Pathophysiology: Acute Kidney Injury, Chronic Kidney Disease

what lab value changes would you expect with kidney disease?

all of the above

BUN:SCr > 20:1 pushes you to ____________ thinking

prerenal

volume depletion =

↓ renal perfusion

NSAID blocks renal prostaglandins → _____________________ constriction → further ↓GFR.

afferent arteriole

can cause AKI in tenuous perfusion states because they dilate the efferent arteriole, dropping intraglomerular pressure → GFR dips. risky in bilateral renal artery stenosis, dehydration, or with NSAIDs

ACEi/ARB

blunt prostaglandin-mediated afferent dilation → ↓GFR, especially dangerous in dehydration, HF, cirrhosis, CKD.

NSAIDs

abrupt decline in kidney function over hours-days (KDIGO: ↑SCr ≥0.3 mg/dL in 48h, or ≥1.5× baseline within 7 days, or UOP

acute kidney injury

abnormalities of kidney structure/function ≥3 months (e.g., eGFR

chronic kidney disease

can AKI and CKD co-exist?

absolutely: AKI on CKD is common and has worse outcomes. CKD kidneys are fragile; small hits cause big swings.

↓perfused blood → RAAS/ADH kick in → kidneys concentrate urine, retain Na⁺/water → BUN reabsorbed more than creatinine → BUN:SCr >20. fix the hemodynamics.

prerenal AKI

actual parenchymal damage. UA (urinalysis) gives you the tea (muddy brown casts in ATN; WBCs/eosinophils in AIN; RBC casts/protein in GN).

intrinsic AKI

obstruction → hydronephrosis; think prostate, stones, pelvic masses; ultrasound helps.

postrenal AKI

CKD progression loop: nephron loss → surviving nephrons ____________________ (↑intraglomerular pressure) → sclerosis → more loss. meanwhile, phosphate retention + ↓vitamin D → hypocalcemia & ↑PTH; ↓EPO → anemia; metabolic acidosis from ↓NH₄⁺ excretion; hyperkalemia as GFR falls.

hyperfilter

abrupt drop in kidney function (hours-days).

if it bounces back within 48 h → "rapid reversal."

if it lingers 2-7 days → persistent.

acute kidney injury

after 7 days, AKI is called _______________ (the in-between zone).

acute kidney disease

if kidney impairment lasts >90 days (≥3 months) →

chronic kidney disease

(perfusion problem): not enough blood getting to the kidney.

prerenal

(parenchymal damage): tubules, interstitium, glomeruli, or vessels are injured.

renal

(plumbing problem): obstruction from kidney → urethra.

postrenal

mechanism: ↓ renal blood flow (RBF) → ↓ glomerular pressure → __________________ → oliguria, ↑ SCr/BUN.

↓ GFR

dilate the afferent arteriole (bring blood in).

prostaglandins

constricts the efferent arteriole (keep pressure in the glomerulus).

angiotensin II

prolonged _________________ → tubular hypoxia → ATN (intrinsic AKI).

ischemia

what are some prerenal causes?

all of the above

NSAIDs: block _________________ → afferent constriction → ↓GFR.

prostaglandins

ACEi/ARBs: block __________________ → efferent dilation → ↓glomerular pressure → ↓GFR.

angiotensin II

balanced tone in aa (afferent) and ea (efferent) keeps intraglomerular pressure up → good GFR.

normal

pressure drops → GFR falls.

low flow state

aa dilates (via prostaglandins) and ea constricts (via ang II) to raise pressure and rescue GFR.

autoregulation

dilate the afferent arteriole (more blood in).

prostaglandins (PGE₂/PGI₂)

constricts the efferent arteriole (pressure stays in the glomerulus).

angiotensin II

normal/low perfusion + intact autoregulation → GFR ____________________.

maintained

add an NSAID → block COX → ↓ PGE₂/PGI₂ → afferent can't dilate → ___________________ → prerenal AKI.

↓ GFR

add an ACEi/ARB → block ang II → efferent dilates → pressure leaks out → ________________ → prerenal AKI.

↓ GFR

where do PGs work and what do they do?

all of the above

block PGs with NSAIDs → Na⁺/water _______________ (edema, HTN, CHF), hyperkalemia / type 4 RTA, hyponatremia, and AKI (prerenal ± ischemic ATN).

retention

ATN (acute tubular necrosis)

tubules

what are some causes of intrinsic AKI?

all of the above

what is the pathology of ATN?

all of the above

a drug-triggered, idiosyncratic (can't predict), delayed hypersensitivity reaction that inflames the interstitium ± tubules.

acute interstitial nephritis

usual culprits of AIN:

all of the above

urinalysis of AIN contains:

white blood cells

immune-mediated glomerular inflammation. think immune complexes, complement activation, and proliferative lesions.

glomerulonephritis

glomerulonephritis is associated with:

streptococcal infection

clues of glomerulonephritis:

all of the above

management of glomerularnephritis:

nephrology and biopsy

(back-pressure from downstream blockage). less common, but a must-not-miss because it's fixable.

postrenal AKI

places a block can live in postrenal AKI:

all of the above

select all that apply:

clues of postrenal AKI

1. anuria/intermittent anuria, suprapubic fullness, flank pain; can also be silent in elderly.

