Recurrence of primary disease is one of the major risks for allograft loss after pediatric RTx. The risk of recurrence of FSGS/SRNS after pediatric RTx in particular can be up to 86% in idiopathic ...cases. There is a need for consensus recommendations on its prevention and treatment. The CERTAIN study group has therefore performed a thorough literature search based on the PICO model of clinical questions to formulate educated statements to guide the clinician in the process of decision‐making. A set of educated statements on prevention and treatment of FSGS/SRNS after pediatric RTx has been generated after careful evaluation of available evidence and thorough panel discussion. We do not recommend routine nephrectomy prior to transplantation; neither do we recommend abstaining from living donation. Special attendance needs to be given to those patients who had already experienced graft loss due to FSGS/SRNS recurrence. Early PE or IA with or without high‐dose CsA and/or rituximab seems to be most promising to induce remission. The educated statements presented here acknowledge that FSGS/SRNS recurrence after pediatric RTx remains a major concern and is associated with shorter graft survival or even graft loss. The value of any recommendation needs to take into account that evidence is based on cohorts that differ in ethnicity, pre‐transplant history, immunosuppressive regimen, definition of recurrence (eg, clinical and/or histological diagnosis) and treatment modalities of recurrence.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
EBV DNA monitoring is currently the main strategy to identify renal transplant recipients potentially at risk of EBV complications. EBV miRNA expression is markedly altered in different disease ...presentations associated with EBV. We performed a longitudinal assessment of the impact of rituximab on circulating EBV miRNA in 3 paediatric kidney transplant recipients.
Forty-two miRNAs encoded within 2 EBV open reading frames (BART and BHRF) were examined over a 28-month period using miRNA qPCR custom panels. EBV DNA was measured using qPCR and lymphocyte subsets were measured by flow cytometry.
Patients were 3 years post kidney transplant and received cycles of rituximab infusions. Treatment with rituximab caused an immediate depletion of the circulating B cells and reduced the expression of the miRNAs and EBV DNA levels. About 4 months post treatment, as the circulating B cells repopulated, EBV miRNAs levels increased. A total of 29 plasma samples were studied and between 4 and 34 EBV miRNAs were detected. A significant correlation was observed between the numbers of EBV miRNAs expressed and the EBV DNA level (r = 0.63, p = 0.001).
We provide an in-depth longitudinal assessment of the impact of rituximab on specific circulating EBV miRNA expression in three paediatric kidney transplant recipients. Rituximab treatment resulted in the reduction of EBV miRNA expression and EBV DNA viral loads. Larger studies are required to determine whether EBV miRNA levels could be useful biomarkers to predict transplant recipients at risk of developing post-transplant lymphoproliferative disease.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
3.
An unusual case of nephrotic syndrome Wildes, Dermot Michael; Fitzsimons, Aisling; Doyle, Brendan ...
Pediatric nephrology,
2024-May-23, 2024-05-23, 20240523
Journal Article
Peer reviewed
Open access
Alport syndrome is a genetically heterogenous disorder resulting from variants in genes coding for alpha-3/4/5 chains of Collagen IV, which results in defective basement membranes in the kidney, ...cochlea and eye. The syndrome has different inheritance patterns and historically, was thought of as a disease affecting solely males.
A 15-year-old female presented with pedal oedema, hypertension and proteinuria. She underwent a kidney biopsy which showed findings in keeping with focal segmental glomerulosclerosis. Her condition was refractory to steroids. Steroid-resistant nephrotic syndrome genetics were sent, revealing a rare pathogenic variant in the COL4A5 gene.
Heterozygous females with X-linked Alport syndrome can develop chronic kidney disease and hearing loss. Clinicians should be mindful when reviewing kidney histology to include Alport syndrome as a differential for female patients. COL4A3-5 genes should be included in all steroid-resistant nephrotic syndrome genetic panels.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Background
Eculizumab for the treatment of atypical hemolytic uremic syndrome (HUS) is a standard of care. Central nervous system (CNS) involvement in Shiga toxin–producing
Escherichia coli
...(STEC)-HUS is associated with increased morbidity and mortality. There is no consensus on the use of plasma exchange and/or eculizumab. We report a series (
n
= 4) of children with CNS involvement in STEC-HUS with excellent outcomes after treatment with eculizumab only and supportive therapies.
Methods
A retrospective chart review of patients with CNS involvement in STEC-HUS is managed with supportive therapies and eculizumab only.
