PRE-EXISTENT PERITUBULAR CAPILLARY BASEMENT MEMBRANE MULTILAYERING
IN LIVING RELATED RENAL TRANSPLANTATION:
A PUZZLING CASE REPORT
N Knops1, R Van Damme-Lombaerts1, R Zeevaert1, E Levtchenko1, E Lerut2
1
Department of Pediatric Nephrology and Solid Organ Transplantation, University Hospitals Leuven,
Belgium; 2 Department of Morphology and Molecular Pathology, University Hospitals Leuven,
Belgium
Case Report:
A 12-year-old boy was referred because of a steroid resistant nephrotic syndrome with microscopic
haematuria. His own previous and family history was unremarkable. GFR was normal and further
blood tests revealed no signs of infection, complement activation or autoimmune disease. The
diagnosis of FSGS was confirmed on renal biopsy and the patient was consequently treated with
different therapeutic regimes (MMF, cyclosporine and tacrolimus). None resulted in a sustained
remission and GFR gradually deteriorated. Aged 17, a new renal biopsy showed progressive FSGS
(collapsing type). Six years after initial presentation haemodialysis was started, followed by a bilateral
nephrectomy because of persistent proteinuria (histology: ”end stage kidney”). His mother offered to
donate a kidney. Genetic analysis revealed a heterozygous polymorphism, R229Q, in NPHS2. The
mother carried the same polymorphism together with another heterozygous unknown splice mutation
c.873+7 A>G in intron 7. Since the R22Q polymorphism is found in 2-4% of the healthy population1
and mother had no proteinuria, she was accepted as a kidney donor. At the age of 19 renal
transplantation (RTx) was performed. Light microscopy (LM) of the baseline biopsy was normal, but
proteinuria (0.65g/day) re-occurred after a few days and disappeared after plasmapheresis (PP)
sessions. However, moderate proteinuria (1.2 gr/day recurred after PP discontinuation, while serum
creatinine remained stable +/- 1.5 mg/dl). An allograft biopsy 3 months post-RTx revealed no
significant light microscopic abnormalities. No peritubular C4d deposition or HLA antibodies
(Luminex) were found. Electron microscopy (EM) demonstrated podocyte foot effacement together
with multilayering (5-6 layers) of the basement membrane in 2 out of 10 randomly examined
peritubular capillaries (PTC). Repeat allograft biopsies, 4 and 7 months post-RTx, demonstrated
progressive basement membrane multilayering (5-6 layers) in 3 and 4 out of 10 PTC respectively,
suggesting the diagnosis of chronic rejection2, 3. As this histological diagnosis was clinically
unexpected, EM was also performed on the donor (baseline) biopsy. Remarkably, this also showed
basement membrane multilayering (5-6 layers) in 5 out of 10 PTC as well as focal podocyte foot
process effacement, indicating that the histological lesions were pre-existent in the asymptomatic
donor and were not related to rejection.
Conclusion:
1. We demonstrated that the finding of severe PTC basement membrane multilayering after RTx (5-6
layers in ≥3 random PTC) is not specific for chronic rejection and can be pre-existent. This raises the
question whether the definition of severe basement membrane multilayering of the PTC by Ivanyi et al
(= 7 layers in ≥1/10 PTC or 5-6 layers in ≥3 PTC) as a sign of chronic rejection2, 3 should be
reconsidered.
2. We furthermore describe PTC basement membrane multilayering together with podocyte
effacement in a non-proteinuric donor carrying heterozygous NPHS2 mutations. It is not clear whether
the re-occurrence of proteinuria in the recipient is related to the histological and genetic abnormalities.
1.
2.
3.
Caridi G, Gigante M, Ravani P, et al. Clinical features and long-term outcome of nephrotic syndrome associated
with heterozygous NPHS1 and NPHS2 mutations. Clin J Am Soc Nephrol. Jun 2009;4(6):1065-1072.
Ivanyi B. Transplant capillaropathy and transplant glomerulopathy: ultrastructural markers of chronic renal
allograft rejection. Nephrol Dial Transplant. Apr 2003;18(4):655-660.
Ivanyi B, Kemeny E, Szederkenyi E, Marofka F, Szenohradszky P. The value of electron microscopy in the
diagnosis of chronic renal allograft rejection. Mod Pathol. Dec 2001;14(12):1200-1208.