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No data exist on the epidemiology of children incidentally diagnosed with advanced kidney failure (KF) during evaluation for non-specific symptoms. This is likely related to unrecognized symptoms and signs of CKD. The objective of our study was to evaluate incidentally diagnosed patients with advanced KF requiring long-term kidney replacement therapy (KRT). An IRB-approved retrospective chart review of children who started KRT with dialysis (hemo- or peritoneal) was conducted. Included were children with no prior knowledge or diagnosis of underlying kidney disease with chronic kidney disease (CKD) disease stage 4 (GFR 15–29 mL/min/1.73 m2) or 5 (GFR

The National Kidney Foundation's Kidney Disease Outcomes Quality Initiative (KDOQI) has provided evidence-based guidelines for hemodialysis vascular access since 1996. Since the last update in 2006, there has been a great accumulation of new evidence and sophistication in the guidelines process. The 2019 update to the KDOQI Clinical Practice Guideline for Vascular Access is a comprehensive document intended to assist multidisciplinary practitioners care for chronic kidney disease patients and their vascular access. New topics include the end-stage kidney disease "Life-Plan" and related concepts, guidance on vascular access choice, new targets for arteriovenous access (fistulas and grafts) and central venous catheters, management of specific complications, and renewed approaches to some older topics. Appraisal of the quality of the evidence was independently conducted by using a Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach, and interpretation and application followed the GRADE Evidence to Decision frameworks. As applicable, each guideline statement is accompanied by rationale/background information, a detailed justification, monitoring and evaluation guidance, implementation considerations, special discussions, and recommendations for future research.

Apolipoprotein L1 (APOL1) risk variants G1 and G2 are known to result in risk for kidney disease in patients of African ancestry. APOL1-associated nephropathy typically occurs in association with certain environmental factors or systemic diseases. As such, there has been increasing evidence of the role of interferon (IFN) pathways in the pathogenesis of APOL1-associated collapsing glomerulopathy in patients with human immunodeficiency virus (HIV) infection and systemic lupus erythematosus, 2 conditions that are associated with high IFN levels. Collapsing glomerulopathy has also been described in patients receiving exogenous IFN therapy administered for various medical conditions. We describe a patient with a genetic condition that results in an increased IFN state, stimulator of IFN genes (STING)-associated vasculopathy with onset in infancy (SAVI), who developed collapsing glomerulopathy during a flare of his disease. The patient was found to have APOL1 G1 and G2 risk variants. This case supports the role of IFN in inducing APOL1-associated collapsing glomerulopathy.

Objective: To evaluate the prevalence and factors associated with the risk of acute kidney injury (AKI) in pediatric patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and multisystem inflammatory syndrome in children (MIS-C).Study Design: We performed a retrospective chart review of 113 patients with SARS-CoV-2 infection with or without MIS-C admitted at Children's Hospital of Michigan (CHM) from March to August 2020. Patient demographic details, laboratory data, imaging studies, echocardiography reports, and treatment data were collected.Results: Of the 92 patients included in the final analysis, 22 (24%) developed AKI with 8/22 (36%) developing stage 3 AKI. The prevalence of AKI was much higher in patients with MIS-C 15/28 (54%) vs. those with acute SARS-CoV-2 infection 7/64 (11%), (p < 0.001). Overall, when compared to patients without AKI, patients with AKI were older in age (11 vs. 6.5 years, p = 0.007), African American (86 vs. 58%, p = 0.028), had MIS-C diagnosis (68 vs. 19%, p < 0.001), required ICU admission (91 vs. 20%, p < 0.001), had cardiac dysfunction (63 vs. 16%, p < 0.001), required inotropic support (59 vs. 6%, p < 0.001) and had a greater elevation in inflammatory markers. In a multivariate analysis, requirement of inotropes [Odds Ratio (OR)−22.8, p < 0.001], African American race (OR-8.8, p = 0.023) and MIS-C diagnosis (OR-5.3, p = 0.013) were the most significant predictors for AKI. All patients had recovery of kidney function, and none required kidney replacement therapy.Conclusion: Children with acute SARS-CoV-2 infection and MIS-C are at risk for AKI, with the risk being significantly greater with MIS-C. The pathogenesis of AKI in acute SARS-CoV-2 infection appears to be a combination of both renal hypo-perfusion and direct renal parenchymal damage whereas in MIS-C, the renal injury appears to be predominantly pre-renal from cardiac dysfunction and capillary leak from a hyperinflammatory state. These factors should be considered by clinicians caring for these children with a special focus on renal protective strategies to aid in recovery and prevent additional injury to this high-risk subgroup.

While the causes of chronic kidney disease (CKD) are different in children than their adult counterparts, many comorbidities are commonly encountered by both populations. Particularly concerning is that these entities contribute to the decrease in lifespan in children with CKD. Amongst these conditions are hypertension, anemia, and electrolyte abnormalities. While these can cause metabolic derangements individually, they each contribute to the development and progression of cardiovascular disease, which in turn, exponentially increases mortality (Vidi Curr Opin Pediatr 30 (2): 247-251, 2018). It has been estimated that the mortality rate of children with CKD is 30 times higher than their healthy peers (Ferris et al. Blood Purif 41 (1-3): 205-10, 2016). As these conditions are each treatable, optimization of medical management can lessen the risk of death in this high-risk population. Hypertension remains underdiagnosed in children with CKD despite a high prevalence. The American Academy of Pediatrics released the Clinical Practice Guideline for Screening and Management of High Blood Pressure in Children and Adolescents in 2007, in which experts outline the need for aggressive diagnosis and treatment of hypertension. While the mainstay of anemia management remains correction of iron deficiency and erythropoiesis stimulating agents, long-acting erythropoietic agents offer an alternative option to traditional management. Electrolyte abnormalities including metabolic acidosis and hyperkalemia must be addressed in order to optimize clinical outcomes. The care of children with CKD remains complex with the need for a wholistic approach. Although the injury initiates within the kidneys, the associated comorbidities have systemic consequences. Some of these include hypertension, anemia, and electrolyte abnormalities. The early identification of these conditions as well as aggressive treatment can improve the health of these children.

