RENAL DISEASE CHAPTER 7

Learning Objectives Upon completing this chapter, the reader will be able to Differentiate among renal diseases of glomerular, tubular, interstitial, and vascular origin. Describe the processes by which immunologic damage is caused to the glomerular basement membrane. Define glomerulonephritis. Describe the characteristic clinical symptoms, etiology, and urinalysis findings in acute poststreptococcal and rapidly progressive glomerulonephritis, Goodpasture syndrome, Wegener’s granulomatosis, and Henoch-Schönlein purpura.  Name three renal disorders that also involve acute respiratory symptoms.

Learning Objectives (cont’d) Differentiate between membranous and membranoproliferative glomerulonephritis. Discuss the clinical course and significant laboratory results associated with immunoglobulin A nephropathy. Relate laboratory results associated with the nephrotic syndrome to the disease process. Compare and contrast the nephrotic syndrome and minimal change disease with regard to laboratory results and course of disease. State two causes of acute tubular necrosis. Name the urinary sediment constituent most diagnostic of renal tubular damage.

Learning Objectives (cont’d) Describe Fanconi syndrome, Alport syndrome, uromodulin-associated renal disease, and renal glucosuria. Differentiate between diabetic nephropathy and nephrogenic diabetes insipidus. Compare and contrast the urinalysis results in patients with cystitis, pyelonephritis, and acute interstitial nephritis. Differentiate among causes of laboratory results associated with prerenal, renal, and postrenal acute renal failure. Discuss the formation of renal calculi, composition of renal calculi, and patient management techniques.

Introduction Disorders throughout the body can affect renal function and produce abnormalities in the urinalysis The kidneys are consistently exposed to potentially damaging substances

Classification Glomerular disorders Tubular disorders Interstitial disorders

Glomerular Disorders Majority are of immunologic disorders Immune complexes from immunologic reactions throughout the body Increased serum immunoglobulins are deposited on the glomerular membranes Immune system mediators: complement migrate and produce change and damage to membranes Nonimmunologic Chemicals and toxins, deposition of amyloid material and acute phase reactants, electrical charge interference, membrane thickening

Glomerular Disorders (cont’d)

Glomerular Disorders (cont’d) Glomerulonephritis General term for sterile, inflammatory process affecting the glomerulus Causes blood, protein, and casts in urine Types of glomerulonephritis progress through various disorders Acute glomerulonephritis to chronic glomerulonephritis to nephrotic syndrome to renal failure

Acute Poststreptococal Glomerulonephritis (AGN) Fever, edema around the eyes, oliguria, and hematuria Immune complexes deposit on glomerular membranes Hematuria, proteinuria, oliguria Red blood cell (RBC) casts, dysmorphic RBCs Hyaline and granular casts White blood cells Anti–group A streptococcal enzyme tests Group A streptococcal infections from organisms with M protein in the cell wall Rapid anti–group A streptococcal enzyme tests Ease in diagnosis Decline in incidence

Rapidly Progressive (Crescentic) Glomerulonephritis More serious acute form → renal failure Systemic immune disorders Macrophages damage capillary walls Fibrin = permanent damage to capillary tufts Urinalysis similar to AGN progresses to more abnormal, elevated protein, low glomerular filtration rate (GFR) May have increased fibrin degradation products (FDP), cryoglobulins and IgA immune complex depositions

Goodpasture’s Syndrome Morphological changes resembling crescentric GN Autoimmune disorder against glomerular and alveolar basement membranes Cytotoxic antibody following viral respiratory diseases Antiglomerular basement membrane antibody Hemoptysis, hematuria, proteinuria, RBC casts Chronic glomerulonephritis to end-stage renal failure is common

Wegener’s Granulomatosis Inflammation and granulomas in small blood vessels of kidney and respiratory system Key to diagnosis Antineutrophilic cytoplasmic antibody (ANCA) Neutrophils initiate immune response, producing granulomas Pulmonary symptoms first, then hematuria, proteinuria, RBC casts, elevated BUN and creatinine levels Immunofixation for p-ANCA/c-ANCA

