APPLIED AKI & CRITICAL CARE NEPHROLOGY · VOLUME 5

Chapter 1

Defining & Staging

Acute Kidney Injury

●Orientation & Knowledge◆Visualise & Map■Clinical Reasoning▲Safety & Evidence★Patient Decisions✓Apply & Test

Chapter Preamble

Signals declared

Sig-D — Diagnostic (primary). The chapter's work is to define acute kidney injury, separate it from its mimics, and stage it reproducibly from a creatinine change and a urine-output trend.
Sig-V — Evidence-dense (secondary). The KDIGO thresholds, the prognostic weight of each stage, and the standing of damage biomarkers rest on large cohorts and consensus statements, so the chapter grades what it asserts and fires the absolute-risk table.

Levels populated and omitted

Populated (17): L1–L5, L7, L8, L10–L14, L18–L22. The diagnostic spine drives the reference tables, decision rules, cases, pitfalls, and board items; the evidence signal drives the absolute-risk table (L14) and reflective prompts (L21).

L6 concept maps — omitted. No Sig-M; this chapter classifies and detects rather than explaining pathophysiology, which Chapters 2 and 7 carry.
L9 implications triads — omitted. Mechanism-to-action triads need a mechanistic spine the definition chapter does not build.
L15 / L16 preference-sensitive map and SDM scripts — omitted. Staging is effective care, not a values-driven choice (no Sig-E); the shared-decision content sits in the capstone, Chapter 18.
L17 documentation templates — omitted. No procedure or prescription generates a standalone note here; the staging note folds into the L18 cheat sheet.

● Phase A Orientation & Knowledge

Phase A · Level 1

Learning Objectives

By the end of this chapter you should be able to:

Apply the KDIGO 2012 criteria to label a patient as having AKI from a creatinine change, a urine-output trend, or both.
Stage AKI 1 to 3 from the worst creatinine ratio and the urine-output record, and state what each stage should trigger in monitoring and referral.
Explain why serum creatinine lags injury, and predict the situations in which it over- or under-estimates the true GFR.
Separate true AKI from a pseudo-rise in creatinine caused by drugs that block tubular secretion, and avoid mislabelling.
Choose between functional and damage biomarkers for a given question, and interpret a damage-positive, creatinine-negative result.
Place a patient on the AKI–AKD–CKD continuum using the time elapsed and the trajectory.
Estimate a missing baseline creatinine defensibly, and name the error each method introduces.

Phase A · Level 2

Executive Summary

AKI is a syndrome — an abrupt fall in GFR captured through a lagging surrogate (creatinine) and a function marker (urine output) — not a diagnosis in itself.
KDIGO sets three independent triggers; meeting any one is enough: a rise of at least 0.3 mg/dL in 48 hours, a rise to at least 1.5 times baseline within 7 days, or urine output below 0.5 mL/kg/h for at least 6 hours.
Stage on the worst value the patient reaches, not the value on the chart when you happen to look.
Creatinine is a late, lagging, muscle-dependent marker; a “normal” creatinine in a frail, cachectic, or cirrhotic patient can hide a halved GFR.
In non-steady-state AKI the measured creatinine always trails the real GFR, so a flat early value does not exclude evolving injury.
Urine output is the more sensitive trigger and often flags AKI hours before creatinine moves, but it is the less specific one.
Several drugs — trimethoprim, cimetidine, cobicistat, dolutegravir — raise creatinine by blocking its tubular secretion without touching GFR. That is pseudo-AKI, not AKI.
Damage biomarkers (NGAL, KIM-1, TIMP-2×IGFBP7) detect tubular stress before creatinine rises; cystatin C is a muscle-independent function marker.
A damage-positive, creatinine-negative result — “subclinical AKI” — carries a worse prognosis than a double-negative; the injury is real even when function looks preserved.
Higher AKI stage predicts higher in-hospital death, more dialysis, and more long-term CKD: a graded dose-response, not a single threshold.
AKI (up to 7 days), AKD (7 to 90 days), and CKD (beyond 90 days) form one continuum; a patient can move between them.
A defensible baseline matters more than a perfect one: a prior outpatient value beats a back-calculated estimate, which beats nothing.
Staging is reproducible effective care — it standardises who gets watched, who gets referred, and whose nephrotoxins get stopped.