No data exist on the epidemiology of children incidentally diagnosed with advanced kidney failure (KF) during evaluation for non-specific symptoms. This is likely related to unrecognized symptoms and signs of CKD. The objective of our study was to evaluate incidentally diagnosed patients with advanced KF requiring long-term kidney replacement therapy (KRT).An IRB-approved retrospective chart review of children who started KRT with dialysis (hemo- or peritoneal) was conducted. Included were children with no prior knowledge or diagnosis of underlying kidney disease with chronic kidney disease (CKD) disease stage 4 (GFR 15-29 mL/min/1.73 mOf 177 patients initiating KRT during the study period, 26 (15%) were categorized as incidental advanced KF. This cohort with mean age 12.25 years consisted of 42% males, 54% African Americans included 46% with glomerular, and 54% with non-glomerular etiology for kidney failure. Vomiting (42%) and fatigue (39%) were most common, while growth failure (19%) and hyperkalemia (7%) were less frequent on initial presentation. Anemia (100%), hypertension (96%), hyperparathyroidism (96%), and hyperphosphatemia (92%) were the most frequently seen CKD comorbidities. Chronic KRT was started within 24 h in 62% and within 2 weeks in 88% of the cohort.Under-diagnosis of patients with advanced KF is most likely related to milder non-specific clinical symptoms and normal growth in the majority of patients. A higher resolution version of the Graphical abstract is available as Supplementary information.

Purpose We report the case of a 2-year-old girl with end-stage renal disease managed by peritoneal dialysis (PD) who developed methicillin-resistant staphylococcal osteomyelitis of the left shoulder and was successfully treated with intraperitoneal (IP) administration of vancomycin for 2 weeks followed by oral clindamycin therapy. Summary The patient was hospitalized with tactile fever and a 3-day history of worsening fussiness. Radiography of the left shoulder showed findings indicative of osteomyelitis. Vancomycin was administered via central venous line for 3 days, during which time the patient underwent PD 24 hours a day. After magnetic resonance imaging revealed proximal humeral osteomyelitis, septic arthritis of the shoulder joint, and osteomyelitis of the scapula, the patient underwent incision and drainage of the left shoulder joint. Both blood and joint drainage cultures grew methicillin-resistant Staphylococcus aureus that was sensitive to vancomycin. The patient’s central venous catheter was removed on hospital day 4; due to difficulties with peripheral i.v. access and a desire to avoid placing a peripherally inserted central venous catheter, vancomycin administration was changed to the IP route, with vancomycin added to the PD fluid. During IP treatment, serum vancomycin levels were maintained at 13.5 to 18.5 mg/L, and the calculated ratio of vancomycin area under the curve to minimum inhibitory concentration was maintained above 400. After completing a 14-day course of IP vancomycin therapy, the patient was switched to oral clindamycin, with subsequent complete resolution of osteomyelitis. Conclusion IP vancomycin was effective for treatment of invasive S. aureus infection in this case. This approach should be considered in patients undergoing PD for whom peripheral i.v. access options are limited and/or not preferred.

Central venous catheters are used frequently in patients on hemodialysis as a bridge to a permanent vascular access. They are prone to frequent complications, including catheter-related bloodstream infection, catheter dysfunction, and central vein obstruction. There is a compelling need to develop new drugs or devices to prevent central venous catheter complications. We convened a multidisciplinary panel of experts to propose standardized definitions of catheter end points to guide the design of future clinical trials seeking approval from the Food and Drug Administration. Our workgroup suggests diagnosing catheter-related bloodstream infection in catheter-dependent patients on hemodialysis with a clinical suspicion of infection (fever, rigors, altered mental status, or unexplained hypotension), blood cultures growing the same organism from the catheter hub and a peripheral vein (or the dialysis bloodline), and absence of evidence for an alternative source of infection. Catheter dysfunction is defined as the inability of a central venous catheter to (1) complete a single dialysis session without triggering recurrent pressure alarms or (2) reproducibly deliver a mean dialysis blood flow of >300 ml/min (with arterial and venous pressures being within the hemodialysis unit parameters) on two consecutive dialysis sessions or provide a Kt/V≥1.2 in 4 hours or less. Catheter dysfunction is defined only if it persists, despite attempts to reposition the patient, reverse the arterial and venous lines, or forcefully flush the catheter. Central vein obstruction is suspected in patients with >70% stenosis of a central vein by contrast venography or the equivalent, ipsilateral upper extremity edema, and an existing or prior history of a central venous catheter. There is some uncertainty about the specific criteria for these diagnoses, and the workgroup has also proposed future high-priority studies to resolve these questions.

