Atypical Antiglomerular Basement Membrane Disease in a Pediatric Patient Successfully Treated with Rituximab.

Classic antiglomerular basement membrane (anti-GBM) disease is an exceedingly rare but extremely aggressive form of glomerulonephritis, typically caused by autoantibodies directed against cryptic, conformational epitopes within the noncollagenous domain of the type IV collagen alpha-3 subunit. Pathologic diagnosis is established by the presence of strong, diffuse, linear staining for immunoglobulin on immunofluorescence microscopy. Recently, patients with atypical clinical and pathologic findings of anti-GBM disease have been described. These patients tend to have an indolent clinical course, without pulmonary involvement, and laboratory testing rarely reveals the presence of anti-GBM antibodies. Specific guidelines for the treatment and management of these patients are unclear. Here, we describe a case of atypical anti-GBM disease in a young child who presented with hematuria and prominent proteinuria. Throughout the course of his illness, creatinine remained normal. He was conservatively treated with steroids and rituximab, resulting in resolution of his clinical symptoms and normalization of laboratory findings.

Community-Based Epidemiology of Hospitalized Acute Kidney Injury.

BACKGROUND: Acute kidney injury (AKI) may lead to short- and long-term consequences in children, but its epidemiology has not been well described at a population level and outside of ICU settings. METHODS: In a large, diverse pediatric population receiving care within an integrated health care delivery system between 2008 and 2016, we calculated age- and sex-adjusted incidences of hospitalized AKI using consensus serum creatinine (SCr)-based diagnostic criteria. We also investigated the proportion of AKI detected in non-ICU settings and the rates of follow-up outpatient SCr testing after AKI hospitalization. RESULTS: Among 1 500 546 children, the mean age was 9.8 years, 49.0% were female, and 33.1% were minorities. Age- and sex-adjusted incidence of hospitalized AKI among the entire pediatric population did not change significantly across the study period, averaging 0.70 (95% confidence interval: 0.68-0.73) cases per 1000 person-years. Among the subset of hospitalized children, the adjusted incidence of AKI increased from 6.0% of hospitalizations in 2008 to 8.8% in 2016. Approximately 66.7% of AKI episodes were not associated with an ICU stay, and 54.3% of confirmed, unresolved Stage 2 or 3 AKI episodes did not have outpatient follow-up SCr testing within 30 days postdischarge. CONCLUSIONS: Community-based pediatric AKI incidence was ∼1 per 1000 per year, with two-thirds of cases not associated with an ICU stay and more than one-half not receiving early outpatient follow-up kidney function testing. Further efforts are needed to increase the systematic recognition of AKI in all inpatient settings with appropriate, targeted postdischarge kidney function monitoring and associated management.

Hypercalcemia: a consultant's approach.

Due to their daily involvement in mineral metabolism, nephrologists are often asked to consult on children with hypercalcemia. This might become even more pertinent when the hypercalcemia is associated with acute kidney injury and/or hypercalciuria and renal calcifications. The best way to assess the severity of hypercalcemia is by measurement of plasma ionized calcium, and if not available by adjusting serum total calcium to albumin concentration. The differential diagnosis of the possible etiologies of the disturbance in the mineral homeostasis starts with the assessment of serum parathyroid hormone concentration, followed by that of vitamin D metabolites in search of both genetic and acquired etiologies. Several tools are available to acutely treat hypercalcemia with the current main components being fluids, loop diuretics, and antiresorptive agents. This review will address the pathophysiologic mechanisms, clinical manifestations, and treatment modalities involved in hypercalcemia.

Hyperammonemia in review: pathophysiology, diagnosis, and treatment.

Ammonia is an important source of nitrogen and is required for amino acid synthesis. It is also necessary for normal acid-base balance. When present in high concentrations, ammonia is toxic. Endogenous ammonia intoxication can occur when there is impaired capacity of the body to excrete nitrogenous waste, as seen with congenital enzymatic deficiencies. A variety of environmental causes and medications may also lead to ammonia toxicity. Hyperammonemia refers to a clinical condition associated with elevated ammonia levels manifested by a variety of symptoms and signs, including significant central nervous system (CNS) abnormalities. Appropriate and timely management requires a solid understanding of the fundamental pathophysiology, differential diagnosis, and treatment approaches available. The following review discusses the etiology, pathogenesis, differential diagnosis, and treatment of hyperammonemia.

Pediatric renal supportive therapies: the changing face of pediatric renal replacement approaches.

