Outcome and growth of infants with severe chronic renal failure.
We aimed to assess the outcome and growth of infants with severe chronic renal failure (CRF). One hundred and one children presented ...between January 1, 1986, and December 12, 1998, with a glomerular filtration rate (GFR) of <20 mL/min/1.73 m2. The median (range) age at presentation was 0.3 (0 to 1.5) years, and follow-up was 7.6 (1.5 to 13) years. One- and five-year survival rates were 87 and 78%, respectively. The growth of the 81 children who survived over two years was evaluated. Eighty-one percent were enterally fed from age 0.7 (0 to 4.5) years for 1.9 (0.1 to 6.8) years. Forty-six percent had a gastrostomy, and 22% a Nissen fundoplication. Twenty-five were managed conservatively. Twenty were transplanted without dialysis at age 4 (1.7 to 8.5) years, and 36 were dialyzed at age 1.1 (0 to 9.8) before transplantation at age 2.4 (1.3 to 10) years.
The mean (SD) height standard deviation score increased from -2.16 (1.34) at 6 months (N = 63) to -1.97 (1.37) at 1 year (N = 75), -1.79 (1.29) at 2 years (N = 75), -1.33 (1.29) at 3 years (N = 68, P = 0.0006), -1.27 (1.04) at 5 years (N = 47, P = 0.0001), and -0.85 (0.82) at 10 years (N = 18, P = 0.001). The body mass index was in the normal range in the majority of patients.
Mortality in infants with CRF occurs mainly in the first year of life. With early enteral feeding, the mean height standard deviation score is within the normal range from one year of age.
Long-term outcome of peritoneal dialysis in infants Ledermann, Sarah E; Scanes, Maria E; Fernando, Oswald N ...
The Journal of pediatrics,
January 2000, 2000, 2000-Jan, 2000-1-00, 20000101, Letnik:
136, Številka:
1
Journal Article
Recenzirano
Debate continues concerning the treatment of infants with end-stage renal disease. We evaluated progress and outcome of 20 infants with a mean age of 0.34 year (range, 0.02-1 year) in a long-term ...peritoneal dialysis program at a single center. Mean weight at the start of dialysis was 4.8 kg (range, 1.7–11.4 kg), and the duration of dialysis was 17.3 months (range, 1–59 months). Eleven infants received renal transplants, 4 were switched to hemodialysis and then received transplants, 4 died, and 1 continues to receive peritoneal dialysis. There was significant co-morbidity in 6 infants who died or required hemodialysis. Catheter interventions were frequent, with 12 infants requiring at least one replacement. There were 1.1 episodes of peritonitis per patient-year; 70% of infants had 0 to 1 episode. Mean weight standard deviation score (SDS) was −1.6 at the start, −0.3 at 1 year (P = .0008), and 0.3 at 2 years (P = .0008). Height SDSs were −1.8 at the start, −1.1 at 1 year (P = .046), and −0.8 at 2 years (P = .06). Head circumference SDSs were −1.9 at the start, −1.3 at 6 months (P = .003), and −0.9 at 1 year (P = .015). Fourteen of 16 survivors are achieving normal developmental milestones or attend mainstream school. Peritoneal dialysis in infancy is a demanding treatment, but outcome for growth, development, and transplantation justifies this intensive approach. When parents are counseled, the importance of non-renal co-morbidity must be emphasized.
The majority of infants and young children on peritoneal dialysis (PD) require enteral feeding to achieve their growth potential. We report our experience of gastrostomy feeding in 29 children on PD ...over 11 years. Fifteen children, median age 3.9 (0.5-13.3) years had a percutaneous gastrostomy (PEG) or Nissen fundoplication and gastrostomy (N and G) or open gastrostomy (OG) before starting PD (group1). Nine children, age 0.7 (0.5-12.4) years, had a N and G or OG (group 2) and 5, age 5.1 (1-15.1) years, a PEG (group 3) after PD catheter insertion/start of PD. In group 1 (257 months gastrostomy feeding with PD), there were 0.6 episodes of peritonitis/patient year. Nine PEGs were replaced electively after 27 (19-50) months, with bleeding from an embedded flange the only complication. One PEG replaced by a button ruptured the track, causing Candida peritonitis. In group 2 (130 months G and PD), there were 1.4 episodes of peritonitis/patient year. Two children developed paraoesophageal hernias, which were successfully repaired. Four children in group 3 developed peritonitis soon after PEG placement. Two transferred to haemodialysis, 1 remained on PD after treatment of Candida peritonitis and 1 subsequently died. Only 2 of the 17 children who have had renal transplants still need gastrostomy feeds. We recommend placement of a PEG or OG if an anti-reflux procedure is necessary prior to starting PD. Placement of a PEG while on PD is contraindicated, but an OG is a safe alternative procedure.