Management of blood pressure in children with pheochromocytoma and other catecholamine‐secreting tumors (CSTs) is unique and challenging. The authors report a single‐center experience using sequential α‐adrenergic blockade (phenoxybenzamine), increased fluid intake, and β‐blockade for presurgical management of 10 CSTs in children. In this retrospective review, mean duration for blood pressure control in preparation for surgery was 4.5±2.6 weeks. Intraoperative hypertension was noted transiently (

There has been recent emphasis on increased arteriovenous fistula (AVF) use and decreased central venous catheter use in hemodialysis (HD) patients. The International Pediatric Fistula First Initiative was founded via collaborative effort with the Midwest Pediatric Nephrology Consortium to alert nephrologists, surgeons, and dialysis staff to consider fistulae as the best access in pediatric HD patients. A multidisciplinary educational DVD outlining expectations and strategies to increase AVF placement and usage in children was created. Participants were administered a survey previewing and postviewing to identify barriers to placement and usage of AVF in children. A total of 52 surveys were subdivided as either "dialysis staff" or "proceduralist" at five centers. Thirty-three percent of respondents were unaware if their practice was following published guidelines. Sixty-five percent of respondents stated they referred to a dedicated vascular access surgeon at their respective institutions. Methods used to monitor AVF function included physical exam, venous pressure monitoring, and ultrasound dilution. Vascular access was placed within 3 months in only 35% of patients. Interdisciplinary communication problems between surgeons, interventional radiologists, and nephrologists were identified as a major barrier. Lack of AVF usage was often due to maturation failure. Routine access rounds did not occur in any centers. Regarding monitoring, 74% of the respondents use physical exam, 26% use venous pressure monitoring, and 9% use ultrasound dilution. Ninety-three percent of dialysis staff stated they would change practice patterns following the intervention; however, 12% of surgeons stated they would alter practice patterns. To our knowledge, this is the first report to identify barriers to placement of AVF in children from the perspectives of multidisciplinary team members including pediatric nephrologists, surgeons, interventional radiologists, and multidisciplinary dialysis staff.

An internal permanent vascular access [arteriovenous fistula (AVF) or arteriovenous graft (AVG)] is preferred over central venous catheters (CVC) for chronic hemodialysis. However, CVC remain the most commonly used access in children. The objective of this study was to evaluate our experience with AVF.We conducted a retrospective chart review of children aged 1-18 years on chronic hemodialysis from 2001 to 2012. Patients were divided into three time periods: 2001-2005, 2006-2009 and 2010-2012. A systematic approach to AVF placement was introduced in our department in 2006 which resulted in a greater number of AVF being placed and used, but the access failure rate was still higher than desired. In 2010, a more experienced vascular surgeon was contacted to perform AVF surgery in our most difficult AVF candidates.Sixty-five AVF were created in 55 patients (67.3 % male). The median age of the patients was 14 (3-18) years. Forty-one (63.1 %) AVF were used successfully, and this number increased from 52.6 to 57.6 to 92.3 % over the three time periods, respectively. Over time, AVF use rates increased and CVC use decreased. By 2012 only 7.7 % of our patients were using a CVC. The primary patency rate was 42.9 % at 1 year; secondary patency rates were 100 and 93.8 % at 1 and 2 years, respectively. Infection and hospitalization rates were higher for CVC than for AVF [0.8 vs. 0.1 infections per access-year (p 0.001) and 0.9 vs. 0.2 hospitalizations per access-year (p 0.001)].With a dedicated approach and vascular access team it is possible to decrease CVC and increase AVF use in children on hemodialysis. In our study, increased AVF use resulted in decreased access-related infection and hospitalization rates.

The care of children with end-stage renal disease (ESRD) is highly specialized and often poorly understood by nonpediatric providers and facility/institution administrators. As such, this position paper has been created to offer provider, facility, and institutional guidance regarding the components of care necessary for children receiving dialysis. Key differences between adult and pediatric dialysis units are highlighted. Responsibilities and expectations of the members of the interdisciplinary dialysis team are outlined as they pertain specifically to the care of pediatric dialysis patients. Physical and staffing requirements of the dialysis facility are reviewed, again focusing on unique needs and challenges faced by the pediatric dialysis care team. Among these, vascular access options and proper planning of ESRD care are underscored. Pediatric quality-of-life metrics differ significantly from adult quality variables, and proper tools for assessment must be used. Endorsed by the Council of the American Society of Pediatric Nephrology (ASPN), this position paper serves as a reference tool for the provision of care to pediatric patients with ESRD.

Steroid-resistant nephrotic syndrome (SRNS) causes 15% of chronic kidney disease (CKD). Here we show that recessive mutations in FAT1 cause a distinct renal disease entity in four families with a combination of SRNS, tubular ectasia, haematuria and facultative neurological involvement. Loss of FAT1 results in decreased cell adhesion and migration in fibroblasts and podocytes and the decreased migration is partially reversed by a RAC1/CDC42 activator. Podocyte-specific deletion of Fat1 in mice induces abnormal glomerular filtration barrier development, leading to podocyte foot process effacement. Knockdown of Fat1 in renal tubular cells reduces migration, decreases active RAC1 and CDC42, and induces defects in lumen formation. Knockdown of fat1 in zebrafish causes pronephric cysts, which is partially rescued by RAC1/CDC42 activators, confirming a role of the two small GTPases in the pathogenesis. These findings provide new insights into the pathogenesis of SRNS and tubulopathy, linking FAT1 and RAC1/CDC42 to podocyte and tubular cell function., Steroid-sensitive nephrotic syndrome (SRNS) can cause CKD and necessitate kidney transplant. Here the authors identify FAT1 mutations by homozygosity mapping and whole-exome sequencing in families with SRNS and provide functional mouse and zebrafish evidence that FAT1 is required for normal glomerular and tubular function and that FAT1 mutations can cause SRNS.

