Long-term outcome of nephropathic cystinosis: a 20-year single-center experience

Abstract

Nephropathic cystinosis (NC) is a severe disease that is complicated by early-onset chronic renal failure (CRF) and other complications related to cystine deposition in tissue. Since the 1980s, the prognosis of NC has dramatically improved after the introduction of cysteamine treatment. Limited data are available documenting improvement in prognosis. We reviewed our long-term data (follow-up 6.3-27.8 years) on 23 patients followed in the past 26 years. Overall, stage III CRF was reached at 10 years of age in >90% of patients, whereas >80% reached end-stage renal disease before the age of 14 years. Three patients died during the follow-up. Our analysis shows a clear improvement in renal outcome (p = 0.001) and linear growth (p = 0.04) in patients treated more recently. Improvement in the evolution of renal function was significantly associated with early initiation of cysteamine (p = 0.006), with the dose of cysteamine (p = 0.04), and with the use of angiotensin-converting enzyme inhibitors (p = 0.01). Nonrenal long-term complications are similar to previously reported data. Of note, 3/23 patients developed rare forms of primary tumors that were successfully treated. In conclusion, our experience shows a significant improvement in the renal and nonrenal complications of cystinosis over the past decades and highlights the importance of early diagnosis in order to initiate cysteamine as soon as possible.

Improvement in the Renal Prognosis in Nephropathic Cystinosis

“…Finally, no information was available on those starting RRT beyond the age of 20 years. Nevertheless, the mean age of onset of RRT in our cohort (12.8 years) was slightly higher compared with that recently reported from Australia and New Zealand (12.3 years in 2008) (26) and was comparable with that recently reported from a single center in Italy (8).…”

“…A recent observational study from Italy suggested a positive effect of angiotensin-converting enzyme (ACE) inhibitors on renal function survival in patients with NC (8). Unfortunately, we could not evaluate the role of ACE inhibitors or any other supportive therapies because these data were not available.…”

“…Partial treatment with cysteamine is not very effective in retarding the progression of ESRD (6,8). "Adequate" therapy includes an early diagnosis, thereby early initiation of cysteamine, possibly before 2 years of age, a strict 6-hour schedule, and regular monitoring of intraleukocyte cystine levels to adapt the daily dose (9).…”

A Randomized Controlled Crossover Trial with Delayed-Release Cysteamine Bitartrate in Nephropathic Cystinosis

“…Retrospective data analyses have demonstrated that kidney functional decline, and perhaps other organ functions, can be delayed and sustained, respectively, when a biomarker of the efficacy of cystine depletion, white blood cell (WBC) cystine, is ,2 nmol 1/2 cystine/mg protein (11,12). There have been no prospective trials with Cystagon for the therapy of cystinosis.…”

Cysteamine Modulates Oxidative Stress and Blocks Myofibroblast Activity in CKD

“…Before the availability of cysteamine, most patients with nephropathic cystinosis developed ESRD within the first decade of life. 9,10 Its efficacy as a renoprotective agent in nephropathic cystinosis is well established, yet the specific protective mechanisms remain incompletely understood. There is no question that cysteamine dramatically lowers intracellular levels of cytotoxic cystine, but this effect alone does not fully explain its renoprotective effects and led us to consider an alternative mechanism of action.…”