Abstract：
BACKGROUND: In patients with steroid-resistant nephrotic syndrome (SRNS), the presence of monogenic variants influences therapeutic strategies. Large cohort studies reported the detection of monogenic variants in approximately 30% of patients with SRNS. However, these cohorts included many patients, such as those with symptomatic proteinuria, who did not meet the strict diagnostic criteria for pediatric nephrotic syndrome (NS). Therefore, we investigated the proportion of causative monogenic variants detected in patients who strictly met the diagnostic criteria of SRNS and explored their clinical characteristics.
METHODS: We examined pediatric SRNS cases with genetic analysis conducted in our hospital. Cases satisfying all of the following criteria were included: (1) age at onset 1-18 years, (2) serum albumin at onset ≤ 2.5 g/dl, (3) persistent heavy proteinuria, and (4) no complete remission after 4 weeks of steroid monotherapy.
RESULTS: The proportion of detected monogenic variants was 12% (22/185) among all patients. The proportion was only 7% (9/129) in patients with edema at disease onset compared with 38% (9/24) in those without (p < 0.0001). Monogenic variants were rare in patients with acute kidney injury associated with NS (1% (1/11)) or a history of complete remission (4% (2/51)).
CONCLUSIONS: Our study revealed a monogenic cause in 12% of individuals with strictly defined SRNS, a much smaller proportion than previously reported. The presence or absence of edema at the onset was an important factor to distinguish SRNS with monogenic cause from SRNS without. Our results provide further evidence of the SRNS types attributable to monogenic causes.
METHODS: We examined pediatric SRNS cases with genetic analysis conducted in our hospital. Cases satisfying all of the following criteria were included: (1) age at onset 1-18 years, (2) serum albumin at onset ≤ 2.5 g/dl, (3) persistent heavy proteinuria, and (4) no complete remission after 4 weeks of steroid monotherapy.
RESULTS: The proportion of detected monogenic variants was 12% (22/185) among all patients. The proportion was only 7% (9/129) in patients with edema at disease onset compared with 38% (9/24) in those without (p < 0.0001). Monogenic variants were rare in patients with acute kidney injury associated with NS (1% (1/11)) or a history of complete remission (4% (2/51)).
CONCLUSIONS: Our study revealed a monogenic cause in 12% of individuals with strictly defined SRNS, a much smaller proportion than previously reported. The presence or absence of edema at the onset was an important factor to distinguish SRNS with monogenic cause from SRNS without. Our results provide further evidence of the SRNS types attributable to monogenic causes.
摘要：
背景：在类固醇耐药型肾病综合征（SRNS）患者中，单基因变异的存在影响治疗策略。大型队列研究报告了在大约30％的SRNS患者中检测到单基因变异。然而,这些队列包括许多患者，比如有症状的蛋白尿，不符合儿童肾病综合征（NS）的严格诊断标准。因此,我们调查了在严格符合SRNS诊断标准的患者中检测到的致病单基因变异的比例,并探讨了其临床特征.
方法：我们在我院进行了基因分析，检查了小儿SRNS病例。符合以下所有标准的病例包括：（1）发病年龄1-18岁，(2)发病时血清白蛋白≤2.5g/dl,（3）持续性重度蛋白尿，和（4）类固醇单药治疗4周后未完全缓解。
结果：在所有患者中检测到的单基因变异的比例为12%（22/185）。发病时水肿患者的比例仅为7％（9/129），而无水肿患者的比例为38％（9/24）（p<0.0001）。单基因变异在与NS（1％（1/11））或完全缓解史（4％（2/51））相关的急性肾损伤患者中很少见。
结论：我们的研究揭示了12%严格定义SRNS的个体的单基因病因，比例比以前报道的要小得多。发作时是否存在水肿是区分具有单基因原因的SRNS和没有的SRNS的重要因素。我们的结果提供了可归因于单基因原因的SRNS类型的进一步证据。
方法：我们在我院进行了基因分析，检查了小儿SRNS病例。符合以下所有标准的病例包括：（1）发病年龄1-18岁，(2)发病时血清白蛋白≤2.5g/dl,（3）持续性重度蛋白尿，和（4）类固醇单药治疗4周后未完全缓解。
结果：在所有患者中检测到的单基因变异的比例为12%（22/185）。发病时水肿患者的比例仅为7％（9/129），而无水肿患者的比例为38％（9/24）（p<0.0001）。单基因变异在与NS（1％（1/11））或完全缓解史（4％（2/51））相关的急性肾损伤患者中很少见。
结论：我们的研究揭示了12%严格定义SRNS的个体的单基因病因，比例比以前报道的要小得多。发作时是否存在水肿是区分具有单基因原因的SRNS和没有的SRNS的重要因素。我们的结果提供了可归因于单基因原因的SRNS类型的进一步证据。