Phase A · Level 3

Main Narrative

A rising creatinine is a question, not an answer. It tells you the kidney's clearance has fallen; it does not tell you when, why, or how far. The discipline of defining and staging acute kidney injury is the discipline of turning one noisy number into a label the next clinician will read exactly as you did. Get the label right and the rest of the work — finding the cause, protecting what remains, deciding on support — has somewhere to stand.

What counts as AKI

Ask first: has clearance fallen abruptly? KDIGO 2012 answers with three independent triggers, and meeting a single one is sufficient. The first is a rise in serum creatinine of at least 0.3 mg/dL (26.5 µmol/L) over 48 hours — a deliberately small step, chosen because even modest absolute rises predict harm. The second is a rise to at least 1.5 times a baseline known or presumed to fall within the prior seven days. The third is urine output under 0.5 mL/kg/h sustained for six hours or more. The creatinine triggers and the urine-output trigger are alternatives, not partners: a patient making no urine after surgery has AKI before any laboratory result returns.

The two windows do different jobs. The 48-hour window catches a fast, large absolute jump; the seven-day window catches a slower relative climb a single 48-hour snapshot would miss. Apply both, and stage on whichever is met.

How to stage it — and why the stage is the prognosis

Stage on the worst value the patient reaches, not the one on the chart when you review. Stage 1 is a creatinine 1.5 to 1.9 times baseline, or that 0.3 mg/dL absolute rise, or urine output below 0.5 mL/kg/h for six to twelve hours. Stage 2 is 2.0 to 2.9 times baseline, or oliguria for twelve hours or more. Stage 3 is a tripling of creatinine, or a rise to 4.0 mg/dL or higher, or the start of dialysis at any creatinine, or urine output below 0.3 mL/kg/h for a full day, or anuria for twelve hours. Note the asymmetry: any patient who needs dialysis is stage 3 whatever their number, because the decision to support has already declared the severity.

Staging is not bureaucracy. The stage is the prognosis, and it is graded — each step up carries more in-hospital death, more dialysis, more residual CKD. So the stage should change what you do: tighten monitoring, stop the nephrotoxins, review the drug chart for renal dosing, and decide whether this is a nephrology referral or a critical-care conversation.

Why creatinine misleads

Creatinine is convenient and almost always wrong about timing. It is generated from muscle at a roughly constant rate and cleared by filtration, so its level reflects the balance of production and clearance — but only at steady state. Injure the kidney and creatinine does not jump; it climbs over a day or two as the unexcreted load accumulates. During that climb — the creatinine-blind window — the measured value understates the loss of GFR, sometimes badly. A patient whose GFR fell to near zero this morning may still show a near-normal creatinine this afternoon.

Production is the other trap. Less muscle means less creatinine, so the elderly, the cachectic, the cirrhotic, and the spinal-cord-injured run low baselines; their “normal” 0.8 mg/dL may represent a GFR you would accept in no one else, and a rise to 1.6 (still “normal” on many printouts) is a doubling. Dilution compounds this: aggressive resuscitation expands the volume creatinine distributes through, blunting the measured rise just when injury is worst. Wait for creatinine to look abnormal in these patients and you will be late.

When the number lies: pseudo-AKI and the differential of a rising creatinine

Before calling a rising creatinine AKI, ask whether clearance actually changed. Some drugs raise creatinine by blocking its secretion into the tubule — trimethoprim, cimetidine, cobicistat, dolutegravir — so filtered GFR is untouched while the number climbs by 0.2 to 0.4 mg/dL within days of starting the drug, then plateaus. The tell is the pattern: a small, early, stable bump with no change in urine output, no electrolyte disturbance, and a stable cystatin C. Mislabel it as AKI and you may stop a needed antibiotic or launch a fruitless work-up.

The differential of a rising creatinine therefore has three branches: a real fall in GFR (true AKI), a blocked secretion or assay interference (pseudo-AKI), and a falling production or dilution masking a real fall (the hidden AKI of the low-muscle patient). The first needs a work-up, the second needs recognition, the third needs a function marker that does not depend on muscle.

