Mother-child correlation of kidney function: data from the Yamanashi Adjunct Study of Japan Environment and Children's Study (JECS).

BACKGROUND: Individual variation in kidney function can be affected by both congenital and acquired factors, and kidney function in children is possibly correlated with that in their mothers. However, the mother-child correlation in kidney function remains directly unconfirmed. METHODS: We conducted a cross-sectional study of 655 healthy pairs of 7- or 8-year-old children and their mothers as an adjunct study of a nationwide epidemiological study (Japan Environment and Children's Study). RESULTS: Both serum creatinine level (all children, r = 0.324, p < 0.001; girls, r = 0.365, p < 0.001; boys, r = 0.278, p < 0.001) and estimated glomerular filtration rate (eGFR) (r = 0.274, p < 0.001; r = 0.352, p < 0.001; r = 0.195, p < 0.001, respectively) in children were weakly associated with their maternal values. In the single linear regression analyses, maternal values of serum creatinine and eGFR were significantly associated with the children's values. Moreover, several body composition values in children, such as weight-SDS, fat (%), and predicted muscle weight, were also significantly associated with kidney function values in children. In the multiple linear regression analysis for serum creatinine levels in children, in which weight-SDS and predicted muscle weight in children were selected as adjustment factors, maternal serum creatinine level showed a significant positive association (B = 0.214, p < 0.001 in the adjusted model). Moreover, in the multiple linear regression analysis for eGFR value in children, in which fat (%) and predicted muscle weight in children were selected as adjustment factors, maternal eGFR values showed a significant positive association (B = 0.319, p < 0.001). CONCLUSIONS: We directly confirmed mother-child correlations in both serum creatinine levels and eGFR values, particularly in girls. Graphical abstract A higher resolution version of the Graphical abstract is available as Supplementary information.

Urinary fibrin/fibrinogen degradation products measured using an anti-fibrinogen antibody predict orthostatic proteinuria.

BACKGROUND: The aim of this study was to assess the diagnostic value of urinary fibrin/fibrinogen degradation products (uFDP) measured using an anti-fibrinogen antibody in patients with orthostatic proteinuria (OP), and their use in differentiating between OP and glomerulonephritis (GN). METHODS: uFDP were measured using first urine in the morning (supine) and non-first urine during a hospital visit (upright) and then normalized to urine creatinine (uFDP/Cr, ng/mgCr). We compared (i) OP patients (n = 16); (ii) those in remission from nephrotic syndrome (NS, n = 14) and from GN (IgA nephropathy [IgAN], n = 14; Henoch-Schönlein purpura nephritis [HSPN], n = 12); and (iii) those with active GN (IgAN, n = 12; HSPN, n = 19). RESULTS: The uFDP/Cr ratio increased from supine to upright urine in patients with OP (P < 0.001), but decreased in one case. uFDP were excreted in supine urine in 94% of OP patients, with no excretion in NS remission patients or in 92% of GN remission patients (P < 0.001 for both). uFDP/Cr in supine urine was similar between the OP and active GN patients (P = 0.40), whereas proteinuria in supine urine was in the normal range in all OP patients, but was significantly higher in upright urine in the OP patients (P < 0.001). In upright urine, urinary protein/creatinine ratio was significantly lower in patients with OP than in those with active GN (P = 0.005). A uFDP/Cr ratio cut-off of 1,108 ng/mgCr in upright urine correctly differentiated OP from active GN, with a sensitivity of 87.5% and a specificity of 100%. CONCLUSION: Comparison of uFDP levels in supine/upright urine can be reliable for diagnosing OP and for differentiating it from active GN.

Pediatric case of crescentic post-streptococcal glomerulonephritis with myeloperoxidase anti-neutrophil cytoplasmic antibody.

