, thereafter. Molecular profiles and gene expression data will be linked to phenotypic, genetic, and digitalized histological data for comprehensive analyses using systems biology approaches. Analytical strategies were designed to transform descriptive information to mechanistic disease classification for nephrotic syndrome and to identify clinical, histological, and genomic disease predictors. Thus, understanding the complexity of the disease pathogenesis will guide further investigation for targeted therapeutic strategies.

Therapeutic plasma exchange in the treatment of exertional heat stroke and multiorgan failure.

BACKGROUND: Exertional heat stroke (EHS) results in a constellation of systemic inflammatory responses resulting in multiorgan failure and an extremely high mortality. CASE DIAGNOSIS AND TREATMENTS: We present the case of an 11-year-old obese male who suffered EHS with rhabdomyolysis and concurrent renal, pulmonary, and hepatic failure. Conventional therapies including continuous veno-venous hemodiafiltration (CVVHDF) were ineffective in preventing ongoing deterioration in clinical status. Liver biopsy was reported as "extensive hepatocyte ballooning" and liver-kidney transplantation was tentatively planned. CONCLUSIONS: The addition of therapeutic plasma exchange using the Prismaflex® system (Gambro, Lakewood, CO, USA) resulted in a reversal of the inflammatory process and recovery from multiorgan failure. Liver biopsy was not a reliable indicator of irreversible hepatic injury.

A child with BK virus infection: inadequacy of current therapeutic strategies.

In this report, we describe the development of BKVN in the native kidneys of a child with a cardiac transplant. Elevated BK viral DNA load by PCR necessitated a prolonged course of treatment with escalating doses of cidofovir. Despite a reduction in plasma BK viral load, the infection evolved into an invasive CNS disease, resulting in rhomboencephalitis. This case highlights the need for awareness of the possibility of developing multiorgan complications from BKV infection. The current treatment options for BKV tissue invasive disease are inadequate and need to be improved.

Hypertensive crisis in children.

Hypertensive crisis is rare in children and is usually secondary to an underlying disease. There is strong evidence that the renin-angiotensin system plays an important role in the genesis of hypertensive crisis. An important principle in the management of children with hypertensive crisis is to determine if severe hypertension is chronic, acute, or acute-on-chronic. When it is associated with signs of end-organ damage such as encephalopathy, congestive cardiac failure or renal failure, there is an emergent need to lower blood pressures to 25-30% of the original value and then accomplish a gradual reduction in blood pressure. Precipitous drops in blood pressure can result in impairment of perfusion of vital organs. Medications commonly used to treat hypertensive crisis in children are nicardipine, labetalol and sodium nitroprusside. In this review, we discuss the pathophysiology, differential diagnosis and recent developments in management of hypertensive crisis in children.

Fibroblast growth factor 23 and left ventricular hypertrophy in children on dialysis.

BACKGROUND: Elevated fibroblast growth factor 23 (FGF-23) concentrations associate with left ventricular hypertrophy (LVH) and adverse outcomes in adult patients with chronic kidney disease. We hypothesized that similar associations are present in pediatric patients on maintenance hemodialysis. METHODS: In this retrospective study of 26 young patients on chronic hemodialysis, aged 6-21 years, cardiac structure and geometry were measured by echocardiography, and circulating levels of FGF-23 and calciotropic hormones were obtained. RESULTS: FGF-23 levels were uniformly elevated in all patients from three- to 835-fold above the upper limit of normal. The average LV mass index (LVMI) was 43 ± 13 g/m(2.7) and reflected LVH in 55 % of patients. Log-transformed FGF-23 concentrations correlated with LVMI (p = 0.03) and were independently associated with the interventricular septal thickness Z-score (p < 0.001). Concentric LVH was associated with the highest FGF-23 concentrations and the highest LVMI measurements (p < 0.001). Each 1 standard deviation increase in log-transformed FGF-23 levels was associated with a 17 % increase in LVMI. CONCLUSIONS: FGF-23 levels are strongly associated with increased LVMI and with prevalent LVH in pediatric hemodialysis patients. Our cross-sectional findings provide observational evidence supporting the hypothesis linking FGF-23 to cardiac hypertrophy in patients with chronic kidney disease.

