Overview
This lecture covers acute kidney injury (AKI) / acute renal failure (ARF): what it is, how it is classified by the site of the problem (pre-renal, intra-renal, post-renal), and then a detailed treatment of acute tubular necrosis, the commonest intra-renal cause. Nephron structure and the four basic renal processes are revised as the anatomical basis for how tubular damage produces the clinical picture. A worked case, a man with a ruptured abdominal aortic aneurysm, is used to follow ischaemic ATN through its initiation, maintenance and recovery phases and to explain the accompanying disturbances in GFR estimation, acid-base balance and potassium.
AKI / ARF: definition and features
AKI (ARF) is a rapid decline in renal function. Its features are:
- Accumulation of nitrogenous wastes
- Water / ECF imbalance
- Acid-base disturbance
- Oliguria
- A variable course
- Frequently iatrogenic (raised as a question on the slide)
Classification of AKI
Three categories, defined by where the problem sits:
Pre-renal (“functional”)
- Kidney is structurally intact, but blood supply or blood pressure is reduced.
- Less filtration, so a fall in GFR. Tubular function is not affected.
- Causes: hypovolaemia, hypotension, low cardiac output, renal vasoconstriction.
Intra-renal (intrinsic, “structural”)
- Primary damage affects renal structures themselves, for example glomerular disease or ischaemic/toxic damage to renal tubules.
- Tubular damage is the commonest cause. Epithelial damage may obstruct the lumen and impair filtration, tubular absorption and secretion are affected, and a broken epithelial barrier may allow back leak of filtrate.
- Causes: glomerulonephritis, vasculopathies, interstitial nephritis, acute tubular necrosis (ischaemic or nephrotoxic).
Post-renal (“obstructive”)
- Obstruction of urine flow, either within the kidney or in the urinary tract (ureter, bladder, urethra).
- Increased intratubular pressure decreases filtration and tubular flow.
- Causes: intra-renal obstruction such as cell debris or crystals (e.g. urate) blocking the tubule lumen; extra-renal causes including strictures, stones, crystals, clots, tumour (within and outside the tract), prostatic hypertrophy, neurogenic bladder.
Nephron structure and function (revision)
The nephron sits in the renal cortex and medulla with its own blood supply: interlobular and arcuate arteries and veins, afferent arteriole, glomerulus, efferent arteriole, then peritubular capillaries and, for juxtamedullary nephrons, the vasa recta.
Tubule pathway in order: glomerulus (within the glomerular/Bowman’s capsule of the renal corpuscle) → proximal convoluted tubule → nephron loop (loop of Henle: descending limb, thin and thick segments, ascending limb) → distal convoluted tubule → collecting duct → urine. The juxtaglomerular apparatus lies at the vascular pole. Cortical nephrons have short loops; juxtamedullary nephrons have long loops that reach deep into the medulla and are associated with the vasa recta, across the corticomedullary junction.
Four basic renal processes:
- Glomerular filtration: blood arrives via the afferent arteriole into the glomerular capillary, and filtrate passes into Bowman’s capsule and down the tubule.
- Tubular reabsorption: movement from tubule into the peritubular capillary (supplied by the efferent arteriole).
- Tubular secretion: movement from the peritubular capillary into the tubule.
- Urinary excretion: what remains in the tubule leaves as urine.
Acute tubular necrosis (ATN)
- Accounts for 75% of intra-renal ARF.
- Two aetiological groups: ischaemic and nephrotoxic.
- Variable morphology and variable susceptibility.
- Pathogenesis theories: constriction, permeability, obstruction, back leak.
- Runs in three phases: initiation → maintenance → recovery.
Ischaemic ATN
- Precipitants: hypovolaemia, reduced cardiac output, vascular causes.
- Reduced glomerular blood flow means reduced tubular perfusion.
- Result: focal necrosis of tubular epithelium, disruption of the basement membrane, and debris occluding the lumen, affecting the proximal tubule and loop of Henle.
Case: Mr R, ruptured abdominal aortic aneurysm
Course as presented:
- Collapse with marked hypotension.
- A&E: hypotension, acidosis.
- CT: ruptured AAA.
- Theatre: graft repair, 6 hours, 330 mls (urine output over the operation).
- ICU: well perfused, but no urine, with rising urea and creatinine.
- Conclusion: likely AKI (very common post AAA), and likely ATN given the severe prolonged hypotension.
Imaging and operative material shown alongside the case: a normal-calibre aorta compared with a dilated, ballooned aneurysmal segment; axial abdominal CT at the level of both kidneys showing a large rounded structure anterior to the vertebral body consistent with an aneurysmal aorta; intra-operative views of the distended aneurysm sac; and the completed repair with the renal vein above, the native aneurysm sac wrapped around the synthetic ribbed graft.
A four-panel sequence gives the natural history and treatment: (1) normal anatomy, with inferior vena cava, kidney, renal blood vessels, abdominal aorta and right common iliac artery; (2) abdominal aortic aneurysm, a dilated bulge in the abdominal aorta; (3) eventual condition, rupture with haemorrhage spreading through the abdomen; (4) correct surgical repair, the defective segment replaced with a synthetic graft.
Warning
Two of the case CT images were flagged during transcription: one had no legible annotations or measurements to confirm specific findings, and on the other the resolution was too low to read the annotations, date and measurement scale clearly (a “4.0cm” scale marker and a partial “MAY 19” date were visible).
Consequences of ATN in this case
Is the GFR estimate still valid?
- Creatinine clearance suggests a GFR of about 10%.
