Congenital anomalies of the kidneys or lower urinary tract (CAKUT) encompass a spectrum of anomalies that result from aberrations in spatio-temporal regulation of genetic, epigenetic, environmental, ...and molecular signals at key stages of urinary tract development. The Rearranged in Transfection (RET) tyrosine kinase signaling system is a major pathway required for normal development of the kidneys, ureters, peripheral and enteric nervous systems. In the kidneys, RET is activated by interaction with the ligand glial cell line-derived neurotrophic factor (GDNF) and coreceptor GFRα1. This activated complex regulates a number of downstream signaling cascades (PLCγ, MAPK, and PI3K) that control proliferation, migration, renewal, and apoptosis. Disruption of these events is thought to underlie diseases arising from aberrant RET signaling.
RET
mutations are found in 5–30 % of CAKUT patients and a number of Ret mouse mutants show a spectrum of kidney and lower urinary tract defects reminiscent of CAKUT in humans. The remarkable similarities between mouse and human kidney development and in defects due to
RET
mutations has led to using RET signaling as a paradigm for determining the fundamental principles in patterning of the upper and lower urinary tract and for understanding CAKUT pathogenesis. In this review, we provide an overview of studies in vivo that delineate expression and the functional importance of RET signaling complex during different stages of development of the upper and lower urinary tracts. We discuss how RET signaling balances activating and inhibitory signals emanating from its docking tyrosines and its interaction with upstream and downstream regulators to precisely modulate different aspects of Wolffian duct patterning and branching morphogenesis. We outline the diversity of cellular mechanisms regulated by RET, disruption of which causes malformations ranging from renal agenesis to multicystic dysplastic kidneys in the upper tract and vesicoureteral reflux or ureteropelvic junction obstruction in the lower tract.
International guidelines suggest a target culture-negative peritonitis rate of <15% among patients receiving long-term peritoneal dialysis. Through a pediatric multicenter dialysis collaborative, we ...identified variable rates of culture-negative peritonitis among participating centers. We sought to evaluate whether specific practices are associated with the variability in culture-negative rates between low- and high-culture-negative rate centers.
Thirty-two pediatric dialysis centers within the Standardizing Care to Improve Outcomes in Pediatric End Stage Renal Disease (SCOPE) collaborative contributed prospective peritonitis data between October 1, 2011 and March 30, 2017. Clinical practice and patient characteristics were compared between centers with a ≤20% rate of culture-negative peritonitis (low-rate centers) and centers with a rate >20% (high-rate centers). In addition, centers completed a survey focused on center-specific peritoneal dialysis effluent culture techniques.
During the 5.5 years of observation, 1113 patients had 1301 catheters placed, totaling 19,025 patient months. There were 620 episodes of peritonitis in 378 patients with 411 catheters; cultures were negative in 165 (27%) peritonitis episodes from 125 (33%) patients and 128 (31%) catheters. Low-rate centers more frequently placed catheters with a downward-facing exit site and two cuffs (
<0.001), whereas high-rate centers had more patients perform dialysis themselves without the assistance of an adult care provider (
<0.001). The survey demonstrated that peritoneal dialysis effluent culture techniques were highly variable across centers. No consistent practice or technique helped to differentiate low- and high-rate centers.
Culture-negative peritonitis is a frequent complication of maintenance peritoneal dialysis in children. Despite published recommendations for dialysis effluent collection and culture methods, great variability in culture techniques and procedures exists among individual dialysis programs and respective laboratory processes.
Background and objectives
Steroid-resistant nephrotic syndrome (SRNS) due to focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) is a leading cause of end-stage kidney disease ...in children. Recurrence of primary disease following transplantation is a major cause of allograft loss. The clinical determinants of disease recurrence are not completely known. Our objectives were to determine risk factors for recurrence of FSGS/MCD following kidney transplantation and factors that predict response to immunosuppression following recurrence.
Methods
Multicenter study of pediatric patients with kidney transplants performed for ESKD due to SRNS between 1/2006 and 12/2015. Demographics, clinical course, and biopsy data were collected. Patients with primary-SRNS (PSRNS) were defined as those initially resistant to corticosteroid therapy at diagnosis, and patients with late-SRNS (LSRNS) as those initially responsive to steroids who subsequently developed steroid resistance. We performed logistic regression to determine risk factors associated with nephrotic syndrome (NS) recurrence.
