Urology/NephrologyLecture Four – February 28, 2013

Renal Cell Carcinoma

Renal Cell Carcinoma• 2.6% of all adult cancers• 52,190 diagnoses and 12,890

deaths each year• Peaks in 6th decade of life; male-to-

female 2:1• Only significant environmental risk

factor – smoking• Familial predisposition, dialysis-

related cystic disease, genetic abberation can all contribute

• Sporadic tumors are most common• Originate from proximal tubule

cells

Renal Cell Carcinoma• Signs and Symptoms – 60% with gross or

microscopic hematuria; 30% with flank pain or abdominal mass• Triad of flank pain, hematuria, mass – 10-15% - advanced• Fever—paraneoplastic symptom• Metastatsis (cough, bone pain) – 30%

• Increased diagnosis incidentally due to increased use of abdominal imaging

• Labs—hematuria (60%), erythrocytosis in 5% (anemia is more common); hypercalcemia; Stauffer syndrome

• Imaging – abdominal US or CT (most valuable), CXR, bone scans, doppler US

Renal Cell Carcinoma• Radical nephrectomy – primary treatment for localized

RCC• Partial nephrectomy – single kidney, renal disease, or

bilateral cancerous lesions• No effective chemotherapy for metastatic RCC• Prognosis varies with spread of disease• T1-T2 (confined to renal capsule) – 90-100% survival at 5 yrs• T3-T4 50-60% survival• Node-positive tumors – 0-15% survival• Solitary localized metastasis – 15-30% survival

Note – Read Angiomyolipomas p. 1594

Polycystic Kidney Disease

Polycystic Kidney Disease• One of the most common

hereditary diseases (1 in 800)• 50% of pts have ESRD by age

60• 10% of dialysis patients in

the US• 85-90% of pts have mutation

in ADPKD1 on short arm of chromosome 16

• 10-15% of pts have mutation in ADPKD 2 on chromosome 4 – slower disease progression and longer life expectancy

Polycystic Kidney Disease• Abdominal or flank pain• Microscopic or gross hematuria • History of UTIs and/or nephrolithiasis• Family history of PCKD in 75%• 50% or more may have HTN• May have large, palpable kidneys on exam• 40-50% -- concurrent hepatic cysts; may also see

pancreatic or splenic cysts• H&H usually normal• Urinalysis – hematuria, proteinuria

Polycystic Kidney Disease

• US confirms diagnosis• 2+ cysts in pts <30 (88.5% sensitive)• 2+ cysts in each kidney in pts 30-59 (100% sensitive)• 4+ cysts in each kidney in pts 60 or older

• If US results unclear, CT is highly sensitive

Polycystic Kidney Disease• Pain – abdomen or flank; from bleeding into cysts,

infection and nephrolithiasis• bed rest or analgesia; cyst decompression

• Hematuria – rupture of cyst, kidney stone, UTI; resolves in 7 days with bed rest and hydration• Recurrent – possible RCC – especially in men >50 y/o

• Infection – flank pain, fever, leukocytosis, +/- blood cultures, +/- normal UA; CT scan may help diagnose• Antibiotics with good cystic penetration – Bactrim,

fluoroquinolones – may need 2 weeks of IV therapy and long-term oral therapy

• Nephrolithiasis – in up to 20% of pts• 2-3 L/day hydration

Polycystic Kidney Disease• Hypertension – 50% at presentation, most will

eventually developduring disease• Cyst-induced ischemia – RAAS activation• Cyst decompression can improve, plus oral medication

• Cerebral Aneurysms – 10-15% have aneurysms on Circle of Willis; screening arteriography not recommended unless + family history

• Mitral valve prolapse (up to 25%), aortic aneurysms, aortic valve disease, colonic diverticula

• Research continues regarding therapy• Avoiding caffeine, treating HTN, low-protein diet

may help

Glomerulonephritis

Nephritic Spectrum Glomerular Diseases• Glomerulonephritis—inflammatory process renal

dysfunction• Acute (days—weeks), with or without resolution• Chronic with progressive scarring

• See Figure 22-4 p. 894• Symptoms/signs• If nephritic syndrome present, edema is first seen in low

tissue pressure regions (periorbital and scrotal areas)• HTN—sodium retention from acute decrease in GFR• Heavy glomerular bleedinggross hematuria (smoky or

cola urine)

Nephritic Spectrum Glomerular Disorders

Nephritic Spectrum Glomerular Disorders• Labs—may do complement, ANA, cryoglobulins,

hepatitis panel, ANCA, anti-GBM antibodies, ASO titers based on H&P

• Urinalysis—protein, dysmorphic RBCs (abnormal from crossing damaged capillary membrane); RBC casts; proteinura usually <3 grams/day

• Biopsy—consider if no contradindications• Treatment—aggressive treatment of hypertension

and fluid overload; may need dialysis

Postinfectious Glomerulonephritis• Usually due to infectious with nephritogenic

GABHS• Commonly 1-3 wks after pharyngitis or impetigo• Other causes—bacteremia, bacterial pneumonia,

deep-seated abscess, Gram-negative infections, infective endocarditis, and shunt infections

