Bone histology in steroid-treated children with non-azotemic nephrotic syndrome

Patients with nephrotic syndrome (NS) and normal glomerular filtration rate (GFR) frequently exhibit abnormalities of calcium and vitamin D homeostasis, mainly hypocalcemia and reduced circulating vitamin D metabolites. These abnormalities have been linked to alterations of bone histology in adults with non-azotemic NS, particularly osteomalacia and excessive bone resorption. Whether similar abnormalities of bone histology occur in children and adolescents with NS, particularly in those requiring prolonged treatment with corticosteroids, remains largely unknown. Thus, bone histomorphometry and selected bone-modulating hormones were studied in eight children (aged 2–16 years) with normal GFR (range 85–169 ml/min per 1.73 m²) and NS. All patients received corticosteroids for at least 12 months prior to bone biopsy. At the time of bone biopsy, the urine protein/creatinine ratio was elevated (2.1±3.6), while the average concentrations of parathyroid hormone (36±13 pg/ml), 25-hydroxyvitamin D [25(OH) D] (22±14 ng/ml), and 1,25(OH)₂D (59±22 pg/ml) were normal. Bone histomorphometry displayed focal osteomalacia (OM) and mild increased bone resorption in most patients. The mineralization lag time, an indicator of the degree of osteomalacia, correlated with the time elapsed since the original diagnosis of NS (r=0.93, P<0.0005). Overt hyperparathyroidism was not evident, but increased eroded perimeter and elevated bone formation rate (BFR) were evident in two patients, suggesting high-turnover bone disease. The BFR was inversely correlated with the administered dose of prednisone at the time of biopsy (r=–0.78, P<0.05) and one patient exhibited low bone turnover changes. The growth velocity standard deviation score (SDS) at time of biopsy ranged from –1.6 to 3.2, resulting in a height SDS range of –1.9 to 0.6. The height SDS at time of bone biopsy correlated inversely with the dose of administered glucocorticoid (r=–0.71, P<0.05) and with the duration of the disease (r=–0.7, P=0.05). These data, albeit preliminary, demonstrate that children with NS treated with prolonged corticosteroid therapy exhibit bone histopathological changes without a concomitant impairment in GFR. While the OM appears to be related to the disease process, the alterations of bone formation and the adynamic changes are likely the result of the corticosteroid therapy. The potential consequences of these findings on adult bone mass and ultimate height deserve further studies.     

Growth hormone for children with chronic renal failure and on dialysis

We studied all children with CRF who received recombinant human growth hormone (rhGH) for more than a year (mean±SD duration of therapy 3.7±2.5 years) over an 11-year period. There were 32 children. Twenty-one children were conservatively managed, with a mean glomerular filtration rate (GFR) of 24±12 mL min^–1/1.73 m² at the start of rhGH. Their height standard deviation score improved from –2.5±1.4 to –2.1±0.7 at 1 year (P=0.3), –2.0±0.7 at 2 years (P=0.01), and –1.6±0.6 at 3 years (P=0.001). After that there was no improvement. Eleven children were on dialysis, six on haemodialysis (HD) and five on peritoneal (PD). Ht SDS improved from –2.7±0.5 to –2.3±0.5 at 1 year (P=0.02). Thereafter there was no further improvement. RhGH was stopped because of transplantation in 29 patients at a mean±SD age of 12.1±4.0 years. Mean Ht SDS was –1.8±0.8 at transplant and there was no change over the following 5 years. In conclusion, treatment with rhGH resulted in improvement in Ht SDS in conservatively managed CRF for up to 3.0 years and for 1 year in children on dialysis. Discontinuation of rhGH after transplantation resulted in little change in Ht SDS.     