Results
Four patients (75% female) with a median age of 5 years and 11 months (IQR: 23.5–105.5 months) were admitted to a tertiary pediatric nephrology center with CNS involvement in STEC-HUS. Neurological symptoms presented between days 2 and 7 of illness and included ataxia, altered mental status, visual symptoms, and seizures. All had an abnormal MRI brain. All received two doses of eculizumab, 1 week apart (dosing according to weight). Resolution of neurological symptoms was evident at a mean of 60 h post-administration (range: 24–72 h). All patients have complete kidney and neurological recovery at 12-month follow-up.
Conclusion
We present a case series of four children with STEC-HUS and CNS involvement, managed with eculizumab only, in lieu of plasma exchange (as per our previous policy). The marked improvement in symptoms in our cohort supports the use of eculizumab, rather than plasma exchange in the CNS involvement of STEC-HUS.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Abstract Background and Aims Autosomal dominant polycystic kidney disease (ADPKD), commonly caused by pathogenic variants in PKD1 and PKD2 genes, leads to enlarged cystic kidneys and typically ...present in adulthood where ∼70% of affected patients progress to kidney failure by their 7th decade of life. Recently, new genes have been reported that appear to explain some of the previously unresolved ADPKD-like cases. An example is the NEK8 gene, where monoallelic variants are reported to cause early-onset ADPKD with progressive phenotype. We are reporting 4 Irish families with monoallelic NEK8 variants. Method In-depth clinical and radiological evaluations were conducted on 250 families with polycystic kidney disease referred to the Irish Kidney Gene Project. All patients underwent genomic testing using gene-panel and exome Next Generation Sequencing (NGS), while multiple ligation probe amplification analysis of PKD1 or PKD2 was utilized in genetically unresolved families. The American College of Medical Genetics and Genomics guidelines were applied to assess variant pathogenicity. Results To date, 471 individuals representing 250 distinct families (F) have been studied, including 105 (42%) families with two or more individuals (326 individuals). 55.2% have reached end-stage kidney failure, with an average age of 49.1 ± 14.3 years. We identified pathogenic / likely pathogenic variants in 76% (190/250) of families, with variants in PKD1 accounting for 76.8% (146/190) and PKD2 accounting for 15.3% (29/190) of families, respectively. In familial cases with non-PKD1/PKD2 variants, we identified pathogenic variants in a small proportion of families with ADPKD-like phenotypes: IFT140 variants (n = 4), ALG5 (n = 2), 17q12 microdeletion (n = 2) and DNAJB11, ALG8, and ALG9 variants (n = 1 each). Upon thorough review of all genetically unresolved PKD families, 4 (6.7%) families were identified with monoallelic protein-kinase domain NEK8 variants NM_178170.3: p.R45W (in 2 families) and two other missense variants: p.N69D and p.R140L, none of which contained a second NEK8 variant despite extensive analysis. Autosomal dominant segregation was confirmed in two parent-child pairs, whereas the remaining two index patients reported no family history of kidney disease. The median age at the initial presentation was 12 years (IQR: 2.5–27.3), with a median follow-up period of 22.5 years at the last evaluation. The phenotype of all patients was consistent with polycystic kidney disease with the absence of liver and pancreatic cysts. All patients were diagnosed with hypertension at an average age of 15.3 ± 12.2 years. Cerebral aneurysms were detected in two patients (F1: at age 61 years and F4: at age 54 years), while F3 was reported to have childhood-onset frontal bossing, prominence cerebrospinal fluid, and large arachnoid cysts. Approximately 67% 4/6 patients progressed to end-stage kidney failure by the 3rd decade of life. Compared to families with PKD1/PKD2 variants, families with NEK8 variants were characterized by earlier average age at initial presentation (14.5 versus 29.9 years; p 0.01) and progression to end-stage kidney failure (15.5 versus 49.6 years; p < 0.0001). Table 1 summarizes the clinical and genetic characteristics of the reported families. Conclusion We provide further evidence that monoallelic NEK8 variants cause early presentation and progressive ADPKD-like phenotype. Sequencing for monoallelic NEK8 variants in patients with childhood and early-adulthood cystic kidney disease can inform renal prognosis, treatment planning, familial screening and reproductive choices.