Henoch-Schönlein Purpura Children following upper respiratory infections Raised, red patches on skin Blood in sputum and possibly stools Renal involvement is the most serious complication of the disorder Proteinuria and hematuria, RBC casts 50% complete recovery Follow patients for more serious renal problems

Membranous Glomerulonephritis IgG immune complexes cause pronounced thickening on glomerular basement membrane Systemic lupus erythematosus, Sjögren’s syndrome, secondary syphilis, hepatitis B, gold and mercury treatments, malignancy These aid in diagnosis Often unknown etiology Slow progression, remission, nephrotic syndrome Microscopic hematuria, very high protein

Membranoproliferative Glomerulonephritis (MPGN) Type 1: increased cellularity in the subendothelial cells of the mesangium Thickening of capillary walls Type 2: extremely dense deposits in the glomerular basement membrane Poor prognosis Hematuria, proteinuria, ↓ complement Autoimmune disorders, infections, malignancies

Chronic Glomerulonephritis Progression from previous disorders Fatigue, anemia, hypertension, edema, oliguria gradually worsening Hematuria, proteinuria, glycosuria (tubular damage), many types of casts including broad and waxy casts Markedly decreased GFR

Immunoglobulin A Nephropathy (Berger’s Disease) Most common cause of glomerulonephritis IgA complexes on glomerular membrane Increase serum IgA Early macroscopic hematuria from exercise or infection with spontaneous recovery 20 years later: gradual progression to chronic glomerulonephritis Granular and disintegrating RBC casts

Nephrotic Syndrome Acute onset from systemic shock (low blood pressure) or glomerulonephritis complication Glomerular membrane damage and changes in podocyte electrical charges Protein passes through membrane; serum albumin depleted, causing increased lipid production Edema from loss of oncotic pressure Tubular damage

Urinalysis Marked proteinuria >3.5 g/day Fat droplets, oval fat bodies, fatty casts, renal tubular epithelial cells and casts, waxy casts, microscopic hematuria

Minimal Change Disease (Lipid Nephrosis) Children, allergic reactions, immunization, HLA-B12 Heavy proteinuria, edema, transient hematuria; normal BUN and creatinine levels Good prognosis, steroids, remission

Focal Segmental Glomerulonephritis Similar to nephrotic syndrome but affects only certain numbers and areas of glomeruli; podocytes are damaged IgM and C3 immune deposits Moderate to heavy proteinuria; microscopic hematuria Heroin and analgesic abuse, HIV

Alport’s Syndrome Inherited sex-linked and autosomal disorder affecting basement membrane Males more severely affected Macroscopic hematuria with respiratory infections by age 6 years Membrane laminated with thinning; no immune complexes Mild to persistent hematuria, later nephrotic syndrome, renal failure for some

Uromodulin Associated Kidney Diseases (UMKD) Formerly Tamm-Horsfal protein is the only protein produced by the kidney Inherited disorder that results in an abnormal buildup of uromodulin in the tubular cells causing their destruction Patients have elevated serum uric acid and gout at an early age, occurs before renal symptoms

Diabetic Nephropathy Most common cause of end-stage renal disease Glomerular basement membrane thickening Increased proliferation of mesangial cells Increased deposition of cellular and acellular material within matrix of Bowman’s capsule and around capillary tufts Deposition associated with glycosylated proteins from poorly controlled diet Sclerosis of vascular structure Reason for early microalbumin testing

Acute Tubular Necrosis Ischemia: severe decrease in blood flow Trauma, surgery, cardiac failure, electricity, toxogenic bacteria, anaphylaxis Nephrotoxic agents: aminoglycosides, amphotericin B, ethylene glycol, heavy metals, mushroom poisoning, hemoglobin, myoglobin Remove cause and manage symptoms Noticeable renal tubular epithelial (RTE) cells and casts and RTE fragments Hyaline, waxy, granular, broad casts