Results
We analyzed 158 patients; 64 (41%) had recurrence of NS in their renal allograft. Disease recurrence occurred in 78% of patients with LSRNS compared to 39% of those with PSRNS. Patients with MCD on initial native kidney biopsy had a 76% recurrence rate compared with a 40% recurrence rate in those with FSGS. Multivariable analysis showed that MCD histology (OR; 95% CI 5.6; 1.3–23.7) compared to FSGS predicted disease recurrence.
Conclusions
Pediatric patients with MCD and LSRNS are at higher risk of disease recurrence following kidney transplantation. These findings may be useful for designing studies to test strategies for preventing recurrence.
The management of Shiga toxin-producing Escherichia coli (STEC) infections is reviewed. Certain management practices optimize the likelihood of good outcomes, such as avoidance of antibiotics during ...the pre-hemolytic uremic syndrome phase, admission to hospital, and vigorous intravenous volume expansion using isotonic fluids. The successful management of STEC infections is based on recognition that a patient might have an STEC infection, and appropriate use of the microbiology laboratory. The timeliness of STEC identification cannot be overemphasized, because it avoids therapies prompted by inappropriate additional testing and directs the clinician to focus on effective management strategies. The opportunities during STEC infections to avert the worst outcomes are brief, and this article emphasizes practical matters relevant to making a diagnosis, anticipating the trajectory of illness, and optimizing care.
Neonates with serum creatinine (SCr) rise ≥0.3 mg/dL and/or ≥50% SCr rise are more likely to die, even when controlling for confounders. These thresholds have not been tested in newborns. We ...hypothesized that different gestational age (GA) groups require different SCr thresholds.
Neonates in Assessment of Worldwide Acute Kidney Epidemiology in Neonates (AWAKEN) with ≥1 SCr on postnatal days 1-2 and ≥1 SCr on postnatal days 3-8 were assessed. We compared the mortality predictability of SCr absolute (≥0.3 mg/dL) vs percent (≥50%) rise. Next, we determine usefulness of combining absolute with percent rise. Finally, we determined the optimal absolute, percent, and maximum SCr thresholds that provide the highest mortality area under curve (AUC) and specificity for different GA groups.
The ≥0.3 mg/dL rise outperformed ≥50% SCr rise. Addition of percent rise did not improve mortality predictability. The optimal SCr thresholds to predict AUC and specificity were ≥0.3 and ≥0.6 mg/dL for ≤29 weeks GA, and ≥0.1 and ≥0.3 mg/dL for >29 week GA. The maximum SCr value provides great specificity.
Unique SCr rise cutoffs for different GA improves outcome prediction. Percent SCr rise does not add value to the neonatal AKI definition.
In sick neonates admitted to the NICU, improper fluid balance can lead to fluid overload. We report the impact of fluid balance in the first postnatal week on outcomes in critically ill ...near-term/term neonates.
This analysis includes infants ≥36 weeks gestational age from the Assessment of Worldwide Acute Kidney injury Epidemiology in Neonates (AWAKEN) study (N = 645). Fluid balance: percent weight change from birthweight.
mechanical ventilation (MV) on postnatal day 7.
The median peak fluid balance was 1.0% (IQR: -0.5, 4.6) and occurred on postnatal day 3 (IQR: 1, 5). Nine percent required MV at postnatal day 7. Multivariable models showed the peak fluid balance (aOR 1.12, 95%CI 1.08-1.17), lowest fluid balance in 1st postnatal week (aOR 1.14, 95%CI 1.07-1.22), fluid balance on postnatal day 7 (aOR 1.12, 95%CI 1.07-1.17), and negative fluid balance at postnatal day 7 (aOR 0.3, 95%CI 0.16-0.67) were independently associated with MV on postnatal day 7.
We describe the impact of fluid balance in critically ill near-term/term neonates over the first postnatal week. Higher peak fluid balance during the first postnatal week and higher fluid balance on postnatal day 7 were independently associated with MV at postnatal day 7.
ABSTRACT
Posaconazole is an antifungal therapy reported to cause incident hypertension. Hypokalemia is also a known side effect. The combination of hypertension and hypokalemia suggests ...mineralocorticoid excess. We present the case of a 15-year-old adolescent male with hypertensive urgency while on prophylactic posaconazole therapy for a combined immunodeficiency. We identify the mechanism of posaconazole-induced hypertension to be inhibition of the 11β-hydroxylase enzyme, resulting in elevated levels of the mineralocorticoid receptor activator deoxycorticosterone. Loss of function of the 11β-hydroxylase enzyme is responsible for a rare form of congenital adrenal hyperplasia and can be associated with life-threatening adrenal crisis.
