Renal Pathology Flashcards
Important Renal Functions
Regulate fluid volume and acid/base balance of plasma
Excrete nitrogenous waste
Synthesize erythropoeitin, 1,25-dihydroxycholecalciferol and renin
Drug metabolism
Healthy Kidney v. Unhealthy Kidney
Healthy Kidney:
- sodium and water removal
- waste removal
- hormone production
Unhealthy kidney
- fluid overload
- elevated waste such as UREA, CREATININE, and POTASSIUM
- changes in hormone levels which control BP, RBCs, and Ca uptake
Definition of End Stage Renal Disease
GFR - less than 5%
Terminal stage of uremia (urine in the blood)
Systemic manifestations of Chronic Kidney Disease and Uremia
Fluid and Electrolytes
(Dehydration- Edema- Hyperkalemia- metabolic acidosis)
Calcium Phosphate and Bone
(Hypocalcemia- hyperphosphatemia- secondary hyperparathyroidism- renal osteodystrophy)
Hematologic
(Anemia- bleeding)
Cardiopulmonary
(Hypertension-HF Cardiomyopaty- pulmonary edema-)
Gastrointestinal
(Nausea and vomiting- gastritis- esopahgities-colitis MYOPATHY- peripheral)
Neuromuscular
(PRURITUS)
Dermatologic
(DERMATITIS)
Comorbidities of Kidney Failure and end stage renal disease
Diabetes
HTN
Glomoerulonephritis
Immunosuppresion
Chronic Kidney Disease (CKD)
Progressive loss or renal function that persists for 3 months or longer
Five stage classification system for CKD based on the glomerular filtration rate (GFR)
CKD Staging
Stage 1) Kidney Damage with normal or increased GFR (90+)
Stage 2) Kidney damage with normal or mild DECREASE in GFR (60-89)
Stage 3) Moderate decrease in GFR (30-59)
Stage 4) Severe decrease in GFR (15-29 GFR)
Stage 5 (end stage) Less than 15% (or dialysis)
Progressive Kidney Disease
Reduced renal function
Effects on multiple organ systems
Potential manifestations of Kidney Disease
ANEMIA ABNORMAL BLEEDING ELECTROLYTE AND FLUID IMBALANCE HYPERTENSION DRUG INTOLERANCE SKELETAL ABNORMALITIES HOST COMPROMISED BY NUTRITIONAL DEFICIENCIES- Leukocyte dysfunction- more susceptibility to infections
Relationship between CKD and bleeding
Decreased production of von Willebrand factor
Platelets dysfunction- abnormal platelet adhesion and aggregation
Defective platelet production
Renal Osteodystrophy
Decreased renal function
Decreased 1,25-dihydroxyvitamin D production
Reduced intestinal absorption of calcium (hypocalcemia)
Secondary hyperparathyroidism
Inhibition of osteoblasts maturation and matrix remineralization
Renal Osteodystrophy Manifestations
Osteomalacia- ummineralized bone
Osteitis fibrosa- bone resorption with lytic lesions and marrow fibrosis
Osteoesclerosis- enhanced bone density
Spontaneous fractures
Slow healing
Bone growth is impaired
Renal Osteodystrophy Signs and Symptoms
Bone pain
Anorexia
Nausea-vomiting
Generalized gastroenteritis and peptic ulcer disease
Peripheral neuropathy- muscular hyperactivity (twitching)
Bleeding- petechiae
Dental findings for Renal Osteodystrophy
Xerostomia Candidiasis Periodontal disease/gingivitis Gingival bleeding Erosion lingual tooth surface Enamel hypoplasia Narrowing of the pulp chambers Pigmentation of oral mucosa Parotid infections Metallic taste Halitosis Ulcerations Lichen/lichenoid lesions Hairy tongue Uremic stomatitis ( in severe end-stage renal disease)
Halitosis
Sign of renal disease due to increased levels of urea in the body
DDX:
- Diabetes
- Respiratory Infections
- Periodontal disease
Clinical Manifestations of Kidney Disease
Azotemia- Increase blood urea and elevated creatinine levels- glomerular filtration rate
Uremia- biochemical abnormalities- manifestations- peripheral neuropathy
Nephritic Syndrome- hematuria- RBC cast moderate proteinuria and HTN
Nephrotic Syndrome- Glomerular disease- HEAVY proteinuria,edema hyperlipidemia and lipiduria
Acute Kidney Injury
Chronic Kidney Disease
Low albumin leads to low oncotic pressure- EDEMA
Leads to increased sodium and water retention
General trend of Kidney Disease etiology
Glomerular- immunologically mediated (Antigen-antibody interactions which deposit circulating antigen-antibody complexes in the glomerulus)
Tubular- interstitial- toxic or infectious agents
Post-infections glomerulonephritis
Caused by immune complexes that contain streptococcal antigens and specific antibodies that are formed in-situ.