An inadequate nutritional intake is common in infants and young children with chronic and end-stage renal failure (CRF/ESRF), causing poor weight gain and growth retardation. In a programme of ...enteral feeding (EF), growth, nutritional intake and outcome for oral feeding were evaluated in 35 children with CRF/ESRF, mean (range) age 1.6 (0-4.9) years at start of EF for 30 (12-60) months. Twenty-nine had a glomerular filtration rate of 12.1 (6-26) ml/min per 1.73 m(2) and 6 were on peritoneal dialysis. Mean (SD) weight standard deviation scores (SDSs) in the 0 to 2-year age group (n=26) were -3.3 (1.0) 6 months before EF, -3.1 (1.3) at the start, -1.7 (1. 4) at 1 year, (P=0.0003) and -1.4 (1.8) at 2 years, (P=0.0008). Height SDSs were -2.9 (0.7), -2.9 (1.2), -2.2 (1.2) (P=0.008) and -2. 1 (1.3) (P=0.004). Weight SDSs in the 2 to 5-year age group (n=9) were -2.3 (1.2), -2.0 (1.1), -1.1 (1.3) (P=0.002) and -0.9 (1.0) (P=0.04). Height SDSs were -2.8 (0.6), -2.3 (0.7), -2.0 (0.7) and -2. 0 (0.8). There was no change in energy intake as a percentage of the estimated average requirement, nor was this exceeded. Percentage energy from the EF in the 0 to 2 year age group remained unchanged despite an absolute increase in energy intake with age. Twenty-one have had renal transplants, of whom 86% eat and drink normally. Long-term EF prevents or reverses weight loss and growth retardation in children with CRF/ESRF, with the achievement of significant catch-up growth if started before age 2 years.
Objective To contribute further to the understanding of cognitive and psychosocial outcome of children with end‐stage renal disease undergoing long‐term peritoneal dialysis.
Methods In total, 16 ...surviving infants at a single centre beginning peritoneal dialysis in the first year of life were studied. The age range of the children at assessment was 1.6–12.1 years. Children were assessed using the Griffiths Mental Development Scales, the Wechsler Intelligence Scale for Children – Third Edition UK, and the Strengths and Difficulties Questionnaire. Information regarding the child's hospital stay and family background was also collated. A Pearson's Product Moment correlation was used to analyse the results.
Results Although 67% of the children's scores fell within the average range, 87% were within at least two SDs of the norms (mean IQ = 86.6). Psychosocial adjustment measures revealed that 50% of scores fell within the borderline to abnormal category, suggesting that the frequency of psychological difficulties was above that of the normal population.
Conclusions These findings lend support to recent studies indicating that, developmentally, children undergoing long‐term peritoneal dialysis are faring better than in the past. This may indeed be a reflection of improvements in renal treatment and diet. The behavioural results suggest the need to monitor psychological adjustment in this group of children.
Renal Outcome in Patients With Cloaca WARNE, S.A.; WILCOX, D.T.; LEDERMANN, S.E. ...
The Journal of urology,
06/2002, Letnik:
167, Številka:
6
Journal Article
Recenzirano
Cloaca is a complex malformation in which the rectum, vagina and urinary tract open into a single common channel. Functional results after reconstructive surgery have been documented but the renal ...outcome is less clearly understood.
The records of all patients with cloacal malformation treated at our institution from 1980 to 2000 were retrospectively reviewed to determine the renal outcome. All patients underwent serial ultrasound of the urinary tract, voiding cystography, nuclear renography, lumbosacral radiography, and measurement of serum creatinine and glomerular filtration rate when appropriate.
We identified 64 patients 0.5 to 19 years old (mean age 11.2) at the time of the study. Of the 64 patients 53 (83%) were born with a structural abnormality of the urinary tract, including renal dysplasia in 17 (27%), ectopic kidney in 9 (14%), solitary kidney in 8 (13%), duplex kidneys in 6 (9%) and ureteropelvic junction obstruction in 3 (5%). Vesicoureteral reflux was noted in 34 cases (53%) and a sacral abnormality was diagnosed in 36 (57%). The glomerular filtration rate was measured in 38 patients (60%). Chronic renal failure developed in 32 patients (50%) with a glomerular filtration rate of less than 80 ml. per minute per 1.73 m.
2, including 11 (17%) who progressed to end stage renal failure, 4 who (6%) required renal transplantation and 4 who died of chronic renal failure. Of the 32 children with a glomerular filtration rate of less than 80 ml. per minute per 1.73 m.
2 44% had renal dysplasia, 25% had a solitary kidney, 44% had sacral anomalies, 72% had vesicoureteral reflux and 47% had secondary renal scarring.
Renal impairment causes significant morbidity and mortality in patients with a cloacal malformation. These patients need a complete nephrourological assessment in the neonatal period due to the high incidence of urinary tract and sacral anomalies as well as careful post-reconstruction followup.