Which tests change management

Urine output earns its place as a criterion because it moves first. Falling output flags hypoperfusion or obstruction hours before creatinine accumulates, which is why hourly, weight-based measurement — usually via a catheter in the unstable patient — buys time. Its weakness is specificity: a volume-deplete patient appropriately conserving water will be oliguric without intrinsic injury, so read it alongside the clinical picture, never alone.

Biomarkers split by the question they answer. If you are asking how well the kidney is filtering now, that is function — creatinine and cystatin C, the latter useful precisely because it does not depend on muscle. If you are asking whether the tubule is being injured, that is damage — NGAL, KIM-1, IL-18, and the cell-cycle-arrest pair TIMP-2×IGFBP7, which rise within hours of stress. Together they define four quadrants: both normal (no AKI); function down, damage up (overt AKI); function down, damage normal (haemodynamic or pseudo-AKI); and the one that changed practice — function normal, damage up, “subclinical AKI,” where the creatinine is reassuring and the prognosis is not.

Baseline quietly determines all of the above, because every stage is a ratio. If a recent stable outpatient creatinine exists, use it. If not, the lowest inpatient value can serve once the patient is at steady state. Back-calculating a baseline from an assumed GFR of 75 mL/min is the last resort: it manufactures a number and misclassifies anyone whose true baseline differs, usually over-calling AKI in patients who already have CKD.

From AKI to AKD to CKD

One injury, one timeline, three labels. AKI is the abrupt insult and its first seven days. If dysfunction or damage persists but has not yet crossed three months, that is acute kidney disease (AKD) — the convalescent zone KDIGO named to stop these patients vanishing between the acute ward and the CKD clinic. Past ninety days of persistent abnormality, the label is CKD. A patient can travel the whole road or stall anywhere on it, and the same creatinine means something different depending on where in time you are standing.

Where the evidence is firm, and where it is not

The thresholds themselves are consensus, not trial outputs: no randomised study assigned patients to a 0.3 versus a 0.5 mg/dL cut-off. Their justification is that large observational cohorts show these cut-offs separate risk, and the staging system's prognostic gradient — more stage, more death — is one of the most reproduced findings in the field, holding across surgical, medical, and critical-care populations. That part is firm.

Less settled is what to do with the biomarkers. That they predict outcomes is well supported by observational data; whether acting on a damage-positive, creatinine-negative result improves those outcomes is not yet established by interventional trials, and availability and cost vary widely. Treat them as prognostic refinements that sharpen suspicion, not as a licence to start therapy a creatinine would not yet justify.

Phase A · Level 4

Reference Tables

Table 1.1 — KDIGO diagnostic triggers (any one is sufficient)

Diagnostic trigger	Threshold to meet	Time window
Absolute creatinine rise	≥ 0.3 mg/dL (≥ 26.5 µmol/L)	Within 48 hours
Relative creatinine rise	≥ 1.5 × baseline	Known/presumed within 7 days
Urine output	< 0.5 mL/kg/h	Sustained ≥ 6 hours

Table 1.2 — KDIGO staging (stage on the worst value reached)

Stage	Serum creatinine criterion	Urine-output criterion
1	1.5–1.9 × baseline, or ≥ 0.3 mg/dL absolute rise	< 0.5 mL/kg/h for 6–12 h
2	2.0–2.9 × baseline	< 0.5 mL/kg/h for ≥ 12 h
3	≥ 3.0 × baseline, or ≥ 4.0 mg/dL, or any start of dialysis	< 0.3 mL/kg/h for ≥ 24 h, or anuria ≥ 12 h

Table 1.3 — Function versus damage markers

Marker	Type	What it tells you	Main caveat
Serum creatinine	Function	Filtration, at steady state	Lags injury; muscle-dependent
Cystatin C	Function	Filtration, muscle-independent	Shifts with steroids, thyroid, inflammation
NGAL	Damage	Tubular stress and injury	Also rises with systemic inflammation
KIM-1	Damage	Proximal tubular injury	Limited point-of-care availability
TIMP-2×IGFBP7	Damage (stress)	Cell-cycle arrest; early risk	Predicts risk, not yet a treatment trigger

