NHERF1 Loss Upregulates Enzymes of the Pentose Phosphate Pathway in Kidney Cortex

Round 1

Reviewer 1 Report

This work studies the role of NHERF1 in metabolism after cisplatin-induced AKI.

Allover I think the work is sound, the data are mostly negative but that does not bother this reviewer.

The abstract needs to be re-written, it reads like an abstract for a scientific meeting and I don't think antioxidants requires details about statistics etc in the abstract.

For me the biggest drawback and downside of this study is the fact that no Seahorse experiments were performed in both genotypes before and after cisplatin. This would have provided an interesting insight in terms of respiration before after AKI and a possible different response in NHERF knockout mice.

Is LDH different in plasma between genotypes?

This reviewer also thinks that there is room for improvement in terms of the Figures. The numbers should be bigger that one can actually read them, same is true for axis titles. Also better to have axis breaks when the scale doesn't start at Zero.

Might well be worth to measure ATP/UTP in the urine (correct by creatinine) and compare between genotypes under baseline conditions.

Possible to do a bit more analysis on mitochondria? Any better analysis of fission and fusion might be worth looking into. Suggest analysis of Drp1, Mfn1 and Mfn2 by WB.

"Merit Review Award Number R01DK083361 from the United States Department of Veterans Affairs BLR&D Service" I was not aware that the VA does now give out R01s.

Author Response

Please see attachment.

Author Response File: Author Response.pdf

Reviewer 2 Report

This study investigated the mechanism underlining NHERF1 loss. Male wild type (WT) and KO mice were used and treated with vehicle or cisplatin (20 mg/kg dose 28 IP). The rational behind the experiment was clear and straight forward. The manuscript is almost well written. 

While many different sources are used to set up the study in the introduction, little previous evidence is stated. The introduction is thus short and poorly sets up the rationale for the study. More attention to how this study fits into previous work in cisplatin’s mechanism of injury  and inflammation should be added to improve this section.

There are some minor grammar issues that should be fixed in order to aid the accessibility of the results to the reader.

Author Response

Please see attachment.

Author Response File: Author Response.pdf

Round 2

Reviewer 1 Report

Suggest removing headings like "Methods", "Results" etc from the abstract.

Suggest removing (-/-) after the NHERF1 because you don't ever use it again.