nephriticnephroticnephropathynephritis Flashcards
What are the four defining features of nephrotic syndrome?
- proteinuria > 3g/day
- hypoalbuminemia
- hyperlipidemia
- edema
Which renal condition is often associated with solid tumor cancers, NSAIDs, Hep B/C infections, or autoimmune diseases?
Membranous nephropathy
What demographic groups are most often affected by membranous nephropathy?
Mostly caucasian men aged 50-60 yo
What is the clinical presentation of membranous nephropathy?
Swelling of extremities over days to weeks
What urine findings are associated with membranous nephropathy?
- significant proteinuria
- oval fat bodies, lipid/fatty casts with maltese crosses on polarized light
- dyslipidemia
- serum creatinine may be normal or elevated
What are the kidney biopsy findings associated with membranous nephropathy? LM, silver stain, IF, and EM
LM: thick GBM
Silver stain: Spike and dome pattern
IF: Granular IgG stain
EM: sub-epithelial immune-complex deposits
What is the treatment of membranous nephropathy?
RAAS blockade, salt restriction, diuresis, and immunosuppressive therapy if proteinuria is high
What diagnosis is suggested by a patient with 3.5 g/d of proteinuria, bilateral lower extremity edema, and a kidney biopsy with sub-epithelial immune-complex deposits on electron microscopy?
Membranous nephropathy
What renal pathology is associated with HIV infection, lithium medication use, reduced renal mass, or hyperfiltration injury?
Focal segmental glomerulosclerosis
What is the clinical presentation of focal segmental glomerulosclerosis?
HTN is common, edema is often present but not always, hematuria may be present but not always
What are the urinalysis findings associated with focal segmental glomerulosclerosis?
- elevated creatinine (possible but not always present)
- proteinuria (usually nephrotic range, but can be sub-nephrotic)
- hematuria (not always present)
What are the kidney biopsy findings associated with focal segmental glomerulosclerosis? LM, IF, EM
LM: One or more lesions of segmental sclerosis on light microscopy
IF: Scant or non-specific staining of IgM, C3, or C1q
EM: Podocyte foot process effacement (focal or diffuse)
What is the treatment for focal segmental glomerulosclerosis?
- treat underlying conditions/stimuli
- steroids, calcineurin inhibitors, or cellcept
What demographic(s) are commonly associated with minimal change disease?
Children < 6yo
What is the clinical presentation of minimal change disease?
Sudden-onset, “explosive” swelling that involves the face and extremities. May follow infection.
What are the urine findings associated with minimal change disease?
- significant proteinuria
- sometimes hematuria
- oval fat bodies, lipid/fatty casts (with maltese cross)
- renal function usually normal, sometimes constitutes AKI
What are the biopsy findings associated with minimal change disease? LM, IF, EM
LM/IF: normal
EM: diffuse podocyte foot process effacement
What is the treatment of minimal change disease?
Responsive to steroids usually. Next resort is calcineurin inhibitors, cyclophosphamide, and cellcept.
What is the most common cause of nephrotic-range proteinuria?
Diabetes
What are the main criteria associated with nephritic syndrome?
- hematuria with dysmorphic RBCs and/or RBC casts
- proteinuria < 3g/day (sub-nephrotic)
What are the three major categories of nephritic syndromes?
- immune-complex mediated
- pauci-immune
- anti-GBM disease
What is the mechanism of anti-GBM disease?
Autoantibodies binding to type IV collagen in the glomerular basement membrane (can also involve lungs with the alveolar basement membrane)
What is the clinical presentation of anti-GBM disease?
Ill-appearing patient with malaise, weight loss, often with hemoptysis/hypoxia if lung involvement
What are the urine findings associated with anti-GBM disease?
- hematuria with dysmorphic RBCs and casts
- proteinuria <3 g/day
- often quickly rising serum creatinine
What are the kidney biopsy findings of anti-GBM disease? LM and IF
LM: diffuse crescentic glomerulonephritis
IF: linear IgG stain
What is the treatment of anti-GBM disease?