Table 1.4 — Why a creatinine can mislead, and what to do

Pattern	Mechanism	Bedside response
Falsely reassuring (low muscle)	Reduced creatinine generation	Stage from the true baseline; consider cystatin C
Falsely reassuring (dilution)	Volume expansion after resuscitation	Do not exclude AKI on a flat creatinine
Falsely alarming (pseudo-AKI)	Drug blocks tubular secretion	Recognise the drug; recheck the pattern
Lagging (non-steady state)	Accumulation not yet complete	Trend it; lean on urine output and damage markers

Table 1.5 — The AKI–AKD–CKD continuum

Label	Time frame	Defining feature
AKI	≤ 7 days	Abrupt drop in GFR meeting KDIGO criteria
AKD	7–90 days	Persistent dysfunction/damage not yet chronic; includes resolving AKI
CKD	> 90 days	Sustained abnormality of function or structure

Table 1.6 — Setting a baseline creatinine

Method	When to use	Error it introduces
Recent stable outpatient value	Available and steady	Smallest; preferred
Lowest inpatient value	No outpatient value; patient at steady state	May reflect early injury and over-stage
Back-calculation (assume GFR 75)	Nothing else exists	Over-calls AKI in pre-existing CKD

◆ Phase B Visualise & Map

Phase B · Level 5

Imaging & Flowchart Specifications

Figure 1.1 — The creatinine-blind window

Figure 1.2 — The function/damage quadrant

Flowchart 1.A — Is this AKI, and what stage?

Phase B · Level 7

Decision Pathways

IF a creatinine rises by ≥ 0.3 mg/dL within 48 hours, THEN the patient has AKI — even if the value is still within the laboratory's normal range.

IF the patient is oliguric (< 0.5 mL/kg/h for ≥ 6 h), THEN diagnose and stage AKI now; do not wait for creatinine to confirm it.

IF a baseline creatinine is unknown, THEN estimate it explicitly and record which method you used, because every stage is a ratio to that baseline.

IF a small, stable creatinine rise follows a new dose of trimethoprim, cimetidine, cobicistat, or dolutegravir with nothing else changed, THEN suspect pseudo-AKI and confirm with cystatin C before relabelling as AKI.

IF the patient is cirrhotic, cachectic, elderly, or paraplegic, THEN treat a “normal” creatinine as suspect and stage from the true baseline or a muscle-independent marker.

IF the creatinine ratio and the urine-output record point to different stages, THEN assign the higher stage.

IF dialysis is started, THEN the patient is stage 3 regardless of the creatinine at that moment.

IF a damage biomarker is positive while creatinine is normal, THEN treat the patient as higher-risk and intensify monitoring, but do not start kidney-specific therapy a creatinine would not justify.

Clinical Reasoning

■ Phase C Clinical Reasoning

Phase C · Level 8

Clinical Cases

CASE 1POST-OPERATIVE OLIGURIA

The number that hadn't moved yetStaging from urine output before creatinine confirms it

Presentation

A 68-year-old man is six hours out from open aortic repair. Hourly urine output has been 18, 15, 12, then 10 mL over the last four hours; he weighs 80 kg. The 06:00 creatinine is 0.9 mg/dL, unchanged from baseline.

❖ Pause and reflect

Does this patient have AKI, and if so what stage — when his creatinine has not budged?

Analysis

Output has averaged under 0.2 mL/kg/h for several hours, well below the 0.5 mL/kg/h × 6 h threshold. He meets the urine-output criterion for AKI now, and at under 0.3 mL/kg/h approaching 24 h he is heading for stage 3 by output alone. The flat creatinine is the blind window, not reassurance: clearance may have fallen hours ago and the value simply has not caught up.

Plan

Diagnose AKI on the output criterion. Assess and correct perfusion — volume status, cardiac output, intra-abdominal pressure, catheter patency. Stop and review nephrotoxins, dose drugs for a low GFR, and trend creatinine knowing it will lag. Escalate to critical care given the trajectory.

Teaching point

Urine output is the early-warning criterion. Waiting for creatinine in a post-operative oliguric patient costs you the hours when intervention matters most.

Cross-reference

Exercises rules R2 and R6; the lag is Figure 1.1.

CASE 2THE CREATININE BUMP

A rise that wasn't injuryRecognising pseudo-AKI

Presentation

A 34-year-old woman with a urinary tract infection started trimethoprim-sulfamethoxazole four days ago. Creatinine has risen from 0.7 to 1.0 mg/dL. She feels well, urine output is normal, and potassium and bicarbonate are unchanged.