Switch from cyclosporine A to mycophenolate mofetil in nephrotic children

Nephrotoxicity is a well-known adverse effect of cyclosporine A (CyA) treatment in children with steroid-dependent (SD) and steroid-resistant (SR) nephrotic syndrome (NS). We analyzed nine children (age: 3.3–15.7 years, two girls) with SD or SR NS who experienced a significant decrease in their GFR under CyA treatment as measured by inulin clearance (C_IN). Mycophenolate mofetil (MMF) was introduced progressively until doses of 1 g/1.73 m² twice daily were reached. CyA treatment was stopped after introduction of MMF and oral steroids were reduced if possible. After a median follow up of 261 days, no adverse effects of MMF such as diarrhea or hematological anomalies occurred in our patients. After switching from CyA to MMF, those children with SD NS remained in remission without proteinuria and those with SR NS did not show any significant changes in their residual proteinuria. The serum protein level did not change significantly in any of the children analyzed. GFR increased from a mean of 76.9±4.8 to 119.9±5.9 mL/1.73 m² per min (P<0.001). Oral steroid treatment could be reduced from a median [range] prednisone dose of 0.85 [0.26–2.94] mg/kg/d pre-MMF to 0.29 [0–1.1] mg/kg per day (P=0.026), and blood pressure decreased moderately after CyA withdrawal, but the difference did not reach statistical significance. We conclude that a switch from CyA to MMF seems to be safe for children with SDNS and SRNS in terms of side effects as well as disease control, at least in the short term. Interruption of CyA treatment lead to rapid amelioration of kidney function in these children, often associated with steroid sparing, which may lead to additional benefit for growth velocity, blood pressure and physical appearance.     

Clinical course and outcome of idiopathic membranous nephropathy in Japanese children

We retrospectively studied 12 Japanese children (8 boys, 4 girls) with idiopathic membranous nephropathy (IMN), aged 2.9–15.8 (mean 7.7) years at onset. All patients were identified through either screening or a routine urinalysis; proteinuria was present in all, haematuria, which was macroscopic in 4, in 11. Three had nephrotic syndrome (NS) at or soon after onset. Stages on electron microscopy, performed in 10 patients, were I in 3, II in 5 and III in 2. Steroids alone or with cyclophosphamide were administered to 5 patients, including the 3 patients showing NS. Complete remission of proteinuria occurred in 8 patients 0.3–1.6 (mean 0.6) years after onset, and proteinuria did not recur. After a follow-up of 1.6–11.6 (mean 5.9) years, these 8 patients were in complete remission and the remaining 4 had only mild proteinuria; none had hypertension or impaired renal function. Thus, we infer that IMN in Japanese children may have a better course and outcome than IMN in non-Japanese children. Based on a comparative study of Japanese (previously reported cases added to ours) and non-Japanese (mostly Caucasian) children with IMN, this was confirmed: it is possible that steroid therapy in Japanese patients is more effective in inducing remission of NS and preserving renal function.     

Recurrent nephrotic syndrome after transplantation: Early treatment with plasmaphaeresis and cyclophosphamide

Steroid-resistant nephrotic syndrome (NS) with focal glomerulosclerosis (FGS) and its recurrence after transplantation are mainly seen in children. The recurrence rate approximates 30% and the graft loss is about half this. Several therapeutic regimens have been proposed, giving conflicting results. In an attempt to remove a putative circulating factor and inhibit its production by lymphocytes, three patients with biopsy-proven FGS in the native kidney were included in a prospective uncontrolled trial using early plasmaphaeresis followed by substitutive immunoglobulins in association with methylprednisolone pulses and cyclophosphamide instead of azathioprine over a 2-month period. The patients were girls, aged 6.5, 13.3 and 15.8 years, who received a cadaveric transplant; concomitant immunosuppression included prednisone and cyclosporine A. All three patients exhibited early recurrence of the NS and were treated 5–10 days after the onset of proteinuria. Rapid and sustained remission was achieved in all patients within 12–24 days on therapy. One patient experienced a late acute but steroid-sensitive rejection episode; another suffered from septic ankle arthritis as a complication of reinforced immunosuppression. The latter girl had a second late recurrence of proteinuria that was controlled within 7 weeks. With a 18-to 27-month follow-up, all three patients have normal renal function, normal blood pressure and no proteinuria. We conclude that intensive therapy using plasmaphaeresis, steroid pulses and cyclophosphamide over a 2-month period can induce complete remission in children with early recurrence of NS after transplantation.     