The incidence and prevalence of end stage renal disease (ESRD) continue to rise in the pediatric population. From a modality perspective, hemodialysis (HD) has been used in the majority of incident ESRD patients. The most impactful breakthrough in HD was the creation of the native arteriovenous fistula (AVF) by Brescia and Cimino in 1966. This radiocephalic AVF has become the signature surgical treatment to prepare a patient to receive optimal HD care. Years later, arteriovenous grafts (AVGs) were developed by surgically interposing a synthetic material between the arterial and venous systems. These gained favor for a few reasons: technically easier to place, ability to place in patients whose native vessels were undersized, and ability to cannulate for dialysis initiation sooner than with an AVF. Central venous catheters (CVC) are a mainstay in HD, but for the past 10–15 years, there has been a strong movement away from CVCs for long term HD in favor of AVF. While CVCs are now considered a poor choice for long term vascular access, they are often necessary in children with hemodialysis dependent ESRD who are awaiting maturation of a permanent vascular access. Uncuffed, temporary catheters, which are typically used for a week or less, are often needed in the setting of intoxications and severe acute kidney injury. The major problems with CVC (both tunneled, cuffed and temporary, uncuffed) include infection and thrombosis. The most common means by which a catheter may become infected are migration of cutaneous organisms along the portal of entry (on the external surface of the catheter) to the catheter tip (most common with short-term, uncuffed catheters, and direct contamination of the catheter or its hub by contact with hands or contaminated fluids or devices. The thrombotic and central venous stenosis risks of a HD catheter are lower when placed into the right IJ vein as opposed to the subclavian, and as such it is the site of first choice for a tunneled HD catheter. Novel insights into vascular access failure pathogenesis and treatment strategies are ongoing. Neointimal hyperplasia and its role in access failure are actively being studied; the goal being improved long term vascular access survival with reduced need for interventions to maintain patency. Similarly, improving safety of dialysis CVC’s for short term use and rarely long term use has focused on infection prevention strategies to reduce the likelihood of catheter exit site and catheter related bacteremia. In summary, pediatric vascular access is a cornerstone of hemodialysis provision in children with ESRD. While AVFs and AVGs are preferred, CVCs are still utilized in this setting. Ongoing studies continue to evolve to focus on optimizing outcomes in pediatric and adult vascular access in dialysis.

Despite current guidelines, variability exists in the workup of hypertensive children due to physician preferences. The study evaluates primary vs secondary hypertension diagnosis from investigations routinely performed in hypertensive children. This retrospective study included children 5 to 19 years with primary and secondary hypertension. The proportions of abnormal laboratory and imaging tests were compared between primary and secondary hypertension groups. Risk factors for primary vs secondary hypertension were evaluated by logistic regression and likelihood function analysis. Patients with secondary hypertension were younger (5-12 years) and had a higher proportion of abnormal creatinine, renal ultrasound, and echocardiogram findings. There was no significant difference in abnormal results of thyroid function, urine catecholamines, plasma renin, and aldosterone. Abnormal renal ultrasound findings and age were predictors of secondary hypertension by regression and likelihood function analysis. Children aged 5 to 12 years with abnormal renal ultrasound findings and high diastolic blood pressures are at higher risk for secondary hypertension that requires detailed evaluation.

Low birth weight is associated with diminished renal function. However, despite African Americans being at increased risk of low birth weight and chronic kidney disease, little is known about the association between birth weight and renal function in diverse groups. We examined racial differences in the relationship of birth weight and renal function among healthy young children.Birth weight and serum creatinine data were available on 152 children (61.8% African American; 47.4% female) from a birth cohort. Estimated glomerular filtration rate (eGFR) was calculated using the bedside Schwartz equation and gender- and gestational-age-adjusted birth weight Z-scores using the US population as a reference. Race-specific linear regression models were fit to estimate the association between birth weight Z-score and eGFR.Mean age was 1.5 ± 1.3 years at first eGFR measurement. African Americans had lower eGFR than non-African Americans (median eGFR = 82 vs. 95 ml/min per 1.73 m(2); p = 0.06). Birth weight was significantly and positively associated with eGFR among African American (p = 0.012) but not non-African American children (p = 0.33).We provide, for the first time, evidence suggesting that birth weight is associated with renal function in African American children. Future work is needed to determine if prenatal programming helps explain racial disparities in adult health.

Membranous nephropathy (MN), also known as membranous glomerulonephritis, is a pathologic condition associated with an immune complex deposition within the glomerulus resulting in glomerular dysfunction. Clinical manifestations of MN include proteinuria, hematuria, overt nephrotic syndrome, and in some cases renal dysfunction. In adults, MN is the most common primary glomerulopathy associated with the nephrotic syndrome, accounting for approximately 25–35% of adults diagnosed with this condition [1–3]. In children, MNmay present as the nephrotic syndrome or as asymptomatic proteinuria and is considered to a much less common condition than that seen in adults [4, 5]. MNmay be idiopathic or secondary to infections, autoimmune diseases, or medications. Recent breakthrough discoveries regarding the pathogenesis of idiopathic MN have reenergized the field and should aid clinicians going forward with regard to developing novel means to monitor and treat patients with membranous nephropathy [6–8].