❖ Pause and reflect

Is this AKI — and would you stop the antibiotic?

Analysis

The pattern argues against true injury: a small, early rise that has plateaued, no oliguria, no electrolyte disturbance, beginning just after a drug that blocks creatinine's tubular secretion. Trimethoprim competes for the same transporter, raising the measured creatinine while filtration is unchanged. A cystatin C, which does not use that pathway, would be expected to sit normal.

Plan

Do not reflexively stop a working antibiotic. Confirm the mechanism with cystatin C if available, document the suspected pseudo-rise, and expect the creatinine to return to baseline within days of finishing the course.

Teaching point

Not every rising creatinine is AKI. A drug history reframes the number before a work-up does.

Cross-reference

Exercises rule R4; the false-alarm row of Table 1.4.

CASE 3THE 'NORMAL' CREATININE

Hidden injury in a low-muscle patientStaging from the true baseline

Presentation

A 72-year-old man with cirrhosis and visible muscle wasting is admitted with diarrhoea. Creatinine is 1.3 mg/dL; a clinic value two months ago was 0.6 mg/dL. He is making 0.4 mL/kg/h of urine.

❖ Pause and reflect

His creatinine is barely above the lab's upper limit — is he in AKI, and what stage?

Analysis

Against his own baseline of 0.6, a value of 1.3 is more than double — stage 2 by the creatinine ratio, and his output also meets stage 1. The lab's generic “normal” range is irrelevant; in a wasted cirrhotic, low creatinine generation means even a halved GFR can read “normal.” He likely has hepatorenal physiology or volume depletion on a perilously low reserve.

Plan

Stage as AKI 2 from the personal baseline. Treat volume status, hold diuretics and nephrotoxins, and escalate the hepatorenal work-up. Track him with a muscle-independent lens — cystatin C, or where available a measured clearance — rather than the raw creatinine.

Teaching point

Stage against the patient's own baseline, never the laboratory's reference interval. The frailest kidneys hide behind the most innocent-looking numbers.

Cross-reference

Exercises rule R5; the falsely-reassuring rows of Table 1.4.

CASE 4FLAT CURVE, RISING MARKER

Subclinical AKI in sepsisReading the function/damage mismatch

Presentation

A 55-year-old woman with pneumonia and septic shock has a stable creatinine at 0.9 mg/dL and adequate urine output on noradrenaline. A urinary TIMP-2×IGFBP7 sent on the unit's protocol returns markedly elevated.

❖ Pause and reflect

She does not meet a KDIGO trigger. Is anything wrong with her kidneys, and does the marker change anything?

Analysis

By creatinine and output she has no AKI. But the damage marker says her tubules are under cell-cycle-arrest stress — the subclinical quadrant, function normal but damage positive. Cohorts show these patients carry a higher risk of progressing to overt AKI and worse outcomes than the double-negative patient. The marker is prognostic, not yet a therapeutic trigger.

Plan

Do not relabel her as AKI on the biomarker alone, but treat her as high-risk: optimise haemodynamics, scrub the drug chart for nephrotoxins, avoid contrast where you can, and monitor creatinine and output more closely than the protocol minimum. Reserve kidney-specific escalation for when a KDIGO trigger actually fires.

Teaching point

A positive damage marker with a normal creatinine is a warning, not a diagnosis — it sharpens vigilance without licensing treatment the function data do not support.

Cross-reference

Exercises rule R8; the subclinical quadrant of Figure 1.2; the evidence caveat in L13.

Phase C · Level 10

Clinical Pearls

A creatinine inside the “normal” range can still be AKI — the 0.3 mg/dL trigger is absolute, not a breach of the reference interval.

Stage on the worst value, not the latest value.

Urine output flags AKI earliest; creatinine confirms it latest.

Any patient started on dialysis is stage 3, whatever the creatinine reads.

Every stage is a ratio — so an unknown baseline is a clinical problem, not a clerical one.

In the cachectic, cirrhotic, or elderly, a low creatinine is a low signal, not a healthy kidney.

Fluid resuscitation dilutes creatinine; a flat value during a big resuscitation does not exclude injury.