PURPOSE OF REVIEW: The term 'renal replacement therapy' has been employed for describing dialytic interventions for acute and chronic patients. The implications of this terminology do not correctly reflect the extent that we are able to address native renal function. Provision of correct terminology to describe dialytic therapies may provide insight and investigation into the 'nonreplaceable' aspects of renal function in the acute and chronic settings. RECENT FINDINGS: The terms 'chronic kidney disease' and 'acute kidney injury' have replaced the terms chronic renal failure and acute renal failure, respectively. Changing terminology has improved definitions and clinical care in these patient groups. Improvements in dialytic therapies have not been paralleled by changes in our understanding of the native renal function components that are not replaced during dialysis. SUMMARY: A paradigm shift in our understanding of replacement of renal function is necessary. The terminology of 'renal replacement therapy' should be supplanted by more appropriate terminology, 'renal supportive therapy'. The benefits of employing terminology that adequately reflects the extent to which we can offer supportive dialytic treatment to our acute and chronic patients may be realized as a significant stimulus for scientific investigation and clinical care improvements.

Urine calcium/citrate ratio in children with hypercalciuric stones.

Hypercalciuria is a common cause for stone formation in children. The aim was to delineate the role of urinary citrate in hypercalciuric children for protection against calcium stone formation. We evaluated random urine calcium, citrate, and creatinine in 149 controls, 78 hypercalciuric nonstone formers, and 34 hypercalciuric children with stone. Urine citrate/creatinine was highest in hypercalciuric nonstone formers 899 +/- 351 compared with controls 711 +/- 328 and stone formers 595 +/- 289 (p < 0.01 vs. both). Calcium/creatinine ratio was similar in hypercalciuric stone and nonstone formers, but significantly higher than controls. Consequently, urine calcium/citrate ratio (mg/mg) increased from control 0.17 +/- 0.17 to 0.41 +/- 0.23 (p < 0.001) in hypercalciuric nonstone formers, and to 0.65 +/- 0.46 in stone formers (p < 0.001 compared with other groups). Area under receiver operating characteristic curve combined with multilevel risk analyses found calcium/citrate ratio of 0.326 to provide good discrimination between control and stone formers. We found 5th percentile for random urine citrate/creatinine ratio in school-aged children to be 176 mg/g, elevated urinary citrate excretion in hypercalciuric children to be protective against stone formation, and urine calcium/citrate ratio to be a good indicator for risk of stone formation. Whether intervention in hypercalciuric children to lower urine calcium/citrate <0.326 will provide protection against stone formation needs to be studied.

Effect of amphotericin B lipid complex (ABLC) in very low birth weight infants.

The aim of this retrospective, case-control study was to determine the effect of the amphotericin B lipid complex (ABLC) on serum creatinine (SCr), blood urea nitrogen (BUN), sodium (Na), and potassium (K) in very low birth weight (VLBW) infants. Medical records of all VLBW infants who were admitted to our Neonatal Intensive Care Unit between May 1998 and May 2006 and had received ABLC for at least 2 weeks were reviewed for patient demographics, use of medications (ABLC, diuretics, xanthines, indomethacin, vancomycin, gentamicin, pressors, and inotropes), fluid intake, urinary output, and serum electrolytes. Thirty-five patients who received ABLC were identified and matched by gestational age (GA) to 35 patients who served as controls. Infants who received ABLC had an average GA of 25.7 +/- 2.1 weeks and a birth weight of 764 +/- 196 g. Between day 1 and 14 of ABLC treatment, the BUN decreased from 17.5 +/- 11.5 to 10.5 +/- 6.8 mg/dl (p = 0.01), the SCr varied between 0.78 +/- 0.32 and 0.69 +/- 0.32 mg/dl, Na varied between 136.6 +/- 5.8 and 137.8 +/- 3.6 mEq/l, and K varied between 4.8 +/- 0.9 and 4.9 +/- 0.6 mEq/l, respectively. Based on these results, we conclude that treatment with ABLC for 2 weeks did not increase BUN or SCr, nor decrease Na or K in VLBW infants.

Reversal of hypercalcemic acute kidney injury by treatment with intravenous bisphosphonates.

We present the details of three children with hypercalcemia-induced acute kidney injury (AKI). After traditional therapy with fluids, loop diuretics, steroids and calcitonin had failed to correct the hypercalcemia, they were given treatment with low doses of intravenous (i.v.) pamidronate, which resulted in normalization of serum calcium and kidney function. In one child Doppler renal ultrasound revealed dampened arterial blood flow, which resolved with normalization of serum calcium. On the basis of cumulative data and our experience, we suggest that i.v. application of bisphosphonates be moved from the second to the first line of treatment of hypercalcemic AKI.

Use of the multipurpose drainage catheter for the provision of acute peritoneal dialysis in infants and children.