Steroids + cyclophosphamide + plasmapheresis
“aggressive disease requires aggressive treatment”
What is the classic clinical scenario associated with post-infectious GN?
A child who had pharyngitis with group A beta-hemolytic strep infection approximately 10-14 days ago
What is the clinical presentation of post-infectious GN?
- symptom onset 1-2 weeks after strep pharyngitis (or longer for impetigo)
- fever, malaise
- HTN, edema, sometimes oliguria and gross hematuria
What are the urine findings of post-infectious GN?
- hematuria with dysmorphic RBCs and casts
- proteinuria
- elevated serum creatinine
- low complement levels
What are the kidney biopsy findings associated with post-infectious GN? LM, IF, EM
LM: glomerular hypercellularity or proliferation
IF: lumpy-bumpy appearance of IgG, IgM, and C3 staining
EM: large sub-epithelial immune complex deposits (“humps”)
What is the treatment for post-infectious GN?
Usually just treat lingering infection, possibly add steroids if severe
What demographic group(s) are most likely affected by lupus nephritis?
Women > men, usually child-bearing age
What is the clinical presentation of lupus nephritis?
- edema, HTN
- systemic lupus signs (rash, joint pain, muscle pain, ulcers, pleuritis, pericarditis)
What are the urine findings of lupus nephritis?
- hematuria (usually microscopic)
- proteinuria (variable amount, can be nephrotic range)
- +ANA, +anti-dsDNA
- low complement levels
What is the treatment of lupus nephritis with mild kidney involvement?
Supportive, focused on systemic SLE management
What is the treatment of lupus nephritis with active inflammation/necrosis on biopsy?
High-dose steroids and immune modulators (cyclophosphamide, cellcept)
What condition is known as IgA vasculitis?
Henoch-Scholein purpura
What is the clinical presentation of IgA nephropathy?
Presents 1-2 days post-URI or GI illness with gross hematuria and hypertension
What are the urine findings of IgA nephropathy?
- gross or microscopic hematuria with dysmorphic RBCs and/or casts
- normal or elevated serum creatinine
- normal serum complement levels
What are the kidney biopsy findings of IgA nephropathy? LM, IF, EM
LM: mesangial proliferation
IF: IgA deposits
EM: mesangial/paramesangial immune-complex deposits
What is the treatment for IgA nephropathy with mild proteinuria?
ACE-I or ARB +/- fish oil and low-salt diet
What is the treatment of IgA nephropathy with high proteinuria?
Treat with ACE-I or ARB +/- fish oil and low salt diet as well as steroids
What is the treatment of IgA nephropathy with rapidly rising serum creatinine?
Cyclophosphamide (with maintenance care like ACE-I, ARB, fish oil, low salt diet)
What are the urine findings associated with membranoproliferative glomerular nephritis?
- hematuria
- proteinuria (can be nephritic or nephrotic range)
- low C3
What are the kidney biopsy findings associated with membranoproliferative glomerular nephritis? LM, PAS stain, IF, EM
LM: mesangial proliferation and “lobular” glomeruli
PAS: “tram track” appearance due to GBM splitting
IF: C3 and IgG stain
EM: immune-complex deposits
What is the clinical presentation of granulomatosis with polyangiitis?
- fever, weight loss, malaise
- nasal crusting, nosebleeds, “saddle nose deformity”
- chronic sinusitis
- dyspnea, hypoxia, hemoptysis
- palpable purpura
- usually middle-aged/older people
What are the urine findings of granulomatosis with polyangiitis?
- hematuria with dysmorphic RBCs and casts
- variable proteinuria (<3g/day)
- elevated serum creatinine
- c-ANCA
What are the kidney biopsy findings of granulomatosis with polyangiitis?
Necrotizing crescentic glomerulonephritis
What is the treatment for granulomatosis with polyangiitis?
High dose steroids and cyclophosphamide (depends on level of organ damage)
What is the clinical presentation of microscopic polyangiitis?
- fever, weight loss, malaise
- palpable purpura
- peripheral nerve involvement
- hemoptysis, dyspnea, hypoxia
What are the urine findings of microscopic polyangiitis?