A Helmet to the Flank Davis, T. Keefe, MD; Agrawal, Garmina, MD; Tiefenbrunn, Matthew, MD
American family physician,
07/2014, Letnik:
90, Številka:
2
Journal Article
Recenzirano
Physical examination revealed a heart rate of 82 beats per minute, respiratory rate of 20 breaths per minute, and a blood pressure of 130/74 mm Hg. Analgesic nephropathy, sickle cell disease, sickle ...cell trait, and diabetes mellitus are risk factors.6 Computed tomography findings may include small, lobulated kidneys; blunting and clubbing of the renal calyces at the papillary tips; calcification of necrotic papillae; and sloughed papillae observed as triangular filling defects within the collecting system. Summary Table Diagnosis Symptoms Preferred imaging modality Radiographic findings Congenital ureteropelvic junction obstruction Asymptomatic or intermittent flank pain Ultrasonography Hydronephrosis with tapering of dilated renal pelvis at the level of the proximal ureter Congenital ureterovesical junction obstruction Asymptomatic or intermittent flank pain Ultrasonography Hydronephrosis, megaureter Renal cell carcinoma Triad of flank pain, gross hematuria, and renal mass is the classic presentation Unenhanced CT followed by three-phase CT Enhancing renal mass Renal papillary necrosis Painful or painless hematuria Computed tomographic urography Small, lobulated kidneys; blunting and clubbing of renal calyces; filling defects from sloughing and calcification of papillae and contrast pooling into the site of sloughed papillae Traumatic kidney rupture Hematuria, flank pain, possible hemodynamic instability Three-phase CT Tissue injury, subcapsular hematoma, contrast extravasation, perinephric or retroperitoneal fluid collection CT = computed tomography.
To provide the pediatric intensivist an in-depth understanding of citrate as regional anticoagulant during continuous renal replacement therapy.
We searched the PubMed.gov database using the initial ...key words: citrate anticoagulation title AND continuous; citrate title AND pediatric AND continuous; prospective pediatric renal replacement AND citrate; and regional citrate anticoagulation. Additional searchers were performed using EMBASE, CINAHL, and SCOPUS with similar keywords and limits. Further articles were gathered from bibliographic references of relevant studies and reviews. Only articles published in English were reviewed.
In the pediatric population, there are no prospective interventional or randomized studies comparing regional versus systemic anticoagulation. However, there are 11 (retrospective and prospective observational studies) in the pediatric population using citrate anticoagulation. These studies have shown that regional citrate anticoagulation in the pediatric population can be effective, provide equivalent circuit survival, and decrease bleeding compared with heparin anticoagulation. In the adult population, there are six prospective randomized controlled trials comparing the efficacy of regional citrate anticoagulation versus heparin. Two systematic reviews with meta-analysis of these six trials have been performed. The adult data on the use of regional citrate anticoagulation during continuous renal replacement therapy show a decreased risk of bleeding and at the least equivalent circuit survival as compared to heparin. Current pediatric and adult studies support regional citrate anticoagulation as an effective alternative to systemic heparin anticoagulation in most patient populations.
Continuous renal replacement therapy is the most common modality of renal replacement in the critical care setting. Regional anticoagulation is an ideal option in a critically ill child after recent surgery or with coagulopathy. Therefore, regional citrate anticoagulation in the pediatric critical care population requiring renal replacement therapy is commonly employed. Complications of citrate anticoagulation can be avoided with a greater understanding of the properties and clearance of citrate. Continued reporting of observational data and the development of prospective multicenter trials using citrate anticoagulation are needed to ensure safe and standardized care in the pediatric population.
Objectives:
This study aims to assess the feasibility of using hemofiltration for ammonia clearance in low body weight infants with an inborn error of metabolism.
Design:
A study of two cases.
...Setting:
Quaternary pediatric hospital (Saint Louis Children's Hospital) NICU and PICU.
Patients:
Infants <6 months of age with an ICD-9 diagnosis of 270.6 (hyperammonemia).
Interventions:
Continuous renal replacement therapy (CRRT).
Measurements and Main Results:
We measure serum ammonia levels over time and the rate of ammonia clearance over time. Continuous renal replacement therapy was more effective than scavenger therapy alone (Ammonul™) for rapid removal of ammonia in low weight infants (as low as 2.5 kg).
Conclusions:
Continuous renal replacement therapy is technically feasible in low weight infants with severe hyperammonemia secondary to an inborn error of metabolism.
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