Frequency and prognosis of peritoneal dialysis-associated peritonitis in children.

BACKGROUND: Peritonitis is the leading cause of peritoneal dialysis (PD) discontinuation. However, few data concern risk factors of peritonitis development and catheter removal caused by treatment failure in pediatric patients. METHODS: This single-center, retrospective study analyzed data from pediatric patients who underwent chronic PD between March 2002 and June 2022. The incidence rates of peritonitis by the person-year method were calculated, and they were stratified by patient age groups. Risk factors for peritonitis development and catheter removal were also analyzed by multivariate analysis using logistic regression model. RESULTS: Ninety patients were enrolled, and 62 peritonitis episodes were observed in 41 (46%) patients. The incidence rate of peritonitis was 0.21 episodes per patient-year, which was the highest in children aged under 2 years old (0.26 episodes per patient-year). Moreover, 44 (71%) cases were successfully cured by antibiotics alone, although 17 (27%) cases required catheter removal, and 4 (6%) cases transitioned to chronic hemodialysis because of peritoneal dysfunction. One patient died. The risk factor for peritonitis development and catheter removal caused by treatment failure was PD insertion at under 2 years old (odds ratio = 2.5; P = 0.04) and Pseudomonas aeruginosa (odds ratio = 11.0; P = 0.04) in the multivariate analysis. P. aeruginosa was also a risk factor for difficulty in re-initiating PD (P = 0.004). CONCLUSIONS: The incidence rate of peritonitis was the highest in children under 2 years old. P. aeruginosa peritonitis is a risk factor for catheter removal and peritoneal dysfunction.

Feasibility of discontinuing immunosuppression in children with idiopathic nephrotic syndrome.

BACKGROUND: Despite adverse events associated with the long-term use of immunosuppressants, their long-term discontinuation remains challenging in children with idiopathic nephrotic syndrome. Relapse and resumption of immunosuppressants after discontinuation and associated risk factors were analyzed. METHODS: This single-center retrospective cohort study included children with frequently relapsing/steroid-dependent nephrotic syndrome (FRNS/SDNS) or steroid-resistant nephrotic syndrome (SRNS) who initiated immunosuppressant treatment between 2010 and 2020. Patients treated with immunosuppressants for less than two years, those with genetic SRNS, and those with continuation of immunosuppressants were excluded. RESULTS: Sixty-eight patients with FRNS/SDNS or SRNS discontinued immunosuppressants. Discontinuation of immunosuppressants was more frequently tried in patients with less relapse on initial immunosuppressants and less rituximab administration. Of 68 patients who discontinued immunosuppressants, 45 (66%) relapsed and 31 (46%) resumed immunosuppressants with a median follow-up of 39.8 months (IQR 24.6-71.2 months) after discontinuation. The relapse-free survival rates were 40.0%, 35.3%, and 35.3% in 1, 2, and 3 years from discontinuation of immunosuppressants, respectively. Relapse on initial immunosuppressants (HR 2.038, 95%CI 1.006-4.128, P = 0.048) and the relapse-free interval before discontinuation of immunosuppressants (HR 0.971, 95%CI 0.944-0.998, P = 0.037) were significant risk factors associated with relapse after the discontinuation of immunosuppressants, adjusting for sex, age at immunosuppressant treatment initiation, SRNS, and rituximab use. CONCLUSIONS: Long-term discontinuation of immunosuppressants can be feasible in patients without a relapse on initial immunosuppressants, those with longer relapse-free interval before discontinuation of immunosuppressants, and those without a relapse for one year after discontinuation of immunosuppressants. TRIAL REGISTRATION: Not applicable.

Association between the time of initial relapse and subsequent relapses in patients with childhood-onset idiopathic nephrotic syndrome.

BACKGROUND: Nephrotic syndrome relapse within 6 months is a known risk factor for steroid-dependent nephrotic syndrome/frequently relapsing nephrotic syndrome (SDNS/FRNS), but the risk of early development of SDNS/FRNS and initiation of immunosuppression therapy remains unknown. METHODS: Patients with childhood-onset idiopathic nephrotic syndrome who had the first relapse within 6 months were enrolled. We analyzed the relationship between the time of the first relapse or the time of initial remission and incidence of SDNS/FRNS or initiation of immunosuppression therapy. RESULTS: Forty-five patients were enrolled. Twenty out of 23 patients (87%) with the first relapse within 30 days after discontinuing initial steroid therapy experienced a second relapse within 30 days after discontinuing steroid therapy. Additionally, most patients in this group (96%) experienced a second relapse within 6 months after the onset and were diagnosed as SDNS/FRNS at this time. In this group, the incidence of SDNS/FRNS development within 6 months was 96%. In contrast, the incidence of SDNS/FRNS development within 6 months was 18% in patients with the first relapse more than 30 days after steroid discontinuation. The incidence of initiation of immunosuppressive agents within 6 months was 83% in the former group and 14% in the latter group. CONCLUSIONS: Most patients with the first relapse within 30 days after discontinuing steroid therapy developed SDNS/FRNS and were administered immunosuppressive agents within 6 months. Thus, it might be reasonable to start immunosuppression therapy in this group without waiting for the second relapse.

