Kidney

• Azotemia is a biochemical abnormality that refers to an elevation of blood urea nitrogen (BUN) and creatinine levels, related largely to a decreased glomerular filtration rate (GFR). It is a typical feature of both acute and chronic kidney injury. Prerenal azotemia is encountered when there is hypoperfusion of the kidneys that impairs renal function in the absence of parenchymal damage. Postrenal azotemia is seen whenever urine flow is obstructed
• Acute kidney injury is characterized by rapid decline in GFR within hours to days with concurrent dysregulation of fluid and electrolyte balance, and retention of metabolic waste products normally excreted by the kidney including urea and creatinine
• Kidneys serve as an endocrine organ, secreting hormones such as erythropoietin, renin, and prostaglandins, and regulating vitamin D metabolism
• Nephritic syndrome is caused by inflammatory glomerular disease and is dominated by the acute onset of either grossly visible hematuria or microscopic hematuria with dysmorphic red cells and red cell casts on urinalysis, diminished GFR, mild to moderate proteinuria, and hypertension
• Rapidly progressive glomerulonephritis (RPGN) is a form of nephritic syndrome with rapid decline in GFR within hours to days
• Renal diseases are responsible for a great deal of morbidity and mortality, with more than 660,000 Americans having end-stage renal disease (ESRD) in 2015, two-thirds maintained on dialysis at a cost of approximately $72,000 per person annually
• Chronic kidney disease is defined as the presence of a diminished GFR persistently less than 60 mL/min/1.73 m2 for at least 3 months, from any cause, and/or persistent albuminuria
• Acute kidney injury occurs in more than 2 million people worldwide and is a major risk factor for the development of chronic kidney disease and ESRD
• Causes of pre-renal azotemia

  • Hypotension
  • Excessive fluid losses from any cause
  • Effective intravascular volume decreased due to shock, volume depletion, congestive heart failure, cirrhosis of the liver
• Nephrotic syndrome is characterized by heavy proteinuria (more than 3.5 g/day), hypoalbuminemia, severe edema, hyperlipidemia, and lipiduria (lipid in the urine)
• Isak Dinesen: 'What is a human but an ingenious machine designed to turn, with “infinite artfulness, the red wine of Shiraz into urine"?'
• Asymptomatic hematuria or proteinuria, or a combination of these two, is usually a manifestation of subtle or mild glomerular abnormalities
• Human kidneys convert more than 1700 L of blood per day into about 1 L of highly concentrated fluid called urine, excreting waste products of metabolism, regulating the body’s concentration of water, salt, calcium, phosphorus, and other anions and cations, and maintaining the appropriate acid-base balance of plasma
• Clinical manifestations of uremia

  • Secondary involvement of the gastrointestinal system (e.g., uremic gastroenteritis)
  • Peripheral nerves (e.g., peripheral neuropathy)
  • Heart (e.g., uremic fibrinous pericarditis)
• Millions of people are affected annually by nonfatal kidney diseases, including infections of the kidney or lower urinary tract, kidney stones, and urinary obstruction
• Clinical manifestations of renal disease

  • Grouped into reasonably well-defined syndromes
• The availability of dialysis and the success of renal transplantation have improved the outlook for patients
• Tubular destruction


  Increases intraglomerular pressure, inducing glomerular injury
• Principal systemic manifestations of chronic kidney disease and uremia

  • Fluid and Electrolytes: Dehydration, Edema, Hyperkalemia, Metabolic acidosis
  • Calcium Phosphate and Bone: Hyperphosphatemia, Hypocalcemia, Secondary hyperparathyroidism, Renal osteodystrophy
  • Hematologic: Anemia, Bleeding diathesis
  • Cardiopulmonary: Hypertension, Congestive heart failure, Cardiomyopathy, Pulmonary edema, Uremic pericarditis
  • Gastrointestinal: Nausea and vomiting, Bleeding, Esophagitis, gastritis, colitis
  • Neuromuscular: Myopathy, Peripheral neuropathy, Encephalopathy
  • Dermatologic: Sallow color, Pruritus, Dermatitis
• All forms of chronic kidney disease

  Ultimately damage all four components of the kidney, culminating in end-stage kidneys
• Recognizing the early signs and symptoms of kidney diseases is of particular clinical importance
• Study of kidney diseases

  Divided into those that affect the four basic morphologic components: glomeruli, tubules, interstitium, and blood vessels
• Severe glomerular damage

  Impairs the flow through the peritubular vascular system
• Functional reserve of the kidney is large, and much damage may occur before there is evident functional impairment
• Approach to studying kidney diseases

  • Useful because the early manifestations of disease affecting each component tend to be distinct
  • Some components seem to be more vulnerable to specific forms of renal injury
  • Anatomic and functional interdependence of the components of the kidney means that damage to one usually secondarily affects the others
• Azotemia is the bioche
• Glomerular diseases are major problems in nephrology
• NC1 domain in the collagenous suprastructure is important for helix formation and assembly of collagen monomers into the basement membrane suprastructure
• Chronic kidney disease affects 11% of all adults in the United States, predominantly older adults, end result of various renal diseases, commonly diabetes and hypertension, major cause of death from renal disease
• Glomeruli may be injured by a variety of causes
• Evolution from normal renal function to symptomatic chronic kidney injury progresses through stages defined by measures of serum creatinine, estimates of reduction in GFR
• Glycoproteins (laminin, entactin) and proteoglycans (heparan sulfate, perlecan) attach to the collagenous suprastructure
• Glomerular basement membrane (GBM) consists of collagen (mostly type IV), laminin, polyanionic proteoglycans (mostly heparan sulfate), fibronectin, entactin, and several other glycoproteins
• Antigens in the NC1 domain are targets of antibodies in anti-
• Chronic kidney disease causes significant systemic abnormalities
• Clinical manifestations of renal diseases

  • Azotemia is the biochemical manifestation of acute or chronic kidney injury characterized by elevated 1DN or elevated serum creatinine, reflecting a reduction in GFR
  • Acute kidney injury can be reversible or progress to chronic kidney disease, generally irreversible
  • Nephrotic syndrome results in abnormal filtration, leading to heavy proteinuria, edema, and metabolic disturbances
  • Nephritic syndromes involve hematuria, azotemia, hypertension, and sub-nephrotic proteinuria
  • Diseases involving tubules and interstitium may have manifestations of nephritic syndrome, specific defects in tubular function, or acute/chronic kidney disease without defining features
  • End-stage renal disease has GFR less than 5% of normal, the terminal stage of uremia
  • Renal tubular defects are dominated by polyuria, nocturia, and electrolyte disorders, result of diseases affecting tubular structures or causing defects in specific tubular functions
  • Urinary tract obstruction and renal tumors have varied clinical manifestations based on specific anatomic location and nature of the lesion
  • Urinary tract infection characterized by bacteriuria and pyuria, may affect kidney (pyelonephritis) or bladder (cystitis)
  • Nephrolithiasis manifested by severe pain (renal colic) and hematuria, often with recurrent stone formation
• Systemic abnormalities caused by chronic kidney disease

  • Listed in Table 20.1
• Type IV collagen forms a network suprastructure in the GBM to which other glycoproteins attach
• Proteoglycan content of the GBM

  • May contribute to its permeability characteristics
• The glomerulus is impermeable to proteins of the size of albumin