Clinical Presentation:
-Abrupt onset of malaise, fever, nausea, oliguria, and
hematuria 1 to 2 weeks after recovery of a sore
throat
- Nephritic syndrome (RBCs in urine)
- Periorbital edema
- Mild to moderate hypertension
-Slight elevation in BUN
Histology:
- Interstitial edema- swelling of endothelial cells
obliteration of the capillary lumens
-Hypercellularity reaction (infiltration of inflammatory
cells, proliferation of endothelial & mesangial cells &
form some crescents…)
- RBC casts in tubules
Immunofluorescence:
Granular deposits of IgG and C3 in the mesangium and along the subepithelial basement membrane
Electron Microscopy:
Discrete, electron-dense deposits on the epithelial side of the membrane; “buzz word” for this is “HUMPS”
Most recover
Goodpasture Disease
antiGBM
Severe glomerular injury characterized by rapid and progressive loss of renal function
Immunological related- antibodies directed at components of the glomerular basement membrane (collagen type lV)
Light Microscopy:
- Hypercellular rxn
- Dominated by Crest formation
- focal or segmental necrosis
Immunofluorescence:*
- Linear deposits of IgG and C3 along the basement
membrane (ribbon-like)
Lung hemorrhage-( pulmonary renal syndrome)
No consistent trigger
Reduced urine output Hemoptysis Edema Recent URI is common Anti-GBM antibody titer- positive
Membranous Nephropathy
Rapid onset of NEPHROTIC syndrome
Chronic immune mediated characterized by diffuse thickening of the glomerular capillary wall
Most cases are Primary (75%):
- NSAIDs- gold- captopril- penicillamine- SLE
-Malignancies ( lung-colon-melanoma) lymphoma
-Infections (hepatitis) syphilis
- Other autoimmune disorders like Sarcoidosis-
Sjogren- RA
Immunofluorescence:
Accumulation of diffuse, granular deposits of IgG and C3 along the subepithelial side of the basement membrane, in situ
EM:
- Basement membrane material is laid down between the deposits formed between the basement membrane and the overlying epithelial cells with effacement of podocyte processes; buzzword is “SPIKES”
Minimal Change Disease
Benign NEPHROTIC disorder seen in children 2-6 years of age
90% idiopathic- thought to be likely involved wih immune system dysregulation
Glomerular injury-increase glomerular permeability
Massive proteinuria with perserved renal function; mostly Albumin is lost
GFR normal
Sometimes after a respiratory infection or immunization
GOOD RESPOND TO CORTICOSTEROIDS***
Renal biopsy- Electron microscopy- podocyte effacement. Normal by light microscopy
Frequent lipid and protein in the proximal tubules called “LIPOID NEPHROSIS”
Immunofluorescence:
No Ig or complement deposition
Common symptom of Minimal Change Disease
Periorbital Edema
Focal Segmental Glomerulosclerosis
Most common Nephrotic syndrome in adults in the US (children can be affected)
Acute or subacute onset
Higher incidence of hematuria, reduced GFR, hypertension, azotemia.
