Renal Diseases and Glomerular Disorders

Renal Diseases

• Renal diseases can affect renal function, producing abnormalities in urinalysis.
• Kidneys filter blood to remove waste, making them susceptible to damaging substances.
• Renal disease is often classified as glomerular, tubular, or interstitial based on the affected area.

Glomerular Disorders

• Result from immunologic disorders, with immune complexes forming due to immunologic reactions, leading to increased serum immunoglobulins (IgA) being deposited in glomerular membranes.
• Complement, neutrophils, lymphocytes, and monocytes are attracted to the affected area, causing damage to the membranes.
• Damage includes cellular infiltration and proliferation, leading to glomerular basement membrane thickening.

Nonimmunologic Causes of Glomerular Damage

• Exposure to chemicals and toxins affecting tubules.
• Disruption of the electrical membrane charges (nephrotic syndrome).
• Amyloid material deposition from systemic disorders involving chronic inflammation.
• Thickening of the basement membrane associated with diabetic nephropathy.

Glomerulonephritis

• A sterile, inflammatory process affecting the glomerulus.
• Characterized by blood, protein, and casts in urine.
• Multiple types exist, potentially progressing from one form to another (e.g., rapidly progressive glomerulonephritis to chronic glomerulonephritis, nephrotic syndrome, or renal failure).

Acute Poststreptococcal Glomerulonephritis (AGN)

• Marked by sudden onset symptoms consistent with glomerular membrane damage (fever, edema, fatigue, nausea, hypertension, oliguria, and hematuria).
• Commonly appears in children and young adults after respiratory infections caused by specific strains of group A β-hemolytic streptococci with M protein in the cell wall.
• Treatment focuses on managing secondary complications until immune complexes are cleared and inflammation subsides, leading to no permanent kidney damage.

Acute Glomerulonephritis - Urinalysis Findings

• Marked hematuria, proteinuria, oliguria, and presence of red blood cell casts, dysmorphic RBCs, hyaline and granular casts, white blood cells (WBCs).
• Elevated Blood Urea Nitrogen (BUN) during acute stages.
• Positive Antistreptolysin O (ASO) test.
• Urinalysis results return to normal after membrane damage repair, potentially showing microscopic hematuria lasting until repair.
• RBC casts are a characteristic finding.

Rapidly Progressive (Crescentic) Glomerulonephritis

• Poorer prognosis, often ending in renal failure.
• Symptoms often begin with immune complex deposition in the glomerulus (e.g., as a complication of another form of glomerulonephritis or systemic lupus erythematosus).
• Damage by inflammatory cells (e.g., macrophages) results in capillary wall damage, releasing cells and plasma into Bowman space, causing crescentic formations that cause permanent capillary damage.

Rapidly Progressive (Crescentic) Glomerulonephritis - Urinalysis Findings

• Similar lab results to AGN but become more abnormal as the disease progresses.
• Markedly elevated protein levels and significantly decreased glomerular filtration rates.

Goodpasture Syndrome

• Morphological changes to the glomeruli, resembling rapidly progressive glomerulonephritis.
• Associated with autoimmune disorder.
• A cytotoxic autoantibody targets glomerular/alveolar basement membranes following viral respiratory infections causing destruction.
• Anti-glomerular basement membrane antibody present in patient serum.
• Initial complaints include hemoptysis and dyspnea followed by hematuria.

Goodpasture Syndrome - Urinalysis Findings

• Proteinuria, hematuria, and RBC casts are frequent.
• Progression to chronic glomerulonephritis and end-stage renal failure is common.

Granulomatosis With Polyangiitis (GPA)

• Formerly known as Wegener granulomatosis.
• Characterized by granuloma-producing inflammation of small blood vessels, primarily in the kidney and respiratory system.
• Antineutrophilic cytoplasmic antibody (ANCA) detected in serum.
• Pulmonary symptoms often present first, followed by renal involvement (hematuria, proteinuria, RBC casts) and elevated serum creatinine and BUN levels.

Testing for ANCA

• Serum incubation with ethanol or formaldehyde-fixed neutrophils.
• Indirect immunofixation to detect antibodies attached to neutrophils.
• p-ANCA: perinuclear pattern if serum incubation is with Ethanol
• c-ANCA: granular pattern if serum incubation is with Formalin/Formaldehyde.

Henoch-Schönlein Purpura

• Primarily occurs in children after upper respiratory infections.
• Characterized by raised, red skin patches.
• Respiratory and gastrointestinal symptoms, including blood in sputum and stools.
• Renal involvement is a significant complication, ranging from mild to severe proteinuria and hematuria with RBC casts.

Membranous Glomerulonephritis

• Thickening of the glomerular basement membrane due to immunoglobulin G immune complex deposition.
• Associated with diseases like SLE, Sjögren's syndrome, secondary syphilis, and hepatitis B.
• Laboratory findings include microscopic hematuria, elevated protein excretion, and rare RBC casts.

Membranoproliferative Glomerulonephritis

• Marked by varying cellular alterations in the glomerulus and its peripheral capillaries.
• Type 1: increased cellularity in subendothelial cells, mesangium thickening of capillary walls.
• Type 2 (dense deposit disease): extremely dense deposits in the glomerular basement membrane, tubules and Bowman capsule.
• Type 3: subepithelial and subendothelial deposits.

Membranoproliferative Glomerulonephritis - Continued

• Mostly in children.
• Poor prognosis; Type 1 patients progress to nephrotic syndrome.
• Type 2 patients may experience chronic glomerulonephritis symptoms after renal transplant.

Membranoproliferative Glomerulonephritis - Lab Findings

• Hematuria
• Proteinuria
• Decreased serum complement levels.
• Association with autoimmune disorders, infections, and malignancies.

Chronic Glomerulonephritis

• Progressive damage to the glomerulus, leading to chronic glomerulonephritis and end-stage renal disease (ESRD).
• Gradual worsening symptoms include fatigue, anemia, hypertension, edema, and oliguria.

Chronic Glomerulonephritis - Lab Findings

• Hematuria
• Proteinuria
• Glucosuria
• Presence of broad casts
• Increased BUN and creatinine levels
• Electrolyte imbalance

Immunoglobulin A Nephropathy (IgAN)

• AKA Berger Disease; immune complexes with IgA deposited on glomerular membranes.
• Most common cause of glomerulonephritis in children and young adults.
• Increased levels of serum IgA often associated with mucosal infections.

Immunoglobulin A Nephropathy - Lab Findings

• Macroscopic hematuria after infection or strenuous exercise
• Asymptomatic microhematuria
• Elevated serum IgA levels
• Gradual progression to chronic glomerulonephritis and ESRD

Nephrotic Syndrome

• Marked by massive proteinuria (greater than 3.5 g/day), low serum albumin levels, high serum lipid levels, and pronounced edema.