Glomerular Diseases Flashcards
Albumin
is the only measurable protein in urine on a urine dipstick. If have a positive urine dipstick for protein (albumin) you need to quantify with either a 24- hour urine collection or protein-creatinine / albumin-creatinine ratio on a random urine sample
Level of proteinuria is diagnostically helpful to distinguish tubulointerstitial disease vs glomerular disease
> 150mg/g- < 200mg/g = tubulointerstitial or glomerular disease
> 3500mg/g = glomerular disease
Albumin-creatinine ratio
measures albumin in urine
If positive and have retinopathy then diagnosis is diabetic nephropathy
30-300 mg/g “microalbuminuria”
> 300 mg/g = overt proteinuria
Protein-creatinine ratio
is used to measure proteinuria
Proteinuria if a marker of renal parenchymal and glomerular disease and an independent predictor of progressive kidney disease, cardiovascular disease, and peripheral vascular disease
If you see proteinuria and hematuria on UA
suspect glomerular disease/injury
Molecule smaller than 3 nm can pass freely through the filtration membrane into the capsular space
Molecules includes:
Water
Electrolytes
Glucose
Amino acids
Nitrogenous wastes
Vitamins
Kidney infections and trauma commonly damaged the filtration membrane and allow protein (albumin) and blood cells to filter through
3 potential etiologies for Acute Kidney Injury
1-Pre-renal: low perfusion (60-70%)
Hypovolemia, hypotension
2-Post renal: obstruction to flow (5-10%)
BPH, urolithiasis, outlet obstruction
3-Intrarenal: intrinsic disease (25-40%)
1- Tubules ( Acute Tubular Necrosis)
2- Interstitium (Acute interstitial nephritis)
3-Glomerulus (Glomerulonephritis) RBC casts!!
Nephrotic Syndrome
General
Disease of the glomerulus, urinary excretion > 3.5 g protein in 24 hours
Hypoalbuminemia( < 3.0g/dL; nl 30g/L), hypercholesterolemia, edema and increase risk of thrombosis secondary to loss of protein S, C, and antithrombin III
Prognosis depends on cause and extent of renal damage
In USA most common cause is DM
Presentation
Urine: Albuminuria > 3.5g/day, “frothy”
Anasarca
Hypercholesteremia
Podocyte effacement on electron microscopy
Nephrotic Syndrome
primary vs secondary
Primary
results intrinsic process limited to kidney
Minimal change nephrotic syndrome (children post virus, tx w steroids)
Focal segmental glomerulosclerosis (black patients, HTN, heroin, HIV)
Membranous nephropathy (white patients, SLE, viral hepatitis, malaria)
IgA nephropathy
Secondary
systemic disease process with renal involvement
Diabetes ( yearly screen albuminuria)
Autoimmune Diseases
Systemic Lupus Erythematous
Amyloidosis
Sjogren syndrome
Sarcoidosis
Infection ( HIV, HCV,HBV)
Pre-eclampsia
Primary ( idiopathic) – glomerular injury is an intrinsic process limited to the kidney
Secondary – glomerular lesion is a result of a systemic disease with renal involvement
Nephrotic Syndrome
NAPHROTIC syndrome
Na + decrease
Albumin decrease
Proteinuria > 3.5 g/day
Hyperlipidemia
Renal vein thrombosis
Orbital edema
Thromboembolism
Infection (loss of immunoglobulins in urine)
Coagulopathy ( loss of antithrombin III, protein c/s in urine)
Nephrotic Syndrome
Work up
Urinalysis: proteinuria, lipiduria, glycosuria, hematuria, “foamy” urine
Microscopic examination of urine: RBC casts, granular casts, hyaline casts, fatty casts; oval fat body ( maltese cross)
BMP: low albumin ( < 2.5 g/dL), azotemia, hyperlipidemia, serum creatinine often normal
Renal biopsy
Collect a 24-hour urine to measure urinary protein: > 3.5 g of protein
Nephrotic Syndrome
Treatment
Rx: ACE-Inhibitors, loop diuretics to manage fluid overload; steroids ( work better in children); statins for hyperlipidemia
Education: Na and fluid restriction; no excessive protein/K intake, no NSAIDS
Strict blood pressure control: < 130/80 mmHg
Considerations: anticoagulation if thrombus present, if relapse or steroid non-responder may use cyclophosphamide, cyclosporine, or tacromilus
Pneumococcal vaccination
Nephrotic syndrome
Clin man / PE
Clinical Presentation:
Malaise, abdominal discomfort, anorexia, edema (face/scrotum) , oliguria, weight gain, shortness of breath, “frothy” urine
Physical Findings:
Skin stria, edema, retinal sheen, ascites, hypertension
Often mistaken for CHF
Primary Nephrotic Spectrum Diseases
Minimal Change Disease
Most common cause of proteinuric renal disease in children ( 80% of cases)
Causes
Primary
Idiopathic
Secondary
Following a viral upper respiratory infection
Associated with neoplasms ( leukemia/lymphoma)
Associated with hypersensitivity III reactions ( NSAIDs, Antibx, Bee stings)