Proteinuria is more non-selective
POOR RESPONSE TO CORTICOSTEROIDS
50% progress to ESRD in 10 years
Similar presentation to minimal change
More common in black people 4-7 fold increase. More men than females
Principal etiology of ESRD- sclerosis progresses- GLOBAL sclerosis**
Focal Segmental Glomerulosclerosis etiology
Incidence of primary and secondary forms has been increasing steadily
May be secondarily assoc with HIV, heroin nephropathy, sickle cell dz, and morbid obesity
As a secondary event
- Scarring from a previous necrotizing event
Adaptive response to loss of renal tissue
- Congenital abnormalities, reflux nephropathy, hypertension
Uncommon inherited form of nephrotic syndrome linked to mutations in genes that encode the protein products nephrin and podocin.
What is the hallmark of FSGN on histology?
epithelial damage
Light micro: focal and segmented lesions; mesangial collapse and sclerosis
Electron micro: Degeneration and focal
disruption of epithelial cells with diffuse effacement of foot processes, (podocytes)
Immunofluorescence:
IgM and C3 in the sclerotic areas and the mesangium
Difference between Minimal Change Disease and FSGN
Spontaneous remission is rare
Children have a better prognosis with Minimal Change Disease
Poor response to corticosteroids therapy in FSGN
Whereas minimal change disease (MCD) shows normal histology, FSGS is associated with sclerosis under the microscope with proteinuria.
Progression to chronic kidney dz, with 50% developing ESRD within ten years
IgA Nephropathy (Berger Disease)
Common worldwide (most common glomerulonephritis)
Mesangial IgA immune deposits
Glomerulonephritis of varying severity
Idiopathic or after an upper respiratory tract infections or gastroenteritis; gross hematuria
Hematuria lasts a few days, subsides, and returns every few months
Maintain normal kidney function for decades
15-40% will develop chronic renal failure over a period of 20 years
Occurs with increased frequency in individuals with gluten enteropathy and liver disease
5-10% develop acute nephritic syndrome with some developing rapidly progressive glomerulonephritis
Alport Syndrome
Defective type IV collagen- glomerular basement membrane
X linked autosomal dominant/autosomal recessive forms exist
Nerve deafness, lens dislocation, posterior cataracts and corneal dystrophy
Manifested by hematuria and progression to chronic renal failure
Males
Variability age of onset
EM: Irregular thickening and thinning of the GBM with splitting and lamination of the lamina densa
Buzzword: “Basketweave appearance”
Diabetic nephropathy
Leading cause of CKD
ESRD occurs in up to 40% of diabetics
Histopath changes are similar for type I and type II diabetics
Three lesions are encountered:
Glomerular
Renal vascular (arteriolosclerosis)
Pyelonephritis
Diabetic microangiopathy- glomerular lesions and thickening of basement membranes
Pyelonephritis (kidney infection spreading from UTI)
Causes of Secondary Glomerulonephropathies
SLE- 50 % renal involvement
(predominant effects females)
Diabetes- arteriolosclerosis- microangiopathy- pyelonephritis
Sickle cell disease
Lupus Nephritis
Renal disease in > 50% of patients
Clinical Presentation: Persistent proteinuria
Nephritic synd; Nephrotic synd; Rapidly Progressing Glomerular Nephritis; Membranous; Acute and chronic renal failure
Pathogenesis: Immune complex deposition;
Anti-dsDNA antibodies deposited within the mesangium and non-uniformly along the basement membrane
In situ and immune complex deposition
Wide variability in injury patterns
Six different classes of systemic lupus classified pathologically
Lesions seen in Diabetic Nephropathy (Kimmelstiel- Wilson Disease)
Glomerular lesions:
Capillary BM thickening
Diffuse mesangial sclerosis
Nodular glomerulosclerosis
Tubular lesions:
BM thickening
Microangiopathy:
- Hyaline sclerosis of the afferent and efferent arterioles
Sickle cell disease Nephropathy