Comparison of growth in primary Fanconi syndrome and proximal renal tubular acidosis

To compare the difference between primary proximal renal tubular acidosis (PRTA) and Fanconi syndrome (FS), and to find out possible risk factors for growth retardation, we studied the long-term growth, clinical, laboratory, and radiological findings associated with the treatment of six children with primary FS and 15 children with PRTA. The ages of the children with FS were much older than those with PRTA at initial diagnosis (7.03±3.82 vs. 1.63±1.56 years). The height standard deviation score (SDS) at the start of treatment was significantly lower in FS than in PRTA. Catch-up growth was noted in PRTA at the end of follow-up (initial height SDS –2.13±1.10 vs. last height SDS –1.33±1.43, P=0.023 by paired t-test), whereas apparent linear growth impairment was found in FS in terms of overall growth velocity index (82.70±8.37%) and height SDS (initial –3.25±0.95 vs. last –3.15±0.31, P=0.791). There was also a higher rate of rickets occurrence in FS (3/6 vs. 0/15 in PRTA). Hypophosphatemia during the follow-up period was more frequent for FS than PRTA (69.2±26.1% vs. 7.0±25.8%, P<0.001), whereas metabolic acidosis (blood HCO₃<20 mmol/l) was less efficiently corrected in PRTA (49.1±20.5% vs. 25.2±21.6% in FS, P=0.028). Moreover, the height SDS correlated well with the mean serum P level during the treatment period in these patients (R=0.528, P=0.014 for all children; R=0.917, P=0.01 for FS patients). Our data suggest that metabolic acidosis may not be the sole factor causing growth impairment in FS. Correction of metabolic acidosis may indeed improve growth in PRTA but not in FS. This study indicates that factors other than metabolic acidosis, such as phosphate depletion and delayed diagnosis/treatment, should be considered to be important causes of growth retardation in FS.     

Value of urinary excretion of microalbumin in predicting glomerular lesions in children with isolated microscopic hematuria

Urinary microalbumin excretion was assessed in 76 children with asymptomatic microscopic hematuria in whom the presence of proteinuria, hypertension, reduced renal function, hypercalciuria, urinary tract infection or structural abnormality of the urinary tract had been excluded. All children underwent a percutaneous kidney biopsy to determine whether microalbumin excretion can be used as a marker to predict the source of hematuria. Microalbumin excretion was considered normal if the urinary ratio of microalbumin to creatinine (MA/Cr ug/mg) was 30. Twenty-two (29%) had microalbuminuria (MA/Cr 96±30 ug/mg) and 54 (71%) had normal albumin excretion (MA/Cr 13±2 ug/mg). Of those with normoalbuminuria, 38 (70%) had normal renal tissue, 15 (28%) thin glomerular basement membrane (TGBM) disease and 1 (2%) IgA nephropathy. In contrast, 20 (91%) of those with microalbuminuria had IgA nephropathy and 2 (9%) had TGBM disease. The mean urinary MA/Cr ratio for all IgA children was 89±32 ug/mg higher compared with a value for the children with TGBM disease (14 ±3 ug/mg, P <0.001) or children whose renal biopsy appeared normal (11±2 ug/mg, P <0.001). Statistical analysis revealed no significant differences between the mean MA/Cr ug/mg ratio for children with TGBM disease and those with normal glomerular findings. Fourteen of the 20 children with IgA nephropathy who also had microalbuminuria were treated with an angiotensin-converting enzyme (ACE) inhibitor. Over a mean follow-up of 51 months, none developed overt proteinuia; hematuria resolved and microalbuminuria returned to normal in eight (57%) during therapy with the ACE-inhibitor. In contrast, hematuria persisted and prtoteinuria developed in the other untreated children. None of the children with TGBM disease developed overt proteinuria after a mean of 51 months. Hematuria was persistent in children with TGBM disease, but often resolved in those whose biopsies were completely normal. These data suggest that determination of urinary microalbumin excretion is warranted in the routine examination of children with isolated microscopic hematuria. Routine screening for microalbuminuria may help to identify a subgroup of patients with IgA nephropathy who are at high risk for progressive kidney disease and need more intensive therapy and closer follow-up.     

