Urine, clearance and kidney hormones
1Why this matters
Mr. Novak, 63, has type 2 diabetes and high blood pressure, and feels perfectly well. His routine blood test shows a plasma creatinine of 1.6 mg/dL, up from 1.0 three years ago, and his urine shows a trace of albumin. It looks like a small change. It means he has lost roughly a third of his filtering capacity. To read numbers like these, you need renal clearance, what normal urine contains and what the kidneys do when they start to fail.
2What this builds on
3Quick check before you start
1. A healthy adult's glomerular filtration rate is about:
- 12.5 mL/min
- 125 mL/min
- 1,250 mL/min
Show the answer
GFR is about 125 mL/min, which adds up to about 180 L of filtrate a day.
- 12.5 mL/min:
- Correct: 125 mL/min:
- 1,250 mL/min:
2. For any substance, the amount excreted equals:
- Filtered + reabsorbed − secreted
- Filtered − reabsorbed + secreted
- Filtered only
Show the answer
Reabsorption returns some of the filtered load to the blood; secretion adds more to the tubular fluid.
- Filtered + reabsorbed − secreted:
- Correct: Filtered − reabsorbed + secreted:
- Filtered only:
3. What does ADH do in the collecting duct?
- Inserts aquaporins so water can leave the duct
- Adds sodium channels to principal cells
- Pumps salt into the medulla
Show the answer
ADH acts through cAMP to put aquaporins into the apical membranes of principal cells. Aldosterone adds sodium channels; the thick ascending limb pumps salt.
- Correct: Inserts aquaporins so water can leave the duct:
- Adds sodium channels to principal cells:
- Pumps salt into the medulla:
4How it works, step by step
- Muscle breaks down a small share of its creatine phosphate into creatinine at a steady rate.Creatinine enters the plasma at a constant rate, set mainly by muscle mass.
- The glomeruli filter creatinine freely, and the tubule reabsorbs none of it.Its excretion rate is roughly GFR × plasma creatinine.
- Chronic kidney disease destroys nephrons and lowers GFR.Less creatinine is filtered each minute, so it builds up in the plasma.
- Plasma creatinine keeps rising until GFR × plasma creatinine again equals production.At the new steady state, half the GFR gives double the plasma creatinine, which is how labs estimate GFR.
- As GFR falls further, the kidneys also fail to excrete potassium, acid and water and to make EPO and calcitriol.Hyperkalemia, acidosis, fluid overload, anemia, bone disease and uremia follow, until dialysis or a transplant takes over.
5Core concepts
6A common mistake
The wrong idea: A creatinine that is only a little above normal means the kidneys are only a little damaged.
What actually happens: Plasma creatinine and GFR are inversely related: halving GFR doubles creatinine. Going from 1.0 to 1.5 mg/dL means GFR has fallen by about a third, and going from 1.0 to 2.0 means half the filtering capacity is gone. Early kidney disease often hides behind a creatinine that still looks nearly normal, which is why labs report an estimated GFR and why doctors check urine for albumin.
7Check yourself
Anything you miss goes into your review queue.
1. A man collects 2,880 mL of urine in 24 hours. His urine creatinine is 60 mg/dL and his plasma creatinine is 1.5 mg/dL. What is his creatinine clearance?
- 80 mL/min
- 115,200 mL/min
- 45 mL/min
- 120 mL/min
Show the answer
First turn the volume into a flow: 2,880 mL ÷ 1,440 min = 2.0 mL/min. Then C = (60 × 2.0) ÷ 1.5 = 80 mL/min, below normal.
- Correct: 80 mL/min: Correct. V = 2 mL/min, and 120 ÷ 1.5 = 80.
- 115,200 mL/min: 115,200 uses the whole day's volume as if it were a per-minute flow. Divide by 1,440 minutes first.
- 45 mL/min: 45 uses 1.5 mL/min for V and 2.0 for P, swapping them. V is 2.0 and P is 1.5.
- 120 mL/min: 120 is U × V without dividing by the plasma concentration.
2. A person's GFR is 120 mL/min. A drug that is freely filtered has a renal clearance of 40 mL/min. What does the tubule do with it overall?
- Net secretion
- Neither reabsorption nor secretion
- Net reabsorption
- It can't be judged without the urine volume
Show the answer
Filtration alone would give a clearance equal to GFR, 120 mL/min. A clearance of only 40 means two thirds of what was filtered came back to the blood: net reabsorption.
- Net secretion: Net secretion would push clearance above GFR.
- Neither reabsorption nor secretion: Filtration alone, like inulin, gives a clearance equal to GFR.
- Correct: Net reabsorption: Correct. Clearance below GFR means net reabsorption.
- It can't be judged without the urine volume: The urine volume is already built into the clearance value; comparing clearance with GFR is enough.
3. Mr. Haas, 66, had a plasma creatinine of 1.0 mg/dL a year ago. It is now steady at 2.0 mg/dL. His muscle mass hasn't changed. About how has his GFR changed?
- It has doubled
- It has fallen by only about 10%
- It hasn't changed
- It has fallen by about half
Show the answer
He makes creatinine at the same rate, and at steady state excretes it at that rate: excretion ≈ GFR × plasma creatinine. For the product to stay the same while plasma creatinine doubles, GFR must have halved.
- It has doubled: A higher GFR would clear creatinine faster and lower its plasma level.
- It has fallen by only about 10%: A one-unit rise looks small, but creatinine and GFR move in inverse proportion; doubling the level means halving the GFR.
- It hasn't changed: With steady production, a lasting rise in plasma creatinine means excretion per unit of plasma fell.
- Correct: It has fallen by about half: Correct. Double the creatinine, half the GFR.
