Clinical, pathological, and genetic characteristics of cases with asymptomatic proteinuria not manifesting nephrotic syndrome at onset: a single-center retrospective study

Clin Exp Nephrol. 2022 May;26(5):453-459. doi: 10.1007/s10157-021-02174-w. Epub 2022 Feb 3.


Background: Cases with asymptomatic proteinuria (ASP) not manifesting nephrotic syndrome often pathologically show focal segmental glomerulosclerosis (FSGS). However, characteristics of those cases had not been intensively studied so far.

Methods: We retrospectively reviewed clinical, pathological, and genetic characteristics of 37 children (median age, 9.3 years) who underwent renal biopsy for persistent isolated proteinuria (urine protein-to-creatinine ratio: UP/C, > 0.2 g/g) between 2003 and 2019. Targeted next-generation sequencing (NGS) was utilized for all patients with FSGS, excluding those with secondary FSGS.

Results: At biopsy, all patients with FSGS (N = 14) had UP/C ≥ 0.5 g/g and the median UP/C was significantly higher in those with FSGS than those with minor glomerular abnormalities (MGA) (N = 23) (1.49 vs. 0.53 g/g, P < 0.001). Causative variants were found in seven patients with FSGS (TRPC6, WT1, ACTN4, and INF2 in 3, 2, 1, and 1 patient, respectively): all gene variants were in genes manifesting autosomal dominant inheritance mode. The proportion of the perihilar variant was significantly higher in the genetic FSGS patients than in the non-genetic FSGS patients (4/7 vs. 0/7, P < 0.05). Kaplan-Meier analysis showed that the renal survival rate after ASP diagnosis was significantly lower in the genetic FSGS patients than in the non-genetic FSGS and the MGA patients (P < 0.001).

Conclusions: UP/C was a simple and useful predictive parameter for the diagnosis of FSGS. APS without nephrotic syndrome at onset may be associated with autosomal dominant causes of FSGS, especially in those with the perihilar variant.

Keywords: Asymptomatic proteinuria; Autosomal dominant variants; Focal segmental glomerulosclerosis; Next-generation sequencing; Perihilar variant; Renal biopsy; Urine protein-to-creatinine ratio.

MeSH terms

  • Child
  • Female
  • Glomerulosclerosis, Focal Segmental* / complications
  • Glomerulosclerosis, Focal Segmental* / diagnosis
  • Glomerulosclerosis, Focal Segmental* / genetics
  • Humans
  • Kidney / pathology
  • Male
  • Nephrotic Syndrome* / complications
  • Nephrotic Syndrome* / diagnosis
  • Nephrotic Syndrome* / genetics
  • Proteinuria / complications
  • Proteinuria / diagnosis
  • Proteinuria / genetics
  • Retrospective Studies