A small, stable creatinine bump just after trimethoprim or cimetidine is usually pseudo-AKI.

Cystatin C earns its keep when muscle mass makes creatinine untrustworthy.

Damage markers rise in hours; function markers rise in days.

Damage-positive, creatinine-negative is the worst-prognosis quadrant creatinine alone cannot see.

A damage biomarker predicts risk; it does not yet authorise treatment.

Oliguria is sensitive but not specific — a volume-deplete patient conserves water without intrinsic injury.

Back-calculating a baseline from GFR 75 over-calls AKI in anyone with pre-existing CKD.

The seven-day window catches slow climbs the 48-hour window misses; apply both.

AKD is the convalescent label that keeps recovering AKI patients from disappearing before the CKD clinic.

Safety & Evidence

▲ Phase D Safety & Evidence

Phase D · Level 11

Red Flags & Never-Do

Panel A — Red flags

▲

Anuria — no urine at all — points to obstruction, a vascular catastrophe, or cortical necrosis until proven otherwise; image and decompress without delay.

▲

A creatinine doubling inside 24 hours signals a severe, fast insult — rhabdomyolysis, major haemodynamic collapse, obstruction — so escalate, do not observe.

▲

AKI with hyperkalaemia, a rising potassium, or an ECG change is an emergency regardless of stage.

▲

Oliguria that persists despite restored perfusion suggests established intrinsic injury, not pre-renal physiology — stop chasing it with fluid.

▲

A “normal” creatinine in a shocked or wasted patient with falling output — trust the output and the trajectory, not the number.

Panel B — Never do

✖ NEVER — exclude AKI because the creatinine is within the reference range.

✖ NEVER — wait for creatinine to rise before acting on documented oliguria.

✖ NEVER — stage AKI without first establishing or explicitly estimating the baseline.

✖ NEVER — label a rising creatinine as AKI before excluding a secretion-blocking drug.

Phase D · Level 12

Common Pitfalls

Pitfall 1 — The reference-interval trap

✖

WRONG Reporting “no AKI — creatinine normal at 1.1” when it rose from 0.7 two days ago.

✓

RIGHT Calling AKI on the 0.4 mg/dL, > 1.5× rise, even though 1.1 looks normal.

✉

WHY KDIGO triggers score changes from baseline, not breaches of a reference interval.

Pitfall 2 — Staging from the latest value

✖

WRONG Staging from the creatinine on the chart at the moment of review.

✓

RIGHT Staging from the worst value the patient reached in the episode.

✉

WHY Severity is defined by the peak insult; the current value may already be recovering.

Pitfall 3 — The reflexive drug stop

✖

WRONG Stopping a working antibiotic the moment creatinine ticks up by 0.3.

✓

RIGHT Checking first whether the drug blocks creatinine secretion and the pattern fits pseudo-AKI.

✉

WHY Pseudo-AKI looks like AKI on the number but spares GFR; a reflexive stop causes harm.

Pitfall 4 — Reassured by dilution

✖

WRONG Accepting a flat creatinine as proof the kidneys are fine during a 6-litre resuscitation.

✓

RIGHT Treating dilution as a confounder and leaning on urine output and the trend.

✉

WHY Volume expansion lowers measured creatinine independent of GFR.

Pitfall 5 — Treating the biomarker

✖

WRONG Starting kidney-protective therapy because a damage biomarker came back high.

✓

RIGHT Using the marker to raise vigilance while waiting for a function criterion to fire.

✉

WHY Damage markers are prognostic; no trial yet shows that treating on them improves outcomes.

Phase D · Level 13

Evidence Grading

GRADE

HIGH CONFIDENCE

The effect is real and the estimate is stable.

RCTs at low risk of bias; multiple concordant prospective cohorts; meta-analyses.

GRADE

MODERATE CONFIDENCE

The effect is likely real but may shift with new data.

Observational studies, registries, mechanistic human studies.

GRADE

LOW CONFIDENCE

Rests on physiology, reasoning, or consensus rather than outcomes.

Pathophysiological reasoning; extrapolation; consensus without outcomes.