Body growth of children with steroid-resistant nephrotic syndrome

Whilst it is assumed that body growth is retarded in children with steroid-resistant nephrotic syndrome (NS), the degree of growth failure and the pathomechanisms involved are poorly understood. We collected serial growth data in 45 children (24 males) with steroid-resistant NS usually from onset to end-stage renal disease (ESRD) during childhood (n=10) or until final height was attained (n=27). Mean follow-up time was 9 (2–19) years. Mean initial standardized height was –0.3±1.2 standard deviation scores (SDS). Mean final height was +0.4 SDS in males and –1.0 SDS in females (sex difference not significant). In 16 patients with serum creatinine levels consistently <1.2 mg/dl, mean final height SDS was 0.3 SDS higher than that obtained within 6 months of onset. In contrast, 9 children who entered ESRD lost an average of 1.3 SDS from the initial record to ESRD (P=0.017). In prepubertal patients without renal insufficiency, mean height SDS decreased during corticosteroid treatment by 0.3 SDS, followed by a partial catch-up after discontinuation of treatment; the change from initial to final height SDS was inversely correlated with the total prednisone dose given (r=–0.50, P=0.03). In 16 prepubertal children with serial height and serum protein measurements who were off steroids and maintained normal creatinine levels, mean individual albumin concentrations correlated with the change in height SDS per year (r=0.65, P=0.0006) and in boys with final height (r=0.73, P=0.03). In conclusion, growth in steroid-resistant NS depends on the preservation of renal function, the cumulative dose of steroids applied, and the severity of hypoproteinemia. Received: 15 July 1998 / Revised: 30 November 1998 / Accepted: 11 December 1998     

Growth of children following the initiation of dialysis: a comparison of three dialysis modalities

Maintenance dialysis usually serves as an interim treatment for children with end-stage renal disease (ESRD) until transplantation can take place. Some children, however, may require dialytic support for an extended period of time. Although dialysis improves some of the problems associated with growth failure in ESRD (acidosis, uremia, calcium, and phosphorus imbalance), many children continue to grow poorly. Therefore, three different dialysis modalities, continuous ambulatory peritoneal dialysis (CAPD), cycler/intermittent peritoneal dialysis (CPD), and hemodialysis (HD), were evaluated with regard to their effects on the growth of children initiating dialysis and remaining on that modality for 6–12 months. Growth was best for children undergoing CAPD when compared with the other two modalities with regard to the following growth parameters: incremental height standard deviation score for chronological age [–0.55±2.06 vs. –1.69±1.22 for CPD (P<0.05) and –1.80±1.13 for HD (P<0.05)]; incremental height standard deviation score for bone age [–1.68±1.71 vs. –2.45±1.43 for CPD (P=NS) and –2.03±1.28 for HD (P=NS)]; change in height standard deviation score during the dialysis period [0.00±0.67 vs. –0.15±.29 for CPD (P=NS) and –0.23±.23 for HD (P=NS)]. The reasons why growth appears to be best in children receiving CAPD may be related to its metabolic benefits: lower levels of uremia, as reflected by the blood urea nitrogen [50±12 vs. 69±16 mg/dl for CPD (P<0.5) and 89±17 for HD (P<0.05)], improved metabolic acidosis, as indicated by a higher serum bicarbonate concentration [24±2 mEq/l vs. 22±2 for CPD (P<0.05) and 21±2 for HD (P<0.05)]. In addition, children undergoing CAPD receive significant supplemental calories from the glucose absorbed during dialysis. CAPD, and possibly, other types of prolonged-dwell daily peritoneal dialysis appear to be most beneficial for growth, which may be of particular importance for the smaller child undergoing dialysis while awaiting transplantation.     

Long-term linear growth of children with severe steroid-responsive nephrotic syndrome

The present study was designed to evaluate the risk of permanent linear growth impairment in a selected group of 42 children with steroid-dependent nephrotic syndrome (SDNS) and 14 children with frequently relapsing nephrotic syndrome (FRNS). Longitudinal height measurements were available in all patients from the onset of the disease for a mean follow-up of 11.7±3.5 years. During the prepubertal period, patients lost 0.49±0.6 height SD score (HtSDS) (P<0.001). Twenty-three patients have reached their final height with an average loss of 0.92±0.8 HtSDS from the onset of their disease (P<0.001) and 0.68±0.7 from their target HtSDS (P<0.001). The pubertal growth spurt was mildly delayed in male but not female patients. Steroid therapy, calculated as the mean duration of prednisone (PDN) treatment or as the average cumulative PDN dose, was the only predictor of poor growth evolution. Partial catch-up growth occurred after PDN withdrawal. Children with early onset NS and adolescent patients, who were still receiving PDN after the age of 9 years in girls and 11 years in boys, were at higher risk for HtSDS loss. In conclusion, children with severe steroid-responsive NS are at risk of permanent growth retardation secondary to prolonged courses of steroid treatment.     

