The Outcome of Childhood Immunoglobulin A Nephropathy with Acute Kidney Injury at the Onset of the Disease-National Study.

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.

Predictors of Progression in IgA Nephropathy in Childhood.

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 in Children: A Multicenter Study in Poland.

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 m2 (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.

Increased Serum IgA in Children with IgA Nephropathy, Severity of Kidney Biopsy Findings and Long-Term Outcomes.

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.

Imaging of bone in the diagnostics of renal osteodystrophy in children with chronic renal failure.

BACKGROUND: In the last two decades considerable advances have been made in the development of imaging tests of the skeletal system. This progress in diagnostic techniques, along with the growing availability of the tests, renders it necessary to review and evaluate their suitability for daily clinical practice. The aim of this article is to compare the results of radiological testing of bone with densitometrical, histomorphometric, and biochemical tests in children with chronic renal failure. MATERIAL AND METHODS: The research involved 31 children with renal failure, of whom 10 were being treated conservatively, 17 by continuous ambulatory peritoneal dialysis (CADO), and 4 by hemodialysis (HD). In all these children, radiological examinations of bone were performed in the arms, knees, and hips, along with tests for the serum concentration of parathormone (iPTH), calcium (Ca), and phosphates (P), and for the activity of alkaline phosphatase (AP). Bone density tests by the DXA method and bone biopsies were also performed. On the basis of radiological evaluation, the patients were divided into two groups: Group I, consisting of 14 children with a normal bone structure image, and Group II, consisting of 17 children with bone atrophy. RESULTS: No statistically significant differences were discovered in the mean values of the tested biochemical parameters between the two groups. The mineral density of total body was normal in 9 of the 14 patients in Group I (64%), and in 7 of 17 (41%) from Group II. The mineral density of total lumbar spine gave similar results. Lower bone density results were obtained in Group II than in Group I, though only in the case of the lumbar spine were the differences statistically significant. In Group I, 5 cases were discovered of chronic osteodystrophy without osteomalacia and hyperparathyroidism (NB), 2 cases of adynamic bone disease (ABD), 4 cases of hyperparathyroidism (HP), 2 cases of moderate hyperparathyroidism (MHP), and one mixed form (Mix); in Group II, there were 6 NBs, 2 ABDs, 1 case of osteomalacia (OM), 5 HPs, and 3 mixed. Radiological examinations revealed one male in Group I with features of prior Perthes's disease, one with fibrous cortical defect, and four cases of valgity of the coxa valga. In Group II, there were 3 children with radiological changes typical for osteomalacia, and in 1 case typical radiological signs of hyperparathyroidism. CONCLUSIONS: Given the lack of consistency in the results of the tests here presented, an entire panel of available tests should be performed for the comprehensive evaluation of the status of the skeleton.

[Results of treatment with recombinant human growth hormone in children with growth retardation in end-stage renal disease]. / Wyniki leczenia rekombinowanym ludzkim hormonem wzrostu niskoroslosci dzieci ze schylkowa niewydolnoscia nerek.

The aim of the study was to estimate the results of recombinant human growth hormone (rhGH) treatment in children with end-stage renal disease (ESRD). 60 growth retarded children with ESRD (mean age 11.2 +/- 7.2 years) were treated with rhGH at a dose of 1-1.1 IU/kg/week. The time of observation was 24 months. Thirty children completed first year, 18--second year of treatment. The mean growth velocity prior to the treatment was 3.03 +/- 1.9, during first year of the study--7.52 +/- 2.42, during second year 6.68 +/- 2.87 cm/year. The negative correlation between growth velocity and patient's age (r = -0.39; p < 0.05) suggest the better growth results in younger children during rhGH treatment. The rhGH therapy is effective method of treatment in growth retarded children with ESRD. Side effects are rare.

[Bone mineral density in children with end-stage renal disease]. / Badanie gestosci kosci u dzieci ze schylkowa niewydolnoscia nerek.

