2 Glomerulonephritis & Cystic Diseases Flashcards
The basic filtering unit of the kidney
Glomerulus
Glomerular disease is any damage to the major components of the glomerulus, with includes…
Podocytes
Glomerular Basement Membrane (GBM)
Capillary endothelium
Mesangium
What are the two classifications of glomerular disease?
Nephritic (ie glomerulonephritis)
Nephrotic
Glomerular disease is considered to be focal when…
<50% of glomeruli are involved
Glomerular injury that is limited to the kidney
Primary glomerular disease
Renal abnormalities resulting from a systemic disease
Secondary glomerular disease
Diseases that present in the nephritic spectrum and usually signify an inflammatory process —> renal dysfunction
Glomerulonephritis (GN)
What is the etiology of glomerulonephritis?
Most often, the cause is related to the deposition of IMMUNE COMPLEXES in the glomerulus
In the US, glomerulonephritis comprises ______% of all cases of ESRD
25-30%
What are the three diagnoses on the Nephritic spectrum (from least to most severe)?
Asymptomatic glomerular hematuria
Nephritic syndrome
Rapidly progressive glomerulonephritis
Microscopic or macroscopic hematuria with or without proteinuria (<1 g/d)
Asymptomatic glomerular hematuria
Acute kidney injury with proteinuria of 1-3 g/d, hematuria, RBC CASTS, edema, and hypertension
Nephritic syndrome
Acute kidney injury with proteinuria of 1-3 g/d, hematuria, RBC casts, and systemic symptoms
Rapidly progressive glomerulonephritis
All of the conditions on the nephritic spectrum can lead to …
Chronic glomerular disease (chronic kidney disease w/ or w/o hematuria, proteinuria, HTN, late-stage GN)
What is the hallmark urine appearance for someone with Nephritic syndrome?
Smokey or cola-colored urine
What are the hallmark “glomerular hematuria” findings
Dysmorphic RBCs (MICKEY MOUSE RBCs)
RBC casts
________ on urine microscopy is pathognomic for nephritic syndrome
RBC casts
Proteinuria in nephritic syndrome is usually
Subnephrotic (<3g/day)
What will the patient’s creatinine look like in nephritic syndrome?
Elevated (acute decrease in GFR)
B/c decreased kidney function
Besides hematuria, mild proteinuria, and elevated creatinine, what other clinical findings suggest nephritic syndrome
Oliguria (decreased urine output)
Edema (periorbital, peripheral - less prominent than in nephrotic syndrome)
HTN
Most severe and clinically urgent end of the nephritic spectrum
Rapidly Progressive Glomerulonephritis
Progressive loss of renal function over a comparatively short period of time
Characteristic morphologic finding that you can appreciate on biopsy in cases of Rapidly Progressive Glomerulonephritis
Crescent formation
Nonspecific response to severe injury to the glomerular capillary wall
Major causes of hematuria in younger patients
Transient/unexplained
UTI****
Stones
Major causes of hematuria in older patients
CANCER***
(Bladder, kidney, prostate)
BPH
Distinguishing extraglomerular from glomerular hematuria:
Color
Extra: Red or pink
Glomerular: “cola-colored”
Distinguishing extraglomerular from glomerular hematuria:
Clots
Extra: May be present
Glomerular: Absent
Distinguishing extraglomerular from glomerular hematuria:
Proteinuria
Extra: Usually absent
Glomerular: May be present (<3g/day)
Distinguishing extraglomerular from glomerular hematuria:
RBC morphology
Extra: Normal
Glomerular: Dysmorphic (mickey mouse)
Distinguishing extraglomerular from glomerular hematuria:
RBC casts
Extra: Absent
Glomerular: May be present
How do you workup a suspected case of glomerulonephritis
Urine dipstick: looking for protein and blood
Urine microscopy: looking for RBCs, WBCs, RBC casts
Serologic testing: • Creatinine (GFR) • ANA and anti-DS DNA Ab • Complement • ANCA (C-ANCA and P-ANCA) • Anti-GBM antibodies • Antistreptolysin O titer
Renal biopsy
Management of glomerulonephritis is dependent upon…
The underlying cause
Management of complications (HTN, fluid overload)
ACE/ARB - consider for antiproteinuric therapy
Nephrology referral or consult
• Immunosuppressive meds
• Possibly dialysis if profound AKI
Acute nephritic syndrome or RPGN warrants immediate hospitalization
What are the possible types of GN that will show a positive ANCA?
If no extra-renal disease —> ANCA-associated crescentic GN
If systemic necrotizing vasculitis —> Microscopic polyangitis
If respiratory necrotizing granulomas —> Granulomatosis with polyangitis
If asthma and eosinophilia —> Eosinophilic granulomatosis with polyangitis
What are the different types of GN that can occur with anti-glomerular basement membrane (GBM) antibodies?