- hematuria with dysmorphic RBCs and casts
- proteinuria (< 3g/day)
- elevated serum creatinine
- p-ANCA
What are the kidney biopsy findings of microscopic polyangiitis?
Necrotizing crescentic glomerulonephritis
How many patients with diabetes go on to develop nephropathy?
30% of patients
What are the four phases of the natural history of diabetic nephropathy?
1) hyperfiltration (silent)
2) microalbuminuria
3) macroalbuminuria
4) advanced nephropathy/failure
What changes occur at the glomeruli in the silent phase of diabetic nephropathy?
Hyperfiltration and hypetrophy, basement membrane thickening
How long does the silent phase of diabetic nephropathy last?
10 years
What is the defining clinical feature of the incipient phase of diabetic nephropathy?
Microalbuminuria - small amounts of albumin are spilled from blood into urine (30-300 mg/day)
What are the pathological changes associated with the microalbuminuria phase of diabetic nephropathy?
- further thickening of GBM and tubular basement membrane
- mesangial matrix expansion (collagen, fibronectin)
- mesangial matrix expansion (diffuse or nodular Kimmelstiel-Wilson lesions)
What co-morbidity of diabetes often occurs around the same time as the microalbuminuria phase of diabetic nephropathy?
diabetic retinopathy
What is the clinically defining feature of overt diabetic nephropathy?
Macroalbuminuria in excess of 300 mg/day
What is the average rate of GFR decline during the macroalbuminuria phase of diabetic nephropathy?
6-12 ml/min/year
What is the risk of progression of macroabluminuria phase diabetic nephropathy to ESRD without treatment?
50% in 10 years, 75% within 15 years
What factors influence hyperfiltration in diabetic nephropathy?
- glomerular hypertrophy
- afferent arteriolar vasodilation
- efferent arteriolar vasoconstriction
(mediated by angiotensin II)
What three pathological changes in diabetic nephropathy contribute to proteinuria?
- GBM thickening
- podocyte damage/detachment/fusion
- hemodynamic effects, intraglomerular hypertension
What pathological features of diabetic nephropathy correlate to reduced GFR?
- mesangial matrix expansion (obliteration of capillary surface area)
- tubulointerstitial fibrosis (nephron loss and further damage)
What is the initial stimulus of diabetic nephropathy?
Hyperglycemia
How does hyperglycemia contribute to kidney damage in diabetic nephropathy?
It leads to production of advanced glycation end products (altered protein structure) or reactive oxygen species (cell damage)
What are key cytokines of diabetic nephropathy?
TGF-beta (hypertrophic, profibrotic), VEGF, angiotensin-II (profibrotic)
What is the goal A1c level in treatment of diabetic nephropathy?
Under 7%
What are the most recent blood pressure control guidelines for patients with diabetic nephropathy?
<130/80
Should ACE-I and ARBs be used together to treat diabetic nephropathy?
No - studies show that using both together can cause AKI and hyperkalemia
What is the function of SGLT2 inhibitors?
They block the action of sodium-glucose co-transporters in the proximal tubule, leading to urinary glucose loss and improved management of diabetes
What does a dense-pink hyaline appearing nodule in the mesangium suggest?
Diabetic nephropathy - Kimmelstiel-Wilson lesion
What are the two infectious classes of tubulointerstitial disease?
Acute pyelonephritis, chronic pyelonephritis
What are four non-infectious classes of tubulointerstitial disease?
- drug-induced interstitial nephritis
- ishchemia
- metabolic derangements
- physical damage
What is the pathophysiology of analgesic-induced nephropathy?
Acetaminophen/phenacetin = oxidative damage
Aspirin = prostaglandin synthesis inhibitor leading to vasoconstriction and reduction of blood flow to an already ischemic papilla
What are the three phases of acute tubular necrosis?
Initiation, maintenance, and recovery
What are causes of acute tubular necrosis?
Ischemia, drug/toxicity, severe glomerular disease, acute papillary necrosis
What is postural proteinuria?
Observed only when subject assumes an upright position
What transmembrane protein crosses the podocyte slit diaphragm?
nephrin (2 molecules interlock)
What is the mechanism of albuminuria in minimal change disease/nephrotic syndromes?