Although prednisone is the treatment of choice for nephrotic syndrome (NS) in childhood, the dosing regimen varies between 60 mg/m(2)/day, as recommended in early studies, to the often prescribed 2 mg/kg/day dose, which is used in common practice. Mathematical models have demonstrated that weight-based dosing can be less than body surface area (BSA)-based dosing in smaller children. To test our hypothesis that weight-based dosing would result in altered treatment outcomes in children with NS, we analyzed a cohort of 56 children (mean age 5.4 ± 3.8 years) treated with a weight-based dosing regimen. Theoretical underdosing of corticosteroids was tested by calculating a relative underdosing percentage (RUP), which was defined as the dose difference between the theoretical BSA-based dose and the actual weight-based doses divided by the BSA-based dose × 100. We found that the mean "actual" prednisone dose in our patients was 43.6 ± 19.3 mg/day; in contrast, the mean theoretical BSA-based dose was calculated to be 48.8 ± 16.7 mg/day. Among the 56 patients, 43 (76.7%) were initial responders, of whom 58% followed a frequently relapsing (FR) course. RUP was significantly higher in FR (16.6 ± 7.9%) than in infrequent relapsers (8.7 ± 9.8%) (P = 0.03). RUP was not significantly different among initial responders and nonresponders. Based on these results, we conclude that prednisone underdosing, when dosing is prescribed according to weight, does not affect the initial response to treatment, but it does increase the likelihood of a FR course in responders.

Iron deficiency (ID) contributes to the development of anemia in patients with chronic kidney disease (CKD). The frequency of ID in children with early CKD has not previously been reported. This was a retrospective chart review of children with CKD stages 2 and 3 followed at the CKD clinic of Children's Hospital of Michigan. ID was defined as low ferritin and transferrin saturation20%. Patients on iron supplements were considered as iron-deficient cases. There were 50 patients included in the study (72% male) with a mean age of 10.31 (±5.21). The mean glomerular filtration rate (GFR) was 55.4 ml/min/1.73 m(2) (±14.61). ID was present in 42% of patients, out of whom almost half (42.9%) presented with anemia. Females had a higher frequency of ID (64.3%). The frequency of ID with anemia increased from 4.3% to 29.6%, (p = 0.03) in stage 2 to stage 3 CKD, respectively. The frequency of ID without anemia also increased with progression of CKD from stage 2 to stage 3, however, the difference was not statistically significant. ID is frequent in patients with early CKD. Monitoring of iron tests and treatment of ID is important in this population of patients.

Arterial wall stiffness is a recognized complication in children with chronic kidney disease (CKD). Vascular abnormalities in these patients are shown to predate cardiac abnormalities such as left ventricular hypertrophy and diastolic dysfunction. The etiology of vascular abnormalities in these patients currently is not clear. This study explored the relationship between various parameters of calcium-phosphorus metabolism including 25-hydroxy vitamin D and arterial wall stiffness in pediatric patients with CKD. This study investigated a cohort of 43 children with CKD who had no history of underlying congenital or structural cardiac disease. The Augmentation Index (AI), a measure of peripheral arterial reflective properties using radial artery tonometry, was used as an indirect measure of central aortic stiffness. Serum biochemical markers of calcium-phosphorus metabolism were simultaneously measured. Univariate testing showed that AI correlated with worsening kidney function. Serum 25-hydroxy vitamin D levels were low and correlated negatively with AI (r = -0.39; p < 0.05). Multiple regression analysis showed that 25-hydroxy vitamin D was the only significant independent predictor of increased central arterial stiffness in the subgroup of children receiving hemodialysis. No association was observed between AI and any other measured biochemical parameter of calcium-phosphorus metabolism. This is the first study to investigate pediatric patients with CKD that suggests an association between nutritional vitamin D deficiency and increased arterial stiffness in children with CKD. The pathophysiologic mechanisms of vitamin D that regulate increased arterial stiffness need to be integrated further in pediatric CKD patients.

Similar to adults, stone disease in the pediatric patient may present clinically as flank/abdominal pain or hematuria. Unlike in adults, pediatric stone disease is less frequent and is often associated with an underlying metabolic disorder. Because of the 50% likelihood of finding an underlying metabolic cause for stone formation in younger children, a metabolic workup is recommended for all children with stone disease, including first-time stone formers. Stone analysis, when available, can be very helpful in determining an underlying cause. If needed, all modalities of minimally invasive surgical treatment are possible for children with stones. Surgical approaches may be needed to achieve the goal of nephron preservation. Aggressive fluid intake is the mainstay of prevention for all forms of stone disease, but specific therapy targeted to the most likely underlying metabolic abnormality is often used. Newer data are now linking stone disease to CKD, thereby emphasizing the need for a better understanding and potentially more aggressive treatment approach. With increasing frequency of stone disease in the pediatric patient and increasing survival of these patients into adulthood, the adult caregiver must become familiar with different causes and treatment approaches to stone disease in young adult patients in whom disease onset began in childhood.

The main aim of this study was to compare the response to trivalent inactivated influenza vaccine in children who received a kidney transplant and were on steroid-free versus steroid-based immunosuppression. Groups: 1. Kidney transplant recipients on steroid-free immunosuppression (n = 27); 2. Kidney transplant recipients on steroid-based immunosuppression (n = 39); 3. Healthy controls (n = 21). Hemagglutination inhibition titers against 2007–2008 A/H1N1 and A/H3N2 and B strains were measured before and 8 weeks postvaccination. Postvaccination geometric mean titers to A/H1N1 were significantly lower among both transplant groups than controls (p = 0.025 and 0.015, respectively). Postvaccination titers to H3N2 and B strains were not statistically different between groups. Proportions of participants developing seroprotection were not different among groups. Both kidney transplant groups seroconverted less than controls for A/H1N1 (p = 0.0002) and were no different from controls for B. For A/H3N2, the steroid-free group had the weakest seroconversion (p = 0.008), possibly due to mycophenolate-enhanced exposure and a younger age. Overall, children after kidney transplantation demonstrated a good serologic response to the inactivated influenza vaccine although somewhat lower than controls. Steroid-free immunosuppression did not seem to present an advantage in antibody response. Data on inactivated influenza vaccine safety and efficacy was collected and demonstrated absence of acute rejection or laboratory-proven influenza for 6 months postvaccination.

