Expression of nephrin,podocin, α-actinin,and WT1 in children with nephrotic syndrome

Recently, nephrin, podocin, -actinin, and WT1, which are located at the slit diaphragm and expressed by the podocyte, were found to be causative in congenital/familial nephrotic syndrome (NS), but their role in acquired NS remains unclear. We studied their expression in NS with the aim of disclosing their possible role in the development of proteinuria. Immunofluorescence, confocal microscopy, and image analysis were used to study the expression and the distribution in 19 children with primary NS, 9 with isolated hematuria, and 9 controls. All the children with NS presented with heavy proteinuria and foot process effacement was identified by electron microscopy. No proteinuria and foot process effacement was seen in the group with hematuria. A dramatic decrease of podocin expression was found in NS (86.66±22.74) compared with control groups (P=0.014). Furthermore, we also found the pattern of distribution of nephrin, podocin, and -actinin changed in children with NS. In conclusion, a dramatic decrease of podocin expression and abnormal distribution of nephrin, podocin, and -actinin were found in children with NS. No differences were found in children with isolated hematuria, suggesting involvement of these molecules in the development of proteinuria in primary NS.     

Vitamin E therapy in IgA nephropathy: a double-blind,placebo-controlled study

IgA nephropathy is the world's most common primary glomerulonephropathy. Recent evidence in a rat model implicated excessive production of oxygen-free radicals in the pathogenesis and suggested that vitamin E-treatment ameliorated progression. We studied this antioxidant therapy on the glomerular filtration rate (GFR), proteinuria and hematuria in biopsy-proven IgA nephropathy in children. The duration of treatment or placebo was 2 years, with vitamin E treatment consisting of 400 IU/day in children weighing <30 kg, and twice that dose for those >30 kg. We measured GFR at entry, midpoint and exit. At baseline and at 4-month intervals after randomization, urinary protein/creatinine ratios and urinalysis were examined. The mixed model procedure with log transformation was used in data analysis to test treatment difference as well as the potential time effect. Fifty-five patients were randomized and 38 completed at least 1 year of follow-up. At entry, the clinical characteristics were not different between the treatment and placebo groups. There was a trend toward better preservation of GFR in vitamin E-treated versus placebo patients, 127±50 vs. 112±31 ml/min/1.73 m², respectively (P=0.09). The urinary protein/creatinine ratio was significantly lower in the vitamin E-treated group vs. placebo; 0.24±0.38 vs. 0.61±1.37 (P<0.013). However, there was no difference in the prevalence of hematuria between the groups. Vitamin E treatment in our study patients was associated with significantly lower proteinuria, but no effect on hematuria. While there was a trend toward stabilization of GFR in the vitamin E-treated patients, long-term treatment and follow-up are needed to determine whether antioxidant therapy is associated with preservation of renal function in IgA nephropathy.     

Cyclosporin A for the treatment of severe Henoch-Schönlein glomerulonephritis

We evaluated the efficacy of cyclosporin A (CyA) for treating pediatric patients with severe Henoch-Schönlein glomerulonephritis (HSP-GN) and nephrotic-range proteinuria. Seven pediatric HSP-GN patients (5 boys, 2 girls) were treated with CyA, with a mean age of 10.6 years at diagnosis (range 7.2–15.2 years) and mean follow-up times of 6.0 years (range 4.4–8.9 years) from diagnosis and 5.2 years (range 3.4–7.7 years) from the beginning of the CyA treatment. All had developed nephrotic-range proteinuria within 1–3 months of the HSP diagnosis. A renal biopsy was performed on all the patients, and two showed rapidly progressive glomerulonephritis. They all received additional angiotensin converting enzyme inhibitor medication and one to three types of immunosuppressive treatment had been tried in five of the seven patients before CyA was initiated at a mean interval of 0.7 years after diagnosis (range 0.1–2.0 years). All the patients responded to the CyA treatment within a mean of 1.4 months (range 1 week to 4 months). Four patients achieved a stable remission and had been without CyA treatment for a mean of 3.7 years (range 2.9–5.3 years) by the end of the follow-up. Three patients seemed to become CyA dependent, since they developed proteinuria when the treatment was stopped. CyA treatment had been started significantly earlier (P=0.045) in the former group (mean 0.2 years, range 0.1–0.3 years) than in the latter (mean 1.5 years, range 1.2–2.0 years). Renal function was preserved in all patients, the glomerular filtration rate, plasma cystatin C, serum albumin, and serum creatinine being within normal limits at the end of the follow-up. We conclude that CyA treatment for severe treatment-resistant HSP-GN is promising, since four of the seven patients enjoy stable remission and all have retained their renal function after a mean follow-up of 6.0 years. However, some patients seem to develop CyA-dependent nephritis.The results were presented as a poster at the 36th meeting of the European Society for Pediatric Nephrology in Bilbao     

