Kidney Res Clin Pract 2019 Jun; 38(2): 186-195  
Renal tubular P-glycoprotein expression is reduced in plasma cell disorders
Cihan Heybeli1 , Mehmet Asi Oktan1 , Hayri Ustun Arda1 , Serkan Yildiz1 , Mehtat Unlu2 , Caner Cavdar1 , Aykut Sifil1 , Ali Celik1 , Sulen Sarioglu2 , Taner Camsari1
1Division of Nephrology, Department of Internal Medicine, Dokuz Eylül University, Izmir, Turkey
2Department of Pathology, Dokuz Eylül University, Izmir, Turkey
Correspondence to: Cihan Heybeli
Division of Nephrology, Department of Internal Medicine, Dokuz Eylül University, 35340 Narlıdere/Balçova, Izmir, Turkey. E-mail:
Received: November 6, 2019; Revised: February 19, 2019; Accepted: March 5, 2019; Published online: June 30, 2019.
© The Korean Society of Nephrology. All rights reserved.

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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.
Keywords: Amyloidosis, Immunoglobulin light chains, Multipl myeloma, P-glycoprotein


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