7.1 Kidney function and Disease

What are the three main functions of the kidneys?

• Excretion: urea, creatinine, uric acid, uraemic toxins

• Homeostasis: regulation of Na⁺, K⁺, Mg²⁺, Ca²⁺, PO₄⁻, H⁺; retention of HCO₃⁻, water, albumin, amino acids, glucose

• Endocrine: renin, erythropoietin, 1,25(OH)₂ vitamin D₃

What is the functional unit of the kidney?

The nephron. It consists of the glomerulus, Bowman's capsule, proximal tubule, loop of Henle, distal tubule, and collecting duct.

Which hormones regulate nephron function and what do they each do?

• ADH (antidiuretic hormone): water reabsorption in collecting duct

• Aldosterone: sodium reabsorption in distal tubule/collecting duct

• PTH (parathyroid hormone): Ca²⁺ reabsorption; PO₄⁻ excretion; 1,25(OH)₂-vitamin D₃ synthesis

What is the role of renin in renal endocrine function?

The kidney synthesises renin, which cleaves angiotensinogen → angiotensin I → angiotensin II. Angiotensin II stimulates the adrenal cortex to release aldosterone, promoting Na⁺ reabsorption and water retention.

What are the functions of each region of the nephron?

• Proximal tubule: main reabsorption (glucose, amino acids, Na⁺, HCO₃⁻, water)

• Loop of Henle: concentration of filtrate

• Distal tubule: secretion (H⁺, K⁺, NH₄⁺)

• Collecting duct: water reabsorption (ADH-regulated)

What reduces GFR, and what does proteinuria lead to?

GFR is reduced by glomerulonephritis, diabetes, hypertension, and nephrotoxins (e.g. analgesics, heavy metals). Proteinuria causes ↓ GFR and inflammation/scarring of renal tubules leading to nephron loss.

What is reabsorbed in the proximal convoluted tubule?

100% glucose (with Na⁺ symport), amino acids, oligopeptides, vitamins, lactate; 65% Na⁺; 67% water; 80–90% bicarbonate. Creatinine is secreted here.

Define renal clearance.

"The volume of plasma from which a given substance is removed by filtration during its passage through the kidney." It is a function of GFR, tubular secretion, and tubular reabsorption.

What is the formula for renal clearance?

Clearance = (U × V) / P
Where U = urinary concentration of substance, V = urine volume per unit time, P = plasma concentration of substance.

What conditions must a substance meet to be used to measure GFR via clearance?

• Freely filtered at the glomerulus

• Not secreted or reabsorbed in the tubule

• Non-toxic and easily measurable

• The glomerulus is the sole route of excretion

Define GFR and state its normal value and units.

GFR = "the volume of plasma from which a given substance is removed by glomerular filtration per unit time." Normal GFR ≈ 140 mL/min. Corrected for body surface area; units = mL/min/1.73 m².

What eGFR cut-offs define CKD and kidney failure?

• eGFR < 60 mL/min/1.73 m²: Chronic Kidney Disease (CKD)

• eGFR < 15 mL/min/1.73 m²: Kidney failure

• UACR > 30 mg/g may indicate CKD even with eGFR ≥ 60

How is eGFR estimated using creatinine?

Using the MDRD equation:
Male GFR = 186 × (SCR ÷ 88.4)⁻¹·¹⁵⁴ × AGE⁻⁰·²⁰³
Female GFR = male GFR × 0.742
Reported with every lab creatinine result.

Why is urinary creatinine preferred over serum creatinine for detecting GFR changes?

Urinary creatinine has greater sensitivity than serum creatinine in determining changes in GFR. Serum creatinine only rises once GFR has fallen to ~50% of normal.

Describe the biochemical origin of creatinine.

Creatinine is a by-product of muscle metabolism. Creatine ↔ phosphocreatine (via creatine kinase). 1–2% of creatine/phosphocreatine spontaneously converts to creatinine per day. Its quantity is related to muscle mass.

Why is creatinine described as "convenient but insensitive" as a marker of renal function?

• GFR must fall to half before serum creatinine rises detectably

• Creatinine depends on age and body size (muscle mass)

• It is freely filtered but some tubular secretion occurs, adding variability

Describe the biochemical origin and handling of urea.