Interim evidence of the renoprotective effect of the angiotensin II receptor antagonist losartan versus the calcium channel blocker amlodipine in patients with chronic kidney disease and hypertension: a report of the Japanese Losartan Therapy Intended for Global Renal Protection in Hypertensive Patients (JLIGHT) Study

Background. Insufficiency of renal function and high blood pressure influence each other and eventually result in life-threatening endstage renal disease. It has been proposed that proteinuria per se is a determinant of the progression of chronic kidney disease (CKD). The therapeutic strategy for patients with proteinuric CKD and hypertension should therefore be targeted with a view not merely toward blood pressure reduction but also toward renoprotection. Methods. We examined the effect of the angiotensin (AT)₁ receptor antagonist losartan and the calcium channel blocker amlodipine, throughout a period of 12 months, on reduction of blood pressure and renoprotection. This was done by assessing amounts of urinary protein excretion, serum creatinine (SCr), and creatinine clearance (CCr) in patients with hypertension (systolic blood pressure [SBP] 140mmHg or diastolic blood pressure [DBP] 90mmHg) and CKD (male, body weight [BW] 60kg: 1.5 SCr < 3.0mg/dl; female or male BW < 60kg: 1.3 SCr < 3.0mg/dl), manifesting proteinuria of 0.5g or more/day. Losartan was administered once daily at doses of 25 to 100mg/day, and amlodipine was given once daily at 2.5 to 5mg/day. No antihypertensive combination therapy was allowed during the first 3-month period. Results. A 3-month interim analysis revealed that, despite there being no difference in blood pressure between the two groups, there was a significant reduction in 24-h urinary protein excretion in the losartan group (n = 43), but there was no change in the amlodipine group (n = 43). Analysis of stratified subgroups with proteinuria of 2g or more/day and less than 2g/day showed that losartan lowered proteinuria by approximately 24% in both subgroups, while amlodipine lowered proteinuria by 10%, but only in the subgroup of less than 2g/day (NS). SCr and CCr did not change throughout the period of 3 months in either group. No severe or fatal adverse event was experienced in either group during the study period. Conclusions. Losartan appeared to be efficacious for renoprotection in patients with proteinuric CKD and hypertension, with the mechanism being independent of its antihypertensive action.     

The underlying diseases and follow-up in Taiwanese children screened by urinalysis

To date, the underlying diseases and follow-up of Taiwanese children screened by urinalysis have not been reported. The grading of urine abnormalities varied from grade A (microscopic hematuria only), grade B (light proteinuria only), grade C (light proteinuria and microscopic hematuria) to grade D (heavy proteinuria). From January 1991 to August 1998, 630 students, aged 6-15 years and with positive urinary screening, were admitted to our hospital for further evaluation. Of these, 573 students had confirmed abnormal findings, 298 were boys, 275 were girls, and 294 students received a renal biopsy and have had regular follow-up visits. This study was designed to retrospectively elucidate: (1) the relationship between grading of urine abnormality and underlying disease; (2) the relationships among hypertension, grading of urine abnormality, and underlying disease; (3) the underlying disease of low serum C3 level; and (4) to determine whether urinary screening progressively decreased the number of students with end-stage renal disease (ESRD) annually. The results show that glomerular nephritis (GN) is still one of the major causes of urinary abnormalities. The most-important secondary GN was systemic lupus erythematosus (SLE) with lupus nephritis. One-quarter of the patients fulfilled at least four of the revised American Rheumatology Association (ARA) criteria for SLE at first administration, while the others who fulfilled only two to three of the revised ARA criteria had gradually developing signs and symptoms of SLE at follow-up. The percentage of SLE patients amongst anti-nuclear antibody (ANA) positive children was 72%. Membranoproliferative GN is very rare. The distribution of hypertension was 8.2% in grade A, 10.7% in grade B, 9.7% in grade C, and 28.9% in grade D urinary abnormality. There were statistical differences between grade D and either grade A or B or C (P<0.05). Lower serum C3 levels were found only in a minority of patients, including those with SLE. In this series, focal segmental glomerular sclerosis (FSGS) and active class IV lupus nephritis patients were found early enough to receive methylprednisolone pulse plus cyclosporine A therapy. To date there have been only 2 cases (5%) of FSGS with impaired renal function, and none of the lupus nephritis patients are in the predialysis stage. In conclusion, GN is still the major cause of urinary screening abnormality. ANA study is indicated in all Chinese students with abnormal urinary screening. The correlations between the severity of proteinuria and hypertension showed more-severe proteinuria in patients with nephritis as well as in those with hypertension.     