Hereditary and Metabolic Disorders Fanconi syndrome Generalized proximal convoluted tubule reabsorption failure Inherited with cystinosis and Hartnup disease Acquired: heavy metals, outdated tetracycline Complication of multiple myeloma, renal transplant Glycosuria and electrolyte imbalance

Nephrogenic Diabetes Insipidus Two types Nephrogenic: failure of tubules to respond to antidiuretic hormone (ADH), inherited sex-linked recessive or lithium and amphotericin B exposure, polycystic kidneys and sickle cell anemia Neurogenic: failure to produce ADH Urine: pale yellow, low specific gravity (SG), possible negative results for other tests

Renal Glycosuria Affects only the reabsorption of glucose Inherited as autosomal recessive Decreased number of glucose transporters in tubules Decreased affinity of transporters for glucose Glycosuria with normal blood glucose level

Tubulointerstitial Diseases Infections and inflammations affecting the interstitium and the tubules Most common renal disease is urinary tract infection (UTI) Cystitis (bladder infection) is very common Untreated: progresses to upper urinary tract Many WBCs, bacteria, increased pH, mild proteinuria, hematuria WBCs in urine called pyuria

Acute Pyelonephritis Ascending movement of bacteria Conditions affecting emptying of bladder Calculi, pregnancy, reflux of urine from bladder to ureters Rapid onset, urinary frequency, burning, lower back pain Urinalysis: similar to cystitis with one exception: presence of WBC casts

Chronic Pyelonephritis Damage to tubules, possible renal failure Congenital structural defects causing reflux are most common cause Can affect emptying of collecting ducts Often diagnosed in children Early urinalysis similar to acute pyelonephritis Later granular, waxy, and broad casts; increased protein, hematuria, ↓ SG

Acute Interstitial Nephritis Allergic reaction causing inflammation of interstitium and tubules Medication allergy to penicillin, methicillin, ampicillin, cephalosporins, NSAIDs, thiazide diuretics Discontinue and use steroids to treat Urinalysis, hematuria, proteinuria,↑ WBCs, WBC casts, no bacteria Hansel stain for eosinophils

Renal Failure Acute and chronic forms Chronic renal failure Progression from original disorders to end-stage renal disease GFR <25 mL/min, ↑↑ BUN and creatinine levels, electrolyte imbalance, isosthenuria, proteinuria, renal gycosuria; ↑ granular, waxy, broad casts

Acute Renal Failure Sudden onset, often reversible Decreased blood flow (prerenal), acute disease (renal), renal calculi and tumors (postrenal) Urinalysis related to cause RTE cells = decreased blood flow RBCs = glomerular damage WBCs and casts = infection/inflammation Urothelial cells = possible bladder tumor

Causes of Acute Renal Failure Prerenal Decreased blood pressure/cardiac output Hemorrhage Burns Surgery Septicemia Renal Acute glomerulonephritis Acute tubular necrosis Acute pyelonephritis Acute interstitial nephritis

Causes of Acute Renal Failure (cont’d) Postrenal Renal calculi Tumors Crystallization of ingested substances

Renal Lithiasis Renal calculi (kidney stones) in calyces and pelvis of kidney, ureters, bladder Staghorn, round and smooth, barely seen Severe back pain radiating from lower back to legs when passing Lithotripsy: high-energy shock waves break up stones Also surgical removal

Renal Lithiasis (cont’d) Formation conditions similar to crystals pH, concentration, urine stasis No exact cause of formation known Increased in the summer, dehydration Types of stones 75% calcium oxalate or phosphate Magnesium ammonium phosphate (stuvite) UTI and ↑ pH, like triple phosphate crystals Uric acid: increased purine diet Cystine: hereditary cystinosis