Report of a Brazilian multicenter study on nephropathic cystinosis

Abstract

Introduction: The Brazilian Multicenter Nephropathic Study Group, founded in 1999, is currently composed of 16 pediatric nephrology units, which are coordinated by the Pediatric Nephrology Unit of Instituto da Criança--HCFMUSP. This Study Group intends to better know our patients, their special characteristics and facilitates the treatment.

Objective: To present an update on the demographics of the ongoing study participants with interest on renal function status, response to therapy, and extra-renal complications.

Methods: Patient recruitment to the study is based on informed consent and has been supported by the Brazilian Society of Nephrology, by the creation of an electronic homepage and by the participation in medical meetings and publications in medical periodicals. Our study protocol involves the initial and follow-up questionnaire, the measurement of intraleukocyte cystine content, initiation and follow-up therapy with cysteamine, and clinical patient follow-up based on a protocol of subsidiary exams.

Results: We identified 102 patients (42 females) with nephropathic cystinosis in Brazil since 1999. Forty-six children are followed at the Instituto da Criança/SP, 15 at the Hospital Pequeno Príncipe/PR, 12 at the UNICAMP/SP, 10 at the Unidade de Transplante Renal - HCFMUSP/SP and 3 at the Santa Casa/SP; the remaining patients are followed at the Instituto da Criança and at their respective doctors' offices in different nephrology services in Brazil. Of these patients, 23/102 (22.5%) have normal renal function, 19/102 (18.6%) are in chronic renal failure with conservative treatment, 26/102 are on dialysis (18 on peritoneal dialysis and 8 on hemodialysis), and 34/102 received a renal transplant. The extra-renal involvement diagnosed was: hypothyroidism in 63 patients, diabetes mellitus in 8 patients, muscular involvement in 7 patients, a compromised central nervous system in 5 patients, hepatic complications in 5 patients, and deglutition dysfunction in 2 patients. During this period, 10/102 patients died. Cysteamine has been used by 81/102 patients (20 children started the therapy under 2 years of age). Growth parameters were improved by cysteamine, mainly in the youngest patients. We used recombinant growth hormone in 15 patients with persistent low growth velocity and stature z score under 2.5%. We could also observe a delay in appearance of extra-renal complications in patients receiving cysteamine.

Conclusion: Our study demonstrates the importance of a multi-center study for recruitment, diagnosis and management of rare diseases. This study promotes access to the adequate treatment with profound impact on the quality of life.