Elizabeth C. Jackson

IgA nephropathy: long-term prognosis for pediatric patients.

OBJECTIVE The determination of the ultimate prognosis for patients with IgA nephropathy diagnosed in childhood requires long-term follow-up of identified patients. The purpose of this study was to obtain such follow-up for patients from two centers where the disease has been diagnosed for more than 20 years. METHODS Clinical data at the apparent onset of symptoms and renal histologic data were obtained for 103 patients in whom IgA nephropathy was diagnosed before age 18 years. Clinical status at last follow-up was obtained from office records or from direct contact with the patient. Predicted kidney survival was determined by the Kaplan-Meier method. Follow-up of more than 10 years from the time of biopsy was available for 40 of the patients. RESULTS Fourteen of the patients have progressed to end-stage renal disease; three others have progressive chronic renal insufficiency as defined by an estimated creatinine clearance of less than 50 ml/min per 1.73 m2. Severity of the renal histologic findings and the degree of proteinuria at the time of biopsy were associated with poor outcome. For all patients, predicted kidney survival from the time of apparent onset was 94% at 5 years, 87% at 10 years, 82% at 15 years, and 70% at 20 years. Age at clinical onset and gender were not associated with poor outcome, but black race and severity of renal histologic findings were. CONCLUSION With follow-up into adulthood, the outcome for pediatric patients with IgA nephropathy appears to be as serious as that reported in adult patients. Follow-up of a pediatric patient with persistent clinical findings should be maintained after the patients care is transferred to a physician caring for adults.

Tacrolimus-based immunosuppression with steroid withdrawal in pediatric kidney transplantation: 4-year experience at a moderate-volume center

Abstract: Tacrolimus‐based immunosuppression with steroid withdrawal in pediatric kidney transplantation was pioneered at the University of Pittsburgh but is not broadly practiced at other centers. We present our 4‐year experience with a modified Pittsburgh protocol at our own moderate‐volume center. Seventeen pediatric kidney transplant recipients were treated with a tacrolimus‐based immunosuppressive regimen involving steroid withdrawal over 6–12 post‐transplant months in most cases and followed for up to 49 months. Patient and graft survival as well as graft function were excellent, and beneficial effects on several cardiovascular parameters were noted. Complications included fungal infections, glucose intolerance and post‐transplant lymphoproliferative disease and were generally managed successfully. While awaiting longer‐term follow‐up data, we conclude that tacrolimus‐based immunosuppression with steroid withdrawal in pediatric kidney transplantation is potentially beneficial and feasible even at centers managing a rather small number of recipients.

Bilateral ureteral obstruction associated with Henoch-Schoenlein purpura.

Abstract. Renal involvement is common in Henoch-Schoenlein purpura (HSP) and, while ureteral obstruction has been described in patients with the disease, it is rare. We report a female with HSP who developed bilateral ureteral obstruction from peri-ureteral vasculitis and subsequent ureteral ischemia. Hydronephrosis and typical findings on contrast urography indicated the diagnosis.

Effect of the Nephrotic Syndrome on the Concentration of Serum Complement Components

The concentration of 12 component and four control proteins of the complement system was measured in serum from 43 children with a nephrotic syndrome, which subsequently proved to be steroid-responsive, and from 13 children with focal glomerulosclerosis (FGS) and was compared with values from 197 normal subjects. Of classical pathway complement components, 40% of patients had low C1q levels and 20%, low C2 levels. Mean serum levels of C1s, C4, C1INH, and C4bp were elevated. Of alternative pathway components, factors B and I were low in one third, while levels of C3 and H were commonly elevated. Of the terminal components, only C8 and C9 were low. In five patients with FGS with hypoalbuminemia without edema, all component levels were normal. With the exception of C1q, C1s, and C8, high molecular weight (mol wt) components were in high concentration and low mol wt components in low concentration. The three exceptions may be explained by the subunit structure of C1 and C8. From a practical standpoint, the study indicates that edematous patients with a nephrotic syndrome may have low serum levels of C1q and C2, simulating classical pathway complement activation such as commonly occurs in glomerulonephritis. However, low levels of C4, and possibly C1s, can be used as indicators of classical pathway activation since their levels are not reduced by a nephrotic syndrome.

