Kidney Functions and Diseases Overview

Kidney Functions

• Excretion of metabolic waste products
• Regulation of body water and salt
• Maintenance of acid-base balance
• Secretion of hormones

Kidney Disease Classification

• Categorized by the affected part of the kidney: glomeruli, tubules, interstitium, and blood vessels
• Glomerular diseases are often immune-mediated
• Tubular and interstitial diseases are often caused by toxic or infectious agents

Clinical Manifestations of Renal Diseases

• Azotæmia: Elevated blood urea nitrogen (BUN) and creatinine levels, often due to decreased glomerular filtration rate (GFR). Caused by prerenal, renal, or postrenal disorders
• Uræmia: Constellation of symptoms associated with high BUN levels

Major Renal Syndromes

• Acute nephritic syndrome: Acute onset of visible blood in urine (hæmaturia), protein in urine (proteinuria), and high blood pressure (hypertension). Classic presentation of poststreptococcal glomerulonephritis (GN).
• Nephrotic syndrome: Heavy proteinuria (more than 3.5 g/day), low albumin in blood (hypoalbuminæmia), severe swelling (œdema), high blood fat (hyperlipidæmia), and fat in urine (lipiduria).
• Asymptomatic hæmaturia or proteinuria: Manifestation of mild glomerular disease.
• Acute renal failure: Characterized by decreased urine output (oliguria or anuria) and azotæmia. Caused by glomerular, interstitial, or acute tubular injury.
• Chronic renal failure: Characterized by all uræmia symptoms and signs

Urinary Tract Infection (UTI)

• Characterized by bacteria in urine (bacteriuria) and pus in urine (pyuria)

Nephrolithiasis

• Renal stones

Glomerular Diseases Structure

• Glomerular capillary wall:
  • Thin layer of fenestrated endothelial cells (70-100 nm in diameter)
  • Glomerular basement membrane (GBM) with a thick central layer (lamina densa) and two thinner layers (lamina rara interna and lamina rara externa).
  • Visceral epithelial cells (podocytes) with foot processes interdigitating with the lamina rara externa.
  • Mesangial cells supporting glomerular tuft, embedded within the mesangial matrix.
• Glomerulus is highly permeable to water and small solutes but impermeable to large molecules like albumin (70,000 Daltons), permeability depending on molecule size and charge.
• Barrier function depends on integrity of GBM, anionic proteins in the wall, and podocytes.

Pathogenesis of Glomerular Diseases

• Immune mechanisms: Most primary glomerulonephritis, and many secondary cases are immune-related
• Four patterns of glomerular injury:
  • Immune complex deposition: Circulating immune complexes trapped in glomeruli, causing injury. Deposits can be in mesangium, subendothelial, or subepithelial areas. Immunofluorescence shows granular deposits.
  • Immune complex in situ:
    • Anti-GBM antibodies: Linear deposits on immunofluorescence; can also affect alveoli (Goodpasture's syndrome).
    • Heymann's nephritis: Antibodies reacting with podocyte antigens, showing diffuse granular pattern.
    • Antibodies to nonglomerular antigens: Reaction with various antigens – cationic molecules, DNA, bacteria, large aggregated proteins (IgG) and immune complexes.
  • Cell-mediated immune glomerulonephritis
  • Other mechanisms:
    • Epithelial cell injury: From antibodies to visceral epithelial cells, toxins, and cytokines
    • Renal ablation glomerulopathy: Glomerulosclerosis as an adaptive response in unaffected glomeruli due to disease burden.

Nephrotic Syndromes Causes

• Primary glomerular diseases: Minimal change disease, membranous GN, focal segmental glomerulosclerosis, membranoproliferative GN, others
• Systemic diseases: Diabetes, amyloidosis, SLE, drugs (gold, penicillamine, heroin), infections, malignancy, miscellaneous

Minimal Change Disease

• Frequent cause of nephrotic syndrome in children
• Normal glomeruli on light microscopy, loss of podocyte foot processes on electron microscopy
• Podocytes appear lipid-laden
• Unknown pathogenesis
• Usually responsive to corticosteroids, but relapse is common
• Chronic renal failure is rare

