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     

Effect of enalapril on proteinuria after kidney transplantation

We studied the effect of enalapril, an inhibitor of angiotensin-converting enzyme (iACE), on proteinuria and renal function in recipients of renal allografts. Twenty-two patients with post-transplant nephrotic syndrome were treated with incremental doses of enalapril for 1 year. Urinary protein excretion decreased after 2 months of treatment from a mean of 8.9 g/day (range 4.0–18.9 g/day) to 4.5 g/day (range 0.4–10.0 g/day; P<0.01) and remained significantly low for the rest of the study. However, in the same period, creatinine clearance did not change significantly; it went from 47.8 ml/min (range 17.1–110.3 ml/min) before treatment to 44.2 ml/min (range 16.5–88.5 ml/min) after 2 months of iACE therapy. Analysis of individual data showed that there was a significant reduction in proteinuria in 14 of the 22 patients and that the rate of deterioration of renal function did not increase in 17 of the 22 patients. We did not observe any serious side effects of enalapril administration. The results of our study prove that iACE can be used safely and effectively to reduce post-transplant proteinuria.     

Efficacy of mizoribine followed by low-dose prednisone in patients with idiopathic membranous nephropathy and nephrotic-range proteinuria

Abstract

Background: Idiopathic membranous nephropathy (IMN) patients with persistent high-grade proteinuria are at the highest risk for developing end-stage renal failure. We previously reported the effects of treatment with mizoribine followed by low-dose prednisone treatment in 4 IMN patients. The purpose of the present study was to further assess the effects of this combined treatment in a larger study group. Method: Thirteen patients with IMN and nephrotic-range proteinuria received combined treatment. Mizoribine was initiated at a dose of 150?mg/day, and 2–3 months later, 20?mg/day prednisone was added to the mizoribine regimen. The dosage of prednisone and/or mizoribine was tapered according to the urinary protein-to-creatinine ratio (P/C). We evaluated patient responses for up to 12 months after the initiation of combination therapy. Results: Before treatment, patient urinary P/C ranged from 3.7 to 15.9?g/g. Although these values did not decrease during mizoribine monotherapy, all patients showed dramatic P/C decreases over the course of combination therapy. At 3, 6, and 12 months after combination therapy, 15%, 31%, and 62% of patients attained complete remission, respectively, and all patients were in partial or complete remission 6 months after combination therapy. No notable side effects were observed. Conclusion: The addition of prednisone after mizoribine monotherapy can be beneficial for all IMN patients with nephrotic-range proteinuria syndrome. The risks associated with immunotherapy can be decreased by initially prescribing mizoribine alone, which might act as a base for establishing therapy, followed by low-dose prednisone treatment.     

Long-term therapy with enalapril in patients with nephrotic-range proteinuria

The effect of enalapril on urinary protein excretion and renal function was studied in six paediatric patients with various renal diseases causing nephrotic-range proteinuria. In three younger children (aged 7 – 9 years) with steroid-resistant nephrotic syndrome, enalapril at a dose of 0.5 mg/kg per day given for 24 months yielded a temporary reduction of proteinuria in one child, a moderate and steady decrease in another and a complete disappearance of proteinuria in the third. Three adolescents, aged 17 years, took enalapril for 24 months at a dose of 20 mg/day. We observed no effect on proteinuria in one patient with Alport syndrome, a complete disappearance of urinary protein in one patient with membranoproliferative glomerulonephritis and a moderate decrease in the third patient who had idiopathic steroid-resistant nephrotic syndrome. Enalapril therapy resulted in an important reduction of proteinuria in two patients and a moderate decrease in three others. However this therapy was accompanied by a fall in glomerular filtration in all subjects, which was very marked in two patients. This fall in glomerular filtration may, however, simply reflect the natural course of the disease. Received June 2, 1995; received in revised form and accepted March 7, 1996     

Losartan and enalapril are comparable in reducing proteinuria in children with Alport syndrome

Background

A previous subgroup analysis of a 12-week, double-blind study demonstrated that losartan significantly lowered proteinuria versus placebo and amlodipine and was well tolerated in children (1–17 years old) with proteinuria secondary to Alport syndrome. The present subgroup analysis of the open-label, extension phase of this study assessed the long-term efficacy and tolerability of losartan versus enalapril.

Methods

Patients who had completed the double-blind study were re-randomized to losartan or enalapril and followed for proteinuria and renal function for up to 3 years.

