{
  "docId": "019dd923-622c-750b-8b97-5cb48bf2a635",
  "docSlug": "b8afd3741673",
  "documentTitle": "Chinook Therapeutics Inc (KDNY)",
  "authorId": "51_Muddy_Waters",
  "authorName": "Carson C. Block",
  "documentKindSlug": "research-note",
  "documentKindLabel": "Research note",
  "sourceTypeSlug": "short_seller",
  "sourceTypeLabel": "Short seller",
  "presentationDate": "2023-05-16 00:00:00",
  "orientation": "portrait",
  "aspectRatio": 0.77272725,
  "pageNumber": 7,
  "pageCount": 36,
  "prevPage": 6,
  "nextPage": 8,
  "slideType": "research-note",
  "function": "expose_contradiction",
  "density": "dense",
  "nDataPoints": 6,
  "notes": "The text argues that the rapid reversal of UACR effects upon drug cessation indicates a transient hemodynamic impact rather than structural renal improvement.",
  "elementsJson": [
    "paragraph",
    "footnote"
  ],
  "metadataConfidence": 0.95,
  "imagePath": null,
  "slideHref": "/slides/019dd923-622c-750b-8b97-5cb48bf2a635/7",
  "deckHref": "/decks/019dd923-622c-750b-8b97-5cb48bf2a635",
  "deckJsonHref": "/decks/019dd923-622c-750b-8b97-5cb48bf2a635.json",
  "deckAnchorHref": "/decks/019dd923-622c-750b-8b97-5cb48bf2a635#slide-7",
  "components": [
    {
      "bbox": null,
      "kind": "callout",
      "text": "These results are far more consistent with a frank hemodynamic effect of atrasentan: endothelin blockers increase kidney outflow more than they increase kidney inflow, without necessarily improving kidney filtration.",
      "attrs": null,
      "subkind": null,
      "toolName": "Visual emphasis",
      "toolSlug": "visual-emphasis",
      "confidence": null,
      "componentId": "019dd953-25b7-709e-b8cf-d10bec38e909",
      "frameworkName": null,
      "frameworkSlug": null
    },
    {
      "bbox": {
        "h": 0.15,
        "w": 0.78,
        "x": 0.11,
        "y": 0.09
      },
      "kind": "paragraph",
      "text": "The above table shows a remarkably rapid effect on albuminuria at the beginning and end of the treatment period. If albuminuria is, in this case, to be taken as an indicator of renal health, we should expect the albuminuria to (1) decline slowly after drug initiation, as the kidney improves, and (2) remain lower than at baseline after drug cessation. As we see, neither of these are the case: albuminuria declines sharply as soon as treatment is initiated, and then, more importantly, differences between groups disappear after drug cessation.",
      "attrs": null,
      "subkind": "paragraph",
      "toolName": null,
      "toolSlug": null,
      "confidence": null,
      "componentId": "577bb289-57f3-4f78-8ee6-967937b38ab4",
      "frameworkName": null,
      "frameworkSlug": null
    },
    {
      "bbox": {
        "h": 0.11,
        "w": 0.78,
        "x": 0.11,
        "y": 0.32
      },
      "kind": "paragraph",
      "text": "This seemingly is not the result we would see if we were looking at a drug that slowed renal decline, because patients’ kidneys are working no better than placebo patients’ after the trial ends. These results are far more consistent with a frank hemodynamic effect of atrasentan: endothelin blockers increase kidney outflow more than they increase kidney inflow, without necessarily improving kidney filtration. The result is an elevated risk of heart failure, due likely to anemia, fluid retention, and resulting cardiac stress, with no real efficacy for kidney repair.",
      "attrs": null,
      "subkind": "paragraph",
      "toolName": null,
      "toolSlug": null,
      "confidence": null,
      "componentId": "d6a9627c-10c5-4bae-a652-ae70100db439",
      "frameworkName": null,
