Polycystic Kidney Disease Notes

Kidney Anatomy and Function

  • Main Functions:
    • Maintain electrolyte balance.
    • Maintain fluid balance.
    • Remove waste from the blood.
    • Produce Erythropoietin (required for RBC production in bone marrow).
    • Activate vitamin D (required for calcium reabsorption from the intestines).
    • Produce renin (required for BP control).
    • Maintain acid-base homeostasis (pH).
      • Kidneys regulate long-term acid-base balance by regulating hydrogen concentration and HCO3- concentration.

Nephron Anatomy and Function

  • Anatomy (functional unit):

    • Glomerulus: A network of capillaries.
    • Bowman's Capsule
      • High pressure forces material from the glomerulus into Bowman's capsule.
      • Bowman's capsule contains tiny holes that allow small molecules such as urea to enter.
      • Other small molecules that are useful also enter Bowman's capsule (salts, glucose, water) - ultrafiltration.
    • Proximal Convoluted Tubule (PCT)
      • First site of water reabsorption into the bloodstream.
      • Major site for water, amino acid, and glucose reabsorption.
      • Water reabsorption occurs via passive diffusion and active transport (Na/K pump).
    • Loop of Henle
      • Descending Limb
        • Highly permeable to water, impermeable to ions, causing significant water reabsorption.
      • Ascending Limb
        • Impermeable to water, highly permeable to ions.
    • Distal Convoluted Tubule (DCT) and Collecting Duct
      • Final site of reabsorption in the nephron.
      • Permeability to water varies depending on hormonal stimuli, regulating blood osmolarity, volume, pressure, and pH.

  • Selective Reabsorption:

    • The process in the tubules results in:
      • Filtered blood with necessary salts and nutrients.
      • Urine with waste products.

GFR and CKD

  • Glomerular Filtration Rate (GFR):

    • A test to determine how efficiently kidneys remove/filter waste and excess fluid from the blood.
    • Suggests if a person may suffer from CKD.

  • Kidney Function Stages:

    • CKD Stage 1: 90-89

  • Creatinine:

    • A better clinical indicator of renal disease because it's related to age, tissue mass, and underlying diseases (less fluctuating).
    • Not broken down or filtered elsewhere.

  • Urea:

    • Based on diet, so it may fluctuate.

Incidents of PKD in the UK

  • PKD:

    • Total of people in the UK with PKD is 70,000.

  • ADPKD:

    • Estimated 1 in every 1000 to 2500 people in the UK.

  • ARPKD:

    • Estimated around 1 in 20,000 babies are born with the condition.

PKD: Causes, Signs & Symptoms

  • High BP (Hypertension):

    • Caused by increased activity of the renin-angiotensin system (RAAS), leading to increased renin release.
      • Possibly caused by focal ischemia (blood vessels shrink and undergo apoptosis) due to cyst expansion and extracellular volume expansion.
    • Cysts prevent the kidney from filtering extra fluid from the blood.

  • Blood in the Urine (Hematuria):

    • Bursting of cysts in the kidneys (due to inflammation) or of small blood vessels around the cysts.

  • Subarachnoid Hemorrhage:

    • Due to berry aneurysm (bulging of blood vessel) because of the same mutation causing PKD (polycystin is important in maintaining fibroblasts and collagen; if compromised, it becomes weak, and high BP causes aneurysm over time).

  • Increased Size of Abdomen:

    • Due to enlarged kidneys.

  • Urinary Tract or Kidney Infections:

    • Cysts draw bacteria toward the urinary tract.

  • Kidney Stones:

    • Due to calcium not being absorbed (decreased vitamin D production), causing accumulation of calcium in the kidney.

Complications of PKD

  • Intracranial Aneurysm:

    • Same as subarachnoid hemorrhage.

  • Liver Cyst:

    • Same mutation as PKD1.
      • Reduced albumin production (albumin prevents leakage and makes vessels more intact).
        • Reduced oncotic pressure leads to peripheral edema.