Results

Twenty-seven patients with Alport syndrome were randomized to losartan (0.44-2.23 mg/kg/day; n?=?15) or enalapril (0.07-0.72 mg/kg/day; n?=?12). The least-squares (LS) mean percent change from week 12 in urinary protein to creatinine ratio (UPr/Cr was +1.1 % in the losartan group versus a further 13.9 % reduction in the enalapril group (GMR [95 % CI]?=?1.2 [0.7, 2.0]); the LS mean change from week 12 in estimated glomerular filtration rate (eGFR) was ?6.4 ml/min/1.73 m² in the losartan group versus ?9.1 ml/min/1.73 m² in the enalapril group. The adverse event incidence was low and comparable in both treatment groups.

Conclusions

In children with proteinuria secondary to Alport syndrome, losartan maintained proteinuria reduction, and enalapril produced a further proteinuria reduction over the 3-year study period. Both agents were generally well tolerated.     

Effect of diet, enalapril, or losartan in post-diarrheal hemolytic uremic syndrome nephropathy

Proteinuria is the main indicator of renal disease progression in many chronic conditions. There is currently little information available on the efficacy, safety, and individual tolerance of patients with post-diarrheal hemolytic uremic syndrome (D+ HUS) nephropathy to therapies involving diet, enalapril, or losartan. A multicenter, double-blind, randomized controlled trail was conducted to evaluate the effect of a normosodic–normoproteic diet (Phase I) and the effect of normosodic–normoproteic diet plus enalapril (0.18–0.27 mg/kg/day) or losartan (0.89–1.34 mg/kg/day) (Phase II) on children with D+ HUS, normal renal function, and persistent, mild (5.1–49.9 mg/kg/day) proteinuria. Dietary intervention reduced the mean protein intake from 3.4 to 2.2 mg/kg/day. Of 137 children, proteinuria normalized in 91 (66.4 %) within 23–45 days; the remaining 46 patients were randomized to diet plus placebo (group 1, n = 16), plus losartan (group 2, n = 16), or enalapril (group 3, n = 14). In groups 1, 2, and 3, proteinuria was reduced by 30.0, 82.0, and 66.3%, respectively, and normalized in six (37.5%), three (81.3%), and 11 (78.6%) patients, respectively (χ²= 8.9, p = 0.015). These results suggest that: (1) a normosodic–normoproteic diet can normalize proteinuria in the majority of children with D+ HUS with mild sequelae, (2) the addition of enalapril or losartan to such dietary restrictions of protein further reduces proteinuria, and (3) these therapeutic interventions are safe and well tolerated. Whether these short-term effects can be extended to the long-term remains to be demonstrated.     

Enalapril in children with Alport syndrome

Ten pediatric patients with Alport syndrome received enalapril for 5 years. There were nine boys. Eight patients have the X-linked form of the disease and two the autosomal recessive form. The median age at the start of treatment was 10.25 years. Only one patient was hypertensive. The starting dose of enalapril was 0.05 mg/kg; the target dose was 0.5 mg/kg per day. The median dose given effectively was 0.24, 0.37, 0.45, 0.43, and 0.49 mg/kg per day at years of study 1, 2, 3, 4, and 5, respectively. The median urinary protein/creatinine ratio was 1.58 g/g (range 0.49–4.60) before treatment. This decreased to 0.98, 1.09, 1.35, 1.11, and 1.38 g/g after 1, 2, 3, 4, and 5 years, respectively. The median creatinine clearance at baseline was 100 ml/min per 1.73 m² (range 82–133) and after 5 years 92 ml/min per 1.73 m² (range 22–115). Three patients did not reach the target dose of enalapril because of orthostatic hypotension. One of them was the only patient to develop chronic renal failure within 5 years. The present study indicates that enalapril reduces urinary protein excretion and preserves glomerular filtration in Alport patients as a group. However, there was individual variation, as in most studies of patients with proteinuric nephropathies given inhibitors of the angiotensin-converting enzyme.     