Steroid-resistant nephrotic syndrome: the influence of race on cyclophosphamide sensitivity

Steroid-resistant (SR) forms of nephrotic syndrome (NS) have a poorer outcome in blacks compared to other racial groups. In this study, 223 children with SRNS, aged 1–16 years old, were analysed retrospectively for the period 1976–2004. Treatment schedules included oral cyclophosphamide (2–3 mg/kg) with prednisone 0.5–1 mg/kg (maximum 60 mg) only (n=90); prednisone on alternate days with methylprednisolone (30 mg/kg, maximum 1 g) and oral cyclophosphamide (n=117); oral prednisone on alternate days, three doses of intravenous methylprednisolone on alternate days and monthly doses of intravenous cyclophosphamide (500–750 mg m⁻² dose⁻¹×7 doses monthly) (n=10); or cyclosporine 5 mg kg⁻¹ day⁻¹ adjusted to a trough level of 150–200 mg/ml (n=6). We compared the clinical and biochemical characteristics and outcome using different forms of therapies. A total of 183 (82.1%) underwent biopsy; 84 (45.9%) were Indian and 99 (54.1%) were black. Sixty-six (36.1%) had minimal change NS, 66 (36.1%) had focal segmental glomerulosclerosis (FSGS), 15 (8.2%) had a proliferative form of NS, and 36 (19.7%) had other forms of NS. Of the 84 Indian children biopsied, 58 (69.0%) were in complete remission, including 29 of 40 (72.5%) treated with oral cyclophosphamide and prednisone only. Of the 99 black children who were biopsied, 20 (20.2%) achieved complete remission; none of those treated with oral cyclophosphamide and prednisone only achieved complete remission. Of the 40 Indian children who were not biopsied who received only oral prednisone and cyclophosphamide, 32 (80%) achieved complete remission. This study shows Indian children with SRNS respond better to treatment than black children (69.0 vs. 20.2%). Since 80% of Indian children with SRNS responded to a trial of oral cyclophosphamide and prednisone, we propose the use of oral cyclophosphamide therapy in non-black children before embarking on renal biopsy.     

Treatment of severe IgA nephropathy in children

We treated ten children with severe IgA nephropathy (IgAN) [proteinuria > 1g/day, hypertension, renal insufficiency, segmental sclerosis, crescent formation and/or glomerular basement membrane (GBM) deposition of IgA] with prednisone and azathioprine for 1 year. Following the year of therapy, seven of the ten children underwent a repeat kidney biopsy. All biopsies were scored for activity (percentage of glomeruli demonstrating crescent formation, degree of mesangial proliferation and interstitial infiltrate; maximum score = 9) and chronicity (percentage of glomeruli demonstrating fibrous crescents, segmental sclerosis, global sclerosis, and degree of tubular atrophy and interstitial fibrosis; maximum score = 12). After 1 year of therapy, the protein excretion of all the children decreased significantly (P<0.01) from 4052±3190 mg/day to 1692±1634 mg/day. The activity score decreased significantly (P<0.01) from 4.35±0.94 prior to therapy to 2.28±0.75 after therapy while the chronicity score was unchanged (5.42±1.7 vs 5.85±2.0). The percentage of glomeruli demonstrating cellular crescents decreased (P<0.05) from 21.2±21.7% prior to therapy to 0.94±2.4% after therapy. Mesangial deposition of IgA persisted but GBM deposition of IgA was less prominent after therapy. During the follow-up period (mean 2.6 years, range 9 months–7.5 years), one child required brief retreatment for biopsy-confirmed recurrence of active disease, two children have developed renal insufficiency due to progressive scarring in the absence of inflammation, while the remaining seven are stable. We suggest that treatment with prednisone and azathioprine may be beneficial in children with severe IgAN and that a controlled clinical trial is warranted.     