Quantification of proteinuria in children using the urinary protein-osmolality ratio

A prospective study was conducted to determine the correlation of early morning urinary protein/osmolality ratio (mg/l/mosmol/kg) with 24-h urinary protein excretion (mg/m²/day). Study patients consisted of 53 children (aged 1 month to 15 years). Early morning urine samples and 24-h urine samples were collected and analyzed. In group 1 (children without proteinuria), early morning urinary protein/creatinine ratio (Uprot/Ucr, mg/mg) was 0.061±0.011 and the protein/osmolality ratio (Uprot/Uosm, mg/l/mosmol/kg) was 0.073±0.014. Twenty-four hour urinary protein excretion in group 1 had no significant correlation with Uprot/Ucr or Uprot/Uosm. In group II (children with proteinuria), Uprot/Ucr was 5.78±1.10 and Uprot/Uosm was 4.42±1.34. Twenty- four hour urinary protein excretion in group 2 was 1483.6±303.7 mg/m²/day and its correlation with both Uprot/Uosm and Uprot/Ucr was highly significant (r= 0.87, P<0.001 and r=0.88, P<0.001, respectively). The accepted nephrotic level of proteinuria of 40 mg/m²/h coincides with a Uprot/Uosm ratio of 1.9. In conclusion, early morning urinary Uprot/Uosm is a simple and potentially useful test for 24-h urinary protein excretion, and possibly could be used safely for the assessment of the degree of proteinuria in children. Received: 13 April 1999 / Revised: 23 February 2000 / Accepted: 15 August 2000     

醛固酮灌注诱导大鼠肾小球损伤

目的:研究醛固酮(Ald)灌注对大鼠肾小球损伤及依普利酮的干预作用。方法:18只雄性Sprague-Dawley大鼠随机分为Ald灌注组(A)、依普利酮治疗组(E)、空白对照组(C)3组,分别皮下埋置渗透性微泵,A、E组均以1.5μg/h的浓度持续灌注Ald,E组以100 mg/(kg.d)依普利酮灌胃,C组由DMSO代替Ald,测定28 d内大鼠血压及蛋白尿,于第28天处死动物,测定血浆Ald水平,取肾脏观察病理改变。结果:A和E组血浆Ald水平均显著升高。A组血压和尿微量白蛋白排泄率(UAER)从第7天起均较同期C组增高(P<0.05),E组血压和UAER均较同期A组显著降低(P<0.05)。A组肾小球系膜细胞轻度增殖,系膜外基质轻度增宽,少数肾小球出现段性硬化;足突节段性融合,部分足细胞和系膜细胞有凋亡小体形成,E组病变较A组减轻。结论:血浆Ald水平持续增高有致肾小球损伤作用。     

贝那普利与缬沙坦治疗慢性肾病蛋白尿及高血压

目的:观察贝那普利与缬沙坦单用及联用治疗慢性肾脏病患者蛋白尿及高血压的临床疗效和安全性.方法:75例慢性肾病合并高血压患者随机分为贝那普利组(n=28)、缬沙坦组(n=26)、贝那普利与缬沙坦联用组(n=21),观察治疗前、治疗第4周和第8周的血压、24 h蛋白尿定量、血尿素氮(BUN)、血清肌酐(SCr)和血尿素(SUA)等指标.结果:三组患者治疗后血压和24 h蛋白尿定量较治疗前明显下降(P<0.01),且联用组较缬沙坦组和贝那普利组降蛋白尿作用更显著(P<0.05).三组患者治疗前后BUN,Scr无明显变化,但缬沙坦组及联用组治疗后SUA较治疗前明显下降(P<0.05).结论:贝那普利与缬沙坦联用对慢性肾脏病合并高血压患者具有良好的降蛋白尿和降压作用.     

Effects of Eicosapentaenoic Acid Supplementation on Immunoglobulin A Nephropathy

Eicosapentaenoic acid (EPA), which is purified from fish oil, attenuates inflammatory responses by decreasing eicosanoid and cytokine production. EPA reportedly improves renal survival in patients with immunoglobulin (Ig)A nephropathy; however, this is unconfirmed. We studied the effects of EPA on IgA nephropathy patients. Eighteen biopsy-confirmed IgA nephropathy patients (aged 31 ± 3 years) were enrolled. The prognoses based on glomerular findings were good (N = 5), relatively poor (N = 12), and poor (N = 1). EPA was administered at 1.8 g/day for 12 months. Five biopsy-confirmed IgA nephropathy patients were enrolled as control subjects. Administration of other drugs used to treat IgA nephropathy was not changed. The estimated creatinine clearance (eCCr), serum creatinine (Cr) concentration, urinary protein creatinine ratio (U/P), and other clinical parameters were checked. In the EPA group, the Cr went from 0.8 ± 0.2 mg/dL to 0.7 ± 0.2 mg/dL after 12 months of EPA treatment, and the U/P went from 550 ± 580 mg/g Cr to 330 ± 920 mg/g Cr. The values did not differ significantly; however, Cr and U/P tended to improve, with no adverse effects from the EPA. The eCCr improved significantly (99 ± 7–110 ± 8 mL/min, P = 0.001) in the EPA group, but not in the control group (126 ± 12–120 ± 13, P > 0.05). The effect of EPA in patients with IgA nephropathy is not pronounced, but these results suggest that EPA is a safe and worthwhile supplement to the drugs used to treat this disease.