High incidence of initial and late steroid resistance in childhood nephrotic syndrome.

BACKGROUND: Conventional wisdom states that greater than 80% of children with nephrotic syndrome (NS) respond to steroid treatment, remain steroid-sensitive during subsequent relapses, and consequently have a favorable long-term prognosis. In contrast, steroid resistance is believed to be associated with a high risk of developing chronic renal failure. Recent reports suggest that the histologic pattern of NS in children may be changing, but whether the change is accompanied by a parallel change in steroid sensitivity is unknown. METHODS: Initial and subsequent steroid responsiveness was evaluated in all children aged 1 to 18 years who presented with newly diagnosed NS to the 2 pediatric nephrology referral centers in southeastern Louisiana between 1994 and 2003. NS was defined as presence of edema, heavy proteinuria, and serum albumin concentration below 2.5 g/dL. Steroid sensitivity (SS) was defined as total resolution of proteinuria and edema, and partial response to steroids (PR) was defined as loss of edema with continuing proteinuria. RESULTS: There were 210 new cases of NS. Forty-one patients (20%) had immune complex glomerulonephritis. Six patients were excluded because of incomplete data availability. Of the remaining 163 patients, 115 (71%) were SS and 23 (14%) achieved PR during the initial 4 weeks of treatment; 25 (15%) were steroid-resistant (SR). Follow-up data were available for 91 of the 115 initially SS patients; 19 subsequently became steroid-resistant. Thus, at least 45% of the patients with new-onset NS did not have typical childhood steroid-responsive NS. Initial steroid resistance was more likely in African American children and in children with older age at onset (11.5 vs. 4.6 years). Development of steroid resistance after initial SS was associated with shorter interval to the first relapse (2.2 vs. 5.4 months) and having the first relapse during the initial steroid treatment. CONCLUSION: Compared to previous reports, our results show a higher incidence of initial and subsequent steroid resistance, characteristics not consistent with typical minimal change NS with a benign prognosis. The results suggest that in the current era, NS in children may not be as benign as indicated by earlier studies.

Effect of urinary tract infection on ureteropelvic junction obstruction in a rat model.

OBJECTIVES: When a partially obstructed kidney becomes infected, more rapid and extreme renal parenchymal damage appears to occur than might result from either infection or obstruction alone. Previously, we showed that either bacteriuria or partial obstruction in congenital unilateral hydronephrosis causes elevated renal pelvic pressures in a rat model. In this same model, we examined the combined effects of partial upper tract obstruction and bacteriuria on renal pelvic and bladder pressures. METHODS: Female rats from an inbred colony in which more than one half are born with unilateral obstructive hydronephrosis were studied. Type 1 piliated Escherichia coli was instilled into the bladder. Two to 6 days later, the bladder and renal pelvic pressures were measured during varying urinary flows (less than 2 to more than 30 mL/kg/hr). All animals were killed and the kidneys and bladder grossly and histologically assessed. Hydronephrosis was determined at pathologic examination. RESULTS: Eight rats had congenital unilateral hydronephrosis; five were normal. Acute inflammation was found in all bladder and renal specimens. In hydronephrotic, infected kidneys, the renal pelvic pressures exceeded those in nonhydronephrotic, infected kidneys at all urinary flow rates. Bladder capacity and pressures did not differ between the two groups. CONCLUSIONS: This model demonstrates that the combination of infection and obstructive hydronephrosis in this model causes renal pelvic pressure elevation that is higher than that associated with either infection or obstructive hydronephrosis alone. These data demonstrate the compound effect that infection and obstruction may have on the kidney and offers an explanation for why this clinical situation is more likely to be associated with greater renal parenchymal injury than either alone.