Often resolves with a course of high-dose steroids ( 4 weeks)
Biopsy not always needed (renal biopsy would reveal nearly normal glomeruli- thus “ minimal change”
Primary Nephrotic Spectrum Diseases
Membranous Nephropathy
Most common cause of primary adult nephrotic syndrome
Causes
Primary (70% of cases)
Autoimmune process – IgG attacks phospholipase A2 receptor → podocyte injury
Secondary (30% of cases)
Associated with infections, malignancy, autoimmune disease, and certain drugs
50% of patients progress to ESRD over 3-10 years
Higher risk for hypercoagulable state than other forms of nephrosis
Particular predisposition for renal vein thrombosis
Secondary Nephrotic Spectrum Diseases
Diabetic Nephropathy
with tx
Most common cause of ESRD in the United States
More likely to develop in patients with type I diabetes
Develops ~10 years after the onset of diabetes
Progresses in stages
microalbuminuria → nephrotic proteinuria = decline in GFR
Treatment: strict glycemic control and ACEi
Secondary Nephrotic Spectrum Diseases
Complications
Thromboembolism (venous or arterial)
Caused by ahypercoagulablestate:
Antithrombin III (anticoagulation factor) lost in theurine
Increased hepatic production of proclotting factors
Exacerbated byvolume depletion or diuretic use
Hemoconcentration→platelet aggregation → thrombus formation
Deep vein thrombosis, pulmonary embolism , and renal vein thrombosis are most common
Hyperlipidemia
Lowoncotic pressurefromalbuminuria→ increased hepatic lipoprotein production
Excessive serumlipids are lost in theurine(lipiduria)
Can contribute to accelerated atherosclerosis
May require treatment with a statin
Infection
Particularly increased risk ofStaphylococcus andStreptococcus pneumoniae infections
Increased risk is due to:
Loss ofimmunoglobulins in theurine
Treatment with immunosuppressive medications
Vaccinations are important for prevention
Vitamin D deficiency
Vitamin D-binding protein is lost in the urine
Anemia
Urinary losses of erythropoietin and transferring may lead to iron-resistant microcytic hypochromic anemia
Nephrotic Syndrome Summary
Presentation: Proteinuria > 3.0 g/day, hypoalbuminemia, edema, dyslipidemia
Initial Test: urine analysis, 24-hour urine or spot urine
Most accurate test: biopsy
Treatment: steroids, ACE-I
Minimal Change Disease-pediatric, associated with Hodgkin’s lymphoma and NSAIDS, facial swelling, microscopy: effacement of foot processes
Focal Segmental Glomerulosclerosis: associated with sickle cell, HIV, heroin abuse; microscopy : effacement of foot processes
Membranous Nephropathy- thickened GBM, microscopy: spike and dome patterns and effacement of foot processes
Glomerulonephritis AKA nephritic syndrome
general
Damage of the renal glomeruli by deposition of inflammatory proteins in the glomerular membranes secondary to immunologic response- leads to RBC and protein loss in urine
The more glomeruli affected the worse the disease and prognosis
Proteinuria is variable; acanthocytosis is pathognomonic
60% of cases are in children 2-12 yoa
Excellent prognosis in children, worse in adults
Can progress to renal failure in weeks
Can be acute or chronic
Glomerulonephritis AKA nephritic syndrome
acanthocytes
Dysmorphic RBC seen in glomerulonephritis
Proteinuria with dysmorphic RBC (acanthocytes) occurs because the RBC passes thru the glomerulus and is damaged- normal shaped RBC occurs when bleeding is from bladder or urethra
Glomerulonephritis
Pathogenesis
2 main mechanisms of glomerular injury in the nephritic syndromes
Immune complex–mediated
Antigen:
Can be foreign (bacterial) or self (autoimmune disease)
Can be circulating in the bloodstream or fixed in tissues
Antigen + antibody = immune complex → inflammatory response →neutrophils and other inflammatory factors are recruited → tissue damage
Can form in thecirculation (PSGN)
Can also form directly in tissues (anti-GBM disease)
Complement dysregulation
Component of the humoralimmune system
Compromisedglomerular filtration unit → RBC and protein leak into theurine→glomerular filtrationrate decreases
Thealternative pathwayis overactive → inappropriate inflammatory response and neutrophilrecruitment→ tissue damage
Glomerulonephritis
Common etiologies:
Glomerulonephritis
Poststreptococcal glomerulonephritis (PSGN)
IgA nephropathy (Berger’s disease) – most common cause worldwide
Wegener’s disease
Goodpasture syndrome (Anti-GBM antibody disease)
Lupus nephritis
Glomerulonephritis
Clin man
Presentation
Hematuria; “tea or coke colored urine”;
Hypertension
Oliguria or anuria
