Nephrol Dial Transplant (2000) 15: 922-923
© 2000 European Renal Association-European Dialysis and Transplant Association
Letters
The patient with over 100 relapses of minimal change nephrotic syndrome: prolonged complete remission after chlorambucil treatment
Servicio de Nefrología, Hospital 12 de Octubre, Madrid, Spain
Sir,
Minimal change disease accounts for more than 80% of the cases of idiopathic nephrotic syndrome in children. Several studies have demonstrated that more than 90% of patients show a complete disappearance of proteinuria after 6–12 weeks of steroid treatment [1]. However, a considerable proportion of patients, reaching more than 75% in some series, experiences relapses of nephrotic syndrome [2]; cyclophosphamide or chlorambucil treatment, usually administered for 6–12 weeks, leads to prolonged steroid-free remission in most children with frequently relapsing minimal change disease [3,4]. Here we report the exceptional clinical course of a patient that experienced more than 100 steroid-sensitive relapses of minimal change nephrotic syndrome.
Case.
A 41-year-old man was admitted to our hospital because of severe headache and blurred vision. Evaluation on admission disclosed a blood pressure of 220/130 mmHg; the patient was alert but aphasic. Funduscopic examination showed a grade II hypertensive retinopathy. A computed tomographic scan of the brain revealed a left temporal intracerebral haemorrhage. Blood pressure was normalized with i.v. sodium nitroprusside and oral captopril. Laboratory data, obtained at admission were as follows: haematocrit 48%, haemoglobin 15.9 g/dl, leukocyte count 9559/mm3, platelet count 407 000/mm3, serum creatinine 1.1 mg/dl, serum cholesterol 272 mg/dl, total proteins 7.1 g/dl, and albumin 4.5 g/dl. Urinary sediment examination was normal and 24-h proteinuria negative. An abdominal echography showed two kidneys with normal morphology.
Thirty-six years before, at 5 years of age, he had been admitted to another hospital because of a complete nephrotic syndrome: he was treated with steroids (oral prednisone) for 8 weeks, following the protocol of the ISKDC [1]. Proteinuria completely cleared after 2 weeks of treatment and a diagnosis of minimal change nephrotic syndrome was established. In the following 2 years he showed several relapses of the nephrotic syndrome; following the same scheme of oral steroids, complete remissions were obtained on every occasion. Due to the reiterative character of the relapses, his parents decided to treat them without medical control: thus, when pedal and facial oedema was noted, they determined the presence of proteinuria by urine dipsticks. If confirmed, they administered oral prednisone in a manner very similar to the ISKDC protocol. Throughout the following years, the patient continued to show 2–4 relapses per year that were managed with oral prednisone; in the intervals, he was normal, without oedema and the urine was negative for proteinuria. When he was 18 he began to self-control the relapses of nephrotic syndrome: after the self-diagnosis (oedema, positive dipstick) he took prednisone, 60 mg/day for 2 weeks, followed by tapering prednisone doses for another 4 weeks. The patient continued to present 2–4 relapses per year. The estimated number of relapses, by the time of admission to our hospital, was about 108. By the age of 35 years, arterial hypertension (150/95 mmHg) was detected. He followed an irregular treatment with nifedipine.