Plasmapheresis therapy for rapidly progressive Henoch-Schönlein nephritis

Six Japanese children with rapidly progressive Henoch-Schönlein purpura nephritis (HSPN) received multiple drug therapy combined with plasmapheresis (PP). After five courses of PP, multiple drug therapy, including methylprednisolone and urokinase pulse therapy, oral prednisolone, cyclophophamide, dipyridamole, and warfarin was given. At presentation, urine protein excretion and histological indices of the mean activity and chronicity were 245±101 mg/m² per hour, 6.6±1.2, and 1.5±1.3, respectively. After 6 months of therapy, urinary protein excretion had decreased significantly (P<0.001). The activity index decreased significantly at the second renal biopsy performed at a mean interval of 4.3 months after the first (2.8±1.4, P<0.05), while the chronicity index did not change. At the most recent observation, all showed clinical improvement. Two patients had normal urine, three had proteinuria of <20 mg/m² per hour, one had proteinuria of >20 mg/m² per hour, and none had renal insufficiency. Although this case series is without controls, our treatment protocol may be of benefit to children with rapidly progressive HSPN.     

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.     

Effect of cyclosporin a on proteinuria in patients with Alport's syndrome

Eight patients with Alport's syndrome and massive proteinuria (129±60.57 mg/m² per hour) were treated with cyclosporin A (CyA) for 8 months. The average dose of CyA administered to all patients was 4.21±0.26 mg/kg per day and blood CyA levels of 63.4±4.1 ng/ml were attained. In five patients, proteinuria abated during the 3rd week of treatment. In the remaining three, all of whom had low creatinine clearance (82.0, 46.0 and 43.2 ml/min per 1.73 m² respectively), proteinuria persisted but at levels lower than before treatment: 32.5±15.9 mg/m² per hour versus 183.3±29.7 mg/m² per hour. No permanent decrease in creatinine clearance was observed in any of these patients throughout treatment. In those patients in whom proteinuria abated, it reappeared 2 weeks after discontinuation of CyA treatment. We observed no significant increases in angiotensin II plasma levels in our patients during CyA administration. Although we have shown that CyA will reduce massive proteinuria in patients with Alport's syndrome, we cannot yet recommend its use as a therapeutic measure.     

Pulse cyclophosphamide for steroid-resistant focal segmental glomerulosclerosis

 We report the response of ten patients (6 male, 4 female) with steroid-resistant focal segmental glomerulosclerosis (FSGS) to treatment with intravenous pulse cyclophosphamide (IVCP) together with oral prednisone. All patients had been treated with 60 mg/m² oral prednisone daily for 2 months upon initial presentation. IVCP was given monthly at a dose of 500 mg/m² over 6 months. Oral prednisone was given concurrently at 60 mg/m² daily for 2 months and then on alternate days for 4 months, followed by 30 mg/m² on alternate days for 6 months. Prednisone was then tapered monthly by 10 mg and finally discontinued. Five patients failed to respond to steroids from the onset and were considered as primary steroid resistant. Two of these patients achieved sustained remission after IVCP, one patient showed a partial response, with loss of edema, normalization of serum albumin, and persistent proteinuria, while two patients showed no response to IVCP. The other five patients had achieved remission after 2 months of daily prednisone at 60 mg/m² upon initial presentation, but had suffered from more than three relapses per year and had eventually become steroid resistant. They were considered secondary steroid resistant. All five patients achieved sustained remission after IVCP. None of our patients suffered from adverse effects of IVCP. We suggest IVCP as an adjunctive therapy for steroid-resistant FSGS, particularly for patients with secondary steroid resistance. Received: 20 November 1997 / Revised: 30 June 1998 / Accepted: 1 July 1998     

Efficacy and safety of lisinopril for mild childhood IgA nephropathy: a pilot study

Even in children with mild immunoglobulin (Ig)A nephropathy (IgA-N) showing minimal/focal mesangial proliferation, persistent proteinuria seems to be a risk factor for progression of the disease, indicating the need for an effective and safe treatment even in such cases. Studies carried out to date have indicated that angiotensin-converting enzyme inhibitors (ACEIs) reduce urinary protein excretion and preserve renal function in adult IgA-N. However, no prospective study of ACEI only for childhood IgA-N has yet been carried out. In this prospective single-arm pilot trial, we administered lisinopril (0.4 mg/kg per day) as therapeutic treatment to 40 children with mild IgA-N with proteinuria [morning urinary protein/creatinine ratio (uP/Cr) ≥ 0.2 g/g]. Thirty-three patients reached the primary endpoint (uP/Cr < 0.2) during the 2-year treatment period. The cumulative disappearance rate of proteinuria determined by the Kaplan–Meier method was 80.9%. Mean uP excretion was reduced from 0.40 to 0.18 g/m²/day (p < 0.0001). Of the 40 patients treated, five (12.5%) showed dizziness, and four of these five needed the lisinopril dose reduced. However, lisinopril therapy was continued in all patients during the 2-year treatment period. No other side effect, such as cough, was observed. We conclude that the efficacy and safety of lisinopril is seemingly acceptable for the treatment of children with mild IgA-N. The participants in the Japanese Pediatric IgA Nephropathy Treatment Study Group are listed in the Appendix.     