Post-streptococcal glomerulonephritis (PSGN) generally has a good renal prognosis, and immunosuppressive therapies are not needed. However, a few patients present with severe acute kidney injury and extensive crescent formations. The etiology of such patients is not well known, and involvement of anti-neutrophil cytoplasmic antibodies is rarely reported. A 9-year-old girl with rapidly progressive nephritic syndrome was diagnosed with PSGN. A biopsy showed diffuse crescentic glomerulonephritis with immunoglobulin G and C3 deposits; moreover, humps were observed on electron microscopy. After she was administered methylprednisolone pulse therapy and intravenous cyclophosphamide, followed by prednisolone and azathioprine therapy, her urinary abnormalities improved and renal function normalized. However, the myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA) titers gradually increased. We speculated that PSGN may be augmented by increased MPO-ANCA levels. Therefore, the patient is currently being treated with losartan, enalapril, azathioprine, and prednisolone. Although the MPO-ANCA titer remains high, urinary findings show mild proteinuria and her renal function has been norma for 18 months since onset. A progressive clinical course and severe histological findings may indicate the involvement of ANCA in deterioration of condition in patients with PSGN. Furthermore, in such cases immunosuppressive therapies should be considered even in pediatric PSGN.

Autoimmune neutropenia of infancy with recurrent urinary tract infections: a case report.

Autoimmune neutropenia of infancy is characterized by minor intercurrent infections despite severe neutropenia; severe bacterial infections are uncommon. An infant developed recurrent urinary tract infections at 9 and 11 months of age. The identified uropathogens were Escherichia coli and Enterococcus faecalis, respectively. Empirical treatment with carbapenems, as broad-spectrum antibiotics, promptly resolved the infection without sequelae. Febrile neutropenic children with cancer and autoimmune neutropenia can develop urinary tract infections; therefore, in such infants, urine culture should be obtained through catheterization. In febrile neutropenic infants with no apparent fever source, cephalosporin monotherapy should not be selected empirically because Enterococci can be the involved pathogens.

Community-acquired methicillin-resistant Staphylococcus epidermidis pyelonephritis in a child: a case report.

INTRODUCTION: Staphylococcus epidermidis is currently the most frequent pathogen of opportunistic and nosocomial infections worldwide. Most cases of Staphylococcus epidermidis infections are associated with indwelling medical devices and/or immunocompromised conditions. Community-acquired urinary tract infections are rare, particularly among pediatric populations, and clinicians often do not consider Staphylococcus epidermidis as a uropathogen. CASE PRESENTATION: A previously healthy Japanese boy developed pyelonephritis caused by Enterococcus faecalis at 10 months of age. Subsequently, he was diagnosed with severe bilateral vesicoureteral reflux (right side grade V, left side grade III), and was administered trimethoprim/sulfamethoxazole as the prophylaxis. At 18 months of age, he presented with fever. Gram staining of urine obtained through catheterization revealed gram-positive cocci. We suspected pyelonephritis caused by enterococci, and administered oral fluoroquinolone empirically. The fever promptly resolved, and eventually, methicillin-resistant Staphylococcus epidermidis was detected at significant levels in the urine. Thus, our final diagnosis was pyelonephritis caused by community-acquired methicillin-resistant Staphylococcus epidermidis. CONCLUSIONS: Our case indicated that even immunocompetent children without a urinary catheter can develop Staphylococcus epidermidis pyelonephritis. Staphylococcus epidermidis can be underdiagnosed or misdiagnosed as sample contamination in community-acquired urinary tract infections. Therefore, when Gram staining of appropriately obtained urine samples reveals gram-positive cocci, clinicians should take into consideration not only the possibility of enterococci but also staphylococci, including Staphylococcus epidermidis, particularly in children with urinary abnormalities and/or those receiving continuous antibiotic prophylaxis.

Role of ultrasound in revealing complications following percutaneous renal biopsy in children.