2. renal ultrasound

3. foley for bladder, stent or nephrostomy for ureter

Mrs. Eleanor Davis, a 72-year-old woman, is admitted with diarrhea and vomiting for three days. she reports taking ibuprofen for arthritis. on exam, she is hypotensive and dehydrated. what is the likely type of AKI?

•labs: BUN: 48 mg/dL (normal: 7-20 mg/dL), serum creatinine: 2.0 mg/dL (normal: 0.6-1.2 mg/dL), and urine output: low (oliguria)

prerenal

how did NSAIDs worsen Mrs. Eleanor Davis's condition?

block COX → ↓ PGE₂/PGI₂ → no afferent dilation → intraglomerular pressure drops → GFR falls.

what happens to GFR & RBF in Mrs. Eleanor Davis?

RBF already down (dehydration). with NSAIDs, GFR falls further because autoregulation is disabled.

select all that apply:

pathophysiologic effects of AKI

1. GFR: ↓

2. SCr & BUN: ↑

3. urine output: oliguria, anuria

4. volume: hypo- in prerenal; hyper- once kidneys can't excrete water/Na⁺

5. K⁺: tends to ↑

6. metabolic acidosis

7. ↓ ammonium excretion

8. phosphate/Ca²⁺: ↑PO₄³⁻

↓Ca²⁺

9. uremic symptoms

creatinine lags behind real-time _________

GFR

new drug + WBC/WBC casts ± rash/eos → stop the drug, consider steroids.

AIN

hematuria + proteinuria + RBC casts/HTN/edema → serologies + biopsy.

glomerulonephritis

low/erratic UOP or anuria + enlarged prostate/stone risk → ultrasound → drain.

postrenal

a slow, progressive drop in GFR over months-years. usually irreversible, but we can slow it.

chronic kidney disease

fewer working nephrons.

chronic kidney disease

select all that apply:

how does the kidney compensate in CKD?

1. loss of nephron mass → the remaining nephrons pick up the slack.

2. glomerular capillary hypertension

3. proteinuria

why do RAAS blockers (ACEi/ARB) and SGLT2 inhibitors help in CKD?

they lower intraglomerular pressure and cut albuminuria

normal/mildly ↓ GFR with evidence of kidney damage (e.g., albuminuria).

G1-G2

progressively lower GFR.

G3a-G5

kidney failure/ESRD → dialysis or transplant territory.

G5

when nephron number falls (CKD), the kidney "compensates" by turning on RAAS and _______________ through the remaining nephrons.

hyper-filtering

↓ nephron number → RAAS activation and _______________.

hypertension

surviving nephrons hyperfilter: ↑ single-nephron GFR (SNGFR) and _____________________.

↑ intraglomerular (glomerular hydrostatic) pressure

high pressure + high flow → _________________ (albumin leakage) and progressive injury.

proteinuria

chronic pressure/flow injury → glomerulosclerosis and tubulointerstitial fibrosis → late course: ↓ total GFR, ______________, and systemic problems (anemia, bone disease, fluid overload, etc.).

↓ urine output

early compensation (hyperfiltration) becomes _______________ that drives progression.

maladaptation

ACEi and ARBs do what to glomerular hydrostatic pressure?

decrease it

a 55-year-old man with stage 3 CKD is prescribed losartan. why are ACEi/ARBs beneficial in CKD?

lowers efferent arteriole resistance

NSAIDs inhibit prostaglandins → constrict the afferent arteriole → ↓ renal blood flow and ↓ GFR.

renal hemodynamics

can precipitate prerenal AKI, especially with dehydration, HF, cirrhosis, diuretics, or ACEi/ARB use ("triple whammy")

NSAIDs

worsen BP/edema, raise K+, and can accelerate CKD; generally avoid or use sparingly.

NSAIDs

renal hemodynamics: block ang II → dilate efferent arteriole → ↓ intraglomerular pressure (often a small, expected creatinine rise ≤~30%).

ACEi/ARB

ACEi/ARBs are beneficial—reduce ______________ and slow progression by lowering glomerular pressure; cornerstone therapy for proteinuric CKD and diabetic kidney disease.

proteinuria

as GFR falls, substances the kidney mainly clears by filtration rise in the blood.

________________________ (and urea) go up first and most (little renal regulation → plasma level is ~inversely proportional to GFR). that's why it is used to estimate GFR.

creatinine

_________________ rise later: the body initially adapts (↑PTH, ↑FGF-23, bone buffering), but with further GFR loss hyperphosphatemia and metabolic acidosis appear.

phosphate and H⁺

_____________________ (and chloride) usually stay near normal—kidneys and hormones tightly regulate the balance until very late or if intake/diuretics/volume status push things.

sodium

select all that apply:

what are some complications of CKD?

1. Na⁺/water retention

2. hyperkalemia

3. metabolic acidosis

4. CKD-mineral & bone disorder

5. anemia

6. uremia

GFR drops by 50%. which plasma concentration rises the most?

creatinine