Complications and prognosis of patients diagnosed with autosomal recessive polycystic kidney disease in neonatal period.

There are no clinical guidelines for performing nephrectomy in patients with autosomal recessive polycystic kidney disease (ARPKD). Few reports have described the clinical course of ARPKD diagnosed in the neonatal period in detail. Here, we report seven patients diagnosed with ARPKD and treated at our center during the neonatal period. Two died within 48 h of life due to pulmonary hypoplasia. Of the remaining five patients, three had anuria and required for kidney replacement therapy (KRT) within one week after birth, whereas two with a milder phenotype survived without KRT. All three patients who received KRT underwent unilateral nephrectomy and peritoneal dialysis (PD) catheter placement. To prevent fluid leakage, PD was initiated 7-14 days after catheter placement. However, peritoneal leakage occurred in two patients, resulting in peritonitis and discontinuation of PD; one who required long-term hemodialysis contracted a catheter-related bloodstream infection as well as developed subdural and epidural hematomas. Meanwhile, two patients underwent a second nephrectomy within 6 weeks after birth; one developed severe persistent hypotension and neurological complications, while the other died of bacteremia that may have resulted from cholangitis diagnosed on day 67 of life. A severe clinical course, life-threatening adverse events, and severe neurological sequalae may occur in patients with ARPKD who receive KRT in neonatal period.

Postoperative management and complications after abdominal surgery in children receiving peritoneal dialysis.

BACKGROUND: Patients on peritoneal dialysis (PD) may develop PD-related complications that necessitate abdominal surgery. However, when to resume PD and how to prescribe PD fluid after surgery in pediatric patients are unknown. METHODS: Patients on PD who underwent small-incision abdominal surgery between May 2006 and October 2021 were included in this retrospective observational study. The complications after surgery and characteristics of patients with PD fluid leakage were analyzed. RESULTS: Thirty-four patients were included. They underwent 45 surgical procedures, including 23 inguinal hernia repairs, 17 PD catheter repositioning or omentectomy, and 5 others. The median time to resume PD was 1.0 (IQR, 1.0-3.0) days, and the median PD exchange volume at the initiation of PD after surgery was 25 (IQR, 20-30) ml/kg/cycle. PD-related peritonitis occurred in two patients after omentectomy and one after inguinal hernia repair. There was no PD fluid leakage or hernia recurrence among the 22 patients who had a hernia repair. Peritoneal leakage occurred in 3 of the 17 patients who had PD catheter repositioning or an omentectomy and was treated conservatively. No patients who resumed PD 3 days after small-incision abdominal surgery with less than half of PD volume had fluid leakage. CONCLUSIONS: Our findings demonstrated that PD could be resumed within 48 h of inguinal hernia repair with no PD fluid leakage or hernia recurrence in pediatric patients. In addition, resuming PD 3 days after a laparoscopic procedure with less than half of the usual dialysate volume might reduce the risk of PD fluid leakage. A higher resolution version of the Graphical abstract is available as Supplementary information.

Protective Effect of Luminal Uric Acid Against Indomethacin-Induced Enteropathy: Role of Antioxidant Effect and Gut Microbiota.

BACKGROUND: Uric acid (UA) has anti- and pro-inflammatory properties. We previously revealed that elevated serum UA levels provide protection against murine small intestinal injury probably via luminal UA secreted in the small intestine. Luminal UA may act as an antioxidant, preventing microbiota vulnerability to oxidative stress. However, whether luminal UA is increased under hyperuricemia and plays a protective role in a dose-dependent manner as well as the mechanism by which luminal UA exerts its protective effects on enteropathy remains unknown. METHODS: Inosinic acid (IMP) (1000 mg/kg, i.p.) was administered to obtain high serum UA (HUA) and moderate serum UA (500 mg/kg IMP, i.p.) mice. UA concentrations and levels of oxidative stress markers in the serum and intestine were measured. Mice received indomethacin (20 mg/kg, i.p.) to evaluate the effects of UA on indomethacin-induced enteropathy. Reactive oxygen species (ROS) on the ileal mucosa were analyzed. The fecal microbiota of HUA mice was transplanted to investigate its effect on indomethacin-induced enteropathy. RESULTS: IMP increased luminal UA dose-dependently, with higher levels of luminal antioxidant markers. Indomethacin-induced enteropathy was significantly ameliorated in both UA-elevated groups, with decreased indomethacin-induced luminal ROS. The microbiota of HUA mice showed a significant increase in α-diversity and a significant difference in ß-diversity from the control. Fecal microbiota transplantation from HUA mice ameliorated indomethacin-induced enteropathy. CONCLUSIONS: The protective role of luminal UA in intestinal injury is likely exerted via oxidative stress elimination and microbiota composition modulation, preferably for gut immunity. Therefore, enhancing anaerobic conditions using antioxidants is a potential therapeutic target.