If there is lung hemorrhage —> Goodpasture syndrome
If not —> Anti-GBM GN
Glomerulonephritis with (+) antinuclear antibodies
Lupus GN
Glomerulonephritis with (+) Antipathogen antibodies
Postinfectious or peri-infectious GN
Glomerulonephritis with (+) IgA
IgA nephropathy
Glomerulonephritis with (+) Cryoglobulins
Cryoglobulinemic GN
Glomerulonephritis with (+) complement activation
MPGN
The most common cause of primary Glomerulonephritis in the world
IgA Nephropathy
Primary is most common but can also be secondary (cirrhosis, celiac, infectious)
Inciting cause is unknown but susceptibility to IgA nephropathy seems to be inheritable
Greatest frequency of IgA nephropathy is in what populations?
Asians and Caucasians
Peak occurrence in 2nd and 3rd decades of life
Males > Females
What is the pathogenesis of IgA Nephropathy?
Immune complex-mediated GN
IgA deposition in the glomerular mesangium —> inflammatory response
An episode of gross hematuria, usually following a UTI (symptoms often 1-2 days after illness onset)
IgA Nephropathy
Can present anywhere along the nephritic spectrum (rarely nephrotic)
How is IgA nephropathy diagnosed?
Clinical suspicious and laboratory data
Confirmed by kidney biopsy (usually performed for more severe or progressive disease)
What is the spectrum of disease course that IgA Nephropathy might take?
Spontaneous clinical remission in ~ 1/3 of patients
Progression to ESRD occurs in 20-40% of patients
Remaining may have chronic microscopic hematuria and stable creatinine
Which IgA Nephropathy patients should be given an ACE or ARB?
Those wit Proteinuria > 1/day, decreased GFR, or HTN
Higher Risk
Besides ACE/ARB, why other treatments have been tried in IgA Nephropathy?
Glucocorticoids +/- immunosuppressive agents
What is the cause of Poststreptococcal GN?
Infection with nephritogenic strains of group A beta-hemolytic strep - either Pharyngitis or impetigo
More common in children
Twice as common in males than females
What is the pathophysiology of poststreptococcal GN?
Immune-mediated
An immune complex containing a streptococcal antigen is deposited in the affected glomeruli
Triggers COMPLEMENT activation and INFLAMMATION
What are the clinical findings in post-strep GN?
Presentation varies across the nephritic spectrum, with symptoms 1-3 WEEKS AFTER INFECTION
Elevated ASO TITERS
Serum complement levels are LOW
How do you diagnose PSGN?
Clinical findings of acute nephritis with documentation of recent GAS infection
How do you treat PSGN?
Supportive care - resolution often begins within the first two weeks
Prognosis: depends on severity and age of patient
CHILDREN are more likely to fully recover (>90%)
Recurrent episodes are rare
Acute RPGN in which circulating antibodies directed against the GBM
Anti-GBM Disease
Accounts for 10-20% of patients with acute RPGN
Why does anti-GBM disease affect both the kidney and the lung?
Target antigen is also found in the ALVEOLAR BASEMENT MEMBRANE
What does the case distribution of anti-GBM disease look like?
Bimodal distribution
First peak ~age 30 (slight male predominance), more lung involvement
Second peak ~age 60 (female predominance)
What is the difference between anti-GBM disease and Goodpasture Syndrome?
Anti-GBM Disease is the antibodies +GN
Goodpasture is GN + pulmonary hemorrhage
Clinical manifestations of anti-GBM disease?
Often IDIOPATHIC but some genetic predisposition (HLA)
Associations with PULMONARY INFECTION, TOBACCO USE, HYDROCARBON EXPOSURE
Renal involvement = Nephritic spectrum, including RPGN
Pulmonary involvement = Cough, dyspnea, sometimes overt hemoptysis
How is anti-GBM disease diagnosed?
Demonstration of anti-GBM antibodies in serum or kidney biopsy
Test for antineutrophil cytoplasmic antibodies (ANCA)
• Up to 40% will also test positive for ANCA (having both can alter course of treatment/prognosis)
How is anti-GBM disease treated?
Plasmapheresis
Immunosuppressive agents
SEND TO NEPHROLOGY
Immune complex mediated glomerular disease with anti-ds DNA antibodies
Lupus Nephritis
Many possible patterns of injury, most cases present within the nephritic spectrum
Incidence higher in nonwhites
How is Lupus Nephritis diagnosed?
Often suspected by an abnormal UA and/or elevation of serum creatinine
Dx confirmed with renal biopsy
Treatment varies with each class —> nephrology/rheum consult
Henoch-Schoenlein Purpura is another name for …
IgA Vasculitis
Immune-mediated vasculitis characterized by tissue deposition of IgA-containing immune complexes
When might you see IgA Vasculitis?
Most common in children, M>F
Cause is unknown but often post-URI (strep)
Classic tetrad for IgA Vasculitis/Henoch-Schoenlein Purpura
Rash (palpable purpura - but normal platelets)
Arthralgias
Abdominal pain
Renal disease
IgA vasculitis is more common in kids but _______ is more common in adults
Progressive renal disease
Signs of renal involvement typicall appear AFTER the rash —> may present with nephritic or nephrotic syndrome
What is the treatment for IgA Vasculitis?
