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Background: Bloodstream infections (BSIs) are a leading cause of hospitalizations and mortality among patients receiving hemodialysis (HD) therapy, especially those with a central venous catheter (CVC) for dialysis access. The use of chlorhexidine impregnated catheter caps (ClearGuard) has been associated with a decrease in the rate of HD catheter-related BSIs (CA-BSIs) in adults; similar data have not been published for children. Methods: We compared CA-BSI data from participating centers within the Standardizing Care to Improve Outcomes in Pediatric Endstage Kidney Disease (SCOPE) collaborative based on the center's use of ClearGuard caps for patients with HD catheter access. Centers were characterized as ClearGuard (CG) or non-ClearGuard (NCG) centers, with CA-BSI data pre- and post-CG implementation reviewed. All positive blood cultures in participating centers were reported to the SCOPE collaborative and adjudicated by an infectious disease physician. Results: Data were available from 1786 SCOPE enrollment forms completed January 2016–January 2022. January 2020 served as the implementation date for analyzing CG versus NCG center data, with this being the time when the last CG center underwent implementation. Post January 2020, there was a greater decrease in the rate of HD CA-BSI in CG centers versus NCG centers, with a decrease from 1.18 to 0.23 and 0.41 episodes per 100 patient months for the CG and NCG centers, respectively (p = 0.002). Conclusions: Routine use of ClearGuard caps in pediatric dialysis centers was associated with a reduction of HD CA-BSI rates in pediatric HD patients. [ABSTRACT FROM AUTHOR]

Post-infectious glomerulonephritis (PIGN) is an immune complex mediated glomerular injury occurring because of an infection, most commonly with group A beta-hemolytic streptococcus in children. C3 glomerulopathy (C3G) is a distinct clinicopathological entity occurring secondary to dysregulation of alternate complement pathway encompassing both C3 glomerulonephritis (C3GN) and dense deposit disease (DDD). While most patients with PIGN attain complete remission with normalized complement levels by 6–8 weeks after presentation, patients with C3G continue to have hypocomplementemia with high rates of progressive kidney disease. Here, we report a patient diagnosed with dense deposit disease after his initial presentation with PIGN three years prior. While current literature continues to explore the overlapping and distinguishing features of PIGN and C3G, including how underlying defects in the alternate complement pathway may commonly contribute to both diseases, this case further exemplifies the importance of recognizing the clinico-pathogenic features of PIGN and C3G in pediatric patients with glomerulonephritis. [ABSTRACT FROM AUTHOR]

A correction is presented to the article "Use of ClearGuard HD caps in pediatric hemodialysis patients" published in a previous issue of the periodical.

Background: C3 glomerulopathy (C3G) is defined by dominant glomerular deposition of C3 and minimal or no immunoglobulin, with two subtypes—dense deposit disease (DDD) and C3 glomerulonephritis (C3GN)—distinguished by features on electron microscopy (EM). Given that this rare disease has generally unfavorable yet highly variable outcomes, we sought out to review the histopathology, complement/genetic studies, and renal outcomes of pediatric patients with C3G at our institution. Methods: All native kidney biopsies performed in a single pediatric hospital over a 10-year period were reviewed for features of C3G. Of 589 biopsy reports, we identified 9 patients fulfilling the diagnostic criteria for C3G and retrospectively reviewed their clinical chart and renal biopsy findings. Results: We identified 4 patients with DDD, 4 with C3GN, and 1 indeterminate case, with features of both C3GN and DDD. Five patients were positive for one or more nephritic factors (C3NeF, C4NeF, C5NeF) with 1 patient additionally positive for complement factor H (CFH) autoantibody. Genetic testing done in 5 of the 9 patients failed to identify any causative mutations. Three patients showed progressive renal dysfunction over a mean follow-up period of 33 months. Conclusions: Complement and genetic studies are now routinely recommended for patients with a histopathological diagnosis of C3G. Careful interpretation of these studies and their prognostic and therapeutic implications in conjunction with biopsy findings is needed to further understand the pathophysiology of this rare disease in children. [ABSTRACT FROM AUTHOR]