Hemoglobinopathy
Hereditary- mutation lead to structural abnormalities
Sickling of blood cells
Widespread microvascular obstruction-ischemic damage and pain
Variable prognosis
Hematuria, proteinuria and diminished concentrating ability (nephritic syndrome)
Nephrotic syndrome can also occur
Most important features of Sickle Cell Nephropathy
Papillary ischemia and necrosis
Injury due to accelerated sickling of RBC’s in the medullary vasa recta because of low oxygen tension
Acute Kidney Injury (ATN)
Refers to a rapid decline in the glomerular filtration rate and is concurrent with dysregulation of fluid and electrolyte balance
Caused by injury to the glomerular, intersitial, vascular, or tubular areas leading to Ischemia- interruption of blood flow- massive hemorrhage, severe burns, dehydration, prolonged diarrhea, CHF
Direct toxic injury- endogenous (hemoglobin- monoclonal light chains)
exogenous- drugs, radiocontrast dyes, heavy metals and organic solvents
Reduced urine production
Pulmonary edema
Hypotension (ATN) or hypertension ( Intravascular volume expansion)
Peripheral edema- impaired renal salt excretion
Retention of metabolic waste products
May result in oliguria or anuria
Analgesic Nephropathy
Assoc with nonsteroidal anti-inflam drugs (NSAID’s)
Aspirin, celebrex, ibuprofen (advil, motrin), naproxen (aleve)…
NSAID’s are cyclooxygenase inhibitors
Adverse renal effects are related to their ability to inhibit cyclooxygenase-dependent prostaglandin synthesis
The selective COX-2 inhibitors affect the kidney because COX-2 is expressed in kidneys
Analgesic Nephropathy and Acute Kidney Failure
Sudden-onset kidney failure
OTC painkillers: Aspirin, ibuprofen and naproxen
Fluid loss or decreased fluid intake
Wide range: single dose-short term use of not more than 10 days
Risk factors: SLE, advanced age, heavy alcohol consumption
Emergency dialysis- Kidney damage is usually reversible
Toxins causing Tubulointerstitial Nephritis
lead, mercury, arsenic, and cadmium
NSAID-Associated Renal Syndromes
Acute kidney injury
(Decreased synthesis of vasodilatory prostaglandins causing ischemia)
Acute hypersensitivity interstitial nephritis
Acute interstitial nephritis and minimal change disease (nephrotic syndrome)
Injury to podocytes mediated by cytokines released as part of the inflammatory process
Membranous nephropathy (nephrotic syndrome) Unclear pathogenesis
AV fistula
Nondominant arm
Advantages:
Lower infection rates
Higher blood flow rates Lower thrombosis/stenosis rates
Disadvantages:
Longer maturation time
Aneurysm formation
AV Graft
Artificial vessel (graft) made of synthetic material
Forearm
Upper arm
Lower extremity
Advantages:
Can be use sooner
Disadvantages
Pseudoaneurysm formation
Higher infection rates
Blood clots
Infective endocarditis
Occurs in 2% to 9% of patients receiving hemodialysis
Staphylococcal infections that develop at the site of the graft/fistula/catheter
Viridans and lactobacillus
Antibiotic prophylaxis before invasive dental procedures is NOT supported by the AHA , need consultation with MD
Comorbidities
Laboratory Diagnosis of Kidney Disease
Routine Urinalysis
Color, turbidity, pH, specific gravity, protein, glucose, ketones;
Microscopic analysis
Routine Blood Tests
Na, K, Cl, glucose, BUN, creatinine
Azotemia
Biochemical abnormality that refers to an elevation of blood urea nitrogen and creatinine levels
Usually related to a decreased glomerular filtration rate
Types of Azotemia include:
Prerenal azotemia
Hypoperfusion of the kidneys
Postrenal azotemia
Urine flow obstruction distal to the kidney
Intrinsic renal disease
Uremia
When azotemia becomes associated with a constellation of clinical signs and symptoms and biochemical abnormalities, it is termed uremia
Uremia is notable for a number of extrarenal manifestations
Uremic gastroenteritis, peripheral neuropathy, uremic fibrinous pericarditis, etc.
