Introduction: IgA nephropathy (IgAN) is the most common glomerulonephritis worldwide. Decreased glomerular filtration rate is a known risk factor for disease progression. Aim: We aimed to examine ...factors that may contribute to disease progression in children that present with impaired eGFR at the onset of IgAN. Materials and methods: Of the 175 patients with IgAN from the Polish Registry of Children with IgAN and IgAVN, 54 (31%) patients with IgAN who had an onset of renal function impairment (GFR < 90 mL/min) were eligible for the study. All of them were analyzed for initial symptoms (GFR according to Schwartz formula, creatinine, proteinuria, IgA, C3), renal biopsy result with assessment by Oxford classification, treatment used (R—renoprotection, P—prednisone+R, Aza—azathioprine+P+R, Cyc—cyclophosphamide+P+R, CsA—cyclosporine+P+R, MMF—mycophenolate mofetil+P+R), and distant follow-up. Based on the GFR score obtained at the end, patients were divided into two groups: A—GFR > 90 mL/min and B—GFR < 90 mL/min. Results: In the study group, the mean age of onset was 12.87 ± 3.57 years, GFR was 66.1 ± 17.3 mL/min, and proteinuria was 18.1 (0–967) mg/kg/d. Renal biopsy was performed 0.2 (0–7) years after the onset of the disease, and MESTC score averaged 2.57 ± 1.6. Treatment was R only in 39% of children, P+R in 20%, Aza+P+R in 28%, Cyc+P+R in 9%, CsA+P+R in 7%, and MMF+P+R in 3%. The length of the observation period was 2.16 (0.05–11) years. At the follow-up, Group A had 30 patients (56%) and Group B had 24 patients (44%). There were no significant differences in any of the other biochemical parameters (except creatinine) or proteinuria values between the groups and the frequency of the MESTC score ≥ 2 and <2 was not significantly different between Groups A and B. Patients with normal GFR at the follow-up (Group A) were significantly more likely to have received prednisone and/or immunosuppressive treatment than those in Group B (p < 0.05) Conclusions: In a population of Polish children with IgAN and decreased renal function at the onset of the disease, 56% had normal GFR in remote observation. The use of immunosuppressive/corticosteroids treatment in children with IgAN and impaired glomerular filtration rate at the beginning of the disease may contribute to the normalization of GFR in the outcome, although this requires confirmation in a larger group of pediatric patients.
Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenic cause of renal failure. For several decades, ADPKD was regarded as an adult-onset disease. In the past decade, it has ...become more widely appreciated that the disease course begins in childhood. However, evidence-based guidelines on how to manage and approach children diagnosed with or at risk of ADPKD are lacking. Also, scoring systems to stratify patients into risk categories have been established only for adults. Overall, there are insufficient data on the clinical course during childhood. We therefore initiated the global ADPedKD project to establish a large international pediatric ADPKD cohort for deep characterization.
Global ADPedKD is an international multicenter observational study focusing on childhood-diagnosed ADPKD. This collaborative project is based on interoperable Web-based databases, comprising 7 regional and independent but uniformly organized chapters, namely Africa, Asia, Australia, Europe, North America, South America, and the United Kingdom. In the database, a detailed basic data questionnaire, including genetics, is used in combination with data entry from follow-up visits, to provide both retrospective and prospective longitudinal data on clinical, radiologic, and laboratory findings, as well as therapeutic interventions.
The global ADPedKD initiative aims to characterize in detail the most extensive international pediatric ADPKD cohort reported to date, providing evidence for the development of unified diagnostic, follow-up, and treatment recommendations regarding modifiable disease factors. Moreover, this registry will serve as a platform for the development of clinical and/or biochemical markers predicting the risk of early and progressive disease.
The aim of this retrospective study was to assess the usefulness of potential predictors of poor prognosis in IgA nephropathy in children. The study population consisted of 55 children aged 11 ± ...4 years, diagnosed on the basis of the Oxford classification and MEST score of kidney biopsy findings. Proteinuria, glomerular filtration rate (GFR), and the IgA/C3 serum ratio were assessed in all patients twice: at onset and at follow-up. The patients were treated with steroids, immunosuppressive drugs, and/or angiotensin-converting enzyme inhibitors. Follow-up was at 3.9 ± 2.9 (median 2.7) years. The patients were subdivided into two groups: with GFR <90 and ≥90 mL/min at follow-up. ROC AUC curves and logistic regression were used to evaluate the power of prognostic factors. The two groups did not differ regarding the level of proteinuria, MEST score, and the IgA/C3 ratio at onset of disease. There was a significant association between GFR reductions at onset and follow-up (AUC = 0.660; p < 0.05). In patients with nephrotic range proteinuria at onset, proteinuria at follow-up was more frequent compared with other patients (AUC = 0.760; p < 0.05), MEST score ≥3 tended to be associated with reduced GFR (AUC = 0.650; p = 0.07) but not with proteinuria (AUC = 0.608; p = 0.47), and the IgA/C3 ratio was higher (p < 0.05) at follow-up. No significant associations were found between the IgA/C3 ratio at onset and reduced GFR (AUC = 0.565; p = 0.46) or proteinuria at follow-up (AUC = 0.263; p = 0.20). We conclude that predictors of poor outcome in childhood IgAN include the following: GFR reduction, nephrotic range proteinuria at onset of disease, and high MEST score in Oxford classification of kidney biopsy. Despite a higher serum IgA/C3 ratio in children with impaired renal function in long-term follow-up, we failed to demonstrate a significant association between this ratio at onset of disease and reduced GFR or persistent proteinuria at follow-up. Thus, IgA/C3 ratio is not a good foreteller of progression of IgA nephropathy in childhood.
