Kidney Disorders

(A and E from Forbes C, Jackson W: Color Atlas and Text of Clinical Medicine, 2nd ed. St. Louis, Mosby, 2003, p 276, Figs. 6.10, 6.11, respectively; B, C, D, F, G, and H from Henry JB: Clinical Diagnosis and Management by Laboratory Methods, 20th ed. Philadelphia, WB Saunders, 2001, Plates 18-4, 18-12, 18-13A, 18-17, 18-11, 18-14, respectively.)

Table 19-4 Urinalysis

Urinalysis: gold standard test to evaluate renal disease

IV. Clinical Anatomy of the Kidney

A. Blood supply of the kidney

1. Renal cortex receives ∼︀90% of the blood supply.

2. Renal medulla is relatively ischemic due to reduced blood supply.

Renal medulla: relatively ischemic

3. Renal vessels are end-arteries.

a. No collateral circulation

b. Occlusion of any branch of a renal artery produces infarction.

4. Afferent arterioles

a. Contain the juxtaglomerular apparatus

• Produces the enzyme renin

Renal PGE₂: vasodilation afferent arteriole

b. Blood flow is controlled by renal-derived PGE₂ (vasodilator).

c. Direct blood into the glomerular capillaries

5. Efferent arterioles

a. Drain the glomerular capillaries

b. Blood flow controlled by ATII (vasoconstrictor).

ATII: vasoconstrictor of efferent arterioles

c. Eventually become the peritubular capillaries

Nonsteroidal anti-inflammatory drugs inhibit production of PGE₂; therefore, intrarenal blood flow is controlled by the efferent arterioles, whose blood flow is maintained by ATII, a vasoconstrictor. This increases the risk of ischemic damage to the medulla.

B. Structure of the glomerulus (Fig. 19-3)

1. Glomerular capillaries contain fenestrated epithelium.

• Holes in the endothelial surface are important in the filtration process.

2. Glomerular basement membrane (GBM)

a. Composed of type IV collagen

19-3: Schematic of a normal glomerulus. See text for discussion.

(Modified and reproduced with permission from Striker LJ, Olson JL, Striker GL: The Renal Biopsy, 2nd ed. Philadelphia, WB Saunders, 1990.)

GBM: size and charge determine protein filtration

b. Size and charge are the primary determinants of protein filtration.

(1) Heparan sulfate produces the negative charge of the GBM.

(2) Cationic proteins of low molecular weight (LMW) are permeable.

(3) Albumin has a strong negative charge and is not permeable.

Albumin: negative charge; repelled by negatively charged GBM

(a) Loss of the negative charge causes loss of albumin in the urine.

(b) Called selective proteinuria (e.g., minimal change disease)

(4) GBM is permeable to water and LMW (<70,000 daltons) proteins (e.g., amino acids).

c. Causes of GBM thickening

(1) Deposition of immunocomplexes

• Example—membranous glomerulopathy

(2) Increased synthesis of type IV collagen

• Example—diabetes mellitus

3. Visceral epithelial cells (VEC)

a. Primarily responsible for production of the GBM

b. Contain podocytes (foot-like processes) and slit pores between the podocytes

• Serve as a distal barrier for preventing protein loss in the urine

c. Fusion of the podocytes is present in any cause of the nephrotic syndrome.

Fusion of the podocytes: sign of nephrotic syndrome

4. Mesangial cells

a. Support the glomerular capillaries

b. Can release inflammatory mediators and proliferate

• Example—IgA glomerulopathy has mesangial immunocomplex deposits.

5. Parietal epithelial cells

a. Lining cells of Bowman’s capsule

Crescents: proliferation of parietal epithelial cells

b. Proliferation causes “crescents” that encroach upon and destroy the glomerulus.

V. Congenital Disorders and Cystic Diseases of the Kidneys

A. Horseshoe kidney

1. Most common congenital kidney disorder

2. Majority (90% of cases) are fused at the lower pole (Fig. 19-4).

• Kidney is trapped behind the root of the inferior mesenteric artery.

3. Clinical findings

19-4: Horseshoe kidney. Note that the lower poles of the kidneys are fused.

(From Damjanov I, Linder J: Pathology: A Color Atlas. St. Louis, Mosby, 2000, p 211, Fig. 11-3.)

Horseshoe kidney: association with Turner’s syndrome

a. Increased incidence with Turner’s syndrome

b. Danger of infection and stone formation

B. Cystic diseases of the kidney (Table 19-5 and Figs. 19-5 and 19-6)

Table 19-5 Cystic Diseases of the Kidneys

19-5: Renal dysplasia. Note the multicystic deformed kidney and dilated ureter.

(From Damjanov I, Linder J: Pathology: A Color Atlas. St. Louis, Mosby, 2000, p 213, Fig. 11-11.)

