PONE-D-20-33791

Preadmission kidney function and risk of acute kidney injury in patients hospitalized with acute pyelonephritis: a Danish population-based cohort study

PLOS ONE

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Additional Editor Comments:

1.In your paper ,The criteria used for AKI definition as per the guidelines from KDIGO, AKI was defined as an at least 1.5 times relative increase  from preadmission sCr, a relative increase of at least 1.5 in sCr within a period of seven days, or an absolute  increase in sCr of at least 26.5 µmol/l within a period of 48 hours, I was curious how many cases where  diagnosed based on change in creatnine of at least  26.5 µmol/l and what  percentage were diagnosed based on relative increase in creatnine of at least 1.5 from baseline within a period of seven days .As during episode of  AKI creatnine values tend  to fluctuate before it reaches a steady state.

2.Most of the  time treatment in pyelonephritis varies from 7-14 days depending upon infection underlying condition and organism being treated, just curious to know why the criteria of 30-day risk of acute kidney injury was used. As shorter time frame linked to development of AKI immediately after development of pyelonephritis or to resolution of pyelonephritis makes the correlation easier to undestand  and clinically significant as anything later after resolution of pyelonephritis may add other factors in development of AKI

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Reviewers' comments:

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: This is a database study that looks at the incidence of AKI in patients admitted with pyelonephritis, stratified by pre-existing CKD. I think that on whole the conclusions support the data. I did notice that the female predominance of pyelonephritis increases with increasing GFR and the male:female ratio at the lowest eGFR was almost equal. That suggests that advanced CKD may predispose to pyelonephritis, which is an interesting observation. I am also interested by the 10% of cases that occurred more than a week after admission. This may be related to antibiotics but probably does not reflect the infection itself. These points should be addressed in the discussion.

Reviewer #2: **Please note that the authors have acknowledged that Danish law prohibits the sharing of health data, and this can only be accessed by researchers who meet specific criteria to access this confidential data.

I would like to thank the authors for their painstaking endeavor to provide an interesting insight into the association of AKI and acute pyelonephritis. I hope to offer some constructive criticism to enhance the scientific objectives of the authors:

Language and stylistic considerations:

Line 116 - "Measurements seven days before admission were not included to avoid preadmission eGFR being affected of acute illness due to pyelonephritis." - For the sake of clarity, please consider changing to ""Measurements in the seven days preceding admission were not included to avoid preadmission eGFR being affected of acute illness due to pyelonephritis."

Line 118 - "...assuming that all patients were Caucasian, which is a reasonable assumption to make of the Danish population." - This is probably a potential source of error for approximately 9% of the population that have a non-Western background (2017 statistics - citation below). I do not disagree with the authors pragmatic approach, but perhaps this potential (relatively minor) source of error could be included as a limitation of the study.

http://www.dst.dk/en/Statistik/emner/befolkning-og-valg/indvandrere-og-efterkommere/indvandrere-og-efterkommere

Line 242-243 - "A total of 89.3% of the AKI cases (i.e. 1,882 cases) 243 occurred within one week after hospital admission." - For the sake of clarity, please consider changing to "A total of 89.3% of the AKI cases (i.e. 1,882 cases) 243 occurred in the first week from the day of hospital admission." The latter sentence makes it clear that the AKI episode occurred relatively early after te acute illness was diagnosed. The original sentence might mislead readers into thinking that AKI may have occurred after the admission concluded (ie. after the patient was discharged).

Methodology / results considerations:

1. Obstructive nephropathy at baseline would be a major risk factor for both chronic kidney disease and for the subsequent development of pyelonephritis. Was this factor considered?

2. Nephrolithiasis, particularly when obstructive, could result in both AKI and pyelonephritis. This would be an important data point to tease out, if possible. Furthermore, even non-obstructive stones can serve as a nidus of infection and result in a higher likelihood of recurrence of infection (and possibly AKI).

In a retrospective analysis, the authors would be limited by the accuracy of ICD-10 data available from these hospitalizations, but I suspect many readers would also want to know if the above points were considered. If this data is not available or too cumbersome to obtain, please consider acknowledging it as potential limitations.

3. Another interpretation which the authors could consider mentioning is that 89.3% of cases of AKI were diagnosed within the first week from the day of admission, which can likely be attributed to sepsis. However, the remaining ~10% of cases do seem somewhat distant from the original septic insult to be directly attributed to acute pyelonephritis. While the authors do not speculate as to the *cause* of the AKI, it is plausible that potentially nephrotoxic agent exposure (IV contrast, certain antibiotics or NSAIDs for pain relief) may account for the delayed AKI cases. It is hard to say if all this needs to be included, but this could make for some thoughtful discussion, as long as the authors feel that it does not digress too far from their topic of research.

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Reviewer #1: No

Reviewer #2: Yes: Atul Bali, MD

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Preadmission kidney function and risk of acute kidney injury in patients hospitalized with acute pyelonephritis: a Danish population-based cohort study

PONE-D-20-33791R1

Dear Dr. Graversen,

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Kind regards,

Bhagwan Dass, MD

Academic Editor

PLOS ONE

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