IgA nephropathy (IgAN) is the most common form of glomerulonephritis in pediatric population. The clinical presentation of the disease in children ranges from microscopic hematuria to end-stage ...kidney disease. The aim of the study was to retrospectively assess clinical and kidney biopsy features in children with IgAN. We assessed a cohort of 140 children, 88 boys, 52 girls with the diagnosis of IgAN in the period of 2000-2015, entered into the national Polish pediatric IgAN registry. The assessment included the following: proteinuria, hematuria, glomerular filtration rate (GFR), arterial blood pressure, and the renal pathological changes according to the Oxford classification and crescents formation, as modifiable and unmodifiable risk factors. The incidence of IgAN in Poland was set at 9.3 new cases per year. The mean age at onset of IgAN was 11.9 ± 4.3 years, and the most common presentation of the disease was the nephritic syndrome, recognized in 52 % of patients. Kidney biopsy was performed, on average, 1.3 ± 2.0 years after onset of disease. Based on the ROC analysis, a cut-off age at onset of disease for GFR <90 mL/min/1.73 m
(risk factor of progression) was calculated as 13.9 years. Unmodifiable lesions: segmental sclerosis, tubular atrophy/interstitial fibrosis (S1, T1-2) in the Oxford classification and crescents in kidney biopsy were significantly more common in Gr 1 (>13.9 years) compared with Gr 2 (<13.9 years), despite a significantly shorter time to kidney biopsy in the former. We conclude that IgAN in children may be an insidious disease. A regular urine analysis, especially after respiratory tract infections, seems the best way for an early detection of the disease.
The aim of the study was to determine whether an elevated IgA level at the time of the diagnosis of IgA nephropathy has an effect on the severity of kidney biopsy findings and long-term outcomes in ...children. We retrospectively studied 89 children with IgA nephropathy who were stratified into Group 1- elevated serum IgA and Group 2 - normal serum IgA at baseline. The level of IgA, proteinuria, hematuria, glomerular filtration rate (GFR) and hypertension (HTN) were compared at baseline and after the end of the follow-up period of 4.0 ± 3.1 years. Kidney biopsy findings were evaluated using the Oxford classification. The evaluation of treatment included immunosuppressive therapy and renoprotection with angiotensin converting-enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB), or no treatment. The elevated serum IgA was found in 46 (52 %) patients and normal serum IgA level was found in 43 (48 %) patients. No differences were found between the two groups regarding the mean age of patients, proteinuria, and the number of patients with reduced GFR or HTN at baseline. In kidney biopsy, mesangial proliferation and segmental sclerosis were significantly more common in Group 1 compared with Group 2 (p < 0.05). Immunosuppressive therapy was used in 67 % children in Group 1 and 75 % children in Group 2. The Kaplan-Meier survival curves for renal function (with normal GFR) and persistent proteinuria did not differ significantly depending on the serum IgA level at baseline. We conclude that in IgA nephropathy the elevated serum IgA at baseline may be associated with mesangial proliferation and segmental sclerosis contribute to glomerulosclerosis, but has no effect on the presence of proteinuria or on the worsening of kidney function during several years of disease course.
This study evaluated the frequency and severity of pruritus and dry skin in children with chronic kidney disease (CKD). A total of 103 children were included: 72 with CKD stage 3-5 (34 on dialysis ...and 38 treated conservatively without dialysis) and 31 as a reference group. Pruritus was assessed using the 4-item Itch Questionnaire and a visual analogue scale. Skin dryness was evaluated clinically, by non-invasive assessment of epidermis moisturizing and measurement of transepidermal water loss. Pruritus occurred in 20.8% of children with CKD, 18.4% on conservative treatment (receiving supportive care without dialysis) and 23.5% on dialysis. Xerosis was more common in children with pruritus (66.7%) than in those without pruritus (50.9%). Patients with pruritus had a significantly lower estimated glomerular filtration rate and a higher ratio of calcium × phosphate product (Ca × P). In conclusion, CKD-associated pruritus occurs not only in adults, but also in children, and it may already be present in the early stages of CKD.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Autosomal recessive polycystic kidney disease (ARPKD) is a rare monogenic disease with a severe phenotype often presenting prenatally or in early childhood. With its obligate renal and hepatic ...involvement, ARPKD is one of the most important indications for liver and/or kidney transplantation in childhood. Marked phenotypic variability is observed, the genetic basis of which is largely unknown. Treatment is symptomatic and largely empiric as evidence-based guidelines are lacking. Therapeutic initiatives for ARPKD face the problem of highly variable cohorts and lack of clinical or biochemical risk markers without clear-cut clinical end points. ARegPKD is an international, multicenter, retro- and prospective, observational study to deeply phenotype patients with the clinical diagnosis of ARPKD. Initiated in 2013 as a web-based registry (www.aregpkd.org), ARegPKD enrolls patients across large parts of Europe and neighboring countries. By January 2017, more than 400 patients from 17 mostly European countries have been registered in the ARPKD registry study with significant follow-up data. Due to comprehensive retro- and prospective data collection and associated biobanking, ARegPKD will generate a unique ARPKD cohort with detailed longitudinal clinical characterization providing a basis for future clinical trials as well as translational research. Hence, ARegPKD is hoped to contribute to the pathophysiological understanding of the disease and to the improvement of clinical management.
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