Kidney Res Clin Pract.  2019 Jun;38(2):186-195. 10.23876/j.krcp.18.0134.

Renal tubular P-glycoprotein expression is reduced in plasma cell disorders

Affiliations
  • 1Division of Nephrology, Department of Internal Medicine, Dokuz Eylül University, Izmir, Turkey. heybelic@hotmail.com
  • 2Department of Pathology, Dokuz Eylül University, Izmir, Turkey.

Abstract

BACKGROUND
P-glycoprotein (P-gp) transports many chemicals that vary greatly in their structure and function. It is normally expressed in renal proximal tubular cells. We hypothesized that P-gp expression influences light chain excretion. Therefore, we investigated whether renal tubular P-gp expression is altered in patients with plasma cell disorders.
METHODS
We evaluated renal biopsy specimens from patients with plasma cell disorders (n = 16) and primary focal segmental glomerulosclerosis (the control group, n = 17). Biopsies were stained with an anti-P-gp antibody. Loss of P-gp expression was determined semi-quantitatively. Groups were compared for loss of P-gp expression, and clinical variables.
RESULTS
P-gp expression loss was more severe in patients with plasma cell disorders than it was in those with glomerulonephritis (P = 0.021). In contrast, clinical and histological parameters including serum creatinine, level of urinary protein excretion, and interstitial fibrosis/tubular atrophy grade were not significantly different between the groups. P-gp expression loss increased with age in patients with plasma cell disorders (P = 0.071). This expression loss was not associated with serum creatinine, the level of urinary protein excretion or the interstitial fibrosis/tubular atrophy grade. There was no significant association between the severity of P-gp expression loss with the types and serum levels of light chains, isotypes and serum immunoglobulin levels.
CONCLUSION
Renal tubular P-gp expression is significantly down-regulated in patients with plasma cell disorders characterized by nephrotic range proteinuria. Additional studies are needed to determine whether reintroduction of renal tubular P-gp expression would mitigate the proximal tubular injury that is caused by free-light chains.

Keyword

Amyloidosis; Immunoglobulin light chains; Multipl myeloma; P-glycoprotein

MeSH Terms

Amyloidosis
Atrophy
Biopsy
Creatinine
Glomerulonephritis
Glomerulosclerosis, Focal Segmental
Humans
Immunoglobulin Light Chains
Immunoglobulins
P-Glycoprotein*
Plasma Cells*
Plasma*
Proteinuria
Creatinine
Immunoglobulin Light Chains
Immunoglobulins
P-Glycoprotein
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