      "frameworkSlug": null
    },
    {
      "bbox": {
        "h": 0.08,
        "w": 0.78,
        "x": 0.11,
        "y": 0.23
      },
      "kind": "paragraph",
      "text": "At the end of the 30-day follow-up period without study medication, the median UACRs were 737±912 mg/g, 1051±1206 mg/g, and 727±821 mg/g for the placebo, 0.75 mg/d, and 1.25 mg/d groups, respectively. The geometric mean changes from baseline to recovery were -5.3%, +4.3%, and -7.8% for the placebo, 0.75 mg/d, and 1.25 mg/d groups, respectively, thus showing that UACR values returned to baseline values.",
      "attrs": null,
      "subkind": "paragraph",
      "toolName": null,
      "toolSlug": null,
      "confidence": null,
      "componentId": "e0f60d3f-ede1-4d75-883f-6c8dc286ffb2",
      "frameworkName": null,
      "frameworkSlug": null
    },
    {
      "bbox": {
        "h": 0.09,
        "w": 0.78,
        "x": 0.11,
        "y": 0.44
      },
      "kind": "paragraph",
      "text": "The UACR data from SONAR manifests the same effect. It is important to note that in SONAR, the median treatment period was 2.2 years, so atrasentan had considerably more time to exert its rehabilitative influence on patients’ kidneys than it did in RADAR’s 84-week treatment period. Nevertheless, all UACR differences between groups disappear within six weeks of treatment cessation, again suggesting an effect on the biomarker (serum creatinine) that is not accompanied by any real slowing of kidney decline.",
      "attrs": null,
      "subkind": "paragraph",
      "toolName": null,
      "toolSlug": null,
      "confidence": null,
      "componentId": "f729fb4c-9481-4175-821e-5b57a6fcab77",
      "frameworkName": null,
      "frameworkSlug": null
    },
    {
      "bbox": {
        "h": 0.05,
        "w": 0.6,
        "x": 0.11,
        "y": 0.88
      },
      "kind": "source-note",
      "text": "50 https://journals.lww.com/jasn/Fulltext/2014/05000/The_Endothelin_Antagonist_Atrasentan_Lowers.27.aspx\n51 https://repo.dma.dp.ua/6035/1/SONAR.pdf, see Appendix.",
      "attrs": null,
      "subkind": null,
      "toolName": null,
      "toolSlug": null,
      "confidence": null,
      "componentId": "4b55a547-b1fa-4abd-9fc7-b2e75aaef57d",
      "frameworkName": null,
      "frameworkSlug": null
    }
  ],
  "metrics": [],
  "tools": [],
  "frameworks": [],
  "arcBeats": [
    {
      "to": 15,
      "from": 6,
      "beatId": "7c7d9806-d739-4215-b62f-052b350305ec",
      "arcName": "Overcoming the Monster",
      "arcSlug": "overcoming-monster",
      "beatName": "The Struggle",
      "beatSlug": "overcoming-monster-the-struggle",
      "evidence": "The report presents the 'struggle' of analyzing the data and identifying issues",
      "position": 1,
      "confidence": 0.8,
      "parentBeatName": "Development",
      "parentBeatSlug": "development"
    }
  ],
  "loops": [
    {
      "to": 15,
      "from": 6,
      "name": "Pattern Hunter",
      "slug": "02-pattern-hunter",
      "bestFor": "Time-pressed audiences, building consensus, when data is strong",
      "matchId": "437b3fa7-133f-4a21-908b-7e42915fbdb3",
      "evidence": "The report presents a series of data analyses that reveal inconsistencies",
      "position": 0,
      "objective": "To identify patterns in the data that suggest issues with the trial results",
      "structure": "Evidence A -> Evidence B -> Evidence C -> Pattern/Conclusion",
      "confidence": 0.7,
      "description": "Group multiple pieces of evidence that together point to a pattern or conclusion"
    }
  ],
  "imagePathAlt": null,
  "thumbSrc": null,
  "thumbSrcAlt": null,
  "locked": true
}