4. A man loses 1.5 L of blood in a car crash. Predict the change in each variable across the cardiovascular, nervous, endocrine and urinary systems over the first hour.
| Variable | Change |
|---|---|
| Sympathetic activity to the kidneys | — |
| GFR | — |
| Renin release | — |
| ADH release | — |
| Urine volume | — |
| Sodium in the urine | — |
Show the answer
Hemorrhage lowers pressure. The baroreceptor reflex raises sympathetic drive, which constricts the afferent arterioles and releases renin; ADH rises steeply. GFR falls, and the tubule keeps sodium and water, so the man passes a small volume of concentrated, low-sodium urine while his kidneys conserve volume.
- Sympathetic activity to the kidneys: up. Lower arterial pressure reduces baroreceptor firing, and the cardiovascular center raises sympathetic output.
- GFR: down. Low arterial pressure falls below the range autoregulation can cover, and sympathetic nerves constrict the afferent arterioles.
- Renin release: up. Less stretch of the juxtaglomerular cells and more sympathetic stimulation both raise renin.
- ADH release: up. A volume loss of this size, about a quarter of blood volume, is far above the 5 to 10% that triggers ADH.
- Urine volume: down. Less is filtered, and ADH and aldosterone make the tubule reabsorb more of what is filtered.
- Sodium in the urine: down. Angiotensin II and aldosterone raise sodium reabsorption, and pressure natriuresis works in reverse at low pressure.
5. A tumor makes a person's parathyroid glands release too much PTH. How does their urine change?
- More phosphate and less calcium, at first
- Less phosphate and more calcium
- More sodium and less potassium
- More water and lower specific gravity
Show the answer
PTH removes sodium–phosphate symporters from the proximal tubule, so phosphate is lost, and increases calcium reabsorption in the distal tubule, so less calcium is lost per unit filtered. (Over time, blood calcium rises so much that more calcium is filtered, and urine calcium can rise despite PTH.)
- Correct: More phosphate and less calcium, at first: Correct. PTH keeps calcium and loses phosphate.
- Less phosphate and more calcium: This reverses both of PTH's kidney effects.
- More sodium and less potassium: That pattern belongs to ANP-like or anti-aldosterone effects, not PTH.
- More water and lower specific gravity: PTH does not act on the collecting duct's water permeability; that is ADH's role.
6. Mr. Diallo, 59, on hemodialysis, misses two sessions and comes in weak, with a plasma potassium of 7.2 mmol/L. Which consequence is the most immediate danger?
- Anemia from low EPO
- Weak bones from low calcitriol
- An arrhythmia from hyperkalemia
- Itching from retained nitrogen wastes
Show the answer
Without dialysis, his kidneys can't excrete potassium. Hyperkalemia depolarizes cardiac cells and disturbs conduction, which can cause a fatal arrhythmia within hours. It needs emergency treatment and dialysis.
- Anemia from low EPO: Anemia develops over weeks and is not what makes two missed sessions an emergency.
- Weak bones from low calcitriol: Bone disease develops over months to years.
- Correct: An arrhythmia from hyperkalemia: Correct. Potassium at 7.2 threatens the heart now.
- Itching from retained nitrogen wastes: Itching is unpleasant but not life-threatening in the short term.
7. After three days of vomiting, Mr. Lind, 80, takes high doses of ibuprofen for a painful knee. His urine output falls and his creatinine rises. How did the ibuprofen contribute?
- It blocked prostaglandins that were protecting his GFR
- It blocked NKCC2 and caused a large water loss
- It raised his ADH, stopping urine flow
- It crystallized in his ureters and blocked them
Show the answer
Vomiting lowered his blood volume, and his kidneys were relying on prostaglandins to widen the afferent arterioles and protect GFR. Ibuprofen blocks prostaglandin synthesis, the afferent arterioles narrow, and GFR falls: acute kidney injury.
- Correct: It blocked prostaglandins that were protecting his GFR: Correct. Removing the prostaglandin protection lowered GFR.
- It blocked NKCC2 and caused a large water loss: Blocking NKCC2 is what loop diuretics do, not ibuprofen.
- It raised his ADH, stopping urine flow: Ibuprofen does not work by raising ADH, and ADH alone lowers urine volume without raising creatinine.
- It crystallized in his ureters and blocked them: Ibuprofen doesn't form stones in the ureters.
8Summary
Urine is about 95% water, with urea, creatinine, uric acid, ions and the pigment urochrome; normal urine has no glucose, blood or bacteria and almost no protein. Specific gravity (about 1.005 to 1.030) tracks concentration, and a urinalysis adds a dipstick and a microscope. Oliguria is under about 400 mL a day; anuria is almost none. Renal clearance, C = (U × V) ÷ P, is the volume of plasma cleared of a substance per minute. Inulin clearance equals GFR; creatinine clearance estimates it, running a little high because creatinine is also secreted. Clearance below GFR means net reabsorption, above it net secretion. Plasma creatinine rises as GFR falls: half the GFR, double the creatinine. Pressure natriuresis links higher arterial pressure to more sodium and water in urine. ADH keeps water, aldosterone keeps sodium and loses potassium, ANP loses sodium and water, and PTH keeps calcium and loses phosphate; endothelin and sympathetic nerves constrict renal arterioles, and prostaglandins widen them. The kidney itself makes renin, EPO and calcitriol. Acute kidney injury develops over hours to days, chronic kidney disease over more than 3 months; failure brings fluid overload, hyperkalemia, acidosis, anemia, bone disease and uremia, treated by dialysis or transplant. Common disorders are urinary tract infections, kidney stones and incontinence.