- But the estimate may no longer be valid: creatinine clearance only estimates GFR if creatinine is filtered and not reabsorbed, and that is no longer the case once the tubules are damaged.
Acidosis
- Initially a combined acidosis.
- Decreased numbers of functioning tubule cells plus limited tubular flow give decreased bicarbonate synthesis.
- A metabolic acidosis therefore persists.
Potassium
- Steady rise, producing hyperkalaemia.
- Mechanism: decreased functioning tubule cells and limited flow mean decreased renal cell potassium secretion.
- The slide raises day 7 as a question point. [slide does not elaborate]
Recovery phase
By around day 15: urine volumes increase dramatically, biochemistry normalises, and the patient is in the recovery phase.
What is happening:
- The epithelium regenerates.
- Tubular function starts to recover.
- Debris is expelled, giving casts in the urine.
- The epithelium is still immature, with two consequences:
- No HOMG (abbreviation not expanded on the slide), so it is difficult to concentrate the urine.
- Lots of accumulated solutes drive an osmotic diuresis, so watch for volume and electrolyte depletion.
Self-test
- Define acute kidney injury and list its features as given in the lecture.
- List the three classification categories of AKI, with the defining problem in each.
- Explain why tubular function is preserved in pre-renal AKI but GFR falls.
- Describe the four ways in which tubular epithelial damage impairs renal function in intra-renal AKI.
- Distinguish intra-renal from extra-renal causes of post-renal obstruction, with examples of each.
- Describe the tubule pathway of the nephron in order from glomerulus to urine.
- Distinguish cortical from juxtamedullary nephrons.
- List the four basic renal processes and state the direction of movement in each.
- What proportion of intra-renal ARF is due to acute tubular necrosis, and what are its two aetiological groups?
- List the four pathogenesis theories of ATN and the three phases of its course.
- Describe the sequence from hypovolaemia to tubular injury in ischaemic ATN, naming the tubular segments affected.
- Explain why creatinine clearance may no longer be a valid estimate of GFR in established ATN.
- Explain the mechanism of the persisting metabolic acidosis in ATN.
- Predict what happens to serum potassium in ATN and explain why.
- Describe what is happening in the tubule during the recovery phase, and explain why a patient in recovery is at risk of volume and electrolyte depletion.
- A patient collapses with a ruptured AAA, is profoundly hypotensive, undergoes a 6-hour graft repair and arrives in ICU well perfused but anuric with rising urea and creatinine. What is the likely diagnosis, and what in the history supports it?
Answers
Reveal answers
- A rapid decline in renal function, with accumulation of nitrogenous wastes, water/ECF imbalance, acid-base disturbance, oliguria, a variable course, and frequently an iatrogenic contribution.
- Pre-renal (“functional”): reduced blood supply or blood pressure to a structurally intact kidney. Intra-renal (“structural”): primary damage to renal structures. Post-renal (“obstructive”): obstruction of urine flow within the kidney or urinary tract.
- The kidney is structurally intact; only perfusion pressure or flow is reduced, so less filtration occurs and GFR falls, but the tubular cells themselves are undamaged and continue to function.
- Epithelial damage may obstruct the lumen and impair filtration; tubular absorption is affected; tubular secretion is affected; and a broken epithelial barrier allows back leak of filtrate.
- Intra-renal obstruction is blockage of the tubule lumen by cell debris or crystals such as urate. Extra-renal obstruction is of the ureter, bladder or urethra by strictures, stones, crystals, clots, tumour (within or outside the tract), prostatic hypertrophy or a neurogenic bladder.
- Glomerulus in Bowman’s capsule → proximal convoluted tubule → loop of Henle (descending limb, thin and thick segments, ascending limb) → distal convoluted tubule → collecting duct → urine.
- Cortical nephrons have short loops; juxtamedullary nephrons have long loops reaching deep into the medulla and are associated with the vasa recta.
- Glomerular filtration (glomerular capillary → Bowman’s capsule); tubular reabsorption (tubule → peritubular capillary); tubular secretion (peritubular capillary → tubule); urinary excretion (tubule → urine).
- 75% of intra-renal ARF. The two groups are ischaemic and nephrotoxic.
- Theories: constriction, permeability, obstruction, back leak. Phases: initiation, maintenance, recovery.
- Hypovolaemia, reduced cardiac output or a vascular cause reduces glomerular blood flow, which reduces tubular perfusion, causing focal necrosis of tubular epithelium, disruption of the basement membrane and debris occluding the lumen, affecting the proximal tubule and loop of Henle.
- Creatinine clearance is only a valid GFR estimate if creatinine is filtered and not reabsorbed. With damaged tubules that is no longer true, so the apparent value (around 10% in the case) cannot be taken at face value.
- There are fewer functioning tubule cells and tubular flow is limited, so bicarbonate synthesis is decreased; an initially combined acidosis therefore leaves a persisting metabolic acidosis.
- It rises steadily to hyperkalaemia, because decreased numbers of functioning tubule cells and limited flow reduce renal cell potassium secretion.
- The epithelium regenerates and tubular function starts to recover, debris is expelled as casts in the urine, but the epithelium is still immature: there is no HOMG so urine cannot be concentrated, and accumulated solutes drive an osmotic diuresis, hence the risk of volume and electrolyte depletion.
- Likely AKI, which is very common after AAA, and likely ATN specifically. The supporting features are the severe prolonged hypotension (collapse, hypotension in A&E with acidosis, a 6-hour operation with only 330 mls urine) and the fact that he is now well perfused yet still anuric with rising urea and creatinine, so the problem is no longer pre-renal.