Background: Strategies to expand numbers of deceased donor kidneys suitable for pediatric recipients are urgently needed to prevent long-term dialysis-associated morbidity and mortality. Donors designated as increased risk of disease transmission (IRD) are infrequently used in pediatric recipients. We examined outcomes of these kidneys in pediatric patients and the potential to increase the donor pool. Methods: The United Network for Organ Sharing (UNOS) database records presence of IRD in all deceased donors since 2004. All pediatric kidney transplant recipients from 2004 to 2017 were identified and stratified by IRD status, and outcomes were examined. Results: Four hundred seventy-three pediatric kidney transplant recipients received an IRD allograft. IRD donors had lower kidney donor profile index (KDPI); were more likely to be younger, male, and Caucasian; and were more likely to have used drugs. IRD kidneys were more likely to have been biopsied and placed on pulsatile perfusion. Other than an older recipient age, demographic data were not different between groups. Allograft and patient survivals were similar, as were rejection and delayed graft function rates. Compared with adult recipients and adult IRD recipients, pediatric recipients were more likely to have a younger donor, receive a kidney with a lower creatinine, and were less likely to have delayed graft function (p < 0.05). There were no recorded disease transmissions in IRD group. Conclusions: Patient and allograft survivals are similar in IRD and non-IRD kidneys. High-quality IRD organs used in adults represent a large number of donors with excellent outcomes. IRD allografts have a potential to increase transplant volume and should be considered for pediatric patients. [ABSTRACT FROM AUTHOR]

The adult kidney maintains a constant volume and composition of extracellular fluid despite changes in water and salt intake. The neonate is born with a kidney that has a small fraction of the glomerular filtration rate of the adult and immature tubules that function at a lower capacity than that of the mature animal. Nonetheless, the neonate is also able to maintain a constant extracellular fluid volume and composition. Postnatal renal tubular development was once thought to be due to an increase in the transporter abundance to meet the developmental increase in glomerular filtration rate. However, postnatal renal development of each nephron segment is quite complex. There are isoform changes of several transporters as well as developmental changes in signal transduction that affect the capacity of renal tubules to reabsorb solutes and water. This review will discuss neonatal tubular function with an emphasis on the differences that have been found between the neonate and adult. We will also discuss some of the factors that are responsible for the maturational changes in tubular transport that occur during postnatal renal development. [ABSTRACT FROM AUTHOR]

This study examined whether postnatal maternal dietary protein deprivation during the time of nursing can program hypertension when the offspring are studied as adults. Rats were fed either a 6% or 20% protein diet during the second half of pregnancy and continued on the same diet while rats were nursing their pups. The neonates of all of the rats were cross-fostered to a different mother and studied as adults. Adult rats that had a normal prenatal environment but were reared by mothers fed a low-protein diet until weaning (20%-6%) were hypertensive, had a higher renal Na+-K+-2Cl− cotransporter (NKCC2) and Na+-Cl− cotransporter (NCC) protein abundance yet a comparable number of glomeruli, and had higher plasma renin and angiotensin II levels compared to control (20%-20%). Rats whose mothers were fed a 6% protein diet and cross-fostered to a different rat fed a 6% protein diet until weaning (6%-6%) were hypertensive, had elevated plasma renin and angiotensin II levels, and had a reduction in nephron number but had NKCC2 and NCC levels comparable to 20% to 20% offspring. The 6% to 20% had blood pressure and glomerular numbers comparable to 20% to 20% rats. The hypertension resulting from prenatal dietary protein deprivation can be normalized by improving the postnatal environment. Combined prenatal and postnatal maternal dietary protein deprivation and maternal dietary protein deprivation while nursing alone (20%-6%) results in hypertension, but the mechanism for the hypertension in these groups is different. [ABSTRACT FROM PUBLISHER]

Regulation of phosphate homeostasis is critical for many biological processes, and both hypophosphatemia and hyperphosphatemia can have adverse clinical consequences. Only a very small percentage (1%) of total body phosphate is present in the extracellular fluid, which is measured by routine laboratory assays and does not reflect total body phosphate stores. Phosphate is absorbed from the gastrointestinal tract via the transcellular route [sodium phosphate cotransporter 2b (NaPi2b)] and across the paracellular pathway. Approximately 85% of the filtered phosphate is reabsorbed from the kidney, predominantly in the proximal tubule, by NaPi2a and NaPi2c, which are present on the brush border membrane. Renal phosphate transport is tightly regulated. Dietary phosphate intake, parathyroid hormone (PTH), 1,25 (OH)2 vitamin D3, and fibroblast growth factor 23 (FGF23) are the principal regulators of phosphate reabsorption from the kidney. Recent advances in genetic techniques and animal models have identified many genetic disorders of phosphate homeostasis. Mutations in NaPi2a and NaPi2c; and hormonal dysregulation of PTH, FGF23, and Klotho, are primarily responsible for most genetic disorders of phosphate transport. The main focus of this educational review article is to discuss the genetic and clinical features of phosphate regulation disorders and provide understanding and treatment options. [ABSTRACT FROM AUTHOR]

