Alterations in Kidney Cells Could Predict Excess Protein in Urine, Study Suggests

Measuring structural features of specialized kidney cells called podocytes could predict short-term proteinuria — excess proteins in urine — in patients with ANCA-associated glomerulonephritis, according to a new study.

The research, “Podocytes and Proteinuria in ANCA-Associated Glomerulonephritis: A Case-Control Study,” appeared in the journal Frontiers in Immunology.

The degree of proteinuria has been associated with renal outcomes in patients with ANCA glomerulonephritis, a disease characterized by inflammation of the kidney’s filtering units (the glomeruli).

Proteinuria in kidney diseases is usually linked with alterations in podocytes, which are part of the filtration barrier of the glomerular wall. Podocytes have long projections — called foot processes — that wrap around capillaries and connect with foot processes from adjacent podocytes, creating a kind of mesh that filters blood.

Prior studies indicated that disease type, rather than the level of proteinuria, correlates with retraction of the podocytes’ foot processes. Yet, how such changes relate to proteinuria is still scarcely known.

Aiming to address this gap, a team from Europe and New Zealand analyzed the detailed structure and number of podocytes in kidney biopsies of 25 Caucasian patients with ANCA glomerulonephritis and their association with proteinuria at baseline and during follow-up.

The patients’ mean age at biopsy was 55.4 years. All had been followed at the Leiden University Medical Center, in the Netherlands. The most frequent disease subtype was granulomatosis with polyangiitis, in 16 patients. Proteinuria was assessed at 10 weeks and at one year of follow-up.

All patients were treated with prednisone, while all but one received the immunosuppressant cyclophosphamide, later switched to maintenance therapy with azathioprine in 17 patients. At one year of follow-up, the levels of proteinuria were lower in patients on angiotensin converting enzyme inhibitors than in those not receiving this type of treatment.

Patients whose biopsies were categorized as focal had the lowest level of proteinuria at baseline, but no differences across categories were found during follow-up. Of note, this classification system divides kidney biopsies into four groups based on the appearance of glomerular lesions.

Using electron microscopy, researchers observed that the width of podocytes’ foot process (FPW) did not differ comparing patients and the five controls. However, patients with higher proteinuria at baseline had higher FPW compared to the controls.

The data further revealed that proteinuria correlated with the podocytes’ FPW at 10 weeks, but not at one year. Also, the mean number of podocytes was significantly lower in patients compared to controls (15 versus 34 podocytes per glomerulus).

A subsequent analysis showed that biopsies from patients with lower FPW values were most often focal, while those with greater width were more commonly crescentic or mixed class. Yet, proteinuria levels in these two groups did not differ at baseline.

“Our study indicates that podocyte foot process width at baseline could be indicative for proteinuria at short-term follow up,” the scientists stated.

Cautioning that larger studies are required to better assess podocyte morphology in this patient population, the researchers suggested that, for prognosis, a description of the foot process width should be included in the diagnostic report of a biopsy with ANCA-associated glomerulonephritis.