Often self-limited
Supportive care, symptomatic therapy, and targeted therapy to decrease complications
Pauci-Immune Glomerulonephritis is a ___________ vasculitis
ANCA-associated vasculitis
Pauci-Immune GN is caused for what systemic ANCA-associated vasculitides?
Granulomatosis with polyangiitis (GPA)
Microscopic polyangiitis (MPA)
Eosinophilic granulomatosis with polyangiitis (EGPA)
All have similar features on renal histology (absence or paucity of immune deposits on kidney biopsy)
What are the two versions of ANCA?
P-ANCA and C-ANCA
These antibodies produce vascular and tissue damage
What is granulomatosis with polyangiitis (GPA)?
ANCA-associated vasculitis
Rare, complex, multisystem autoimmune disease of unknown etiology
Hallmark features of Granulomatosis with Polyangiitis
NECROTIZING GRANULOMATOUS INFLAMMATION mostly in lungs and kidneys
Pauci-immune vasculitis of small-medium vessels
Upper Respiratory System: chronic sinusitis, SADDLE NOSE DEFORMITY, otitis media, ocular involvement, cough, dyspnea, hemoptysis
Renal manifestations: CRESCENTIC NECROTIZING GLOMERULONEPHRITIS
May also present with fever, malaise, weight lost, arthritis, skin manifestations, polyneuropathy
Typically presents between 35-55
How is Microscopic Polyangiitis (MPA) different from GPA?
ABSENCE OF GRANULOMATOSIS FORMATION and sparing of the UPPER respiratory tract (so no chronic sinusitis, saddle nose)
Age of onset is ~50 (a little older than GPA)
ANCA-associated vasculitis associated with asthma and eosinophilia
Eosinophilic granulomatosis with polyangiitis (EGPA)
Lung, skin, heart, renal, GI, and neuro symptoms
What are the three disease phases for Eosinophilic Granulomatosis with Polyangiitis?
Prodrome phase - allergic disease (asthma or allergic rhinitis)
Eosinophilic/tissue infiltrative phase
Necrotizing vasculitis of the small-medium vessels
How are Pauci-Immune GNs treated?
Consultation/referral to multiple specialists
Immunosuppressants (corticosteroids and cytotoxic agents)
Without treatment, prognosis is poor
C-ANCA is more common with ___________ and P-ANCA more common with ____________.
C-ANCA = GPA
P-ANCE = MPA, EGPA
________ account for 65-70% of all renal masses
Simple Cysts
Typically asymptomatic - most found incidentally on ultrasound
What is the diagnostic objective for simple cysts?
To differentiate them from malignancy, abscess, or polycystic kidney disease
Use U/S and CT
Benign features: smooth, thin walls that are sharply demarcated, does not enhance with contrast
Simple cysts do not enhance with contrast. If something DOES enhance with contrast, it’s more likely to be…
Renal cell carcinoma
Inherited disease that causes an irreversible decline in kidney function
Polycystic Kidney Disease (PKD)
Can be either autosomal dominant or recessive
All racial and ethnic groups affected, M=F
Majority of individuals with PKD eventually require ___________.
Renal replacement therapy (either dialysis or kidney transplant)
Most common genetic cause of CKD
Autosomal Dominant PKD
Variable penetrate, accounts for 10% of patients on dialysis in the US
(+) FHx in 75% of cases
What are the two genes that account for most cases of ADPKD?
PKD1 and PKD2
ADPKD is characterized by …
Massive kidney enlargement due to BILATERAL progressive increase in the number of cysts
Progressive decline in renal function (GFR)
For most patients, renal function remains intact until 4th decade of life
Upt o 50% will have ESRD by age 60 years
What are the renal manifestations of ADPKD?
HTN in >50% Abdominal/flank pain Palpable kidneys Hematuria \+/- proteinuria Hx of UTIs and nephrolithiasis
What are extrarenal manifestations of ADPKD?
Intracranial aneurysms
Hepatic cysts (40-50%)
Pancreatic cysts, splenic cysts, etc
CVD (ie MITRAL VALVE PROLAPSE)
Initial modality for screening and diagnosis of ADPKD
Ultrasound
CT/MRI helpful when U/S unclear
Typical findings - large kidneys and extensive cysts scattered throughout both kidneys
Genetic testing for definitive diagnosis
How do you manage a patient with ADPKD?
Strict BP control, low-salt diet, statins (to prevent CVD)
Avoid caffeine
Supportive therapy
TOLVAPTAN (vasopressin receptor antagonist - helps slow progression of disease)
Dialysis or kidney transplant
Autosomal Recessive PKD primarily affects…
Infant’s and children’s kidneys and hepatobiliary tract
Characterized by BILATERAL markedly enlarged kidneys, progressive renal impairment, and CONGENITAL HEPATIC FIBROSIS (portal HTN)
May have feeding difficulties and growth impairment
How is autosomal recessive PKD diagnosed and treated?
Can be detected by routine antenatal U/S after 24 weeks gestation
Supportive therapy with a multidisciplinary team
