Immunoglobulin G/albumin staining in tubular protein reabsorption droplets in minimal change disease and focal segmental glomerulosclerosis

Abstract

Background Some renal biopsies cannot distinguish minimal change disease (MCD) from primary focal segmental glomerulosclerosis (FSGS) because of inadequate sampling and/or a lack of sampled glomeruli with segmental sclerosis. As protein excretion in MCD has been described as being albumin-selective, we examined whether the ratio of immunoglobulin G (IgG)/albumin staining in protein reabsorption droplets (tPRD) might help distinguish MCD from FSGS. Methods Frozen tissue from 144 native renal biopsies from patients with nephrotic syndrome and a diagnosis of MCD or FSGS [73 MCD, 30 FSGS tip variant (FSGS-tip), 38 FSGS-not otherwise specified (FSGS-NOS), 3 FSGS collapsing] was retrospectively stained by direct immunofluorescence for IgG and albumin; none of these samples showed diagnostic lesions of FSGS. IgG and albumin staining of tPRD were graded on a scale of 0 to 3+ based on the distribution and intensity of staining. Results Mean (standard deviation) IgG/albumin staining ratios were 0.186 ± 0.239 for MCD, 0.423 ± 0.334 for FSGS-tip (P = 0.0001 versus MCD) and 0.693 ± 0.297 for FSGS-NOS (P < 0.0001 versus MCD; P = 0.0001 versus FSGS-tip). Of 84 biopsies with a ratio ≤0.33, 63 (75%) showed MCD, whereas among 21 with a ratio of 1.0, all but one showed FSGS (15 FSGS-NOS). Conclusions In summary, IgG/albumin staining in tPRD was correlated with histologic diagnosis in renal biopsies with MCD and FSGS. A ratio of ≤0.33 was associated with MCD, whereas a ratio of 1.0 was most often seen with FSGS-NOS.

Transition from minimal change disease to focal segmental glomerulosclerosis related to occupational exposure: A case report

“…A positive attitude towards second, or multiple kidney biopsies is needed for uncertain or recurrent MCD patients and early stage FSGS patients. In addition to invasive kidney puncture, urinary myo-inositol, parietal epithelial cell marker staining, and IgG/albumin staining ratio in tubular protein reabsorption droplets are also potential diagnostic markers to differentiate between MCD and FSGS[ 21 - 23 ].…”

A Specific Tubular ApoA-I Distribution Is Associated to FSGS Recurrence after Kidney Transplantation

“…This fact suggests that tubular damage (when present) is hardly responsible for the retention of ApoA-I in the brush border of the tubular cells in recurrent FSGS patients ( Figure 2 and Figure 3 ). Further, a recent report of Bu et al [ 18 ] described that FSGS patients have increased staining of immunoglobulin G/albumin in tubular protein reabsorption droplets when compared to minimal change disease patients. This proves that, even in conditions of heavy proteinuria (>3.5 g/day), the tubular cells of the FSGS patients are actively reabsorbing proteins; hence it is improbable that ApoA-I is retained in the brush border of the tubular cells due to a failure in the reabsorption mechanisms.…”

The Transition From Minimal Change Disease to Focal and Segmental Glomerulosclerosis in a Patient With Nephrotic Syndrome: a Case Report

“…A positive attitude toward a second or multiple renal biopsies is needed for uncertain or recurrent MCD patients and early FSGS patients. In addition to the invasive operation of renal puncture, urinary myo-inositol, PEC marker staining and IgG/albumin staining ratio in tPRD are also potential diagnostic markers to differentiate MCD and FSGS [23,24,25].…”