Urea is produced in the liver from catabolism of protein and nucleic acids (via the urea cycle). >90% excreted by the kidney. Freely filtered at the glomerulus; 40–70% passively reabsorbed in the tubule. Less useful than creatinine — affected by dietary protein, GI bleeding, and urine flow.

What are the types of proteinuria and their causes?

• Overflow: e.g. Bence-Jones protein (Ig light chains) in multiple myeloma

• Glomerular: albuminuria from glomerular defect

• Tubular: β₂- or α₁-microglobulinuria — failure to reabsorb

• Secreted: Tamm-Horsfall glycoprotein (uromodulin) — most abundant protein in normal urine

What are the consequences as GFR progressively falls?

• GFR ~80: ↓ 1-OH vitamin D, ↑ urea, ↑ creatinine, ↑ phosphate

• GFR ~30: Early renal failure, ↑ acid, ↓ HCO₃⁻

• GFR ~20: ↑ potassium

• GFR ~10: Sodium retention, late renal failure

• GFR ~6: Require dialysis / end-stage renal failure

What are the three classifications of acute renal failure (ARF)?

• Pre-renal: failure of blood supply to kidneys (e.g. haemorrhage, heart failure)

• Post-renal: impaired urinary drainage (e.g. stones, malignancy)

• Renal: intrinsic kidney tissue damage (e.g. glomerulonephritis, nephrotoxins, ATN)

What are the biochemical findings in pre-renal ARF?

• ↑ Serum urea and creatinine (urea rises proportionally more than creatinine)

• Metabolic acidosis

• Hyperkalaemia (from ↓ GFR and acidosis)

• High urine osmolality (kidneys try to conserve water)

What are the biochemical findings in pre-renal ARF?

• ↑ Serum urea and creatinine (urea rises proportionally more than creatinine)

• Metabolic acidosis

• Hyperkalaemia (from ↓ GFR and acidosis)

• High urine osmolality (kidneys try to conserve water)

What are the causes of pre-renal ARF?

• Decreased plasma volume: haemorrhage, burns, vomiting, diarrhoea

• Decreased cardiac output

• Local factors: occlusion of renal artery

What are the causes of post-renal ARF?

Obstruction to urine drainage: kidney stones, cancer of the cervix, prostate or bladder. Mechanism: decreased glomerular filtration pressure due to back pressure from blockage.

What are the causes of intrinsic (renal) ARF?

• Acute blood loss (trauma)

• Septic shock

• Glomerulonephritis

• Nephrotoxins: aminoglycosides, analgesics, herbal toxins

• Acute tubular necrosis (ATN)

What is chronic renal failure (CRF) and when do symptoms appear?

CRF is progressive, irreversible kidney tissue destruction. Patients may be symptomless until GFR falls below ~15 mL/min (~10% of normal). Treated by dialysis or transplantation.

What are the main biochemical consequences of chronic renal failure?

• Fluid and sodium dysregulation (↓ tubular water reabsorption)

• Hyperkalaemia (advanced CRF)

• Metabolic acidosis (H⁺ retention)

• ↓ 1,25(OH)₂-vitamin D₃ → dysregulated Ca²⁺/PO₄⁻ metabolism → hypocalcaemia

• Anaemia (failure of erythropoietin synthesis)

Why do CRF patients develop anaemia?

The kidney normally produces erythropoietin, which stimulates red blood cell production in the bone marrow. In CRF, erythropoietin synthesis fails, leading to normocytic, normochromic anaemia.

Why do CRF patients develop bone disease?

Failed kidneys cannot convert vitamin D to its active form, 1,25(OH)₂-vitamin D₃. This leads to ↓ Ca²⁺ absorption from the gut → hypocalcaemia → secondary hyperparathyroidism → dysregulated Ca²⁺ and PO₄⁻ metabolism and renal osteodystrophy.

What is Bence-Jones proteinuria and what does it indicate?

Bence-Jones protein is an immunoglobulin light chain that appears in urine in multiple myeloma or Waldenström's macroglobulinaemia. It represents overflow proteinuria — the plasma concentration exceeds the tubular reabsorption capacity.