BACKGROUND: Prior experience with the Cook (Cook Inc, Bloomington, IN) Teflon rigid catheter (CTC) showed it to be a suboptimal access for acute peritoneal dialysis (PD) treatment in infants and children because of the frequency of catheter-related complications associated with its use. The objective of this study is to report our experience with the bedside-placed flexible Cook Mac-Loc Multipurpose Drainage catheter (CMMDC) for acute PD in critically ill infants, comparing it with the historic Tenckhoff catheter (TC) and CTC use. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: All patients with acute renal failure (ARF) seen in our institution between December 2003 and April 2005 who underwent CMMDC placement for acute PD are included. PREDICTOR: CTCs versus CMMDCs versus TCs. OUTCOMES & MEASUREMENTS: Catheter-related complications and catheter-free survival. RESULTS: 21 infants and children with ARF were treated with acute PD using a CMMDC; 16 patients were post-cardiac surgery and 5 had other diagnoses. Mean patient age was 6.9 +/- 14.4 (SD) months (range, 4 days to 5.2 years; median, 1.6 months). Of 21 catheters, 3 had complications, and in 2 patients, this precluded continuation of PD therapy. In the remaining 18 patients, catheter use continued until recovery from ARF or nonrenal death. All patients achieved target fluid and solute removal with no catheter-related infectious complications. Mean complication-free survival of CMMDCs was 10.5 +/- 7.9 days (range, 2 to 29 days), with the 90% probability of survival at 14 days. Although there was no significant difference between lengths of complication-free survival of CMMDCs and TCs (58 days; P = 0.57), the difference between CMMDCs and CTCs (6 days) was significant (P < 0.001). Likewise, incidences of catheter-related complications with TCs and CMMDCs were similar, and in both cases, significantly less than the incidence associated with CTCs (49%; P < 0.01). LIMITATIONS: Small number of patients and comparison with historic experience. CONCLUSIONS: Use of CMMDCs is associated with the provision of effective dialysis with a satisfactory complication-free survival and should be considered when bedside placement of an acute PD access in infants and children is desired.

Prevention of peritonitis in children receiving peritoneal dialysis.

Peritonitis and catheter-related (exit-site/tunnel) infections are major causes of morbidity in children receiving peritoneal dialysis (PD). Our objective was to evaluate the impact of a combination of prophylactic measures on the rate of peritonitis and catheter-related infections subsequent to their implementation in 2001. This is a single center review of incident patients who received automated peritoneal dialysis (APD) from 1997 to 2004. The causal microorganisms, annualized peritonitis and catheter-related infections rates and the time to infection were reviewed using pooled data from 1997 to 2000 and from 2001 to 2004. Fifty-four patients received PD over 1099 patient months (pm). Twenty-eight peritonitis episodes occurred in 15 patients over 599 pm from 1997 to 2000 (annualized rate (AR): 0.56 infections/patient year). Eight episodes of peritonitis occurred in five patients over 500 pm from 2001 to 2004 (AR: 0.19 infections/patient year) (P = 0.01). Prior to 2001, the median time from dialysis initiation to the first peritonitis episode was 500 days (95% CI, 400-660 days), compared to 1137 days (95% CI, 1050 to +Infinity) from 2001 to 2004 (P = 0.008). The rate of catheter-related infections and time to initial infection during the two periods was not different. We conclude that measures to decrease the frequency of peritonitis can be successfully applied to children and should be incorporated as part of standard care.

Sustained beneficial effect of intravenous bisphosphonates after their discontinuation in children.

We studied if the beneficial effects of bisphosphonates are maintained after their discontinuation, and whether adverse effects may develop. Seventeen children in whom I.V. bisphosphonates were discontinued for at least 12 months were included. Fracture rate (FR), skeletal pain, bone mineral density of total body (TB) and spine L(2-4), skeletal radiographs, bone markers and kidney functions were compared between: (a) before treatment, (b) end of treatment, and (c) last follow-up. Mean treatment duration was 22+/-2 months (6-43) and follow-up 26+/-2 months (18-44). FR (mean +/- SD) decreased from 0.74+/-0.21/year before treatment to 0.35+/-0.11/year after treatment and 0.20+/-0.09/year at follow-up (p<0.05). Three children had bone pain before treatment, six during treatment and none at end of follow-up (p<0.05). TB Z-score increased from -1.24+/-0.50 at baseline to -0.37+/-0.44 at end of treatment and -0.39+/-0.37 at follow-up (p<0.05). Spinal Z-score increased from -1.65+/-0.57 to -0.34+/-0.56 and 0.19+/-0.49, respectively (p<0.05). Bone turnover markers showed sustained effect of bisphosphonates. No adverse effects on kidney functions or skeletal radiographs were noted. We conclude that I.V. bisphosphonates continue to exert their beneficial effect for a mean of 26+/-2 months after their discontinuation; therefore, once therapeutic goals are achieved, the medication can be withheld, followed by periodic re-evaluation.