Graded statements (by evidence type)

Statement	Grade	Basis (evidence type)
Higher AKI stage predicts higher mortality, dialysis, and later CKD in a graded fashion.	A	Large concordant observational cohorts across populations
A ≥ 0.3 mg/dL rise carries prognostic weight even within the normal range.	B	Observational cohorts; the threshold itself is consensus-set
The specific KDIGO cut-offs are the single optimal ones.	C	Consensus definition, not a head-to-head trial
Damage biomarkers detect injury before creatinine and predict outcomes.	B	Prospective observational and diagnostic-accuracy studies
Acting on a damage-positive, creatinine-negative result improves outcomes.	C	No adequately powered interventional trial yet
Cystatin C estimates GFR with less muscle-mass bias than creatinine.	B	Comparative observational and physiological studies
Urine-output criteria detect AKI earlier but less specifically than creatinine.	B	Observational critical-care cohorts

Patient Decisions

★ Phase E Patient Decisions

Phase E · Level 14

Absolute Risk in Natural Frequency

These are natural-frequency estimates for orientation, drawn from pooled observational cohorts; they vary by cause, comorbidity, and setting. They show the prognostic gradient that makes staging worth doing, expressed as how many of 100 comparable patients are affected.

Per 100 hospitalised patients with…	Outcome	Roughly how many	See
Stage 1 AKI	Die in hospital	About 10–15 in 100	Table 1.2
Stage 3 AKI	Die in hospital	About 30–50 in 100	Table 1.2
Stage 3 AKI	Need acute dialysis	About 20–30 in 100	Rule R7
AKI of any stage, surviving to discharge	Have CKD at one year	About 25–30 in 100	Table 1.5
Damage-positive, creatinine-negative	Progress to overt AKI	More than the double-negative group	Figure 1.2 / L13

★ How to read these

Read these as orientation, not promises. The numbers move with cause, comorbidity, and setting; what is stable is the direction — every step up the stage ladder costs survival and kidney function. Communicate them as people out of 100, never as a hazard ratio.

Apply & Test

✓ Phase F Apply & Test

Phase F · Level 18

Cheat Sheet

AKI = any one of: ≥ 0.3 mg/dL / 48 h · ≥ 1.5× baseline / 7 d · UO < 0.5 mL/kg/h ≥ 6 h.

Stage 1: 1.5–1.9× or +0.3 mg/dL · UO < 0.5 for 6–12 h.

Stage 2: 2.0–2.9× · UO < 0.5 for ≥ 12 h.

Stage 3: ≥ 3× or ≥ 4.0 mg/dL or any dialysis · UO < 0.3 for ≥ 24 h or anuria ≥ 12 h.

Stage on the worst value reached.

Higher stage = higher mortality, dialysis, and CKD.

Creatinine lags injury 24–48 h — the blind window.

Low muscle (cirrhosis, cachexia, age, paraplegia) → low creatinine, hidden AKI.

Fluid resuscitation dilutes creatinine — do not be reassured.

Pseudo-AKI: trimethoprim, cimetidine, cobicistat, dolutegravir — secretion blocked, GFR intact.

Cystatin C = muscle-independent function marker.

Damage markers (NGAL, KIM-1, TIMP-2×IGFBP7) rise first; prognostic, not a treatment trigger.

Baseline: outpatient value > lowest inpatient value > back-calculation (over-calls in CKD).

AKI ≤ 7 d → AKD 7–90 d → CKD > 90 d.

Phase F · Level 19

Flashcards

CARD 1

Q. State the three KDIGO triggers for AKI.

Show answer

A. ≥ 0.3 mg/dL rise in 48 h; ≥ 1.5× baseline in 7 d; UO < 0.5 mL/kg/h for ≥ 6 h.

DETAILED. Any single trigger is sufficient; the creatinine triggers and the output trigger are alternatives.

CLINICAL. Oliguria alone diagnoses AKI before any lab returns.

CARD 2

Q. What defines stage 3 AKI?

Show answer

A. ≥ 3× baseline, or ≥ 4.0 mg/dL, or any start of dialysis, or UO < 0.3 mL/kg/h for ≥ 24 h, or anuria ≥ 12 h.

DETAILED. Starting dialysis makes a patient stage 3 at any creatinine.

CLINICAL. Stage 3 is the trigger for an ICU or nephrology conversation.