Chronic kidney disease associated with perinatal HIV infection in children and adolescents.

BACKGROUND: This study describes the incidence, clinical and demographic characteristics, and spectrum of chronic kidney disease (CKD) in youths with perinatal HIV-1 infection. METHODS: Retrospective analysis between May 1993 and December 2006 of subjects with renal disease followed in the Pediatric AIDS Clinical Trials Group 219/219C multicenter study examining the long-term consequences of perinatal HIV infection. Diagnosis confirmation was made utilizing a questionnaire mailed to research sites. Participants with CKD of other etiology than HIV were excluded. Outcome measures were biopsy-diagnosed CKD and, in the absence of biopsy, HIV-associated nephropathy (HIVAN) using established clinical criteria. RESULTS: Questionnaires on 191 out of 2,102 participants identified 27 cases of CKD: 14 biopsy-diagnosed and 6 clinical cases of HIVAN, and 7 biopsy-diagnosed cases of immune complex-mediated kidney disease (lupus-like nephritis, 3; IgA nephropathy, 2; membranous nephropathy, 2). Incidence rates for CKD associated with HIV in pre-highly active antiretroviral therapy (HAART) (1993-1997) and HAART (1998-2002, 2003-2006) eras were 0.43, 2.84, and 2.79 events per 1,000 person years respectively. In multivariate analysis, black race and viral load ≥100,000 copies/mL (rate ratios 3.28 and 5.05, p ≤ 0.02) were associated with CKD. CONCLUSIONS: A variety of immune complex-mediated glomerulonephritides and HIVAN occurs in this population. Black race and uncontrolled viral replication are risk factors for CKD associated with HIV.

Pica: an important and unrecognized problem in pediatric dialysis patients.

OBJECTIVE: Pica is the compulsive consumption of non-nutritive substances, and this disorder may occur more frequently in dialysis patients. The purpose of our study was to determine the prevalence of pica and the associated demographic and metabolic characteristics. DESIGN: Retrospective, cross-sectional analysis. SETTING: Hospital-based, outpatient, pediatric hemodialysis unit. SUBJECTS: Eighty-seven pediatric patients on chronic dialysis therapy were interviewed. Sixty-seven patients were receiving hemodialysis, whereas the remaining 20 were maintained on peritoneal dialysis. The predominantly nonwhite (93%) patient population had a mean age of 17.2 ± 7.2 years. Dialysis efficiency, estimated by urea clearance per patient volume (Kt/V), averaged 1.5 ± 0.5. INTERVENTION: Standard patient interview and documentation of laboratory and dialytic parameters. MAIN OUTCOME MEASURE: Prevalence of pica and associated comorbid conditions. RESULTS: The survey indicated that 46% of patients experienced pica, further divided into simple "ice" pica (34.5%) versus "hard" pica (12.6%). Hard pica included the consumption of chalk, starch, sugar, soap, sand, clay, Ajax cleanser, sponge, wood, and potting soil. Patients on hemodialysis were 8.3 times more likely to have hard pica compared with those on peritoneal dialysis. Greater than 5 years on dialysis was associated with a 3.2 odds ratio of having pica (P = .02). Anemia was the most significant morbid association, occurring at an odds ratio of 4.4 (P = .001) for all pica and 10.6 (P = .004) for hard pica. CONCLUSION: Pica, therefore, is prevalent and potentially harmful, requiring further attention in the nutritional management of pediatric dialysis patients.

Long-term risk of chronic kidney disease in unilateral multicystic dysplastic kidney.