Membranous Glomerulonephritis

• Slowly progressive disease, common in ages 30-50
• Subepithelial immunoglobulin deposits
• Often idiopathic
• Secondary causes: infections (hepatitis B, syphilis), malignancies, SLE, drugs, metabolic disorders
• Diffuse GBM thickening on light microscopy
• Non-selective proteinuria, corticosteroid therapy ineffective
• Chronic renal failure risk, about 40%

Focal Segmental Glomerulosclerosis

• Sclerosis affecting some glomeruli, segmental involvement
• Four types: associated with other conditions (like HIV or heroin addiction), secondary to other GN, a component of glomerular ablation nephropathy, primary
• Primary accounts for 10% of nephritic syndrome
• Non-selective proteinuria, poor response to corticosteroids, higher risk of end-stage renal failure (about 50% within 10 years).

Membranoproliferative Glomerulonephritis

• 5-10% of idiopathic nephritic syndromes
• Characterized by glomeruli with enlarged size, mesangial cell proliferation, leukocyte infiltration
• Thickened GBM with a characteristic "tram-track" appearance on stains
• Poor prognosis

Acute Proliferative (Post-streptococcal) Glomerulonephritis

• Immune complexes, usually following group A β-hemolytic streptococcal infection (pharyngitis or skin infection)
• Uniform increased cellularity affecting all glomeruli, due to endothelial and mesangial cell proliferation, neutrophilic and monocytic infiltration, and possible capillary thrombi and necrosis.
• Subepithelial, subependothelial, and intramembranous immune complex deposits on EM.
• Usually good recovery in children, rare cases develop rapidly progressive GN or chronic renal disease.

Rapidly Progressive (Crescentic) Glomerulonephritis

• Rapid and progressive loss of renal function, severe oliguria
• Glomeruli with crescents formed by parietal epithelial cells and monocyte/macrophage infiltration
• Three types based on etiology:
  • Type I (Goodpasture's syndrome): anti-GBM antibodies, linear IgG and C3 deposits
  • Type II: Immune complexes, complicating poststreptococcal GN, SLE, IgA nephropathy, Henoch-Schönlein purpura.
  • Type III (pauci-immune): Lack of anti-GBM and immune complexes, associated with diseases like polyarteritis nodosa or Wegener's granulomatosis.
• High need for dialysis or transplantation (90% of cases)

IgA Nephropathy (Berger's Disease)

• Common, usually affecting children and young adults
• Gross hæmaturia occurring after respiratory tract infections
• IgA deposits in mesangium
• Histologically, can vary from normal to focal, diffuse mesangioproliferative, or rarely crescentic GN.
• Benign course in children, slowly progressive in adults

Acute Pyelonephritis

• Common suppurative inflammation of kidney and renal pelvis, bacterial infection
• Usually associated with lower UTI
• Bacteria reach the kidney by ascending or hematogenous routes
• Risk factors: partial outflow obstruction, vesicoureteric reflux, pregnancy, urinary tract instrumentation, and diabetes
• Gross appearance: discrete yellow, raised abscesses on kidney surface (scattered or localized)
• Histology: suppurative necrosis or abscess formation

Chronic Pyelonephritis

• Interstitial inflammation, scarring of renal parenchyma and pelvicalyceal system (disrupted).
• Two types: obstructive and reflux-associated
• Uneven interstitial fibrosis with inflammatory cell infiltration, tubule dilation or contraction, atrophic lining epithelium, hyaline casts, vascular changes.
• Glomeruli typically normal or show focal segmental glomerulosclerosis.

Acute Tubular Necrosis

• Most common cause of acute renal failure
• Destruction of tubular epithelial cells
• Two types: ischemic and nephrotoxic
• Necrosis of segments within tubules (especially proximal convoluted tubules and thick ascending limbs of Henle's loops)
• Proteinaceous casts (Tamm-Horsfall proteins, hemoglobin, other plasma proteins), interstitial edema, and inflammatory cells.

Tumors

• Renal Cell Carcinoma: Adenocarcinoma arising from renal tubular cells, 80-90% of kidney tumors
• Wilm's Tumor: Third most common childhood organ cancer; found in children under 10, contains immature glomeruli, tubules, mesenchyme
• Transitional Cell Carcinoma: Affects entire urinary collecting system, common in the bladder
  • Can range from benign papillomas to invasive cancers.