Pediatric Nephrology
Pediatr Nephrol (1992) 6:506 9 IPNA 1992
Editorial comment
Controlled, multi-center trials are needed in pediatric nephrology Stanley A. Mendoza and Bruce M. Tune Departments of Pediatrics, University of California, San Diego and Stanford University Schools of Medicine, California, USA Received April 22, 1992; accepted April 24, 1992
Key words: Nephrotic syndrome - Methylprednisolone Alkylating agent Focal segmental glomernlosclerosis (FSGS) is a progressive condition, often presenting as steroid-resistant nephrotic syndrome and, in many cases, progressing to endstage renal failure. In children, FSGS is the most common progressive glomernlar disease and the second most common cause of end-stage renal failure [1]. This issue of Pediatric Nephrology contains an article by Waldo et al. describing their experience in treating 13 children with steroid-resistant nephrotic syndrome. Three children had biopsy-proven minimal-change nephrotic syndrome and the other 10 had FSGS. They used a protocol involving multiple intravenous infusions of methylprednisolone. Three patients also received a course of oral chlorambucil. The results were disappointing, differing greatly from the outcome reported from our centers in a group of children with steroid-resistant nephrotic syndrome and biopsy-proven FSGS [2-4]. The reasons for these differences are not clear. Our patients were largely either Caucasian or Hispanic, while many of the children reported by Waldo et al. were black. It is important to note, however, that there were a number of differences between the two treatment protocols, some of which may be critical. First, Waldo et al. used a lower dose of methylprednisolone (20 mg/kg) than we did (30 mg/kg). Second, patients who either failed to respond to the initial course of methylprednisolone or who responded partially were not treated further by Waldo et al. In our series, most patients who had a partial initial response achieved complete remission with additional therapy. A pattern of gradual improvement with continued therapy was relatively common. Third, a number of our patients, including many who are currently in a long-lasting remission of their disease, required more than one course of alkylating agent therapy. Waldo et al. did not give more than one course of chlorambucil and they used the alkylating agent in only 3 of 13 patients. Of our 25 patients, 17 had at least one course
of alkylating agent therapy and 7 had more than one course. Fourth, their patients were "rested" for 4 or more weeks of no therapy before starting the methylprednisolone protocol, which was not done in our patients. The purpose of our comments is not to assert that these differences in the two protocols were responsible for the markedly different outcomes in the two series. Instead, these discrepancies illustrate the dangers of comparing uncontrolled clinical observations. We feel strongly, and Waldo et al. agree, that it is essential for the methylprednisolone protocol to be tested in a multi-center controlled clinical trial. If this is not done, anecdotal experiences will continue to accumulate on both sides of the issue and the pediatric nephrology community will never learn the optimal treatment for this condition. An application proposing such a clinical trial has been submitted to the National Institutes of Health.
References 1. US Renal Data System 1991 Annual Data Report (1991) ESRD in children: incidence of reported pediatric ESRD; reported prevalence of pediatric ESRD; causes of pediatric ESRD; methods of treatment of pediatric ESRD; pediatric ESRD patient survival; renal graft survival. Am J Kidney Dis 18 [Suppl 2]: 79-88 2. Griswold WR, Tune BM, Reznik VM, Vazquez M, Prime DJ, Brock P, Mendoza SA (1987) Treatment of childhood prednisone-resistant nephrotic syndrome and focal segmental glomernlosclerosis with intravenous methylprednisolone and oral alkylating agents. Nephron 46: 73 -77 3. Mendoza SA, Reznik VM, Griswold WR, Krensky AM, Yorgin PD, Tune BM (1990) Treatment of steroid-resistant focal segmental glomernlosclerosis with pulse methylprednisolone and alkylating agents. Pediatr Nephrol 4: 303- 307 4. Mendoza SA, Reznik VM, Griswold WR, Krensky AM, Yorgin PD, Tune BM (1991) Treatment of childhood steroid-resistant focal segmental glomerulosclerosis with pulse methylprednisolone and alkylating agents. Proceedings of the XIth International Congress of Nephrology, Tokyo, July 15-20, 1990. Springer-Verlag, Tokyo, pp 1480-1485