The clinical spectrum of renal dysplasia includes the non-functioning multicystic dysplastic kidney (MCDK). We report our experience of the outcome of unilateral MCDK and its contralateral kidney in 101 children with the diagnosis of MCDK from 1985 to 2009. Data collected included urine protein/creatinine ratio, estimated GFR (eGFR), blood pressure, surgical intervention, renal length and abnormalities of the contralateral kidney, and the involution rate. There was a predominance of left-sided MCDK. Diagnosis was made prenatally in 86.7%. Contralateral abnormalities included vesicoureteral reflux (16.8%), UPJ obstruction (4.1%), and megaureter (2.4%). Complete involution of MCDK occurred within 5 years in 60%. Compensatory hypertrophy of the contralateral kidney to >97% occurred in 74.1%. Nephrectomy was performed in 19.8%. There was an increased risk of chronic kidney disease (CKD) stage ≥ 2, and hypertension in those with contralateral abnormalities (p<0.0001; p<0.001 respectively). In those without contralateral abnormalities, hyperfiltration with mean eGFR of 149 ± 13 ml/min/1.73 m(2) was seen in 32% and proteinuria in 9.8%. There was a significantly inverse relationship between proteinuria and eGFR (p<0.0001). In conclusion, children with contralateral abnormalities are at risk for developing decreased kidney function, whereas a substantial number of patients with no obvious contralateral abnormalities have markers of renal injury. Therefore, systematic follow-up of all patients is recommended.

PREFABL: predictors of failure of antibiotic locks for the treatment of catheter-related bacteraemia.

BACKGROUND: Antibiotic lock (ABL) solutions can effectively treat catheter-related bacteraemia (CRB) without the need for catheter exchange. This approach does not increase secondary infectious complications. We evaluated the risk factors that contribute to failure when CRB is treated with ABLs and systemic antibiotics in paediatric haemodialysis patients. METHODS: A retrospective chart review of 72 children on haemodialysis between January 2004 and June 2006 was performed. We evaluated risk factors for ABL treatment using patients' characteristics, CRB/catheter characteristics and patients' biochemical profiles. The first CRB of each catheter was included in the statistical analysis. Our end points were outcome at 2 weeks of treatment and at 6 weeks following treatment. Compound symmetry covariance structure was employed for statistical analysis. RESULTS: We treated 149 CRB in 50 patients. The incidence was 3.4 CRB/1000 catheter days. Thirty CRB failed to be cleared with the use of ABL and systemic antibiotics at 2 weeks of treatment (30/149, 20 vs 80%, P < 0.001). Twenty-four of these catheters required exchange. Thirty-nine of the treated catheters got re-infected within the next 6 weeks (39/125, 31 vs 69%, P < 0.001). CRB aetiology was the only statistically significant independent variable for 2-week outcome (P = 0.033). Coagulase-negative Staphylococcus CRB had higher odds of being cleared at 2 weeks compared with other CRB aetiologies. For the 6-week outcome, the statistically significant independent variables in the final model included age (P = 0.048) and serum phosphorous level (P < 0.001). Younger age and higher serum phosphorous levels were independent risk factors for failure at 6 weeks with re-infection. Area under the receiver operating characteristic (ROC) curve for the model of the 2-week outcome was 0.736 with the percentage of correct predictions at 81.2%. Area under the ROC curve for the model of the 6-week outcome was 0.689 with the percentage of correct predictions at 75.5%. CONCLUSIONS: CRB can effectively be treated with ABLs and systemic antibiotics. CRB aetiology is the only independent variable of early treatment failure. Younger age and higher serum phosphorous levels are independent risk factors for re-infection at 6 weeks.

Two decades of pediatric kidney transplantation in a multi-ethnic cohort.

This study evaluated a 20-yr experience in kidney transplantation in children from a predominantly Hispanic community. A retrospective analysis was carried out in children who received kidney transplants from 1985 to 2005. Of 124 kidney transplants, 81 (65%) were from LD. Racial distribution was Hispanic (48%), followed by AA (24%) and Caucasian (26%). First yr allograft survival was similar in LD and DD and significantly better in LD until seven yr post transplant. eGFR <60 mL/min/1.73 m(2) at one yr post transplant was associated with a median allograft survival of 3.3 yr, compared to 16 yr in those with eGFR > or = 60 mL/min/1.73 m(2) (p < 0.0001). Graft loss in the first five yr was from non-adherence, recurrence of disease, and infections. Those of AA race were more likely to receive a DD and have low socioeconomic status and the poorest median allograft survival compared to Hispanics and Caucasians (6 vs. > or =15 yr; p < 0.001). In conclusion, this predominantly Hispanic cohort emphasizes the disadvantaged profile of AAs compared to other racial groups. Strategies to improve supportive services and living donations in minority populations need to be developed. Long-term renal allograft survival is achievable if GFR is maintained >60 mL/min/1.73 m(2).