Background and objectives: Long-term outcome of patients with chronic kidney disease (CKD) correlates with adequacy of predialysis care. This is best provided in a multidisciplinary clinic that integrates the services of a nephrologist with other staff. There is limited data about such clinics in children. The Children's Hospital of Michigan established a Chronic Renal Insufficiency (CRI) clinic in 2002 to provide comprehensive care to children with CKD. These children receive care from a nephrologist, nurse clinician, transplant coordinator, dietician, social worker, and psychologist. The objective of the study was to compare outcome variables between patients from the CRI clinic and a general nephrology clinic. Design, setting, participants, & measurements: This was a retrospective chart review of 44 patients with CKD stages 2 to 4, who were managed in the general nephrology clinic (1996–2001, n = 20) or the CRI clinic (2002–2007, n = 24) for 1 yr before starting renal replacement therapy (RRT). Laboratory parameters, growth, and dialysis access type at time of RRT were compared between the two cohorts. Results: At RRT, patients from the CRI clinic had better hemoglobin, lower parathyroid hormone and calcium phosphorus product than patients followed in the general nephrology clinic. More patients from the general nephrology clinic had an unplanned initiation of dialysis compared with patients from the CRI clinic (50% versus 10.5%, P < 0.05). Conclusions: This indicates that children followed in a multidisciplinary clinic have better outcome variables and are more likely to achieve K/DOQI targets at initiation of dialysis. They are better prepared for dialysis with electively planned catheter insertion or functioning arteriovenous grafts/fistulae.

Previous studies have indirectly suggested the prescription of antihypertensive medications may contribute to blood pressure control in dialysis patients. Before exploring this largely unknown field, it is necessary to examine if there is diversity in antihypertensive prescription for dialysis patients. The questionnaire by the Midwest Pediatric Nephrology Consortium was mailed to members of American Society of Pediatric Nephrology holding faculty positions in North America and Puerto Rico. Eighty-three (23.9%) of the mailed 357 surveys were analyzable. End-organ damage (43.2% respondents), interdialytic blood pressure levels (35.1%), achievement of dry weight (29.7%), duration of action of medications (25.7%), and underlying diseases (24.3%) were considered as the most important factor(s) in determining antihypertensive medications. For both hemodialysis and peritoneal dialysis patients, dihydropyridine-calcium channel blockers and angiotensin enzyme inhibitors were the most commonly prescribed medications. On scheduled hemodialysis days, 66.7% respondents withheld morning medications. Among them, two-thirds did not withhold all medications; they preferred withholding direct vasodilators (63.2%) > dihydropyridine-calcium channel blockers (50%) > beta-blockers (25%) > angiotensin enzyme inhibitors (21.9%). 60.7% respondents gave medications back postdialysis and 66.1% held medications only for morning dialysis. For nocturnal peritoneal dialysis patients, 85.9% and 91.1% respondents did not avoid certain medications in the evening and morning, respectively. For continuous ambulatory peritoneal dialysis patients, 10.8% respondents preferred giving medications in the morning while 74.3% had no preference. Antihypertensive prescription is quite diverse among pediatric nephrologists and its clinical significance requires further studies.

Background and objective: Severe edema in children with nephrotic syndrome (NS) may be associated with volume contraction (VC) or volume expansion (VE). Usually, severe edema in children is treated with intravenous (IV) albumin and diuretics, which is appropriate for VC patients. However, in VE patients, this can precipitate fluid overload. The objective of this study was to evaluate treatment of severe edema in NS with diuretics alone. Design, setting, participants, & measurements: Thirty NS patients with severe edema were enrolled in this prospective study in two phases. VC was diagnosed based on fractional excretion of sodium (FeNa)

The aim of this study was to characterize clinical features, treatment response, and outcome of idiopathic membranous glomerulonephritis (MGN) in a single-center cohort of children. A retrospective review of biopsy-proven idiopathic MGN in 12 children (mean age 11.9 years) was undertaken. Presentation was nephrotic syndrome (NS) (75%), hematuria/proteinuria (17%), and asymptomatic proteinuria (8%). Ten patients (83%) with NS and nephrotic range proteinuria (NRP) were treated with prednisone, and two patients with non-NRP were not treated with immunosuppressive medications. Steroid response in the treated patients was complete (10%), partial (40%), and absent (50%), respectively. Oral cyclophosphamide was used in seven patients of whom five were steroid resistant, one was steroid dependent, and one was partially responsive. At the mean follow up of 27 months, outcome parameters included an estimated glomerular filtration rate of 128 cc/min per 1.73 m(2), albumin of 4.2 gm/dL, and a urine protein/creatinine ratio of 0.87 [median 0.16 (range 0.02-6.52)]. Remission was complete in 75% of the patients and partial in 17%. One patient (8%) with chronic kidney disease (stage 2) was unresponsive to therapy. Complete remission was significantly associated with the absence of chronic histological changes (p = 0.03). In conclusion, children with NS and/or NRP associated with MGN appear to have a good prognosis when treated with a combination of corticosteroids and cyclophosphamide.