After the adequate control of blood pressure and the recovery of neurological symptoms, the patient was discharged with oral captopril (50 mg/day); due to the amazing history of recurrent relapses, he was advised to attend the outpatient service of nephrology when a new relapse of nephrotic syndrome appeared. Two months after hospital discharge, he presented oedema and positive proteinuria. Physical examination showed mild oedema in both legs; blood pressure was 135/80 mmHg. Laboratory data showed a normal renal function (serum creatinine 0.9 mg/dl) together with the typical biochemical profile of nephrotic syndrome: serum total proteins 5.3 g/dl, albumin 2.2 g/dl, total cholesterol 339 mg/dl; 24 h proteinuria was 8.5 g. Urine sediment was normal. Oral prednisone, 1 mg/kg/day was prescribed for 4 weeks, and tapered in another 6 weeks. Proteinuria was negative by the second week of treatment. One month after prednisone withdrawal, urine remained free of proteins. However, 3 months later he again developed oedema and nephrotic-range proteinuria (9 g/day). On this occasion, we prescribed low-dose oral prednisone (25 mg/day) for 4 weeks, tapered in the following 4 weeks, and chlorambucil (0.2 mg/kg/day) administered for 8 weeks. Proteinuria disappeared again by the second week of treatment; in the following visits, performed every 3–6 months the patient did not show new relapses. After 2 years and a half of chlorambucil cycle the patient remains well, with normal renal function and negative proteinuria. At present, his blood pressure is normal taking captopril 50 mg/day.
Comment.
Those patients with minimal change disease showing more than three relapses per year are defined as frequent relapsers [1,2]. As a general rule, the frequency of relapses progressively decrease after adolescence [5]. Our patient is an exceptionally illustrative example of the relapsing tendency of minimal change nephrotic syndrome. He maintained a regular rhythm of relapses (2–4 per year) from 5 to 41 years. The calculated number of relapses throughout their life exceeded one hundred: interestingly, the nephrotic syndrome continued to show a total sensitivity to corticosteroid treatment despite this amazing number of episodes. Complete remission was always observed during the intervals.
The long-term prognosis of minimal change nephrotic syndrome is favourable. It has been suggested that the short duration of proteinuria (due to the rapid effect of corticosteroids) and its high selectivity could explain the general absence of chronic renal insufficiency in this entity. On the contrary, in other types of nephrotic syndrome the persistence of proteinuria would induce a progressive damage to glomerular and tubulointerstitial structures [6]. Our patient is also clinically relevant regarding this question: after the very unusual number of more than 100 relapses, his renal function is normal and proteinuria negative. Probably, the rapid onset of prednisone self-administration in every relapse, rendering urine totally protein free after few days of treatment, would explain the preservation of a normal renal function. Our patient showed a remarkable tolerance to the repeated cycles of oral prednisone, but it is possible that the severe arterial hypertension with cerebral haemorrhage, that was the cause of his hospital admission, was induced by the cumulative dose of corticosteroids. Finally, our patient is also a good clinical example of the effectiveness of alkylating agents in the treatment of frequent relapsers: after a short cycle of chlorambucil (0.2 mg/kg/day for 8 weeks) a lasting complete remission was obtained. Most studies recommend the prescription of one of such cycles in patients with frequently relapsing minimal change nephrotic syndrome [3,4] because of its effectiveness and low incidence of serious complications.
References
- A Report of the International Study of Kidney Disease in Children. The primary nephrotic syndrome in children: identification of patients with minimal change nephrotic syndrome from initial response to prednisone. J Pediatr1981; 98: 561–564[Medline]
- Mendoza SA, Tune BM. Treatment of childhood nephrotic syndrome. J Am Soc Nephrol1992; 3: 889–894[Abstract]
- Argeitsgemeinschaft für Padiatrische Nephrologie: effect of cytotoxic drugs in frequently relapsing nephrotic syndrome with and without steroid dependence. N Engl J Med1982; 306: 451–454[Abstract]
- Grupe WE, Makker SP, Ingelfinger JR. Chlorambucil treatment of frequently relapsing nephrotic syndrome. N Engl J Med1976; 95: 746–749
- Berns JS, Gaudio KM, Krassner LS, Anderson FP, Durante D, McDonald BM, Siegel NJ. Steroid-responsive nephrotic syndrome of childhood: a long-term study of clinical course, histopathology, efficacy of cyclophosphamide therapy, and effects on growth. Am J Kidney Dis1987; 9: 108–114[Web of Science][Medline]
- Remuzzi G, Ruggenenti P, Benigni A. Understanding the nature of renal disease progression. Kidney Int1997; 51: 2–15[Web of Science][Medline]
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