19-6: Adult polycystic kidney disease. There is complete effacement of normal kidney architecture by cysts within the cortex and medulla of both kidneys.

(From Damjanov I, Linder J: Pathology: A Color Atlas. St. Louis, Mosby, 2000, p 212, Fig. 11-7.)

Renal dysplasia: most common cystic disease in children

VI. Glomerular Disorders

A. Terminology of glomerular disease (Table 19-6)

• Normal glomerulus (Fig. 19-7A)

B. Routine studies on biopsy specimens

1. H&E (hematoxylin and eosin) and other special stains

• Used to help classify the type of glomerular disease

2. Immunofluorescence (IF) stain

a. Identifies patterns and type of protein deposition

b. Linear pattern (Fig. 19-7B)

(1) It is a characteristic finding in anti-GBM disease.

Table 19-6 Nomenclature and Description of Glomerular Disorders

19-7: A, Normal glomerulus. B, Linear immunofluorescence. The uninterrupted smooth immunofluorescence along the glomerular basement membrane is caused by deposition of IgG antibodies directed against the membrane (e.g., Goodpasture syndrome). C, Granular immunofluorescence. Granular irregular deposits in the capillaries are caused by immunocomplex deposition (e.g., poststreptococcal glomerulonephritis). D, Fusion of the podocytes. Arrows show fusion of the podocytes. The finding occurs in all glomerular diseases that present with the nephrotic syndrome (e.g., minimal change disease). E, Subendothelial immunocomplex deposits viewed with electron microscopy. The band of electron-dense material extends around the glomerular basement membrane and hugs the interface of the membrane with the capillary lumen. The arrow points to immune deposits directly beneath the nucleus of the endothelial cell. A thin rim of normal basement membrane (light gray) separates the deposits from the epithelial side of the membrane. The patient had diffuse proliferative glomerulonephritis due to systemic lupus erythematosus. F, Subepithelial immunocomplex deposits viewed with electron microscopy. Arrows point to electron-dense deposits directly beneath the visceral epithelial cells in a patient with poststreptococcal glomerulonephritis. The normal basement membrane has a light gray appearance. G, Poststreptococcal diffuse proliferative glomerulonephritis. The glomerulus is hypercellular due to an increase in neutrophils and mesangial cells. H, Crescentic glomerulonephritis. Arrows point to a proliferation of parietal epithelial cells in Bowman’s capsule, occupying approximately 50% of the entire urinary space. The cells encase and compress the glomerular tuft. I, Diffuse membranous glomerulopathy. The H&E (hematoxylin and eosin)-stained biopsy shows glomerular basement membranes that are uniformly thickened. There is no proliferative component. J, Diabetic glomerulosclerosis. Broken arrow points to an afferent or efferent arteriole that has hyaline arteriolosclerosis, with an increase in proteinaceous material in the wall of the vessel. Solid arrow shows a mesangial nodule containing type IV collagen and trapped protein.

(A, F, and G from Damjanov I: Pathology for the Health-Related Professions, 2nd ed. Philadelphia, WB Saunders, 2000, pp 329, 341, 329, Figs. 13-5A, 13-8C, 13-5B, respectively; B, H from Kumar V, Fausto N, Abbas A: Robbins and Cotran’s Pathologic Basis of Disease, 7th ed. Philadelphia, WB Saunders, 2004, pp 969, 977, Figs. 20-10E, 20-17, respectively;C, E, J from Damjanov I, Linder J: Pathology: A Color Atlas. St. Louis, Mosby, 2000, p 224, 229, Figs. 11-54, 11-64, respectively; D from Laszik ZG, Lajoie G, Nadasky T, Silva FG: Medical diseases of the kidney. In Silverberg SG, Delellis RA, Frable WJ [eds]: Principles and Practice of Surgical Pathology and Cytopathology, 3rd ed. New York, Churchill Livingstone, 1997, p 2079; I from Kern WF, Silva FG, Laszik ZG, et al [eds]: Atlas of Renal Pathology. Philadelphia, WB Saunders, 1999, p 53, Fig. 5-30.)

Linear IF: anti-GBM disease (e.g., Goodpasture syndrome)

• Example—Goodpasture syndrome

(2) Antibodies line up against evenly distributed antigens in the GBM.

• Cannot be detected by electron microscopy

c. Granular (“lumpy-bumpy”) pattern (Fig. 19-7C)

• Usually indicates immunocomplex (IC) deposition in the glomerulus

Granular pattern: immunocomplex type of glomerulonephritis

3. Electron microscopy (EM)

a. Detects submicroscopic defects in the glomerulus; examples:

(1) Fusion of podocytes in the nephrotic syndrome (Fig. 19-7D)

(2) Damage to visceral epithelial cells

b. Detects the site(s) of IC deposition