1. RENAL DISEASE
CHAPTER 7

2. 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.

3. 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.

4. 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.

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

6. Classification Glomerular disorders Tubular disorders
Interstitial disorders

7. 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

8. Glomerular Disorders (cont’d)

9. 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

10. 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

11. 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

12. 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

13. 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

14. 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

15. 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

16. 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

17. 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

18. 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

19. 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

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

21. 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

22. 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

23. 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

24. 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

25. 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

26. 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

27. 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

28. 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

29. 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

30. 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

31. 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

32. 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

33. 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

34. 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

35. 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

36. 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

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

38. 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

39. 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