  • Uremia:

    • Increased levels of urea (solid) because of low GFR due to dysfunctional or blocked nephrons, causing urea to diffuse into the skin.
      • Itchiness.

  • Gastric Bleeding:

    • Leads to anemia.
      • Uremia causes platelet dysfunction, so platelets do not aggregate, preventing activation of the blood clotting cascade.

  • Loss of Appetite:

    • Affects the brain stem.

  • Anemia:

    • Because the kidney produces erythropoietin.
      • Pale skin color.
      • Fatigue.

  • Increased/Frequent Urination:

    • Due to reduced responsiveness of the collecting duct and DCT to ADH.
    • ADH levels increase at night, but if we have PKD, there is decreased responsiveness, so we still go to the toilet.

  • Brain Aneurysm

  • Cardiovascular Disease:

    • Due to left ventricular hypertrophy.
      • High BP.
        • Increased TPR (total peripheral resistance).
        • Increased afterload.
      • Fluid retention (edema).
        • Increased EDV.
        • Increased muscle stretch (preload).
      • Decreased blood volume.
        • Compensatory responses to tissue hypoxemia derived from anemia include increased cardiac output and high blood flow.

  • Edema in the Legs:

    • Due to high BP leading to increased hydrostatic pressure.
    • Liver cyst, decreased plasma protein production (albumin) leading to decreased oncotic/osmotic pressure.
    • Increased protein loss in urine (decreased oncotic pressure).

Causes of Blood Test Abnormalities in PKD

  • Creatinine:

    • Waste product in the blood from muscle activity. Normally removed by the kidneys, but levels rise when kidney function slows down.

  • Urea:

    • Small water-soluble molecule generated in the liver during the catabolism of amino acids and other nitrogenous metabolites. Normally excreted by the kidneys, but accumulates when renal function is impaired.

  • K+:

    • Failure of renal excretion.

  • Reduced Calcium Levels:

    • Low vitamin D leads to low calcium absorption.
      • Kidney forms a protein that activates vitamin D, so there is no activation, therefore lower Vitamin D.
    • Phosphate depresses production of active vitamin D by kidneys.
    • Increased excretion of albumin in urine (calcium binds to albumin).
    • Increased binding to phosphate.

  • Reduced Hemoglobin:

    • Reduced EPO (erythropoietin).
    • Anemia of chronic disease.
    • Cytokines reduce bone marrow responsiveness to EPO.
    • Gastric bleeding.
    • RBC in urine.
    • Hemodilution
      • Dilute RBC (higher volume of blood) reduce levels of Haemoglobin per blood volume.

  • Click Mitral Valve Prolapse

  • SNAP

    • Snap of the stiff mitral valve occurs during late diastole (atrial systole when they contract).

Genetic Basis of PKD

  • Autosomal Dominant PKD:

    • Gene mutation of PKD1 on chromosome 16, which codes for polycystin 1.
      • 71 to 85 percent.
      • Kidney failure occurs at an earlier age.
    • Gene mutation of PKD2 on chromosome 4, which codes for polycystin 2.
      • 15 percent.
      • Milder (present later in life).

  • Autosomal Recessive PKD:

    • Two altered copies of the PKHD1 chromosome 6, which codes for fibrocystin gene in each cell.
      • Parents may be carriers.

Medical Management of PKD

  • Medication for High BP:

    • ACE inhibitors, ARB blockers, angiotensin II antagonists - anything that inhibits the RAAS system.

  • Painkillers

    • Pain in the abdomen and back is a common symptom of PKD. NSAIDS (OTC) pain killers can be used to manage pain

  • Antibiotics

    • PKD patients are at higher risk of developing urinary tract infections (UTIs) due to the cysts in their kidneys. Antibiotics may be prescribed to treat UTIs

  • Dialysis.

Differentiate between Nephritic & Nephrotic Syndrome

  • Nephrotic Syndrome:

    • Involves the loss of significant volumes of protein via the kidneys (proteinuria), which results in hypoalbuminemia.

  • Nephritic Syndrome:

    • Involves hematuria, mild to moderate proteinuria, hypertension, oliguria, and red cell casts in the urine.