The syndrome of autoimmune interstitial nephritis and membranous nephropathy.

A 2-year-old male patient was evaluated for Fanconi syndrome with hypertension and failure to thrive. Renal biopsy revealed autoimmune interstitial nephritis with membranous nephropathy. The patient developed autoimmune hemolytic anemia and intractable diarrhea with villous atrophy of the jejunum. He progressed to end-stage renal disease and was transplanted without recurrent disease. Immune work-up done prior to immunosuppressive therapy showed marked elevation of IgE. Studies of T lymphocyte cytokine production showed normal production of interleukin-4 but depressed levels of interferon-gamma. The simultaneous occurrence of autoimmune interstitial nephritis and membranous nephropathy in a young male represents a unique syndrome. Abnormalities of T lymphocyte subpopulations and their cytokines may be involved in the pathogenesis of this disorder.

Extracorporeal membrane oxygenation in the neonate with congenital renal disease and pulmonary hypoplasia.

Extracorporeal membrane oxygenation (ECMO) is an effective treatment modality for the newborn with refractory hypoxemia. Oligohydramnios can be associated with congenital renal disease (CRD) and can result in respiratory insufficiency from pulmonary hypoplasia, delayed lung maturation, and persistent pulmonary hypertension of the newborn. In this retrospective study, the authors reviewed the outcome of four children with CRD who required ECMO in the neonatal period. Between October 1987 and December 1995, ECMO was used in four newborns with CRD and pulmonary hypoplasia unresponsive to maximal medical management. The causes of CRD were urinary obstruction (2), renal dysplasia (1), and vesicoureteral reflux (1). Neonatal survivors of ECMO with CRD had regular follow-up with a nephrologist, urologist, and pediatrician. Developmental history, assessment of renal function, and a nutritional evaluation were recorded on each visit. The follow-up period ranged from 6 months to 5 years. All patients with CRD were successfully weaned from ECMO. One child died, at 1 month of age, because of renal failure. The estimated glomerular filtration rates in the three survivors were 20, 24, and 60 mL/min/1.73 m2. Growth and development have been delayed in two patients. Based on the author's experience, ECMO may improve the survival of neonates with pulmonary hypoplasia and CRD. Factors associated with successful long-term outcome include (1) renal disease amenable to surgical correction, (2) aggressive nutritional support, and (3) a reliable social support system.

Pulmonary hemorrhage in children with glomerulonephritis.

Pulmonary hemorrhage may occur in patients with immune-mediated glomerulonephritis. This association can be seen in a variety of disorders including systemic lupus erythematosus, vasculitis, Wegener's granulomatosis, anaphylactoid purpura and Goodpasture's syndrome. Immune mechanisms, such as immune complexes and/or autoantibodies, play a role in the pathogenesis of pulmonary and glomerular injury. Acute pulmonary hemorrhage can lead to respiratory failure and has a high mortality. Therapy with immunosuppressive agents such as pulse methylprednisolone and cyclophosphamide will control the hemorrhage and improve pulmonary function in most cases.

Intravenous methylprednisolone and oral alkylating agent therapy of prednisone-resistant pediatric focal segmental glomerulosclerosis: a long-term follow-up.

UNLABELLED: Prednisone-resistant nephrotic syndrome (NS) due to focal segmental glomerulosclerosis (FSGS), the most common acquired disease requiring chronic dialysis and transplantation in children, has a low likelihood of response to alkylating agent therapy. This report summarizes the results of a 0.75-12.5 (average 6.33) year follow-up of 32 pediatric cases of prednisone-resistant FSGS treated with a regimen of high-dose intravenous methylprednisolone (M-P) and alternate-day prednisone, plus an alkylating agent in 25/32. On last followup: 21/32 were in remission [urine protein-to-creatinine ratios (Pru/Cru) < or = 0.2]; 3/32 had mild proteinuria (Pru/Cru > 0.2-0.5); 2/32 had moderate proteinuria (Pru/Cru > 0.5-1.9); and 6/32 remained nephrotic (Pru/Cru > or = 2.0). Of the incomplete or nonresponders; 3/11 progressed to end-stage renal failure; 5/11 had decreased creatinine clearances (CrCl): and 3/11 had persistent proteinuria with normal CrCl. All of the persistently nephrotic children, but none of the complete responders, developed decreased CrCl. All of the complete responders were able to stop treatment; four relapsed but responded well to retreatment. CONCLUSIONS: This regimen of methylprednisolone and alternate-day prednisone, with or without an alkylating agent, is effective in achieving sustained remissions and preserving normal renal function in the great majority of children with FSGS and prednisone-resistant NS.

