具有IV型胶原基因杂合突变的常染色体或X连锁Alport综合征(AS)患者在其一生中发展为终末期肾病的风险为1-20%。我们评估了有/没有肾保护治疗的进行性疾病(慢性肾脏疾病1-4期)风险的患者的长期肾脏结局。
这是一个前景,非干预性,观察性研究,包括对具有杂合突变的AS患者进行4年随访的数据,这些患者的数据集已纳入欧洲Alport注册中心2010年数据库的分析.使用Kaplan-Meier估计和logrank检验,我们前瞻性分析了其中52例患者的更新数据集和13例新数据集(2011年后纳入登记处的患者).治疗的效果,分析肾外症状和遗传模式对肾脏结局的影响.
平均前瞻性随访时间为46±10个月,平均治疗时间为8.4±4.4(中位数7;范围2-18)年.从第一个症状出现到诊断的时间为8.1±14.2(范围0-52)年。在开始治疗的时候,5.4%的患者估计肾小球滤过率<60ml/min,67.6%有蛋白尿,27.0%有微量白蛋白尿。治疗策略包括血管紧张素转换酶抑制剂(97.1%),血管紧张素受体拮抗剂(1名患者),双重治疗(11.8%)和他汀类药物(8.8%)。在前瞻性数据集中的患者中,避免了透析的需要。在新患者中,随访4年后,无肾衰竭风险患者进展到下一个疾病阶段;3例患者甚至在治疗期间退步至较低阶段.
使用肾素-血管紧张素-醛固酮系统阻断剂治疗可预防AS基因杂合突变的AS患者进行性肾衰竭。相当数量的透析老年AS患者可能在这些基因中具有杂合突变(存在于总人口的1%中)作为潜在疾病。因此,对于在致病基因中存在杂合子突变的大多数-如果不是全部-AS患者,提高对及时诊断和治疗的警觉性有可能预防进行性肾衰竭.
Patients with autosomal or X-linked Alport syndrome (AS) with heterozygous mutations in type IV collagen genes have a 1-20 % risk of progressing to end-stage renal disease during their lifetime. We evaluated the long-term renal outcome of patients at risk of progressive disease (chronic kidney disease stages 1-4) with/without nephroprotective therapy.
This was a prospective, non-interventional, observational study which included data from a 4-year follow-up of AS patients with heterozygous mutations whose datasets had been included in an analysis of the 2010 database of the European Alport Registry. Using Kaplan-Meier estimates and logrank tests, we prospectively analyzed the updated datasets of 52 of these patients and 13 new datasets (patients added to the Registry after 2011). The effects of therapy, extrarenal symptoms and inheritance pattern on renal outcome were analyzed.
The mean prospective follow-up was 46 ± 10 months, and the mean time on therapy was 8.4 ± 4.4 (median 7; range 2-18) years. The time from the appearance of the first symptom to diagnosis was 8.1 ± 14.2 (range 0-52) years. At the time of starting therapy, 5.4 % of patients had an estimated glomerular filtration rate of <60 ml/min, 67.6 % had proteinuria and 27.0 % had microalbuminuria. Therapeutic strategies included angiotensin-converting enzymer inhibitors (97.1 %), angiotensin receptor antagonists (1 patient), dual therapy (11.8 %) and statins (8.8 %). Among patients included in the prospective dataset, prevented the need for dialysis. Among new patients, no patient at risk for renal failure progressed to the next disease stage after 4 years follow-up; three patients even regressed to a lower stage during therapy.
Treatment with blockers of the renin-angiotensin-aldosterone system prevents progressive renal failure in AS patients with heterozygous mutations in the genes causing AS. Considerable numbers of aging AS patients on dialysis may have heterozygous mutations in these genes (present in 1 % of total population) as underlying disease. Hence, greater alertness towards timely diagnosis and therapy has the potential to prevent progressive renal failure in most-if not all-AS patients with heterozygous mutations in the causal genes.