Associations between HLA antigens and nephrotic syndrome in African and Indian children in South Africa

The nephrotic syndrome (NS) reported from Southern Africa is distinguished by unusual characteristics in African children and typical features among Indian children. A genetic basis for these differences is explored in 44 African and 33 Indian children with NS in this paper. HLA associations were detected in the 20 Indian children with minimal change NS (MCNS) and 12 African children with membranous NS. Previous studies of HLA antigens, which have all been performed on Caucasian children with MCNS or steroid-responsive NS (SRNS), have detected associations with HLAB and DR locus genes. In this report HLA Bw44, which is part of HLA B12, was found to be significantly more frequent in Indian children with MCNS or SRNS than in controls (45 and 12%, respectively, p less than 0.04; relative risk 5.8). In contrast, African children with membranous nephropathy had a significantly increased frequency of HLA Bw21 (15% in patients and 1% in controls, p less than 0.04; relative risk 22.1). HBsAg was positive in 9 of 11 patients tested in the latter group. We conclude that the interaction between heredity and environmental factors is central to the pathogenesis of membranous nephropathy and similar considerations may be important in the development of MCNS.     

儿童C1q肾病的临床病理特点及治疗

目的 探讨儿童C1q肾病的临床、病理特点及治疗方法。 方法 回顾性分析本院8年来经肾活检确诊的23例C1q肾病患儿临床、病理和预后资料。 结果 C1q肾病占同期肾活检的原发性肾小球疾病的4.78%。23例患儿中,男15例,女8例;年龄10个月~12岁5个月,平均发病年龄（5.0±3.4）岁;肾病综合征（NS） 18例（2例伴镜下血尿）,肾病水平蛋白尿4例（1例伴镜下血尿）,单纯镜下血尿1例。1例NS起病前曾服用2周中药,发病时同时并发急性肾功能不全。3例患儿有肾脏病家族史,其中2例（肾病水平蛋白尿）为姐弟,父亲亦有蛋白尿,基因检测证实为家族性Denys-Drash综合征并发C1q肾病。1例患儿（NS）姐姐亦有大量蛋白尿（未行肾活检）。所有患儿起病时血压均正常,补体正常,抗核抗体、抗dsDNA抗体、抗Sm抗体及乙肝两对半均阴性。18例NS中13例激素耐药（72.2%）,4例激素依赖,1例激素敏感。光镜下,13例为微小病变（MCD）（其中1例伴间质性肾炎）;6例为系膜增生性肾小球肾炎（MsPGN）;4例为局灶节段性肾小球硬化（FSGS）。另9例患儿伴有不同程度的小管萎缩和间质纤维化。免疫荧光下,所有患儿均见系膜区弥漫性C1q≥2+沉积,其中伴IgG沉积18例,IgM沉积18例,IgA沉积8例,C3沉积11例,6例患儿呈“满堂亮”表现。除4例患儿电镜下未见肾小球外,其余19例中4例系膜区见电子致密物沉积。12例激素耐药（包括2例肾病水平蛋白尿者）及3例激素依赖患儿在激素治疗基础上加用静脉CTX冲击;3例激素耐药者加用环孢素A（CsA）口服;1例激素依赖患儿给予足量激素重新诱导;1例单纯镜下血尿患儿及2例Denys-Drash综合征并发C1q肾病患儿仅给予血管紧张素转换酶抑制剂（ACEI）治疗。其中1例患儿CTX冲击满疗程无效后换用CsA治疗;1例患儿CTX冲击满疗程无效后换用FK506治疗。23例患儿中,1例失访,1例治疗时间<3个月未纳入随访对象,2例Denys-Drash综合征目前不能通过药物治疗好转未纳入疗效统计,余19例中,15例完全缓解（78.9%）,2例部分缓解（10.5%）,2例无效（10.5%）。NS患儿总缓解比例94.4%（17/18）,肾病水平蛋白尿患儿总缓解比例50.0%（2/4）。病理为MCD者总缓解比例100.0%,MsPGN者缓解比例83.4%,FSGS缓解比例50.0%。随访末所有患儿血压、肾功能均正常,自身抗体均阴性,补体水平均正常。 结论 C1q肾病罕见,临床以NS或肾病水平蛋白尿为主,且往往激素耐药或激素依赖;病理以MCD为主,也可表现为MsPGN或FSGS。加用其他免疫抑制剂治疗后,MCD和MsPGN者多可获缓解,但FSGS预后欠佳。     