Poly(ADP-ribose)polymerase inhibitors (PARPis) have shown promising activity in patients with BRCA1/2 mutation-associated (BRCA1/2MUT+) ovarian and breast cancers. Accumulating evidence suggests that ...PARPi may have a wider application in the treatment of sporadic high-grade serous ovarian cancer, and cancers defective in DNA repair pathways, such as prostate, endometrial, and pancreatic cancers. Several PARPis are currently in phase 1/2 clinical investigation, with registration trials now being designed. Olaparib, one of the most studied PARPis, has demonstrated activity in BRCA1/2MUT+ and BRCA-like sporadic ovarian and breast cancers, and looks promising in prostate and pancreatic cancers. Understanding more about the molecular abnormalities involved in BRCA-like tumors, exploring novel therapeutic trial strategies and drug combinations, and defining potential predictive biomarkers, is critical to rapidly advancing the field of PARPi therapy and improve clinical outcomes.
Homologous recombination repair deficiency (HRD) is a frequent feature of high-grade serous ovarian, fallopian tube and peritoneal carcinoma (HGSC) and is associated with sensitivity to PARP ...inhibitor (PARPi) therapy. HRD testing provides an opportunity to optimise PARPi use in HGSC but methodologies are diverse and clinical application remains controversial.
To define best practice for HRD testing in HGSC the ESMO Translational Research and Precision Medicine Working Group launched a collaborative project that incorporated a systematic review approach. The main aims were to (i) define the term ‘HRD test’; (ii) provide an overview of the biological rationale and the level of evidence supporting currently available HRD tests; (iii) provide recommendations on the clinical utility of HRD tests in clinical management of HGSC.
A broad range of repair genes, genomic scars, mutational signatures and functional assays are associated with a history of HRD. Currently, the clinical validity of HRD tests in ovarian cancer is best assessed, not in terms of biological HRD status per se, but in terms of PARPi benefit. Clinical trials evidence supports the use of BRCA mutation testing and two commercially available assays that also incorporate genomic instability for identifying subgroups of HGSCs that derive different magnitudes of benefit from PARPi therapy, albeit with some variation by clinical scenario. These tests can be used to inform treatment selection and scheduling but their use is limited by a failure to consistently identify a subgroup of patients who derive no benefit from PARPis in most studies. Existing tests lack negative predictive value and inadequately address the complex and dynamic nature of the HRD phenotype.
Currently available HRD tests are useful for predicting likely magnitude of benefit from PARPis but better biomarkers are urgently needed to better identify current homologous recombination proficiency status and stratify HGSC management.
•Homologous recombination repair deficiency (HRD) is a common feature of high-grade serous gynaecological cancers (HGSC).•Currently, the clinical validity of HRD tests in ovarian cancer is best assessed in terms of PARPi benefit.•Germline and somatic BRCA mutation and genomic instability tests help to predict likely magnitude of benefit from a PARPi.•Existing HRD tests fail to consistently identify a subgroup of patients who derive no benefit from PARPis in most studies.•HRD is a dynamic entity and better biomarkers that capture current homologous recombination proficiency status are needed.
Niraparib is an oral poly(adenosine diphosphate ADP-ribose) polymerase (PARP) 1/2 inhibitor that has shown clinical activity in patients with ovarian cancer. We sought to evaluate the efficacy of ...niraparib versus placebo as maintenance treatment for patients with platinum-sensitive, recurrent ovarian cancer.
In this randomized, double-blind, phase 3 trial, patients were categorized according to the presence or absence of a germline BRCA mutation (gBRCA cohort and non-gBRCA cohort) and the type of non-gBRCA mutation and were randomly assigned in a 2:1 ratio to receive niraparib (300 mg) or placebo once daily. The primary end point was progression-free survival.
Of 553 enrolled patients, 203 were in the gBRCA cohort (with 138 assigned to niraparib and 65 to placebo), and 350 patients were in the non-gBRCA cohort (with 234 assigned to niraparib and 116 to placebo). Patients in the niraparib group had a significantly longer median duration of progression-free survival than did those in the placebo group, including 21.0 vs. 5.5 months in the gBRCA cohort (hazard ratio, 0.27; 95% confidence interval CI, 0.17 to 0.41), as compared with 12.9 months vs. 3.8 months in the non-gBRCA cohort for patients who had tumors with homologous recombination deficiency (HRD) (hazard ratio, 0.38; 95% CI, 0.24 to 0.59) and 9.3 months vs. 3.9 months in the overall non-gBRCA cohort (hazard ratio, 0.45; 95% CI, 0.34 to 0.61; P<0.001 for all three comparisons). The most common grade 3 or 4 adverse events that were reported in the niraparib group were thrombocytopenia (in 33.8%), anemia (in 25.3%), and neutropenia (in 19.6%), which were managed with dose modifications.
Among patients with platinum-sensitive, recurrent ovarian cancer, the median duration of progression-free survival was significantly longer among those receiving niraparib than among those receiving placebo, regardless of the presence or absence of gBRCA mutations or HRD status, with moderate bone marrow toxicity. (Funded by Tesaro; ClinicalTrials.gov number, NCT01847274 .).
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