BACKGROUND: This retrospective case series aimed to investigate the role of ultrasound immediately post-percutaneous renal biopsy (PRB) for detecting post-biopsy complications in pediatric patients. METHODS: Data from 380 (male/female = 209/171) consecutive biopsies of native kidney tissue of 344 children from January 2001 to October 2009 were analyzed to investigate the role of an ultrasound immediately post-PRB and the predictive value of demographic, clinical, and baseline chemistry factors in predicting the risk of post-PRB complications. RESULTS: Post-PRB ultrasound identified hematoma formation in 33 (8.7%) patients. Of the 19 (5.0%) patients whose hematomas were large (≥ 1 cm), post-biopsy courses of 16 patients were clinically complicated. On the other hand, of the 14 patients whose hematomas were small (< 1 cm), all patients but one showed an uncomplicated clinical course. Of the 17 complications, 79.1% were detected within the first 24 hours and 21.9% (cases of resorption fever) between 24 and 144 hours post-PRB. Age ≥ 10 is an independent risk factor for post-PRB complication. CONCLUSIONS: Age ≥ 10 is an independent risk factor for post-PRB complication. After the procedure, the formation of a large hematoma predicted a complicated clinical course.

Methylprednisolone pulse therapy and intravenous cyclophosphamide therapy combined with cocktail therapy in severe pediatric Henoch-Schönlein purpura nephritis patient.

Henoch-Schönlein purpura (HSP) is a common self-limited vasculitis in children. The long-term prognosis depends on renal involvement. In severe Henoch-Schönlein purpura nephritis (HSPN) patients, >50 % have crescent formation and nephrotic syndrome that are important predicted outcomes. Therefore, for such patients, an aggressive immunosuppressive therapy is needed to prevent the progression. However, there is no consensus for an appropriate therapeutic regimen for severe pediatric HSPN patients. In this paper, we have reported on a 6-year-old boy who presented with HSPN with nephrotic syndrome and severe histopathological abnormalities; he was diagnosed with International Study of Kidney Disease in Children (ISKDC) grade IVb. Despite treatment with methylprednisolone pulse therapy, followed by oral prednisolone and dipyridamole; the nephrotic syndrome persisted. Subsequently, intravenous cyclophosphamide therapy (IVCY) (500-1,000 mg m-2 once a month for 7 months; total 6,000 mg m-2) was administered, followed by azathioprine and enarapril. Within 7 months of disease onset, complete remission was achieved. After 22 months of the initial renal biopsy, the second biopsy was performed to confirm treatment efficacy. Histopathological findings improved, and ISKDC grade IIIa was diagnosed. Even after 5 years of HSPN onset, complete remission and normal renal function is maintained. Although our evidence is restricted to single patient, we have shown that MPT and IVCY combined with cocktail therapy may be an effective treatment for severe pediatric HSPN.

Hereditary renal hypouricemia: a cause of calcium oxalate urolithiasis in a young female.

Although renal hypouricemia is mostly asymptomatic, it is known to present a high risk of exercise-induced acute renal failure, especially in young males. However, there is little information regarding the clinical features of urolithiasis as a complication in childhood renal hypouricemia. Here we report a 4-year old female with idiopathic renal hypouricemia who presented with macroscopic hematuria due to obstructive calcium oxalate urolithiasis. She was treated successfully with percutaneous nephrolithotripsy and thereafter hematuria disappeared. Sequence analysis of the patient and her family's URAT1 gene confirmed a nonsense mutation in exon 4 (W258X). To the best of our knowledge, this is the youngest case of hereditary renal hypouricemia caused by URAT1 gene mutation, which was found by hematuria due to calcium oxalate urolithiasis.

Early treatment with methylprednisolone pulse therapy combined with tonsillectomy for heavy proteinuric henoch-schönlein purpura nephritis in children.