Insulin-like growth factor-1, growth hormone-dependent insulin-like growth factor-binding protein and growth in children with chronic renal failure

Insulin-like growth factor-binding protein-3 (IGFBP-3) and insulin-like growth factor-1 (IGF-1) levels were measured by specific radioimmunoassays in children with all degrees of chronic renal failure (CRF). Study group 1 comprised 29 children (10 on dialysis) who had been studied one to four times over 2 years to determine whether IGF-1 and IGFBP-3 levels differed from those in age-matched healthy children and to examine the relationship between these levels and heights. IGF-1 and IGFBP-3 levels did not differ from those in normal children. IGF-1 and IGFBP-3 were significantly correlated, increased with pubertal stage in all children and with age in non-dialysis patients. IGF-1, but not IGFBP-3, correlated with age in dialysis patients. There was no correlation between IGF-1 or IGFBP-3 levels (corrected for age) and height standard deviation score (SDS) in either non-dialysis or dialysis patients. Study group 2 comprised 19 children (7 on dialysis) who were studied prospectively for 1–2 years to examine the relationship between IGF-1 and IGFBP-3 levels, growth rates and nutritional parameters. Mean values of IGF-1 and IGFBP-3 (corrected for age) did not change over 1-year periods, while height SDS fell by –0.38 ±0.21 SD/year in dialysis patients and by –0.11 ±0.29 SD/year in non-dialysis patients. No significant correlations were found between IGF-1 or IGFBP-3 levels and growth rates or nutritional parameters. Thus growth retardation in children with CRF is not related to circulating levels of IGF-1 or IGFBP-3.     

Effect of fosinopril in children with steroid-resistant idiopathic nephrotic syndrome

We aimed to test if fosinopril reduces urinary protein excretion and alleviates renal tubular damage in normotensive children with steroid-resistant idiopathic nephrotic syndrome (SRINS). We also aimed to evaluate whether there are changes in steady-state blood pressure and serum concentrations of serum angiotensin-converting enzyme (ACE) and plasma renin activity or angiotensin II (AT-II) in children under this treatment. Forty-five normotensive patients with SRINS were randomly divided into two groups. Group I was treated with fosinopril and prednisone for 12 weeks, while group II was treated with prednisone alone for the same duration. The values of 24-h urinary protein excretion were 1.25±0.64 vs 2.52±0.56 g/24 h (P<0.05), 1.16±0.45 vs 2.42±0.24 g/24 h (P<0.05), and 1.10±0.41 vs 2.05±0.46 g/24 h (P<0.05) in group I and group II patients, respectively, at 4, 8, and 12 weeks. Patients in group I showed lower serum concentrations of urinary retinol-binding protein and β₂-microglobulin (P<0.01) at the end of the study, but the patients’ blood pressure and components of the renin-angiotensin system (RAS) had no change during treatment. The result suggested that fosinopril significantly reduced proteinuria and alleviated renal tubular damage, but did not influence blood pressure and components of systemic RAS in normotensive children with SRINS.     

Body segment lengths and arm span in healthy men and women and patients with vertebral fractures