The aim of the study was to evaluate bone mineralisation in comparison to chronological age, bone age and high age in children with end-stage renal disease. Fourty-four patients (16 female, 28 male) aged 7-16 years were examined. DXA bone densitometry of total body, bone age evaluated by Greulich-Pyle method and high age were performed in all patients. In our patients bone, and high age were significantly decreased in comparison to chronological age. In contrast mean value of Z-score TG BMD bone and high age compared to mean value of Z-score TB BMD for chronological age were increased significantly. We conclude that bone mineralisation should be compared with or high age not to chronological age in patients with end-stage renal disease.

[Risk factors of adynamic bone disease in children with end-stage renal failure: personal experience]. / Czynniki ryzyka adynamicznej choroby kosci u dzieci ze schylkowa niewydolnoscia nerek--doswiadczenia wlasne.

The aim of the study was to estimate predisposing factors which can cause adynamic bone disease (ABD) and biochemical markers, bone densitometry results, bone histomorphometry in 17 children with this from of the renal osteodystrophy. Half of these of patients were treated with alphacalcidol pulses. In 47% of patients hypercalcemic episodes were noted, 76% had PTH level < 50 pg/ml. Four patients with osteoporosis (low bone volume at histological analysis) were distinguished. Two of them were treated with corticosteroids, 1 was immobilized for a long time.

[Bone metabolism markers and bone histomorphometry in children with chronic renal failure in predialysis period during growth hormone treatment]. / Markery metabolizmu kostnego u dzieci z przewlekla niewydolnoscia nerek leczonych hormonem wzrostu w okresie przeddializacyjnym.

The aim of the study was to estimate biochemical bone metabolism markers and bone histomorphometric parameters in children with chronic renal failure (CRF) treated with recombinant human growth hormone (rhGH). Twelve children with CRF aged 2-13.4 years were treated with rhGH 1-1.1 IU/kg per week and alfacalcidol. Bone biopsies were performed before and after 12 months of therapy. An increase in the biochemical markers of bone formation and bone resorption were noted. A statistically significant increase in mineral apposition rate (MAR) was observed in bone histomorphometry. The administration of active vitamin D metabolites enable proper bone mineralization in fast growing children with CRF during rhGH treatment.

Vitamin D metabolite requirements in dialysed children receiving recombinant human growth hormone.

BACKGROUND: The aim of the study was to assess the requirement of active vitamin D in dialysed children during treatment with recombinant human growth hormone (rhGH). METHODS: Twenty-six children (aged 5-15 years) were treated with rhGH for 6 months. The serum concentration of parathyroid hormone (PTH), alkaline phosphatase (AP), and calcium and phosphorus were measured in two groups of patients studied in the years 1994-1995 (group I) and 1995-1998 (group II) respectively. Group I received a constant dose of alfacalcidol that was sufficient to keep PTH below 200 pg/ml before rhGH treatment began. The serum PTH level was checked every 3 months. Alfacalcidol was administered to group II according to serum PTH levels checked on a monthly basis. RESULTS: In group I the PTH level increased after 3 and 6 months of rhGH treatment from mean level 73+/-60; 155+/-156 and 344+/-249 pg/ml respectively; P<0.05. AP activity increased after 6 months of treatment from 206+/-99 to 325+/-124 U/l respectively; P<0.01. The calcium level decreased from baseline after 3 months of treatment from 2.36+/-0.21 to 2.17+/-0.12 mmol/l respectively; P<0.05. In group II AP activity increased after 3 and 6 months of treatment from 272+/-169 to 332+/-192 and 404. 9+/-219.8 U/l respectively; P<0.01. The mean level of phosphorus decreased after 6 months from 2.15+/-0.28 to 1.70+/-0.39 mmol/l respectively; P<0.01. In group II the mean dose of alfacalcidol increased by 60.9%. CONCLUSIONS: In children with end-stage renal failure, higher doses of vitamin D are needed during rhGH treatment. During rhGH treatment, frequent control of serum PTH level is necessary.