Approximately 500 monogenic causes of chronic kidney disease (CKD) have been identified, mainly in pediatric populations. The frequency of monogenic causes among adults with CKD has been less ...extensively studied. To determine the likelihood of detecting monogenic causes of CKD in adults presenting to nephrology services in Ireland, we conducted whole exome sequencing (WES) in a multi-centre cohort of 114 families including 138 affected individuals with CKD. Affected adults were recruited from 78 families with a positive family history, 16 families with extra-renal features, and 20 families with neither a family history nor extra-renal features. We detected a pathogenic mutation in a known CKD gene in 42 of 114 families (37%). A monogenic cause was identified in 36% of affected families with a positive family history of CKD, 69% of those with extra-renal features, and only 15% of those without a family history or extra-renal features. There was no difference in the rate of genetic diagnosis in individuals with childhood versus adult onset CKD. Among the 42 families in whom a monogenic cause was identified, WES confirmed the clinical diagnosis in 17 (40%), corrected the clinical diagnosis in 9 (22%), and established a diagnosis for the first time in 16 families referred with CKD of unknown etiology (38%). In this multi-centre study of adults with CKD, a molecular genetic diagnosis was established in over one-third of families. In the evolving era of precision medicine, WES may be an important tool to identify the cause of CKD in adults.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
ABSTRACT
Background
Adolescence is a time of significant change for patients, guardians and clinicians. The paediatrician must ensure patients develop the necessary skills and knowledge required to ...transition and to function as an independent entity, with autonomy over their own care. The transfer from paediatric to adult care carries an increased risk of graft-related complications attributable to a multitude of reasons, particularly non-adherence to immunosuppressive medicines and poor attendance at scheduled appointments. This systematic review was conducted to ascertain the transitional care models available to clinicians caring for kidney transplant recipients and to compare the approach in each respective case.
Methods
A systematic review was performed, in a methodology outlined by the PRISMA guidelines. OVID MEDLINE and EMBASE databases were searched for studies that outlined valid, replicable models pertaining to transitional care of paediatric kidney transplant recipients between 1946 and Quarter 3 of 2021. The reference lists of selected articles were also perused for further eligible studies and experts in the field were consulted for further eligible articles. Two investigators assessed all studies for eligibility and independently performed data extraction. Any discrepancies were settled by consensus.
Results
A total of 1121 abstracts were identified, which was reduced to 1029 upon removal of duplicates. A total of 51 articles were deemed appropriate for full-text review and critical appraisal. A total of 12 articles that described models for transition pertaining to kidney transplant patients were included in qualitative synthesis. Every paper utilized a different transition model. All but one model included a physician and nurse at minimum in the transition process. The involvement of adult nephrologists, medical social work, psychology and psychiatry was variable. The mean age for the initiation of transition was 13.4 years (range: 10–17.5 years). The mean age at transfer to adult services was 18.3 years (range: 16–20.5 years).
Conclusions
Despite the well-established need for good transitional care for paediatric solid-organ transplant recipients, models tailored specifically for kidney transplant recipients are lacking. Further research and validation studies are required to ascertain the best method of providing effective transitional care to these patients. Transitional care should become a standardized process for adolescents and young adults with kidney transplants.
BackgroundVascular access is required for haemodialysis (HD), a form of renal replacement therapy required when a child has acute or end stage kidney disease (ESKD). Central venous catheter (CVC) ...line infections are the second most common cause of vascular access loss in the long term HD patient, commonly caused by poor hand hygiene practices, clinical environment or inadequate sterilisation procedures. In the literature the reported rates of infection range from 0.8–4.8 episodes/1000 catheter days in this patient group.AimTo audit CVC line related infection rates in our tertiary HD unit in Temple Street Children’s University Hospital (TSCUH) over a 5 year period.MethodsA retrospective review was carried out on all patients who had HD from January 2012- January 2017 (inclusive) using a CVC.Results/Findings34 patients required HD, of which 44% were female and 56% male.Twenty-three patients (68%) were aged between 5–10 years of age.Dysplastic kidneys was the most common reason for requiring HD (n=9, 26.2%). Eight patients required HD for 1–6 months, 5 patients for 6–12 months, 19 patients for 12–48 months, and 2 patients for >60 months.Five out of 34 children developed CVC line infections with an overall infection rate of 0.22 episodes per 1000 catheter days. Loss of protective caps was the main reason for infection (n=3). Staph-aureous, pseudomonas oryzihabitans, enterococcus faecalis and mixed coagulase negative staphylococci were the identified organisms causing infection.ConclusionsCVC line infections in long-term HD patients attending TSCUH are maintained at a low rate in comparison to published data.Strict application of Aseptic Non Touch Technique shows favourable results without the need for prophylactic antibiotics locks. Future work includes a cost benefit analysis of this practice.
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