Nephrogenic fibrosing dermopathy in children.

Nephrogenic fibrosing dermopathy (NFD) is an entity of unknown etiology that has only been reported in patients with impaired kidney function. It has characteristic diagnostic findings by skin biopsy and due to its systemic involvement in some reported cases, the term "nephrogenic systemic fibrosis" has been recently suggested as more appropriate for the nomenclature of this entity. There is no curative treatment currently available and very few cases have been reported in children. We hereby report two cases so as to alert pediatric health care providers about the existence of this disorder.

Resolution of medullary nephrocalcinosis in children with metabolic bone disorders.

Ultrasonographic resolution of nephrocalcinosis (NC) has been reported in children with furosemide-induced NC, but not in other entities. We report the cases of four children with metabolic bone disease, two with hypophosphatasia and two with X-linked hypophosphatemic rickets, in whom we observed resolution of renal calcifications. At the time of ultrasonographic resolution of NC, 3 of the patients were on anticalciuric diuretics, and all 4 had normal urinalysis, serum creatinine and electrolyte profiles, as well as estimated creatinine clearance. In 3 of the children, evidence of mild tubular dysfunction was found. It thus seems that in some children with bone and mineral disorders who develop NC, ultrasonographic resolution of the renal calcifications can be seen; however, mild tubular dysfunction may remain and require follow-up. Further studies are suggested to explore the possible role of anticalciuric diuretics in promoting the resolution of NC.

Nefrocalsinosis en niños / Nefrocalcinosis in children

Con el advenimiento de estudios de imagen altamente sensibles, como el ultrasonido y la tomografía computada, la nefrocalcinosis (NC) se diagnostica más frecuentemente. Mientras que en muchos casos la NC puede manifestarse de forma leve y reversible, en otros casos puede ser progresiva, causando inicialmente daño tubular y posteriormente daño glomerular. Por lo tanto, el diagnóstico temprano e intervención apropiada son de crucial importancia. Esta revisión abarcará aspectos de la NC en niños, incluyendo etiología, patogénesis, prevención y tratamiento

Nefrocalsinosis en niños / Nefrocalcinosis in children

Con el advenimiento de estudios de imagen altamente sensibles, como el ultrasonido y la tomografía computada, la nefrocalcinosis (NC) se diagnostica más frecuentemente. Mientras que en muchos casos la NC puede manifestarse de forma leve y reversible, en otros casos puede ser progresiva, causando inicialmente daño tubular y posteriormente daño glomerular. Por lo tanto, el diagnóstico temprano e intervención apropiada son de crucial importancia. Esta revisión abarcará aspectos de la NC en niños, incluyendo etiología, patogénesis, prevención y tratamiento(AU)

Proteinuria in rats induced by serum from patients with collapsing glomerulopathy.

BACKGROUND: Primary collapsing glomerulopathy recurs postransplant, raising the possibility of circulating factors implicated in the pathogenesis of the disease. METHODS: To determine the presence of circulating factors in collapsing glomerulopathy patients, we tested serum from those patients in an in vivo assay. Eleven groups of rats received serum from collapsing glomerulopathy patients, idiopathic focal segmental glomerulosclerosis (FSGS) or healthy subjects in its native form, isolated IgG, or serum without IgG. The presence of proteinuria and creatinine clearance were determined. Histopathologic analysis included light, immunofluorescence, and electron microscopy. RESULTS: Collapsing glomerulopathy rats developed proteinuria while rats injected with serum from FSGS and healthy subjects did not. Rats injected with serum of collapsing glomerulopathy in its native form developed marked proteinuria (99.2 +/- 42 mg/24 hours at day 5, P= 0.0001, compared to the baseline), and decreased in creatinine clearance. Rats receiving isolated IgG or serum without IgG from collapsing glomerulopathy developed mild proteinuria (46.5 +/- 8.4 mg/24 hours and 30.9 +/- 11 mg/24 hours, respectively, at day 5 (P= 0.0001). Glomerular tuft retraction and podocyte damage were seen only in collapsing glomerulapthy rats. No abnormalities were found in rats injected with serum from FSGS or healthy subjects. CONCLUSION: Circulating factors in the serum of collapsing glomerulopathy patients produce podocyte damage, whereas such factors are not present in noncollapsing FSGS. IgG eluates from collapsing glomerulopathy produce proteinuria when injected into the rat. Such factors remain in the circulation when serum of patients is adsorbed into protein A, raising the possibility that there are more than one circulating factor present in patients with collapsing glomerulopathy.