[The influence of corticosteroid therapy on selected parameters of bone metabolism in children with nephrotic syndrome]. / Wplyw kortykosteroidów na wybrane parametry metabolizmu kostnego u dzieci z zespolem nerczycowym.

The aim of the study was to evaluate the influence of prednisone therapy on selected parameters of bone metabolism [carboxyterminal propeptide of type I procollagen (PICP), carboxyterminal pyridinoline crosslinked telopeptide of type I collagen (ICTP), alkaline phosphatase (AP), parathormone (PTH), and calciuria (Cau) in children with nephrotic syndrome. Twenty patients (aged 4-15 years, mean: 9.2 years) were treated with prednisone. Blood and urine samples were taken: T0--before prednisone treatment; T1--after two weeks of treatment with prednisone 1-2 mg/kg/24 h; T2--after two weeks of treatment with prednisone 1-2 mg/kg/48 h; T3--after 3 months of treatment with prednisone; T6--in 6th month of treatment with prednisone, at dose 0.2-0.4 mg/kg/48 h. Mean values of PICP, ICTP, AP concentration, and PICP/ICTP ratio found in the T1 period were significantly lower, and mean Cau value was higher in comparison to means of these parameters observed before steroid treatment. After two weeks of prednisone administered every 48 hours mean values of PICP, ICTP concentrations and PICP/ICTP ratio were significantly higher than in the T1 period of treatment. There were no significant differences in mean concentrations of PTH before and during everyday doses of prednisone therapy. Mean value of PTH concentration decreased significantly during T2 in comparison with T1 period of prednisone treatment. Our data demonstrate that short-term treatment with high daily doses of prednisone in children with nephrotic syndrome is associated with increase of calciuria and suppression of serum markers of type I collagen's turnover. Changes of PICP, ICTP, and PICP/ICTP ratio depend on a method of steroid administration. Decreased PICP/ICTP ratio during daily steroid treatment may indicate stronger inhibition of bone formation than bone resorption, but significance of PICP/ICTP ratio in later phases of treatment needs further studies. Present study suggests that prednisone influences bone metabolism directly rather than by stimulating the parathyroids.

The influence of growth hormone treatment on bone metabolism in dialysis patients.

Bone formation markers, PTH intact, and bone mineral density were evaluated in 12 children with end stage renal disease during recombinant human growth hormone (rhGH) treatment. Bone biopsies before rhGH therapy revealed: osteitis fibrosa in one patient, mild lesions in eight, adynamic bone disease in one, and a normal histology in two. PTH intact increased after six months of rhGH in seven children, and was significantly higher in them than in the control group. A positive correlation between PICP concentration after one month and growth velocity within 12 months of rhGH was found. Higher doses of vitamin D are needed in growing children treated with rhGH.

[The effect of decreasing serum calcium in serum during hemodialysis on PTH levels in children with end stage renal disease]. / Wplyw obnizenia stezenia wapnia w surowicy podczas hemodializy na poziom PTH intact u dzieci ze schylkowa niewydolnoscia nerek.

The aim of our study was to evaluate serum Ca and PTH intact levels in children during one hemodialysis session using a low calcium level dialysate (1.25 mEq/l). The study was performed in 6 children with end-stage renal disease. We analysed the parameters of calcium-phosphorus metabolism in children 18 months before the test. In 5 of children the increase of PTH level during hemodialysis was lower than in healthy people. In 3 patients with hyperparathyroidism the basal PTH (PTHb) level before the test was high and increased by 45%, 67% and 118% during hypocalcemic stimulation. In 2 patients suppression of parathyroid function was diagnosed due to low serum PTHb level and small increase during hypocalcemic stimulation. Despite low basal PTH level, one of the patients respond to hypocalcemic stimulation like healthy subjects. Dynamic monitoring of the PTH level during hypocalcemic stimulation is a very useful method of estimation parathyroid gland function and adjusting doses of vitamin D metabolites.