We studied 112 healthy men and 261 healthy women aged 18–92 years, and 34 men and 73 postmenopausal women with vertebral fractures aged 45–90 years to determine (i) whether patients with vertebral fractures have shorter stature before fracture, and (ii) whether the difference between arm span and standing or sitting height can be used to identify patients with fractures. Arm span was measured by using a calibrated extended ruler. Standing height, sitting height and leg length were measured by using a Holtain stadiometer. The results were expressed in absolute term and standard deviation (SD) or Z-scores (mean±SEM). Advancing age was associated with decreased sitting height (r=–0.37 to –0.41, both P<0.01) and a trend towards decreased arm span (r=–0.12 to –0.17, P=0.06 and 0.07) in healthy men and women; leg length was independent of age in both sexes (r=–0.09 to –0.12, NS). In patients with vertebral fractures, sitting height was reduced in women (Z=–0.83±0.14 SD, P<0.01) and men (Z=–1.37±0.21 SD, P<0.01) but only the women had reduced leg length (Z=–0.46±0.15 SD, P<0.01) and arm span (Z=–0.76±0.15 SD, P<0.01). Univariate and multivariate analyses suggest that the predictive ability of the difference between arm span and standing or sitting height to identify patients with vertebral fractures is limited. We concluded that women, not men, with vertebral fractures may come from a population with short stature. The difference between arm span and standing or sitting height cannot be used to predict vertebral fracture risk.     

Idiopathic membranous nephropathy in children

Idiopathic membranous nephropathy (MN) is a rare cause of asymptomatic proteinuria (AP) or nephrotic syndrome (NS) in childhood. To improve our understanding of its clinical course, we retrospectively reviewed 19 cases of idiopathic MN seen in our hospital over a period of 28.5 years, i.e., from January 1977 to July 2005. Eight patients (39%) had AP and 11 (61%) presented with NS. All eight AP patients achieved remission, regardless of treatment modality. Oral corticosteroid was given to all 11 NS patients, but only three of them responded to corticosteroid. Of the eight steroid non-responders, three achieved remissions with the addition of cyclosporine, and the five who were not administered additional immunosuppressive drugs had persistent NS. At the latest evaluation, all six NS patients that achieved remission remained free of proteinuria and had a normal renal function. Moreover, two of the 5 steroid non-responders showed persistent nephrotic-range proteinuria but a stable renal function. The remaining three steroid non-responders progressed into chronic renal insufficiency, and this progression was preceded by renal vein thrombosis (RVT) in two of the three patients. Presentation with NS (P=0.045) and the development of RVT (P=0.010) were identified as poor prognostic factors.     

Angiotensin converting enzyme inhibitors for reduction of proteinuria in children with steroid-resistant nephrotic syndrome

The effects of angiotensin converting enzyme inhibitors (ACEI) on proteinuria, renal function, and serum proteins were evaluated in six children with steroid-resistant nephrotic syndrome and proteinuria of 3–15 g/24h (277±47 mg/m² per hour). Following ACEI, proteinuria decreased from 7,408±2,385 (mean±SEM) to 3,746±1,395 mg/24 h (P<0.05). Creatinine clearance was 87.8±22.6 before and 96.4±23.6 ml/min per 1.73 m² after ACEI. In two patients, inulin and para-aminohippuric acid clearances were normal before and after ACEI, together with parallel reductions of urine protein of 50% and 46%. Clearance of total protein was reduced by 56% following ACEI, compared with reduction in the clearance of gamma globulin by 58% and albumin by 39.5%. No significant change was seen in blood pressure, serum albumin, or total protein following ACEI. After ACEI, diuretic doses were able to be reduced or eliminated in three patients. Reduction of proteinuria was sustained during a followup period of 11–20 months in three patients. ACEI may be of benefit in the clinical management of children with steroidresistant nephrotic syndromes, allowing reduction in diuretic requirements.     

Experience with continuous cycling peritoneal dialysis during the first year of life

The clinical experience in eight infants aged 5.8±2.3 (SD) months at the initiation of continuous cycling peritoneal dialysis (CCPD) is described. BUN, creatinine, albumin, calcium, phosphorus and alkaline phosphatase measurements were performed serially and no changes were seen throughout the follow-up period. Mean total energy and protein intake were 94±8% and 79±9% of the recommended. The initial and final standard deviation scores (SDS) for height were –1.42±1.32 and –2.47±1.36 (P<0.001), respectively. The SDS for body weight and head circumference were –1.67±0.71 and –1.67±1.04, respectively, at the beginning of the study and –1.83±0.98 and –1.88±1.52, respectively, at the end of the period of observation. The incidence of peritonitis was one episode every 11.6 patient months; six patients developed nine hernias. The present study demonstrates that CCPD is an acceptable dialytic modality, with minimal morbidity, for the management of infants awaiting renal transplantation.