High allele discrimination in the typing of single nucleotide polymorphisms of miRNA.

MicroRNAs (miRNAs) belonging to the same family have similar sequences and are difficult to identify. Herein, we report the reverse transcription-hairpin-probe-polymerase chain reaction (RT-Hpro-PCR) technique, which utilises a reverse transcription (RT) primer containing a 5'-end deoxyribonucleic acid (DNA) tag, to detect miRNAs with similar sequences. This strategy follows a two-step RT-PCR method using 6-7-mer RT-primers with a ~ 10-mer tag sequence at the 5'-end and a probe with a hairpin structure (Hpro), including two C-bulges, attached. The findings demonstrate that the specificity of RT could be increased by shortening the complementary part of the RT primer containing a different base, wherein the PCR could successfully progress with the use of 5'-end DNA tag because of an increase in the length of the hybridised tagged primer. This study shows the potential of RT-Hpro-PCR to precisely detect miRNAs with similar sequences, which could help explore the roles of miRNAs in several biological processes.

RT-Hpro-PCR: A MicroRNA Detection System Using a Primer with a DNA Tag.

MicroRNAs (miRNAs) are short RNAs that regulate the expression of complementary messenger RNAs and are involved in numerous human diseases. However, current detection techniques lack the sensitivity to detect miRNAs of low abundance. Moreover, at a length of 20-25 bases, miRNAs are too short for the reverse transcription (RT) polymerase chain reaction (PCR). Here we have developed a new, rapid, and simple miRNA detection system utilizing an RT primer containing a DNA tag at the 5'-end to increase the length of the cDNA. This strategy increases the length of the hybridized tagged primer and the complementary template DNA, as well as the melting temperature of the primer⋅template DNA duplex. PCR efficiency is thus increased, thereby enhancing miRNA detection sensitivity.

Behavioral and cortical EEG evaluations confirm the roles of both CCKA and CCKB receptors in mouse CCK-induced anxiety.

This study investigated the roles of cholecystokinin (CCK)(A) and CCK(B) receptors on CCK-4-induced anxiety-like behaviors in mice through behavioral and neural evaluations. Anxiety-like behaviors in mice were induced by an intracerebroventricular (i.c.v.) administration of CCK-4, which can bind to both CCK(A) and CCK(B) receptors. The effects of CCK(A) and CCK(B) receptor antagonists (devazepide and CI-988, respectively) were examined using mouse anxiety tests (elevated-plus maze and light-dark box) and also by examining neuronal activities through EEG monitoring and c-Fos immunohistochemistry in the cortex and amygdala. CCK-4 (3 µg/kg of body weight i.c.v.) significantly induced mouse anxiety-like behaviors in the anxiety tests and also affected their EEG patterns with respect to pre-drug tracing, resulting in increase in spectral power in relative power distribution in the delta and theta bands (0.5-5 Hz frequency bands) and also in increase in c-Fos immunopositive neuron counts. These CCK-4 effects were completely suppressed by 1.0mg/kg CCK(B) receptor antagonist, CI-988, while the same amount of CCK(A) receptor antagonist, devazepide was partly able to suppress the same effects. These findings indicated that not only CCK(B) receptors but also CCK(A) receptors in the brain play important roles in regulating anxiety-like behaviors in mice. The present study also proposed a possibility that cortical EEG is useful for assessing anxiety.

Ariadne: a database search engine for identification and chemical analysis of RNA using tandem mass spectrometry data.

We present here a method to correlate tandem mass spectra of sample RNA nucleolytic fragments with an RNA nucleotide sequence in a DNA/RNA sequence database, thereby allowing tandem mass spectrometry (MS/MS)-based identification of RNA in biological samples. Ariadne, a unique web-based database search engine, identifies RNA by two probability-based evaluation steps of MS/MS data. In the first step, the software evaluates the matches between the masses of product ions generated by MS/MS of an RNase digest of sample RNA and those calculated from a candidate nucleotide sequence in a DNA/RNA sequence database, which then predicts the nucleotide sequences of these RNase fragments. In the second step, the candidate sequences are mapped for all RNA entries in the database, and each entry is scored for a function of occurrences of the candidate sequences to identify a particular RNA. Ariadne can also predict post-transcriptional modifications of RNA, such as methylation of nucleotide bases and/or ribose, by estimating mass shifts from the theoretical mass values. The method was validated with MS/MS data of RNase T1 digests of in vitro transcripts. It was applied successfully to identify an unknown RNA component in a tRNA mixture and to analyze post-transcriptional modification in yeast tRNA(Phe-1).