There are a number of hypophosphatemic disorders due to renal phosphate wasting that cannot be explained by elevated levels of parathyroid hormone. The circulating factors responsible for the phosphaturia have been designated as phosphatonins. Studies of patients with tumor-induced osteomalacia and other genetic diseases of phosphate metabolism have resulted in the identification of a number of hormones that regulate phosphate homeostasis, including matrix extracellular phosphoglycoprotein (MEPE), secreted frizzled-related protein 4 (sFRP-4), dentin matrix protein 1 (DMP1), fibroblast growth factor 7 (FGF7), fibroblast growth factor 23 (FGF23), and Klotho. Our understanding of the actions of these hypophosphatemic peptides has been enhanced by studies in mice either overexpressing or not expressing these hormones. This review focuses on FGF23 since its regulation is disordered in diseases that affect children, such as X-linked hypophosphatemia, autosomal dominant and recessive hypophosphatemic rickets as well as chronic kidney disease. Recent studies have shown that FGF23 is unique among the FGFs in its requirement for Klotho for receptor activation. Here, we also discuss new potentially clinically important data pointing to the receptor(s) that mediate the binding and action of FGF23 and Klotho. [ABSTRACT FROM AUTHOR]

Phosphate is essential for numerous biological processes, and serum levels are tightly regulated to accomplish these functions. The regulation of serum phosphate in a narrow physiological range is a well-orchestrated process and involves the gastrointestinal (GI) tract, bone, kidneys, and several hormones, namely, parathyroid hormone, fibroblast growth factor 23 (FGF23), and 1,25-dihydroxyvitamin D (1,25 Vitamin D). Although primarily synthesized in the bone, FGF23, an endocrine FGF, acts on the kidney to regulate phosphate and Vitamin D homeostasis by causing phosphaturia and reduced levels of 1,25 Vitamin D. Recent studies have highlighted the complex regulation of FGF23 including transcriptional and post-translational modification and kidney-bone cross talk. Understanding FGF23 biology has led to the identification of novel therapeutic agents to treat diseases that disrupt phosphate metabolism secondary to FGF23. The focus of this review is to provide an overview of phosphate homeostasis, FGF23 biology, and the role of FGF23 in phosphate balance.A higher resolution version of the Graphical abstract is available as Supplementary informationA higher resolution version of the Graphical abstract is available as Supplementary informationGraphical abstract: Phosphate is essential for numerous biological processes, and serum levels are tightly regulated to accomplish these functions. The regulation of serum phosphate in a narrow physiological range is a well-orchestrated process and involves the gastrointestinal (GI) tract, bone, kidneys, and several hormones, namely, parathyroid hormone, fibroblast growth factor 23 (FGF23), and 1,25-dihydroxyvitamin D (1,25 Vitamin D). Although primarily synthesized in the bone, FGF23, an endocrine FGF, acts on the kidney to regulate phosphate and Vitamin D homeostasis by causing phosphaturia and reduced levels of 1,25 Vitamin D. Recent studies have highlighted the complex regulation of FGF23 including transcriptional and post-translational modification and kidney-bone cross talk. Understanding FGF23 biology has led to the identification of novel therapeutic agents to treat diseases that disrupt phosphate metabolism secondary to FGF23. The focus of this review is to provide an overview of phosphate homeostasis, FGF23 biology, and the role of FGF23 in phosphate balance.A higher resolution version of the Graphical abstract is available as Supplementary informationA higher resolution version of the Graphical abstract is available as Supplementary information [ABSTRACT FROM AUTHOR]

While metabolic acidosis is one of the most common complications in patients with chronic kidney disease (CKD), there are several uncommon etiologies that are challenging to diagnose. Here, we describe a patient on peritoneal dialysis who developed high anion gap metabolic acidosis secondary to acquired 5-oxoprolinemia from acetaminophen use. While CKD is a known risk factor for developing this potentially serious complication, this case further highlights how 5-oxoproline accumulation can occur, even with therapeutic dosing of acetaminophen. [ABSTRACT FROM AUTHOR]