Rituximab in Children with Steroid-Dependent Nephrotic Syndrome: A Multicenter,Open-Label,Noninferiority, Randomized Controlled Trial

Steroid-dependent nephrotic syndrome (SDNS) carries a high risk of toxicity from steroids or steroid-sparing agents. This open-label, noninferiority, randomized controlled trial at four sites in Italy tested whether rituximab is noninferior to steroids in maintaining remission in juvenile SDNS. We enrolled children age 1–16 years who had developed SDNS in the previous 6–12 months and were maintained in remission with high prednisone doses (≥0.7 mg/kg per day). We randomly assigned participants to continue prednisone alone for 1 month (control) or to add a single intravenous infusion of rituximab (375 mg/m²; intervention). Prednisone was tapered in both groups after 1 month. For noninferiority, rituximab had to permit steroid withdrawal and maintain 3-month proteinuria (mg/m² per day) within a prespecified noninferiority margin of three times the levels among controls (primary outcome). We followed participants for ≥1 year to compare risk of relapse (secondary outcome). Fifteen children per group (21 boys; mean age, 7 years [range, 2.6–13.5 years]) were enrolled and followed for ≤60 months (median, 22 months). Three-month proteinuria was 42% lower in the rituximab group (geometric mean ratio, 0.58; 95% confidence interval, 0.18 to 1.95 [i.e., within the noninferiority margin of three times the levels in controls]). All but one child in the control group relapsed within 6 months; median time to relapse in the rituximab group was 18 months (95% confidence interval, 9 to 32 months). In the rituximab group, nausea and skin rash during infusion were common; transient acute arthritis occurred in one child. In conclusion, rituximab was noninferior to steroids for the treatment of juvenile SDNS.     

Treatment of IgA nephropathy in children: efficacy of alternate-day oral prednisone

We have previously reported our experience with the use of alternate-day prednisone in the treatment of 6 patients with IgA nephropathy who have clinical or pathological risk factors for disease progression. We have now treated a total of 13 patients and followed them from 4 to 10 years. Patients received an alternate-morning dose of prednisone for 2–4 years. Dosage began at 60 mg/m² for 3 month, was reduced to 30 mg/m² by 1 year and 15 mg/m² by 2 years. At last observation, urinary protein excretion was normal in 12 patients and no patient had hematuria. Twelve patients had normal estimated glomerular filtration rate (GFR) and one had renal insufficiency (GFR=38 ml/min per 1.73 m²). A renal biopsy was performed in 11 patients after 2 years of treatment. Activity score decreased from 5.2 to 4.3 (P=0.03) and chronicity score increased from 2.2 to 2.8 (P=0.12). There were no complications of treatment. When compared with a historical group, the treated patients had a significant improvement in urinalysis (P<0.00001) and preservation of normal GFR (P=0.03). We conclude that alternate-day prednisone therapy may benefit patients with IgA nephropathy. A large prospective controlled trial is needed.     

Prediction of high-degree steroid dependency in pediatric idiopathic nephrotic syndrome

Most patients with idiopathic nephrotic syndrome are steroid-responsive, but about 50% relapse and often become steroid-dependent and exposed to long-term steroid complications. The aim of this study was to determine predictive risk factors for steroid and/or cyclosporine A (CyA) dependence. In France, steroid responsiveness is defined as remission after 1 month of oral prednisone (60 mg/m² per day) and—in the case of persistent proteinuria on day 30—three methylprednisolone pulses (MPP; 1 g/1.73 m² on days 1, 3, and 5). Thirty-five steroid-responsive children, followed between 1999 and 2006, were included in this study. Median age at diagnosis was 4.9 years. All patients initially received prednisone 60 mg/m² per day. Twenty-four of the 35 patients were steroid-dependent, with 12 requiring MPP. Of the latter 12 patients, 83.3% were treated with CyA during follow-up; in comparison, only 16.7% of the patients who did not receive MPP required CyA during follow-up (chi-square test, P = 0.001). T risk for steroid dependence was 100% in our cohort if remission was achieved after day 20. Patients who need MPP are at high risk to require CyA to achieve disease control. By identifying these children, we could use adequate immunosuppressive drugs earlier and reduce morbidity related to steroids and multiple relapses.     