• Viral, fungal, and parasitic infections can also cause

Postinfectious Glomerulonephritis• Signs/Symptoms—varies widely from

asymptomatic glomerular hematuria to nephritic syndrome

• Labs—Low serum complement, may see elevated antistreptolysin-O titers; glomerular hematuria; subnephrotic proteinuria; elevated serum creatinine; red cell casts in urine • renal biopsy shows diffuse proliferative pattern of injury• immunofluorescence shows IgG and C3 in granular

pattern in mesangium and along capillary basement membrane• Electron microscopy shows large, dense subepithelial

deposits

Postinfectious Glomerulonephritis

Postinfectious Glomerulonephritis• Treatment—Underlying infection should be

identified and treated appropriately• Supportive tx—anti-hypertensives, salt

restrictions, diuretics• Corticosteroids do not improve outcome

• Prognosis depends on severity of injury and age of patient• Children—more likely to fully recover• Adults—prone to development of severe disease and CKD

IgA Nephropathy• Berger disease• Primary renal diseaseIgA

deposits in glomerular mesangium

• Associated with hepatic cirrhosis, celiac disease, HIV, CMV

• Most common primary glomerular disease worldwide• most common in children and

young adults• males 2-3 times more

commonly affected than women

IgA Nephropathy• Signs and Symptoms—episode of gross hematuria is the

most common presenting symptom• May see with URI (50%), GI symptoms (10%), flu-like illness (15%)• Red or cola-colored urine 1-2 days after onset• Can range from asymptomatic microscopic hematuria to rapidly

progressive glomerulonephritis

• No serologic tests can help diagnose• Treatment—if >1g/d proteinuria, ACE or ARB

• Target BP <130/80 mmHg, target proteinuria <500 mg/d• If 1-3.5 g/d proteinuria and GFR >70 mL/min, steroids may be helpful• Others—fish oil, kidney transplant if ESRD

• Prognosis—1/3 with spontaneous remission, progressive CKD in 40-50%, remainder with chronic microscopic hematuria and stable Cr

Other forms of glomerulonephritis• Henloch-Schönlein Purpura—small vessel

leukocytoclastic vasculitis; IgA in vessel walls• most commonly in children after an infection• Palpable purpura of LE and buttocks, arthralgia, abdominal

symptoms

• Pauci-immune glomerulonephritis—(ANCA associated)—Wegener granulomatosis, Churg-Strauss disease, and microscopic polyangiitis• Signs and symptoms of systemic inflammatory disease

• Antiglomerular Basement Membrane Glomerulonephritis and Goodpasture Syndrome• Antibodies to epitopes in the glomerular basement

membrane

Nephrotic Syndrome

Nephrotic Syndrome• 1/3 of patients with nephrotic syndrome have systemic

disease• DM, amylodosis, SLE• Remainder—primary renal disease

• Signs and Symptoms—peripheral edema is hallmark• Occurs when serum albumin is <3 g/L• When serum albumin <2 g/dL, arterial underfilling from low

plasma oncotic pressure• Initially in dependent areas, but can become generalized,

including periorbital edema

• Dyspnea pulmonary edema, pleural effusion, diaphragmatic compromise due to ascites

• Increased infections loss of Ig and complement• Increased thrombotic events loss of anticoagulant

factors

Nephrotic Syndrome

Nephrotic Syndrome—Labs • Urinalysis—proteinuria• Spot urine protein to

urine creatine ratio—approximate grams/day of protine lost in urine• few casts or cells—may

have oval fat bodies from lipid deposits in sloughed renal tubular epithelial cells• “grape clusters” or

“Maltese crosses”

Nephrotic Syndrome—Labs • Blood Chemistries—hypoalbuminemia (<3 g/dL) and

hypoproteinemia (<6 d/dL)• Hyperlipidemia50% of patients with early nephrotic

syndrome and more common as disease becomes more severe• Elevated erythrocyte sedimentation rate• Deficiency in vitamin D, zinc, and copper loss

• Renal biopsy—to identify underyling cause—table 22-10• Mainly to see if there is a primary renal disease that may

require or respodne to drug therapy• Chronically and significantly elevated creatinine levels—

irreversible kidney disease—biopsy likely not helpful• Biopsy rarely done in setting of longstanding DM

Nephrotic Syndrome—Treatment • Protein Loss—dietary protein intake should replace daily

urinary protein losses• Protein malnutrition mainly with urinary protein losses >10 g/day• May be mild renal benefit to protein restriction—recommend 0.6-0.8

g/kg/day if GFR <25 mL/min• ACE and ARB reduce protein excretion—can use with caution in

patients with reduced GFR

• Edema—dietary salt restriction, diuretics (thiazides, loops)• Hyperlipidemia—dietary modification, exercise, medication

• Statins are cleared by liver, but pts with CKD are more prone to rhabdomyolysis if taking gemfibrozil plus a statin

• Hypercoagulable state—serum albumin <2 g/dL• Anticoagulants for 3-6 months in patients with evidence of

thrombosis in any location

Questions?