Twenty-five years of infant dialysis: a single center experience.

OBJECTIVE: To perform a retrospective analysis of the long-term outcome of infants with end-stage kidney disease (ESKD) treated at our center during the past 25 years. STUDY DESIGN: The total cohort (n = 52) was divided into era 1 (1983-1995; n = 23) and era 2 (1996-2008; n = 29). Dialysis morbidity, transplantation, and long-term survival rates were assessed and compared between the 2 eras. RESULTS: Average age at initiation of dialysis was 4.4 +/- 5.3 months (range, 0.5-18 months), with 96% begun on peritoneal dialysis. The predominant diagnoses were dysplasia/obstructive uropathy and autosomal recessive polycystic kidney disease. The overall survival rate is 46%, with current age of survivors ranging from 1.5 to 25 years. Mortality rates in the 2 eras were not significantly different. The predominant mortality occurred within the first year. Twenty-four patients received an initial renal transplant at 2.6 +/- 1.7 years of age. Six patients (25%) required a second renal allograft. Increased risk for mortality included African-American ethnicity, oligoanuria, autosomal recessive polycystic kidney disease, and co-morbid diagnoses. CONCLUSIONS: Long-term survival is possible in infants with ESKD, although mortality and morbidity remain high. Technical innovations are needed to accommodate smaller infants undergoing dialysis. Early initiation of dialysis treatment is preferable because prognostic indicators remain poorly defined.

Vitamin D insufficiency and deficiency in children with early chronic kidney disease.

OBJECTIVE: To assess the prevalence of abnormal vitamin D status in children and adolescents with chronic kidney disease (CKD). STUDY DESIGN: This was an outpatient cross-sectional, retrospective study of 258 patients, mean age 12.3 +/- 5.2 years, with an average estimated glomerular filtration rate (eGFR) of 106 +/- 51 mL/min/1.73 m2 (range, 0 to 220 mL/min/1.73 m2). Serum 25-hydroxy-vitamin D [25(OH)D], calcium, phosphorus, and parathyroid hormone levels, as well as selected anthropometric variables, were analyzed. RESULTS: Reduced 25(OH)D concentrations (< 30 ng/mL) were found in 60% of the patients. In 28%, the concentration was < 20 ng/mL, indicating vitamin D deficiency. Patients with more advanced CKD were more likely to have vitamin D deficiency compared with those with incipient CKD or normal GFR (42% vs 26%; P = .03) and displayed more prominent hyperparathyroidism. Suboptimal vitamin D status was similar in males and females, but was significantly more prevalent in older (P < .01), non-Caucasian (P < .01), and overweight (P = .02) patients. Patients with early-stage CKD (eGFR > 60 mL/min/1.73 m2) and with vitamin D deficiency were significantly shorter than their counterparts with 25(OH)D levels > 20 ng/mL (P = .02). CONCLUSIONS: Vitamin D insufficiency and deficiency are very prevalent in pediatric patients across all stages of CKD, particularly in non-Caucasian and obese patients, and may contribute to growth deficits during the earliest stages of CKD.

Renal manifestations in toddlers with Takayasu's arteritis and malignant hypertension.

Three children under the age of 3 years presented with malignant hypertension, proteinuria, and acute kidney injury. Takayasu's arteritis was diagnosed on the basis of clinical symptoms of weight loss and low grade fever in conjunction with elevated sedimentation rate and radiographic evidence of aortic and renal artery stenosis. One patient had a renal biopsy which showed arteriolar sclerosis and focal glomerulosclerosis. All three patients required multiple antihypertensive agents, ultimately including angiotensin receptor blockers and/or angiotensin converting enzyme inhibitors. The vasculitis was treated with pulse corticosteroids followed by cyclophosphamide in one patient and mycophenolate mofetil as maintenance therapy in all. Follow-up has ranged from 2 to 8 years. Although global renal function has normalized in each patient, two have unilateral non-function of one kidney. The last patient has persistent aortic and renal artery stenosis with complex collateralization requiring ongoing medical and anticipated surgical management.