Nephritic Syndrome
Glomerular disease
Dominated by an acute onset of hematuria, RBC casts in the urine, diminished GFR, mild to moderate proteinuria, and hypertension
KEEP IS THE HEMATURIA
Nephrotic Syndrome
Glomerular disease
Dominated by HEAVY proteinuria (3.5 gm/ day)
which leads to a significant loss of serum albumin (hypoalbuminemia,), which leads to low oncotic pressure (edema), which leads to sodium and water retention as well as hyperlipidemia, and lipiduria
Several factors affecting the localization of the antigen, antibody, or immune complexes
Highly cationic antigens tend to cross the basement membrane (subepithelial location)
Highly anionic antigens are excluded (subendothelial location)
Neutral charge complexes tend to localize to the mesangium
Large complexes tend to be excluded from filtration
Glomerular Reactions To Injury
Hypercellularity
- Proliferation of mesangial cells or endothelial cells
- Infiltration of leukocytes
- Formation of crescents
Basement membrane thickening
-Deposition of material (proteoglycans or more type
IV collagen)
-Increased synthesis of proteins
-Formation of additional GBM layers
Hyalinosis
- Accumulation of eosinophilic proteinaceous material which obliterates the capillary lumens
Sclerosis
-Deposition of extracellular collagenous material
Primary Glomerulonephropathies v.
Secondary Glomerular Diseases
Primary Glomerulonephropathies – refer to disorders in which the kidney is the predominant organ involved
Secondary glomerular diseases -- Systemic diseases in which the kidneys are affected
> Systemic lupus erythematosus
>Hypertension
>Diabetes mellitus
>Alport syndrome
Examples of Primary Glomerulopathies
Postinfectious glomerulonephritis Goodpasture syndrome Chronic glomerulonephritis Membranous nephropathy Minimal change disease Focal segmental glomerulosclerosis Membranoproliferative glomerulonephritis (MPGN Type I) Dense deposit disease (MPGN Type II) IgA nephropathy
Diseases that can result in rapidly progressive glomerulonephritis (RPGN)
Anti-GBM antibody
> Type I, Goodpasture syndrome
Immune complex > Lupus nephritis >Henoch-Schonlein purpura >IgA nephropathy > Postinfectious glomerulonephritis
Pauci-immune
> ANCA-associated
>Granulomatosis with polyangiitis
>Microscopic polyangiitis
Diabetic Nephropathy
Arteriolosclerosis
Diabetic microangiopathy
- Glomerular lesions
- Thickening of
basement membranes
Pyelonephritis
Tubulointerstitial Diseases
Ischemic or toxic tubular injury
- Acute tubular necrosis
Inflammatory reactions of the tubules and interstitium
- Tubulointerstitial
nephritis
Acute Tubular Necrosis
is a reversal lesion that occurs in a variety of clinical settings
Most of the clinical scenarios have a period of inadequate blood flow to the peripheral organs
Ischemic acute tubular necrosis
May be associated with hemolytic crises
Mismatched blood transfusions (hemoglobinuria)
Skeletal muscle injury (myoglobinuria)
Characterized by destruction of tubular epithelial cells (pathologic)
Acute suppression of renal function (clinical)
Most common cause of acute renal failure
Causes of Acute Renal Failure
Organic vascular obstruction
-Diffuse involvement of intrarenal vessels from
systemic disease (hypertension)
Severe glomerular disease
-Rapidly progressive glomerulonephritis
Acute tubulointerstitial nephritis
- Hypersensitivity to drugs
Massive infection
- Pyelonephritis
Disseminated intravascular coagulation
Urinary obstruction
- Tumors, prostatic hyperplasia
Acute tubular necrosis
Nephrotoxic Acute Tubular Necrosis
Gentamicin and other penicillin antibiotics
Contrast agents (for CTs and MRIs)
Poisons (mercury)
Organic solvents (carbon tetrachloride)
Pathogenesis:
Two critical events -
Tubular injury
Persistent and severe disturbances in blood flow
So if theres injury to the tubules itself, dysfunction with sodium transport, the kidneys will recognize that dysfunction, further constrict blood vessels and lead to a persistent and severe disturbance to blood flow. Sort of a feedback mechanism that makes things worse without clinical attention.