Protein–osmolality ratio for quantification of proteinuria in children

Proteinuria is an important factor for renal injury and prognosis in many diseases. The most valuable method for evaluation of proteinuria is quantitative protein analysis in appropriately 24-h collected urine. But urine collection is difficult and cumbersome especially in children and working adults. The aim of the present study is to define the usefulness of urinary protein/urine osmolality (Uprot/Uosm) ratio in quantification of proteinuria. One hundred and seventy-one patients whose age ranged between 3 and 14 years were included in the study. Uprot/Uosm (r = 0.85, P < 0.001) and urinary protein/creatinine Uprot/Ucrea (r = 0.81 and P < 0.001) ratios were significantly correlated with 24-h protein excretion. Twenty-four-hour protein excretion was correlated with Uprot/Ucrea (r = 0.76, P < 0.001) and Uprot/Uosm (r = 0.79, P < 0.001) ratios in proteinuric group. But, there was no correlation between Uprot/Uosm and Uprot/Ucrea ratios with 24-h protein excretion in non-proteinuric group. The positive and negative predictive value of Uprot/Uosm ratio of 0.28 mg/l/mOsm/kg was 89.9 and 90.8% and Uprot/Ucrea ratio of 0.24 mg/mg was 85.7 and 90% for estimating proteinuria (above 4 mg/m² h⁻¹). The 95th percentile of Uprot/Uosm ratio was 0.25 mg/l/mOsm/kg and Uprot/Ucrea ratio was 0.27 mg/mg in normal group. The best estimate was Uprot/Uosm ratio of 1.42 (sensitivity 100%, specificity 94.9%) and Uprot/Ucrea ratio of 0.75 (sensitivity 100%, specificity 92.9%) for nephrotic proteinuria (40 mg/m² h⁻¹). Uprot/Uosm which is a reliable and simple method can be used for quantification of proteinuria in pediatric patients with normal renal function. Using Uprot/Uosm ratio for quantification of proteinuria can remove the necessity of 24-h urine collection, urine creatinine measurement and spending additional cost and time if the center measures the urine osmolality routinely in urine analysis.     

RENAL TUBULAR PEPTIDE CATABOLISM IN CHRONIC VASCULAR REJECTION

Chronic vascular rejection (CR) is the commonest cause of renal transplant loss, with few clues to etiology, but proteinuria is a common feature. In diseased native kidneys, proteinuria and progression to failure are linked. We proposed a pathogenic role for this excess protein at a tubular level in kidney diseases of dissimilar origin. We demonstrated in both nephrotic patients with normal function and in those with failing kidneys increased renal tubular catabolisman and turnover rates of a peptide marker, Aprotinin (Apr), linked to increased ammonia excretion and tubular injury. These potentially injurious processes were suppressed by reducing proteinuria with Lisinopril. Do similar mechanisms of renal injury and such a linkage also occur in proteinuric transplanted patients with CR, and if so, is Lisinopril then of beneficial value? We now examine these aspects in 11 patients with moderate/severe renal impairment (⁵¹CrEDTA clearance 26.2 ± 3.3 mL/min/1.73m²), proteinuria (6.1 ± 1.5 g/24 h) and biopsy proven CR. Lisinopril (10–40 mg) was given daily for 2 months in 7 patients. Four others were given oral sodium bicarbonate (Na HCO₃) for 2 months before adding Lisinopril. Renal tubular catabolism of intravenous ^99mTc-Apr (Apr^* 0.5 mg, 80 MBq), was measured before and after Lisinopril by γ-ray renal imaging and urinary radioactivity of the free radiolabel over 26 h. Fractional degradation was calculated from these data. Total 24 h urinary N-acetyl-β-glucoaminidase (NAG) and ammonia excretion in fresh timed urine collections were also measured every two weeks from two months before treatment. After Lisinopril proteinuria fell significantly (from 7.8 ± 2.2 to 3.4 ± 1.9 g/24 h, p < 0.05). This was associated with a reduction in metabolism of Apr^* over 26 h (from 0.5 ± 0.05 to 0.3 ± 0.005% dose/h, p < 0.02), and in fractional degradation (from 0.04 ± 0.009 to 0.02 ± 0.005/h, p <0.01). Urinary ammonia fell, but surprisingly not significantly and this was explained by the increased clinical acidosis after Lisinopril, (plasma bicarbonate fell from 19.1 ± 0.7 to 17.4 ± 0.8 mmol/L, p <0.01), an original observation. Total urinary NAG did fall significantly from a median of 2108 (range 1044–3816) to 1008 (76–2147) μmol/L, p < 0.05. There was no significant change in blood pressure or in measurements of glomerular hemodynamics. In the 4 patients who were given Na HCO₃ before adding Lisinopril, both acidosis (and hyperkalemia) were reversed and neither recurred after adding Lisinopril. These observations in proteinuric transplanted patients after Lisinopril treatment have not been previously described.     