Autoantibody to complement neoantigens in membranoproliferative glomerulonephritis

With the exception of C3 nephritic factor, autoantibody formation has not been commonly associated with membranoproliferative nephritis (MPGN). We measured autoantibodies (nephritic factors) to the C3 convertases C3bBb (NFa) and C3bBbP (NFt), which result in fast and slow C3 activation, respectively, and to a neoantigen on C1q fixed to a solid phase (spC1q) in sera from 29 patients with MPGN type I, 26 with type II, and 28 with type III. Autoantibody formation was common in all MPGN types. An autoantibody to a C3 convertase neoantigen was identified in more than 75% of the hypocomplementemic MPGN sera tested. Anti-C3bBb (NFa) was present in 81% of patients with MPGN type II but was rarely found in either type I or type III. Anti-C3bBbP (NFt) was common in both MPGN I and III. Anti-spC1q was present in 74% of patients with type I and in 38% and 48% of types II and III MPGN, respectively. Patients with MPGN types I, II, and III had one and two serum autoantibodies detected significantly more frequently than did a group of healthy subjects. The presence of any one autoantibody was not specifically associated with the presence of any other autoantibody. The results indicate that multiple autoantibody formation is common in all MPGN types. MPGN II, and possibly MPGN I, tend to form more specific autoantibodies.

Nocturnal Enuresis: Giving the Child a “Lift”

6 uired to assess these pressure and oxygenation responses ust have been about an hour of continuous intensive adjustents of ventilation. In the original report, the newborns’ lood pressure and heart rate did not change. However, the oncept that blood pressure and heart rate alone do not define ardiovascular performance, particularly in preterm infants, as been well developed in The Journal in recent years. In this ssue of The Journal, de Waal et al report a study that used hese same lung recruitment maneuvers in preterm infants ith RDS on highfrequency oscillation. Their evaluation of hese infants’ cardiovascular status revealed a small 17% derease in right ventricular output but no consistent changes in uperior vena cava flow or ductal shunting when pressures ere increased to the opening pressure. The effects of overistention of the adult lung on cardiac output have been well ocumented in animal models and patients. The gas volume f the fully recruited preterm lung is small (30 to 50 mL/kg) elative to the adult lung, and the chest wall is very compliant. he increased mean airway pressures did not influence cariovascular function in these preterm infants with RDS. This recruitment maneuver works in the sense that lung xygenation is improved and an “optimal” pressure for oscilation can be determined. There were no acute safety conerns; cardiovascular status was not compromised, and no air eaks occurred. The information provided by these physiologcal measurements in infants is valuable to the field; however, believe that such a recruitment maneuver is not something he average neonatologist should take home and try, for everal reasons. First, these are demanding and time-consumng assessments. The mean airway pressures used to define the pen lung are high, and in my experience with ventilation of reterm animals, they can cause lung blebs and pneumothoax. Although not evaluated in this clinical experience, lung

Bilateral Ureteral Obstruction Associated With Henoch-Schoenlein Purpura

Renal involvement is common in Henoch-Schoenlein purpura (HSP) and, while ureteral obstruction has been described in patients with the disease, it is rare. We report a female with HSP who developed bilateral ureteral obstruction from peri-ureteral vasculitis and subsequent ureteral ischemia. Hydronephrosis and typical findings on contrast urography indicated the diagnosis.

1639 EFFECT OF THE NEPHROTIC SYNDROME ON THE CONCENTRATION OF SERUM COMPLEMENT COMPONENTS

The concentration of twelve component and four control proteins of the complement system were measured in serum from 43 children with a nephrotic syndrome which subsequently proved to be steroid responsive and from 13 children with focal glomerulosclerosis (FGS) and compared to values from 197 normal subjects. Of classical pathway complement components, 40% of patients had low Clq and 20%, low C2 levels. Mean serum levels of Cls, C4, C1INH and C4bp were elev,ated. Of alternative pathway components, factors B and I were low in one-third while levels of C3 and H were commonly elevated. Of the terminal components, only C8 and C9 were low. In five FGS patients with hypoalbuminemia without edema, all component levels were normal. With the exception of C1q, C1s and C8, high molecular weight components were in high concentration and low molecular weight components in low concentration. The three exceptions may be explained by the sub-unit structure of C1 and C8. From a practical standpoint, the study indicates that edematous patients with a nephrotic syndrome may have low serum levels of C1q and C2, simulating classical pathway complement activation such as commonly occurs in glomerulonephritis. However, low levels of C4 and possibly C1s can be used as indicators of classical pathway activation since their levels are not reduced by a nephrotic syndrome.