Ischemic Damage in ATN
Reversible structural changes:
- Cellular swelling
- Loss of brush border
- Blebbing
- Loss of polarity
- Cell detachment
Irreversible structural changes:
- Necrosis
- Apoptosis
Functional damage:
- Depletion of ATP
- Accumulation of
intracellular calcium
- Activation of proteases
and phospholipases
- Generation of reactive
oxygen species
Result of Ischemic Damage
Recruitment of leukocytes
Luminal obstruction by injured tubular cells
Interstitial edema leading to tubule collapse
Tubuloglomerular feedback
Ischemic vs. Toxic ATN
Ischemic:
Most vulnerable locations are the straight portion of the proximal tubule and the ascending thick limb in the renal medulla
Toxic:
Injury occurs in the proximal convoluted tubules
Hyaline casts are common, particularly in the distal tubules and collective ducts
Interstitial edema and Accumulation of leukocytes in both
Clinical Course of Acute Tubular Injury
Highly variable
- Initiating
- Lasts about 36 hours
- Dominated by the inciting event
- Slight decline in urine output and a rise in BUN
- Maintenance
- Sustained decreases in urine output
- Salt and water overload
- Rising BUN
- Hyperkalemia
- Metabolic acidosis
- Uremia
- Recovery stages
- Steady increase in urine volume (up to 3/L a day)
- Tubules are still damaged, so large amounts of water, sodium, and potassium are lost in the urine
- Hypokalemia becomes a problem
- Increased risk of infection
Prompt and appropriate treatment is the difference between life and death
Tubulointerstitial Nephritis (TIN)
Can be acute or chronic
Distinguished from glomerular diseases by defects in tubular function (impaired ability to concentrate urine, salt wasting, metabolic acidosis) and a lack of glomerular hallmarks (nephritic or nephrotic syndrome)
Causes of Primary Tubulointerstitial Nephritis
Infections Toxins Metabolic Diseases Physical Factors Neoplasms Immunologic Reactions Vascular Diseases Others
Pyelonephritis
One of the most common diseases of the kidney
Defined by inflammation affecting the tubules, interstitium, and renal pelvis
Acute pyelonephritis =
Bacterial infection and is associated with UTI
Chronic pyelonephritis =
More complex pathogenesis
Two routes of infection:
- Hematogenous infection (a systemic infection – if you have a pneumonia, infective endocarditis, some other localized infection or systemic infection within the body)
- Ascending infection (coming from a UTI)
Acute Pyelonephritis
Suppurative inflammation of the kidney
Patchy, interstitial inflammation
Intratubular aggregates of neutrophils
Tubular necrosis
Glomeruli are relatively resistant
- Extensive infections with involve all compartments
Discrete, focal lesions
Wedge shaped areas
can develop frank papillary necrosis, so complete destruction & necrosis of the renal papilla.
If the infection continues to accumulate & pus gathers in the area of the calyces in the kidney, that is what is called pyonephrosis – so pus in the kidney.
& then there can be direct extension into the perinephric soft tissues & you can develop peripnephric abscess which can be in the acute phase or the chronic phase.