Pediatric renal transplantation in Laurence-Moon-Biedl syndrome.

Two cases of renal transplantation in pediatric patients with Laurence-Moon-Biedl syndrome are reported. Immunosuppressive therapy consisted of cyclosporine, prednisone and azathioprine. Renal function has been good but both patients developed morbid obesity.

Pulmonary vasculitis with hemorrhage in anaphylactoid purpura.

We report a 14-year-old female with anaphylactoid purpura (AP) who developed pulmonary hemorrhage with acute vasculitis on lung biopsy. She improved with pulse methylprednisolone, daily prednisone and ventilatory assistance. Pulmonary vasculitis is a rare but serious manifestation of AP.

Multiple thromboses in a premature infant associated with maternal phospholipid antibody syndrome.

Phospholipid antibodies (lupus anticoagulant, cardiolipin) are associated with a syndrome of repeated fetal loss. Mothers with phospholipid antibodies are currently being treated with either prednisone, aspirin, or heparin to prevent fetal death. We describe a neonate whose mother had cardiolipin antibody and recurrent fetal loss and was treated with prednisone and aspirin. Thrombosis was noted in placental fetal vessels. Thromboses developed in the infant's aorta, left renal artery, middle cerebral artery, and superior sagittal sinus. Infants of phospholipid-positive mothers may have vascular thrombosis and should be carefully monitored for signs of thromboembolism.

End-stage renal disease and primary hypogonadism associated with a 46,XX karyotype.

OBJECTIVE: To determine the cause of absent sexual development in a 17-year-old girl with end-stage renal disease. DESIGN: Case study. PARTICIPANT: Seventeen-year-old girl with end-stage renal failure. INTERVENTIONS: None. MEASUREMENTS/MAIN RESULTS: The patient had phenotypically normal external female genitalia, müllerian duct hypoplasia, and no ovaries. Her serum gonadotropin levels were in the castrate range at baseline and after gonadotropin-releasing hormone stimulation. Her karyotype, in lymphocytes and cultured fibroblasts, was 46,XX. Analysis of genomic DNA, following polymerase chain reaction-amplication with oligonucleotide primers corresponding to the Y-encoded zinc finger protein ZFY and the testis-determining SRY gene, showed Y chromosome material in a male control but none in the patient. CONCLUSIONS: The results suggest a diagnosis of Frasier syndrome, a disorder characterized by true gonadal dysgenesis and end-stage renal disease occurring in normal phenotypic girls. Although previously reported only in individuals with a 46,XX karyotype, our studies indicate that Frasier syndrome may also occur in 46,XX girls. Delayed puberty is not uncommon in renal failure. This case illustrates the importance of measuring gonadotropin levels in teenage girls with delayed puberty and renal failure, particularly if the origin of the renal disease is obscure.

Peritoneal dialysis for acute renal failure in children.

Fifty infants and children with acute renal failure were treated with acute peritoneal dialysis between 1987 and 1990. The patients were dialyzed using either a catheter introduced percutaneously over a guide-wire (n = 40) or a Tenckhoff catheter (n = 10). The cause of the acute renal failure was primary renal disease in 17 children, cardiac disease in 19, and trauma/sepsis in 14. Peritoneal dialysis succeeded in controlling metabolic abnormalities, improving fluid balance, and relieving the complications of uremia. The procedure had few major complications. Overall mortality was 50%, reflecting the serious nature of the underlying diseases. We conclude that acute peritoneal dialysis is a safe and effective treatment in most pediatric patients with acute renal failure. Our series of patients treated with acute peritoneal dialysis serves as a basis of comparison for the evaluation of new modalities of therapy in childhood acute renal failure.

Theoretical analysis of the accuracy of calibrated immunoassays for measuring antibody concentration.

The accuracy of calibrated immunoassays for measuring antibody concentration was analysed from a theoretical perspective. The study shows that there are theoretical limits on the accuracy of antibody immunoassays, which are determined by the affinity of the standard and unknown antibodies and the conditions chosen for the assay. As a result of these limits, calibration of an immunoassay with a standard antibody does not automatically ensure accurate measurements of antibody concentration. Extremely large errors may develop in affinity-dependent assays when the affinities of the standard and unknown antibodies are different. Assay conditions and the affinity of the standardizing antibody must be chosen carefully to measure antibody concentration accurately.