[Correlation between osteocalcin and bone histomorphometry in children with chronic renal failure]. / Zaleznosc miedzy osteokalcyna a wskaznikami histomorfometrycznymi kosci u dzieci z przewlekla niewydolnoscia nerek.

The study was performed in 17 children with chronic renal failure, 7 were on hemodialysis, 6 on continuous ambulatory peritoneal dialysis, 4 were treated conservatively. In all, serum levels of alkaline phosphatase, PTH intact and osteocalcin were measured and bone biopsy was performed. We analyzed correlations between biochemical markers of bone metabolism and histomorphometric parameters. The lowest mean serum osteocalcin levels were found in children with adynamic bone disease, the highest with osteitis fibrosa. The serum osteocalcin level was significantly correlated with the dynamic parameter of bone formation rate (BFR), which suggests that this biochemical marker can be of use in discriminating between renal osteopathy with low and high bone turnover. Lack of correlation between serum osteocalcin level and mineralizing surface confirms it significance as a good marker of osteoblastic activity in bone formation but not in bone mineralization.

[The diagnostic value of cytology in children on continuous ambulatory peritoneal dialysis (CAPD)]. / Wartosc diagnostyczna cytozy u dzieci leczonych ciagla ambulatoryjna dializa otrzewnowa (CADO).

Peritonitis is a common clinical problem that occurs in patients undergoing CAPD. Early diagnosis of this complication is difficult in some cases and elevated peritoneal cell count may be a misleading factor in diagnosis. The aim of the study was to determine the cell count in consecutive dialysate exchanges after starting CAPD. Elevated peritoneal cell count was found in 17 of 21 (80%) analyzed periods at the beginning of CAPD. Peritonitis was diagnosed in 5 of these patients and confirmed by culture in 4 and clinical observation in 1. In the remaining 12 cases (70%) the elevated cell count normalized during consecutive exchanges of dialysate. The coexistence of such nonspecific symptoms as fever, abdominal pain of varying intensity, cloudy fluid with or without the presence of fibrin can be the cause of diagnostic mistake and institution of unnecessary antibiotic treatment. In doubtful case, the reduction of the dwell time to 2 hours and observation of the cell count in consecutive exchanges is very helpful, especially if rapid culture diagnosis is not available.

[Results of the treatment of steroid-resistant and steroid-dependent nephrotic syndrome with pulsed doses of prednisolone]. / Wyniki leczenia "uderzeniowymi" dawkami prednisolonu sterydoopornych i sterydozaleznych zespolów nerczycowych.

In 12 children with steroid-resistant and 17 with steroid-sensitive nephrotic syndrome massive doses of prednisolone were used in intravenous infusions ("pulses"). In 8 children with steroid-resistant and 9 with steroid-sensitive nephrotic syndrome very good or good results were obtained. The authors suppose that in a part of the children previous ineffectiveness of this immunosuppressive treatment could have been due to insufficient dosage. Rosette tests before and after pulses demonstrated a reduction of the total number of T-cells after pulses. The change of the ratio of theophylline-resistant to theophylline-sensitive lymphocytes suggests that this reduction was caused mainly by a fall of the number of helper T-cells and non-specific cytotoxic cells.

[Acquired cysts of the kidneys in children with chronic renal failure]. / Nabyta torbielowatosc nerek u dzieci z przewlekla niewydolnoscia nerek.

The study aimed at evaluating an incidence of the acquired cysts of the kidneys in children with chronic renal failure. The study involved 33 children with renal failure treated conservatively with continuous peritoneal dialysis under ambulatory conditions and hemodialyses. CT tomography and sonography were carried out in all patients. The acquired cysts of the kidney were diagnosed in one out of 33 examined patients (3.03%) by ultrasound. This result was confirmed by CT-scanning. It is worth following the development of the cyst in his child waiting for kidney transplantation and further following all dialysed patients with ultrasound performed once per three months and CT-scans in some patients.