Pediatr Nephrol (1992) 6:506 9 IPNA 1992
Editorial comment
Controlled, multi-center trials are needed in pediatric nephrology Stanley A. Mendoza and Bruce M. Tune Departments of Pediatrics, University of California, San Diego and Stanford University Schools of Medicine, California, USA Received April 22, 1992; accepted April 24, 1992
Key words: Nephrotic syndrome - Methylprednisolone Alkylating agent Focal segmental glomernlosclerosis (FSGS) is a progressive condition, often presenting as steroid-resistant nephrotic syndrome and, in many cases, progressing to endstage renal failure. In children, FSGS is the most common progressive glomernlar disease and the second most common cause of end-stage renal failure [1]. This issue of Pediatric Nephrology contains an article by Waldo et al. describing their experience in treating 13 children with steroid-resistant nephrotic syndrome. Three children had biopsy-proven minimal-change nephrotic syndrome and the other 10 had FSGS. They used a protocol involving multiple intravenous infusions of methylprednisolone. Three patients also received a course of oral chlorambucil. The results were disappointing, differing greatly from the outcome reported from our centers in a group of children with steroid-resistant nephrotic syndrome and biopsy-proven FSGS [2-4]. The reasons for these differences are not clear. Our patients were largely either Caucasian or Hispanic, while many of the children reported by Waldo et al. were black. It is important to note, however, that there were a number of differences between the two treatment protocols, some of which may be critical. First, Waldo et al. used a lower dose of methylprednisolone (20 mg/kg) than we did (30 mg/kg). Second, patients who either failed to respond to the initial course of methylprednisolone or who responded partially were not treated further by Waldo et al. In our series, most patients who had a partial initial response achieved complete remission with additional therapy. A pattern of gradual improvement with continued therapy was relatively common. Third, a number of our patients, including many who are currently in a long-lasting remission of their disease, required more than one course of alkylating agent therapy. Waldo et al. did not give more than one course of chlorambucil and they used the alkylating agent in only 3 of 13 patients. Of our 25 patients, 17 had at least one course
of alkylating agent therapy and 7 had more than one course. Fourth, their patients were "rested" for 4 or more weeks of no therapy before starting the methylprednisolone protocol, which was not done in our patients. The purpose of our comments is not to assert that these differences in the two protocols were responsible for the markedly different outcomes in the two series. Instead, these discrepancies illustrate the dangers of comparing uncontrolled clinical observations. We feel strongly, and Waldo et al. agree, that it is essential for the methylprednisolone protocol to be tested in a multi-center controlled clinical trial. If this is not done, anecdotal experiences will continue to accumulate on both sides of the issue and the pediatric nephrology community will never learn the optimal treatment for this condition. An application proposing such a clinical trial has been submitted to the National Institutes of Health.
References 1. US Renal Data System 1991 Annual Data Report (1991) ESRD in children: incidence of reported pediatric ESRD; reported prevalence of pediatric ESRD; causes of pediatric ESRD; methods of treatment of pediatric ESRD; pediatric ESRD patient survival; renal graft survival. Am J Kidney Dis 18 [Suppl 2]: 79-88 2. Griswold WR, Tune BM, Reznik VM, Vazquez M, Prime DJ, Brock P, Mendoza SA (1987) Treatment of childhood prednisone-resistant nephrotic syndrome and focal segmental glomernlosclerosis with intravenous methylprednisolone and oral alkylating agents. Nephron 46: 73 -77 3. Mendoza SA, Reznik VM, Griswold WR, Krensky AM, Yorgin PD, Tune BM (1990) Treatment of steroid-resistant focal segmental glomernlosclerosis with pulse methylprednisolone and alkylating agents. Pediatr Nephrol 4: 303- 307 4. Mendoza SA, Reznik VM, Griswold WR, Krensky AM, Yorgin PD, Tune BM (1991) Treatment of childhood steroid-resistant focal segmental glomerulosclerosis with pulse methylprednisolone and alkylating agents. Proceedings of the XIth International Congress of Nephrology, Tokyo, July 15-20, 1990. Springer-Verlag, Tokyo, pp 1480-1485