Edema of face and eyes in am- progressing to feet and ankles later in the day
glomerulonephritis
Workup and imaging
Elevated creatinine, hematuria and proteinuria with dysmorphic red cells, red cell casts, and white cells
Red cell casts are pathognomonic for acute glomerulonephritis
Spot urine albumin-creatinine ratio/24- hour urine collection can further quantify proteinuria (( < 3 g day))
C3,C4,CH30,C3 levels; anti-GBM titers, ANCA
Antistreptolysin O (ASO) titers – strep infection
Renal ultrasound
Renal biopsy to confirm ( UNLESS diabetic nephropathy w retinopathy)
CXR
Pulmonary edema
Findings suggestive of Wegener’s granulomatosis or Goodpasture’s disease
Glomerulonephritis
Treatment
Steroids and immunosuppressive drugs to control inflammatory response
Plasma exchange ( good pasture syndrome)
Salt and fluid intake reduction
Plasmapheresis- to remove circulating pathogenic autoantibodies
Dialysis if symptomatic or azotemic
Rx:
Ace inhibitors in chronic GN to reduce urinary protein loss
Poststreptococcal glomerulonephritis (PSGN)
general
Most common cause of acute nephritic syndrome in children (5-12 years)
Can present 1–3 weeks after a throat infection caused by specific nephritogenic strains of group A beta-hemolyticStreptococcus
Can present 3–6 weeks after askin infection (impetigo): caused by group AStreptococcus orStaphylococcus aureus
Poststreptococcal glomerulonephritis (PSGN)
Dx
Streptozyme test: measures 5 different antibodies includingantistreptolysin-O after pharyngeal infection
Urinalysis:hematuria with RBC casts, +/–proteinuria
Reduced C3 level
Poststreptococcal glomerulonephritis (PSGN)
Management
Supportive care
Antibiotics: only if the strep infection is still present at the time of diagnosis
Treat hypertension and/or edema:
Loopdiuretics(furosemide)
Sodiumand water restriction
Poststreptococcal glomerulonephritis (PSGN)
HAD STREP
Hypertension
ASO titer positive
Decreased GFR
Swelling
Tea-colored urine
Recent strep infection
Elevated BUN and Creatinine
Proteinuria
IgA Nephropathy (Berger’s Disease)
general and presentation
Most common cause of acute glomerulonephritis
Young men 1-2 days after URI/GI infection
Presentation:
Htn, fever, dark-colored urine, edema
IgA Nephropathy (Berger’s Disease)
Lab findings
Hematuria, RBC casts, proteinuria, specific gravity > 1.02; elevated bun and creatinine, normal complement levels
Gold standard for dx is renal biopsy- will have IgA deposits on biopsy
IgA Nephropathy (Berger’s Disease)
Tx
Ace inhibitors, loop diuretics
Consider corticosteroids if rapid progression or severe disease
Prognosis is good and self-limited disease
Anti–glomerular basement membrane disease (Goodpasture syndrome)
general and Sx
Autoimmune disease characterized by circulating antibodies directed against glomerular and alveolar basement membranes
Presents withrenal andpulmonary involvement(pulmonary–renal syndrome)
Younger individuals (< 30 years) are more likely to:
Develop pulmonary hemorrhage (hemoptysis) and glomerulonephritis
Be critically ill
Older individuals (> 50 years) are more likely to:
Present with isolated glomerulonephritis
Follow a less severe course
Constitutional symptoms
Malaise
Fever and chills
Arthralgia
Weight loss
Anti–glomerular basement membrane disease (Goodpasture syndrome)
labs and imaging
Urinalysis
Low-gradeproteinuria
Gross or microscopichematuria
RBC and granular casts
Renal function tests may show:
↑ BUN and ↑ Creatinine
Serologic testing:
Serum anti-GBM antibodies confirms the diagnosis and are detected using:
ELISA
Indirect immunofluorescence
Imaging
CXR or CT scan chest
Ground-glass or consolidative opacities
Bilateral and diffuse distribution
Glomerulonephritis Summary
Presentation: HTN, edema, and UA:
Hematuria
Dysmorphic red blood cells (acanthocytosis)
Red blood cell casts
Proteinuria < 3.5 g/day
Most accurate test: Biopsy
Treatment: Steroids to control inflammatory response
IGA Nephropathy- gross hematuria post URI
Post Streptococcal-child 1-6 weeks post strep, cola-colored urine, periorbital edema
Rapidly progressive glomerulonephritis with crescent formation:
1- 50-year-old patient who develops renal failure in days/weeks
2-Crescent formation in Bowman’s capsule
Lupus- nephritis, + ANA and Ds-DNA antibodies, low C3 and C4
Goodpasture-nephritis, lung involvement, no URI symptoms
Granulomatosis with polyangiitis (Wegener)-nephritis, sinus problems, hemoptysis, C-ANCA+
Alport-Nephritis, ocular abnormalities, sensorineural hearing loss
Henoch-Schonlein purpura- self-limiting vasculitis in children, palpable purpura of lower extremities and abd pain