BACKGROUND: There is no clear consensus as to which patients with Henoch-Schönlein purpura nephritis (HSPN) at risk of a poor outcome should be treated and what therapeutic regimen should be used. METHODS: Nine children with heavy proteinuric HSPN received prompt initiation of methylprednisolone pulse therapy (MPT) combined with tonsillectomy in a prospective study. RESULTS: At presentation, the mean values for the patients' urine protein excretion (early-morning urinary protein/creatinine ratio), serum IgA, activity index (AI), and chronicity index (CI) were 5.0 ± 5.6 g/g Cr, 135.6 ± 56.5 mg/dl, 4.0 ± 0.7, and 1.7 ± 1.3, respectively. At the second biopsy, conducted approximately 24 months after initiation of therapy, the patients' serum albumin had significantly increased (4.4 ± 0.2, p < 0.01), and the serum IgA and AI had significantly decreased (88.1 ± 30.8 mg/dl, p < 0.05; 2.0 ± 1.2, p < 0.01, respectively), whereas the CI remained unchanged. Proteinuria disappeared within 24 months in all but 1 patient, and hematuria disappeared within 38 months in all patients. No patient showed renal impairment or experienced a recurrence and/or exacerbation of HSP/HSPN. CONCLUSIONS: Early treatment with MPT combined with tonsillectomy is effective in ameliorating the histopathological progression and improving the clinical course of children with heavy proteinuric HSPN.

[Long-term outcome of children treated with the ISKDC regimen for the first episode of INS].

We retrospectively analyzed the long-term outcome of 82 children (SRNS group, 10; SDNS group, 35; IRNS group, 37) who were initially treated with the ISKDC regimen at the Saitama Children's Medical Center. The ISKDC regimen consisted of PSL 60 mg/m2/day for 4 weeks, followed by 40 mg/m2 on alternate days for another 4 weeks. The aims of our study were to identify factors at onset that could predict the relapse pattern after using the initial ISKDC regimen, and to assess the prognosis and renal histology after long-term CsA therapy in 31 children. All of six asymptomatic children without edema and identified by chance proteinuria on a urinary screening program had an extremely favorable clinical course. Initial remission time of 9 or more days and the time interval from the initial therapy to the first relapse were significant predictors of steroid dependency. The sensitivity and specificity of these findings were 100% and 90%, respectively, with a positive predictive value of 95% and a negative predictive value of 100%. In addition, after the introduction of CsA therapy, termination of steroid therapy was achieved in 56% of patients with SRNS, and 64% of SDNS, respectively. However, after CsA therapy was tapered or stopped, most patients (21/20: 95%) developed relapses of NS. Of these, 76% (16/21) returned to SDNS, resulting in the reintroduction of CsA. Ten of 22 patients taking CsA (mean duration 31.3 months) had chronic nephrotoxicity. In conclusion, the initial ISKDC regimen is useful for the early prediction of whether or not the patient will develop SDNS. When pediatric nephrologists introduce CsA therapy in children with SDNS, an alternative strategy after long-term use of the agent should be considered.

A case report of dysosteosclerosis observed from the prenatal period.

Dysosteosclerosis is a sclerosing bone dysplasia with skeletal changes resembling those of osteopetrosis. The disorder is associated with dental anomalies and occasionally mental retardation. Because of the rarity and phenotypic diversity of dysosteosclerosis, it remains unsolved whether or not the disorder is heterogeneous. We report here on an affected boy associated with brain calcification and epilepsy with developmental delay. Prenatal ultrasound revealed ventriculomegaly, and brain CT in the neonatal period showed periventricular calcifications. At 13 mo of age, he presented with generalized convulsion with developmental delay. Metaphyseal sclerosis, metaphyseal undermodeling, and oval-shaped vertebral bodies on skeletal survey warranted a diagnosis of dysosteosclerosis. Retrospective review of radiographs as a neonate showed metaphyseal radiolucency, but not metaphyseal sclerosis. Since then, neither the bone changes nor neurological symptom has progressively worsened up to 4 yr of age. Thus, it is thought that the clinical and radiological manifestations of the sclerotic disorder become obvious during infancy. Brain calcification of prenatal onset may be an essential syndromic constituent of the disorder.