Diagnosis and treatment of renal tubular disorders.

There is a wide variety of renal tubular disorders affecting children. Understanding the pathophysiology of each disease assists in the recognition and treatment of these diseases, which can have profound effects on a child's growth and development. We review some of the more common tubular disorders found in children, emphasizing those conditions in which recent advances have been made in understanding of the specific genetic or physiological defect responsible: Fanconi's syndrome, cystinuria, renal tubular acidosis, and the hypokalemic metabolic alkaloses. Current recommendations are presented for diagnosing and treating these conditions.

Influence of ventilatory mode on target concentrations required for anaesthesia using a 'Diprifusor' TCI system.

This study examined the influence of mode of ventilation (spontaneous or controlled) on the target blood concentrations required to maintain anaesthesia with 'Diprifusor' (a target controlled infusion system for propofol) in 40 healthy, unpremedicated, adult patients undergoing knee arthroscopy. All patients were given alfentanil (10 micrograms.kg-1) and ketorolac (10 mg) immediately before induction and all received a 2:1 mixture of nitrous oxide:oxygen. An initial target blood concentration of propofol of 6.0 micrograms.ml-1 was used in most patients to induce anaesthesia. The blood target concentration required to produce acceptable anaesthetic conditions was not significantly influenced by the mode of ventilation. The mean maintenance target concentration for propofol was 3.9 (SD 0.83) micrograms.ml-1 in the ventilated group and 3.5 (SD 0.82) micrograms.ml-1 in the group of patients breathing spontaneously.

Outcome of antineutrophil cytoplasmic autoantibodies-positive glomerulonephritis and vasculitis in children: a single-center experience.

Vasculitis associated with antineutrophil cytoplasmic autoantibodies (ANCA) can be accompanied by a focal and necrotizing glomerulonephritis that carries a high morbidity. As many as 60% of reported children with ANCA-associated glomerulonephritis progress to end-stage renal disease. Seven children (13.0+/-0.89 years, mean age +/- SEM) with both a focal and necrotizing glomerulonephritis and a positive ANCA titer are described. Presenting symptoms were constitutional (100%) and sinopulmonary (71%); additional renal features included microscopic hematuria (100%), proteinuria (71%), and renal insufficiency (71%). Acute therapy (0 to 2 weeks from diagnosis) included intravenous corticosteroids and intravenous cyclophosphamide for all patients. Induction therapy (2 weeks to 6 months from diagnosis) consisted of cyclophosphamide (100%) and daily corticosteroids (86%) for a minimum of 6 months. Maintenance therapy that followed 6 months of induction therapy consisted of alternate day steroids (100%) combined with either oral azathioprine (50%) or oral cyclophosphamide (50%). Long-term follow-up for 48+/-12 months in all seven patients revealed that only one (14%) patient had end-stage renal disease, whereas the remaining patients had microscopic hematuria (100%), proteinuria (50%), and renal insufficiency (33%). These findings suggest that early recognition and aggressive treatment of children with ANCA-associated glomerulonephritis and vasculitis may result in an improved renal outcome compared with previous reports.

Quantitative morphometry of renal biopsies prior to cyclosporine in nephrotic syndrome.

Use of cyclosporine (CsA) in the management of children with steroid-resistant (SRNS) and steroid-dependent (SDNS) nephrotic syndrome has become increasingly popular in recent years. Although most children receive a renal biopsy prior to initiation of CsA, the relationship between initial renal histology and the subsequent clinical response to CsA is not known. We analyzed the correlation between pre-CsA segmental and global glomerular scarring and interstitial fibrosis and the subsequent response to CsA in 23 children (5.6+/-1.0 years, Mean+/-SEM) with SDNS (n=8) and SRNS (n=15) treated with CsA for 24.2+/-3.8 months and followed for 28.0+/-4.1 months. Complete remission was obtained in 78% of patients within 67.6+/-16 days, while 18% had a partial response and 4% no response. Quantitative histological analysis revealed a trend toward partial rather than complete response with increasing segmental glomerular (P=0.13), global glomerular (P=0.05), and interstitial (P=0.08) scarring, and among patients with minimal change nephrotic syndrome versus IgM nephropathy versus focal segmental glomerulosclerosis. Among complete responders, linear regression analyses revealed no correlation between time to response and pre-CsA glomerular or interstitial scarring. We conclude that increased glomerular or interstitial scarring on a pre-CsA renal biopsy tends to correlate with a partial, rather than complete, response to CsA in childhood nephrotic syndrome.

Long-term cyclosporine therapy for pediatric nephrotic syndrome: a clinical and histologic analysis.

Cyclosporine (CsA) is effective in treating steroid-dependent (SDNS) and steroid-resistant (SRNS) nephrotic syndrome (NS) in children, but because of the potential for chronic nephrotoxicity, its long-term use is controversial. This study reports the results of long-term CsA treatment in 22 children with idiopathic NS. Indications for treatment included SDNS (N = 7) and SRNS (N = 15) children. Pre-CsA histology showed minimal change disease in three patients, immunoglobulin M nephropathy (IgM) in 14 patients, and focal segmental glomerulosclerosis (FSGS) in five patients. All patients had normal initial serum creatinine values. CsA was added to prednisone at 6.3 +/- 0.4 mg/kg per day (mean +/- SE) and adjusted to maintain whole blood trough HPLC levels of 70 to 120 ng/mL for a period of 6 to 53 months (mean, 22 months). Analysis by clinical course revealed that 13 of 15 patients with SRNS (87%) entered remission after a mean duration of CsA treatment of 58 days, whereas seven of seven patients with SDNS were able to be weaned off of daily prednisone therapy. Histologic analysis showed that all five patients with FSGS and 13 of 14 patients with IgM nephropathy either entered remission or were weaned off of daily steroids. Ten of the 22 patients (45%) with complete remission required CsA plus low-dose alternate-day prednisone to maintain remission. Hypertension was seen in eight of 22 patients (36%). No patient had a significant increase in serum creatinine concentration. Renal biopsies performed in 12 patients after 12 to 41 months (mean, 21 months) of CsA therapy showed no nephrotoxicity or disease progression in ten patients. Progression of the previous interstitial fibrosis and tubular atrophy was noted in two patients, suggesting a 17% incidence of CsA nephrotoxicity. This analysis of the long-term risks and benefits of CsA for childhood NS has identified two important findings: (1) combined CsA and alternate-day steroids can be highly effective in inducing complete remission in patients with SRNS and biopsy-proven IgM nephropathy, and (2) long-term use of CsA in moderate doses with closely monitored levels can result in a relatively low incidence of nephrotoxicity.