Abstract: PO2167
A Potential Mechanism of Distal Renal Tubular Acidosis in Patients Treated with Immune Checkpoint Inhibitors
Session Information
- Onco-Nephrology - 1
October 22, 2020 | Location: On-Demand
Abstract Time: 10:00 AM - 12:00 PM
Category: Onco-Nephrology
- 1500 Onco-Nephrology
Authors
- Herrmann, Sandra, Mayo Foundation for Medical Education and Research, Rochester, Minnesota, United States
- Alexander, Mariam P., Mayo Foundation for Medical Education and Research, Rochester, Minnesota, United States
- Romero, Michael F., Mayo Foundation for Medical Education and Research, Rochester, Minnesota, United States
- Zand, Ladan, University of Minnesota, Minneapolis, Minnesota, United States
Background
The main cause of acute kidney injury in patients on immune check point inhibitors(ICI) is acute interstitial nephritis(AIN). However, as their use continues to increase, we observe other renal manifestations being described. Distal renal tubular acidosis(dRTA) has been described, but the mechanism is not clear to date. We hypothesized that an alteration of H+-ATPase or anion exchanger(AE-1) in alpha intercalated cells(α-IC) in collecting duct is affected.
Methods
We present two patients with AIN and dRTA secondary to ICI: Patient#1 with metastatic adenocarcinoma of lung and patient#2 with metastatic melanoma, both treated with anti-PD1-antibodies(pembrolizumab/nivolumab). They had prominent electrolytes abnormalities consistent with dRTA(Figure 1A). Kidney biopsy was performed in each patient which showed diffuse AIN with negative routine immunofluorescence(IF) staining. Both patients had received PPI in addition to ICI therapy and had improvement in their kidney function following steroid therapy and with discontinuation of the drugs. In order to investigate the potential mechanism for developing dRTA, the kidney biopsy frozen sections from patients#1 and#2 were further stained by indirect IF for acid-base transporters in α-IC(α4 and B1)subunits of the vacuolar H+-ATPase(V-ATPase) and the AE1. In order to quantify the staining, data were normalized to a T0 allograft biopsy as control.
Results
α-IC cell markers were decreased in both patients compared to the control as shown in Figure1B. Quantification of AE1,B1-V-ATPase and A4-V-ATPase were all reduced compared to control biopsy, however, staining for other markers of a-IC(c-kit) were not reduced. This suggests a more targeted reduction in V-ATPase subunits that may be immune-mediated.
Conclusion
The reduction in staining for V-ATPase subunit could be related to damage from AIN, however, an immune-mediated process that reduces the expression of V-ATPase in α-IC is likely. Comparing staining of V-ATPase in α-IC in patients with AIN secondary to ICI with and without dRTA in the future will be useful.
Funding
- NIDDK Support