Chronic kidney disease (CKD) is associated with altered calcium-phosphate homeostasis and hyperparathyroidism due to decreased activity of 1alpha-hydroxylase and impaired activation of 25-hydroxyvitamin D3 [25(OH)D3]. In some patients these problems start earlier because of vitamin D deficiency. A retrospective review of patients followed in the chronic renal insufficiency clinic at Children's Hospital of Michigan assessed the prevalence of vitamin D deficiency in CKD stages 2-4 and evaluated the effect of treatment with ergocalciferol on serum parathormone (PTH). Blood levels of 1,25 dihydroxyvitamin D3, 25(OH)D3, and parathormone (PTH) were examined in 57 children (40 boys; mean age 10.6 years). Of 57 subjects, 44 (77.2%) had 25(OH)D3 levelsor =30 ng/ml, with overall mean of 26.4 +/- 14.3 ng/ml. PTH for patients with 25(OH)D3 levels30 ng/ml was 67.84 +/- 29.09 ng/ml and in the remaining patients was elevated, at 120.36 +/- 86.42 ng/ml (p = 0.05). Following ergocalciferol treatment (22), PTH decreased from 122.13 +/- 82.94 ng/ml to 80.14 +/- 59.24 ng/ml (p0.001) over a period of 3 months. We conclude that vitamin D deficiency is common in children with CKD stages 2-4 and is associated with hyperparathyroidism in the presence of normal 1,25 dihydroxyvitamin D3. Its occurrence before significant renal impairment is noteworthy. Early diagnosis and appropriate treatment is emphasized.

Over the last decade, second and third generation cephalosporins have been the most common drugs causing hemolytic anemia (HA). Of these cases, 20% have been attributed to ceftriaxone. The clinical presentation of ceftriaxone-induced HA is usually abrupt with sudden onset of pallor, tachypnea, cardio-respiratory arrest and shock. Acute renal failure (ARF) has been reported in 41% of such cases with a high fatality rate. We report a pediatric patient with ARF complicating ceftriaxone-induced HA who survived. Ceftriaxone is a commonly used drug, and early recognition of HA and institution of supportive care, including dialysis is likely to improve the outcome.

Central venous lines (CVL) continue to be the most commonly used vascular access device for children on hemodialysis (HD). Despite their frequent use, little is known regarding the frequency of CVL-related intradialytic complications that could interfere with delivery of effective dialysis. To better assess this, we conducted a cross-sectional study of ten HD centers within the Midwest Pediatric Nephrology Consortium. Vascular access was provided by CVL in 61 of the 83 patients (73%) included. CVL dysfunction (defined as reduced blood flows, need for reversed lines, or frequent intradialytic alarms) occurred in 46% in the prior month. Treatment for suspected clots occurred in 16 patients. Intraluminal tissue plasminogen activator (tPA) was the preferred treatment for a suspected clot. The survey also inquired about the preferred treatment for documented clots, and intraluminal tPA was most preferred, followed by CVL stripping, CVL removal, CVL brushing, and systemic tPA. As for preventative strategies, most HD centers locked the CVL with intraluminal heparin in concentrations ranging from 1,000 to 5,000 U/ml. In conclusion, catheter usage rates and complications were highly prevalent in pediatric HD units in this study. As treatment strategies varied greatly, future prospective studies are needed to determine the effectiveness of each individual therapy.

Background. Membranous glomerulopathy accounts for 28% of the biopsy-proven systemic lupus erythematosus nephritis in paediatric patients at the time of first biopsy, yet minimal data are available regarding outcomes in this population. Methods. We present a retrospective analysis of 26 paediatric patients with World Health Organization class V lupus nephritis. Patients were subdivided based on renal biopsy findings into the following subclasses: 16 (63%) Va, 2 (9%) Vb, 7 (26%) Vc and 1 (4%) Vd. We evaluated outcomes of renal function and urine protein to creatinine ratio (UPr/UCr). Results. Mean follow-up time was 38.6 (� 22) months. Eight patients at presentation had a glomerular filtration rate (GFR)

Pseudohyponatremia in idiopathic nephrotic syndrome with severe edema is attributed to hyperlipidemia that results in displacement of a portion of water phase of plasma. Current methods of measurement of serum electrolytes are unaffected by hyperlipidemia. In this report we demonstrate that patients with idiopathic nephrotic syndrome with severe edema and true hyponatremia may have an increased rather than normal osmolal gap. We believe that this could be secondary to non-Na+ and non-K+ osmoles in response to plasma-volume contraction secondary to hypoalbuminemia. This observation has implications for management of severe edema in such patients, because fluid restriction could increase their risk for pre–renal failure.

The use of intravenous immunoglobulin (IVIG) in sensiti- zed transplant candidates has resulted in reduced HLA antibody levels and shorter transplant wait times. In addition, the HLA- Matchmaker program has been used to identify acceptable mis- matches to permit transplantation in highly sensitized patients. We used IVIG desensitization in conjunction with high resolution HLA allele typing and HLAMatchmaker grading of donor offers to facilitate successful transplantation in two highly sensitized children who were awaiting second renal transplants. Both patients lost their initial transplant in

Calciphylaxis is a rare, but life-threatening complication of end-stage renal disease (ESRD) that has been reported mostly in adult patients. The exact etiology is unknown, but the disease is commonly associated with a high calcium-phosphorus product and elevated levels of parathyroid hormone (PTH). We herein review the published reports on calciphylaxis in ESRD patients less than 18 years old and report the case of a patient with severe calciphylaxis who presented with lower extremity pain, muscle tenderness and difficulty in walking. The serum PTH was low, and the calcium-phosphorus product was normal. The diagnosis of calciphylaxis was confirmed by a muscle biopsy. Treatment with low calcium peritoneal dialysate and substitution of calcium-based phosphorus binders with sevelamer (Renagel) was unsuccessful. The patient's clinical condition progressed to extensive soft tissue calcification and ulcerating skin lesions. Nine months after the onset of symptoms, the patient died of cardiopulmonary arrest.