Papillary Necrosis
Mainly seen in diabetics, sickle cell disease, and urinary tract obstruction
Usually bilateral
Grossly, see necrosis of the tips of the papilla
Microscopically, see coagulative necrosis
Pyonephritis and Perinephric Abscess
Seen when there is total or near total obstruction
Pus fills up the pelvis, calyces, and ureter
Extension of the inflammation into the surrounding tissues
Healing occurs
Neutrophils are replaced by macrophages, lymphocytes, and plasma cells
Scars form
>Tubular atrophy, interstitial fibrosis, and lymphocytes
> Patchy, jigsaw pattern
> Fibrous depressions on the surface
Chronic Pyelonephritis
Chronic tubulointerstitial inflammation and scarring involve the calyces and pelvis
Reflux nephropathy
Chronic obstructive pyelonephritis
Reflux Nephropathy
More common form
Occurs early in childhood as the result of UTI and congenital vesicoureteral reflux
May be unilateral or bilateral, leading to renal insufficiency
Chronic Obstructive Pyelonephritis
Recurrent infections superimposed on localized or diffuse obstructive lesions
Unilateral in the case of calculi
Bilateral in the case of congenital lesions
Repeated bouts of inflammation and scarring
Drug and Toxin Induced Tubulointerstitial Nephritis
Second most common cause of acute kidney injury (after pyelonephritis)
Injury occurs in at least three ways
- Triggers an interstitial immunologic reaction (hypersensitivity nephritis)
- Causes acute tubular injury
- Causes subclinical but cumulative damage to tubules
Acute Drug-Induced Interstitial Nephritis
Can occur with a variety of drugs: Synthetic penicillins Rifampin Diuretics NSAIDs Allopurinol Others
Fever, esoinophilia, rash (25% of patients), and renal abnormalities
15 days after drug exposure (range of 2-40)
Hematuria
Mild proteinuria
Leukocyturia (eosinophils)
Clinical evidence suggests a hypersensitivity reaction (Type I) Latent period Eosinophilia and rash Not dose related Recurrence after re-exposure IgE elevations (in some patients)
Other cases suggest a T-cell mediated process with granulomatous inflammation and a positive skin test (Type IV)
Multiple Myeloma
Bence-Jones proteinuria and cast nephropathy:
BJ proteins are directly toxic to the tubules
BJ proteins can combine with Tamm-Horsfall proteins and obstruct tubular lumens
Amyloidosis
Free light chains occur in 6-24% of MM patients
Light chain deposition disease:
May deposit in the GBM and mesangium
Hypercalcemia and hyperuricemia
Nephrosclerosis
Describes sclerosis of renal arterioles
Strongly associated with hypertension
Cause and consequence of nephrosclerosis
Medial and intimal thickening of the vessels as a response to a variety of factors
Hyalinization of the arteriolar walls
Patchy ischemic atrophy
Tubular atrophy and interstitial fibrosis
Glomerular changes
Renal Artery Stenosis
Narrowing at the origin of the renal artery by atheromatous plaque (70%)
Fibromuscular dysplasia is the second most common cause
Abnormal fibrous thickening of the intima, media, or adventitia
Renal artery narrowing stimulates renin secretion leading to production of the vasoconstrictor angiotensin II
Hydronephrosis
So as the kidney is backing up things start to dilate. You get progressive atrophy of the kidney. Might be slightly to massively enlarged over time. The important thing is it’s going to decrease it’s functional capacity and people affected will develop chronic kidney disease over time.
Wilm’s Tumor
Most common pediatric renal tumor
Peak incidence is 2 to 5 years
95% occur before 10 years of age
Approximately 5-10% involve both kidneys
Clinical Features: Abdominal mass
Hematuria
Intestinal obstruction
Hypertension
Cure rate is approximately 90%
Renal Cell Carcinoma
Most common adult renal tumor
Accounts for approximately 3% of all newly diagnosed malignancies in the US
Accounts for 85% of all renal malignancies
2:1 male predominance
Smoking is the most significant risk factor
Usually a solitary, unilateral tumor
Propensity for the poles
Tendency to invade the renal vein
Clinical Features of Renal Cell Carcinoma
Classic triad
Costovertebral pain, palpable mass, and hematuria
All three are only seen in about 10% of cases
Hematuria is most reliable but often intermittent
Often silent, large (10 cm), and metastatic at diagnosis
5 year survival is from 60-90%
Treatment is nephrectomy and chemotherapy
The risk of Wilm’s tumor is increased with at least three recognizable groups of congenital malformations associated with distinct chromosomal abnormalities
WAGR syndrome
Denys-Drash syndrome
Beckwith-Weidemann syndrome