CARD 3

Q. Why does creatinine underestimate GFR loss early in AKI?

Show answer

A. It accumulates over 24–48 h, so during the blind window the value trails the true clearance.

DETAILED. Non-steady-state kinetics mean the measured value always lags a falling GFR.

CLINICAL. A flat early creatinine never excludes evolving AKI.

CARD 4

Q. How do you recognise pseudo-AKI?

Show answer

A. A small, early, stable creatinine rise after a secretion-blocking drug, with normal output, electrolytes, and cystatin C.

DETAILED. Trimethoprim, cimetidine, cobicistat, and dolutegravir compete for tubular creatinine secretion.

CLINICAL. Recognising it avoids stopping a needed drug.

CARD 5

Q. What does a damage-positive, creatinine-negative result mean?

Show answer

A. Subclinical AKI — tubular injury without a measurable function drop, carrying a worse prognosis than double-negative.

DETAILED. Defined by the function/damage quadrant; markers include NGAL, KIM-1, TIMP-2×IGFBP7.

CLINICAL. Raise vigilance; do not start kidney-specific therapy on it alone.

CARD 6

Q. Define AKI, AKD, and CKD by time.

Show answer

A. AKI ≤ 7 d; AKD 7–90 d; CKD > 90 d of persistent abnormality.

DETAILED. AKD is the convalescent zone and includes resolving AKI.

CLINICAL. Use AKD to keep recovering patients in follow-up.

CARD 7

Q. Rank the ways to set a baseline creatinine.

Show answer

A. Recent stable outpatient value > lowest inpatient value > back-calculation from an assumed GFR of 75.

DETAILED. Every stage is a ratio to baseline, so the method drives the stage.

CLINICAL. Back-calculation over-calls AKI in pre-existing CKD.

CARD 8

Q. Why stage on the worst value, not the latest?

Show answer

A. Severity is defined by the peak insult; a recovering value understates what happened.

DETAILED. The stage is the prognosis; a falling creatinine does not undo a stage-3 episode.

CLINICAL. Do not downstage a patient simply because they are improving.

Phase F · Level 20

One-Minute Preceptor

SCENE 1

The intern who cleared the oliguric patient

GET A COMMITMENTAsk: “You signed the post-op patient off as no AKI — what made you confident?”

PROBE FOR EVIDENCE“His creatinine was normal” — push: “What was his urine output, and what is the output criterion?”

TEACH A GENERAL RULEUrine output diagnoses AKI before creatinine; under 0.5 mL/kg/h for 6 h is a trigger on its own.

REINFORCE WHAT WAS RIGHTChecking the creatinine was correct; pairing it with the output is what completes the assessment.

CORRECT A MISTAKERe-grade the patient on output now, and act before the creatinine confirms it.

SCENE 2

The resident who stopped the antibiotic

GET A COMMITMENT“You stopped her co-trimoxazole for AKI — talk me through it.”

PROBE FOR EVIDENCE“Creatinine went from 0.7 to 1.0” — ask: “What did her output, potassium, and the timing relative to the drug show?”

TEACH A GENERAL RULEA small, stable rise just after a secretion-blocking drug, with everything else normal, is pseudo-AKI, not injury.

REINFORCE WHAT WAS RIGHTNoticing the creatinine change and taking it seriously was right.

CORRECT A MISTAKERestart the antibiotic if still indicated, confirm with cystatin C, and document the pseudo-rise.

Phase F · Level 21

Reflective Prompts

The KDIGO cut-offs are consensus, not trial-derived. How much should a number whose exact threshold was chosen by committee drive an irreversible decision such as starting dialysis?
Damage biomarkers reliably predict harm, but no trial shows that acting on them helps. Where is your threshold for using prognostic information you cannot yet act on?
Staging standardises care, but a stage-3 label can anchor a team into pessimism. How do you let the stage inform without letting it determine?
If creatinine systematically misleads in your sickest, most wasted patients, what would it take for your unit to adopt cystatin C or a damage marker as routine — and what is stopping you?
AKD was created to stop recovering patients vanishing from follow-up. Does your service actually capture them, or do they fall into the very gap the label was meant to close?

Phase F · Level 22

Board-Style Questions

Q 01

A 60-year-old's creatinine rises from 0.8 to 1.1 mg/dL over 36 hours. By KDIGO, which single change is sufficient to diagnose AKI?