A 17-year-old healthy girl was admitted to our hospital with diffuse abdominal pain and decreased oral intake of about 11 days duration. About a week prior to admission, she had taken naproxen, 250 mg four times a day for 4 days. Physical examination was normal except for diffuse abdominal tenderness on deep palpation. Investigations revealed high serum BUN (42 mg/dl) and creatinine (4.0 mg/dl). Serum electrolytes and complement (C3, C4) levels and urinalysis were normal. Antinuclear-antibody and anti-dsDNA were negative. Kidney biopsy revealed renal papillary necrosis, acute tubular necrosis, and focal interstitial nephritis. A diagnosis of nonoliguric acute renal failure due to naproxen nephrotoxicity was made. She received intravenous hydration, and oral steroids, which was gradually discontinued in 3 months. A follow-up at 4 months revealed normal renal function with a serum creatinine of 1.1 mg/dl, BUN 7 mg/dl, and normal urinalysis. The report highlights a need for caution while using naproxen or any other nonsteroidal anti-inflammatory drugs, even for a short duration.

There has been recent emphasis on increased arteriovenous fistula (AVF) use and decreased central venous catheter use in hemodialysis (HD) patients. The International Pediatric Fistula First Initiative was founded via collaborative effort with the Midwest Pediatric Nephrology Consortium to alert nephrologists, surgeons, and dialysis staff to consider fistulae as the best access in pediatric HD patients. A multidisciplinary educational DVD outlining expectations and strategies to increase AVF placement and usage in children was created. Participants were administered a survey previewing and postviewing to identify barriers to placement and usage of AVF in children. A total of 52 surveys were subdivided as either "dialysis staff" or "proceduralist" at five centers. Thirty-three percent of respondents were unaware if their practice was following published guidelines. Sixty-five percent of respondents stated they referred to a dedicated vascular access surgeon at their respective institutions. Methods used to monitor AVF function included physical exam, venous pressure monitoring, and ultrasound dilution. Vascular access was placed within 3 months in only 35% of patients. Interdisciplinary communication problems between surgeons, interventional radiologists, and nephrologists were identified as a major barrier. Lack of AVF usage was often due to maturation failure. Routine access rounds did not occur in any centers. Regarding monitoring, 74% of the respondents use physical exam, 26% use venous pressure monitoring, and 9% use ultrasound dilution. Ninety-three percent of dialysis staff stated they would change practice patterns following the intervention; however, 12% of surgeons stated they would alter practice patterns. To our knowledge, this is the first report to identify barriers to placement of AVF in children from the perspectives of multidisciplinary team members including pediatric nephrologists, surgeons, interventional radiologists, and multidisciplinary dialysis staff.

Vasculitis associated with antineutrophil cytoplasmic autoantibodies (ANCA) can be accompanied by a focal and necrotizing glomerulonephritis that carries a high morbidity. As many as 60% of reported children with ANCA-associated glomerulonephritis progress to end-stage renal disease. Seven children (13.0+/-0.89 years, mean age +/- SEM) with both a focal and necrotizing glomerulonephritis and a positive ANCA titer are described. Presenting symptoms were constitutional (100%) and sinopulmonary (71%); additional renal features included microscopic hematuria (100%), proteinuria (71%), and renal insufficiency (71%). Acute therapy (0 to 2 weeks from diagnosis) included intravenous corticosteroids and intravenous cyclophosphamide for all patients. Induction therapy (2 weeks to 6 months from diagnosis) consisted of cyclophosphamide (100%) and daily corticosteroids (86%) for a minimum of 6 months. Maintenance therapy that followed 6 months of induction therapy consisted of alternate day steroids (100%) combined with either oral azathioprine (50%) or oral cyclophosphamide (50%). Long-term follow-up for 48+/-12 months in all seven patients revealed that only one (14%) patient had end-stage renal disease, whereas the remaining patients had microscopic hematuria (100%), proteinuria (50%), and renal insufficiency (33%). These findings suggest that early recognition and aggressive treatment of children with ANCA-associated glomerulonephritis and vasculitis may result in an improved renal outcome compared with previous reports.

Sir, We read with great interest the letter sent to your journal by Hirano and Fujinaga [1] in which they describe a retrospective review of children with idiopathic nephrotic syndrome (NS) weighing 30 kg or less at their institution. Based on their results, they concluded that the onset time for relapses after initial therapy was significantly shorter for children in the body weight (BW)-based dosing group than those in the body surface area (BSA)-based group. They also found that the proportion of steroid-dependent NS was significantly higher among children in the BW-based dosing group than among those in the BSA-based group. As acknowledged by these authors, their study findings are limited by the retrospective nature of the study design as well as the small number of patients in each group. The findings of Hirano et al., similar to those which we previously published in Pediatric Nephrology [2], indicate that BW-based dosing andBSA-dosing of steroids are not equivalent when treating patients with idiopathic NS weighing