Symptomatic cholelithiasis in pediatric renal transplant recipients.

We report two cases of symptomatic cholelithiasis in pediatric renal transplant recipients immunosuppressed with cyclosporine (CsA), prednisone and azathioprine. CsA was present in the bile and in the cholesterol gallstones of one patient. The diagnosis of cholelithiasis was established in both cases by abdominal ultrasound examination.

Treatment of steroid-resistant focal segmental glomerulosclerosis with pulse methylprednisolone and alkylating agents.

In children, steroid-resistant nephrotic syndrome due to focal segmental glomerulosclerosis (FSGS) is frequently a progressive condition resulting in end-stage renal disease. There have been no reports of effective treatment for this condition. For the past several years, the Pediatric Nephrology services at the University of California, San Diego and Stanford University Schools of Medicine have treated these patients with a protocol involving infusions of high doses of methylprednisolone, often in combination with oral alkylating agents. Twenty-three children have been treated in this manner with a follow-up of 46 +/- 5 months. Twelve of these children are in complete remission. Six have minimal to moderate proteinuria. Four children remain nephrotic. Each of these children has a normal glomerular filtration rate. One child developed chronic renal failure and subsequently died while on dialysis. These results appear significantly better than previous series of children with FSGS. A controlled, multi-center trial of this protocol has been proposed.

Trimethoprim/sulfamethoxazole-induced renal tubular acidosis.

A child was evaluated for growth failure at the University of California, San Diego. On two occasions the patient had renal bicarbonate wasting, acidosis, and growth failure associated with trimethoprim/sulfamethoxazole (TMP/SMZ) administration. On both occasions, the acidosis resolved and the growth rate normalized following a period without receiving TMP/SMZ. Renal tubular acidosis and growth failure may occur as a result of TMP/SMZ therapy in children.

Follow-up of infants with obstructive uropathy detected in utero and treated surgically postnatally.

Thirty-four infants with obstructive uropathy detected by prenatal ultrasonography at 34 +/- 0.56 weeks (SE) had surgery during the first 2 years of life. The growth and renal function of the 25 children after being followed for over 1 year are described. Twelve children had unilateral disease, and 13 had bilateral disease. All 12 children with unilateral disease grew at or above the fifth percentile and had normal renal function (glomerular filtration rate, 101 +/- 7 mL/min/1.73 m2). Thirteen children with bilateral disease were followed for 26.1 +/- 3.4 months. Growth was good: 10 of the 13 grew at or above the fifth percentile. The serum creatinine was 0.7 +/- 0.2 mg/dL, and the glomerular filtration rate was 91 +/- 10 mL/min/1.73 m2. One child required chronic dialysis. The prenatal diagnosis of urinary tract anomalies followed by early intervention may improve the long-term outcome of children with obstructive uropathy.

Interference with creatinine concentration measurement by high dose furosemide infusion.

Three patients had unmeasurable serum creatinine concentrations using a colorimetric method while receiving high doses of furosemide. The present study shows that enzymatic methods of measuring the serum creatinine concentration should be used in patients receiving high doses of furosemide.

Functional affinity of antibody to the Haemophilus influenzae type b polysaccharide.

The functional affinity, or avidity, of antibody to the capsular polysaccharide of Haemophilus influenzae (Hib-PS) was measured in serum samples from 12 adult male subjects before and after immunization with Hib-PS vaccine. Mean avidity increased from 0.74 nM-1 to 1.5 nM-1 after immunization (P less than .05, paired Student's t test). The Bureau of Biologics reference antiserum had an avidity constant of 12 nM-1, which was the highest of all 25 serum samples studied.

Severe bilateral renal disease: correlation of antenatal and autopsy findings.

We report 20 infants with severe bilateral renal disease examined by prenatal ultrasound and by autopsy. In 17, the prenatal and pathologic diagnoses correlated well. Although the prenatal and autopsy findings differed in the three remaining cases, the autopsy confirmed the presence of severe bilateral renal abnormalities. All 20 pregnancies were complicated by oligohydramnios, which was severe in 60 per cent. Most of these fetuses had malformation of other organ systems. This series supports the utility of prenatal ultrasound examinations, but emphasizes the need for postnatal evaluation of congenital renal disease including pathologic examination of tissue when possible for correct classification and genetic counselling.