Renoprotection by ACE inhibitors after severe hemolytic uremic syndrome

Five patients with severe hemolytic uremic syndrome (HUS) were followed for 10–18 years. Because of proteinuria, arterial hypertension, and reduced glomerular filtration rates, they received either captopril (n=2) or enalapril (n=3), or both (n=1) for 8–15 years. Blood pressure was normalized and proteinuria reduced in all; glomerular filtration improved in three patients and fell moderately in two. Four of the five patients have reached adult age with body weight and height, blood pressure, and serum creatinine levels within the normal range. At the last evaluation, median proteinuria was 220 mg/24 h (range 0–310) and glomerular filtration rate 56 ml/min per 1.73 m² (range 40–127). This long-term study indicates a renoprotective effect of angiotensin-converting enzyme inhibitors in patients with sequelae after HUS.     

Treatment of mesangiocapillary glomerulonephritis with alternate-day prednisone —a report of The International Study of Kidney Disease in Children

It has been claimed that long-term prednisone treatment ameliorates the course of children with mesangiocapillary glomerulonephritis (MCGN). The International Study of Kidney Disease in Children conducted a randomized, double-blinded, placebo-controlled clinical trial in 80 children with idiopathic MCGN, including 42 patients with type I disease, 14 with type II disease, 17 with type III disease, and 7 with nontypable disease. Criteria for admission included heavy proteinuria and a glomerular filtration rate of greater than or equal to 70 ml/min per 1.73 m². Prednisone or lactose, 40 mg/m², was given every other day as a single morning dose. The mean duration of treatment was 41 months, renal failure being the most common reason for termination of therapy. Treatment failure was defined as an increase from baseline of 30% or more in serum creatinine, or more than 35 mol/l. Overall, treatment failure occurred in 55% of patients treated with lactose, compared with 40% in the prednisone group. Life-table analysis showed a renal survival rate (i.e., stable renal function) at 130 months of 61% among patients receiving prednisone and 12% among patients receiving lactose (P=0.07). Of patients with type I or III MCGN, 33% treated with prednisone were treatment failures, compared with 58% in the lactose group. Long-term treatment with prednisone appears to improve the outcome of children with MCGN.     

Long-term effects of levamisole treatment in childhood nephrotic syndrome

The effects of levamisole treatment on long-term outcome were evaluated in a retrospective study of frequently-relapsing (FRNS, n =15), steroid-dependent (SDNS, n =13), and steroid-resistant (SRNS, n =6) nephrotic syndrome in 34 children (21 boys, 13 girls, mean age 5.0±3.4 years) during a 60-month follow-up period. The definition of frequent relapses was 4 relapses per year. The current relapse was treated with prednisolone 60 mg/m² per day for 4 weeks, then with 40 mg/m² every other day for 4 weeks, after which the dose was tapered by 10 mg weekly. From the beginning of the 5th week, levamisole was introduced at a dose of 2 mg/kg per day. The duration of levamisole treatment was 17±7 months. Before starting levamisole treatment the mean level of proteinuria was 2.17±1.34 g/day and the relapse rate was 4.41/year. By the end of levamisole therapy, proteinuria had fallen to 0.142±0.211 g/day and the relapse rate to 0.41/year. No relapse occurred in 23 of the 34 patients during levamisole treatment. In the 24-month follow-up period after the discontinuation of levamisole, 28 children remained in total remission, while 6 had relapses. The cumulative steroid dose before levamisole therapy was 7,564.4±3,497.1 mg/year and following the introduction of levamisole 1,472.9±1,729.9 mg/year ( P <0.0001). We observed reversible neutropenia in 5 patients, but no other side effects were seen. Our findings suggest that in FRNS and SDNS levamisole significantly reduces both the relapse rate and the cumulative steroid dose; therefore, it could be recommended for these patients. In SRNS patients it has also some benefit because proteinuria and the cumulative steroid dose could be reduced significantly.