Nephrin slit diaphragms are disrupted, altering slit pore integrity. Loss of cytoskeletal integrity of podocytes leads to disrupted potential charge of EBM, losing the charge selectivity of the filter
How does nephrotic syndrome lead to edema?
Loss of proteins in the serum leads to fluid retention in the extra-vascular space, which depletes volume for the heart and for kidney perfusion. This triggers a vicious cycle of RAAS activation due to perceived hypovolemia
Why is lipid production increased in nephrotic syndrome?
Increased hepatic lipoprotein synthesis, urinary loss of HDL,anddecreased lipoprotein lipase activity
Why do patients with nephrotic syndromes have altered hemostasis?
Loss of clotting factors in the urine (proteinuria)
Why are nephrotic patients often more susceptible to infection?
Loss of immunoglobulins in urine (proteinuria)
Why do patients with nephrotic syndrome get bone disease?
They lose vitamin D in the urine, which leads to bone degradation from low calcium levels
Why do some nephrotic syndrome patients develop anemia?
Loss of iron-binding proteins in the urine (proteinuria)
What two nephrotic syndromes result from podocytopathy?
Minnimal change disease, focal segmental glomerulosclerosis
What two renal disorders result from chronic primary renal inflammation?
- membranoproliferative glomerulonephritis
- membranous nephropathy
What is the cause of fragmented red blood cells?
Shear stress in microvasculature with thrombi
What is the cause of thrombocytopenia?
Platelet consumption in thrombi
What 4 features of the glomerular microvascular bed make it susceptible to injury?
1) fenestrations
2) high capillary pressure
3) continual exposure to toxins and complement activation because of high blood flow
4) death of glomerular endothelium exposes underlying glomerular basement membrane, which is extremely pro-thrombotic
What are three factors that protect the glomerular microvascular bed?
1) high levels of VEGF in the glomerulus (blood vessel growth factor)
2) complement regulatory proteins (factor H)
3) ADAMTS13 that breaks down vWF multimers to limit platelet aggregation
What is the pentad of thrombitic thrombocytopenic purpura?
Hemolytic anemia, thrombocytopenia, neurologic symptoms, kidney injury, fever
What is the cause of thrombotic thrombocytopenic purpura?
Extremely low ADAMTS13 activity, which leads to large multimers of vWF that increase platelet activation and thrombus formation
What is the normal function of ADAMTS13?
It cleaves large circulating multimers of vWF
What is the treatment for thrombotic thrombocytopenic purpura?
Plasmapheresis and exchange (remove antibody and/or give back the enzyme)
What is the cause of typical HUS?
Shiga-toxin from E Coli O157:H7
What is the mortality of typical HUS?
12% ESRD, 25% longterm renal sequelae
What is the mechanism of shiga toxin?
It enters systemic circulation, binds to Gb3 receptor on glomerular endothelial cells and leads to platelet thrombi
What is the treatment of typical HUS?
Supportive care, plasmapheresis, and eculizimab
What is the prevalence of atypical HUS?
10% of cases not attributed to shiga-toxin
What are causes of atypical HUS?
Familial or sporadic causes of abnormal complement regulation, most commonly defects in factor H
What is the most common cause of atypical HUS?
Mutations in the gene encoding factor H or auto-antibodies to factor H (a regulator of complement activation)
What is the treatment for atypical HUS?
Plasmapheresis and exchange to remove auto-antibody and/or give back factor H to deficient patients, also therapies to block complement activation (eculizimab)
How can strep pneumo cause HUS?
It has neuraminidase production that acts on antigen exposed on surface of endothelial cells
What are characteristics of preeclampsia?
TMA, hypertension, thrombotic microangiopathy in kidney, neurologic features, hemolytic anemia, thrombocytopenia, and edema
What is HELLP syndrome?
A disorder related to anti-VEGF that has features of
Hemolytic anemia
Elevated Liver enzymes
Low Platelets
When does preeclampsia occur?
Usually after the 20th week of pregnancy
What are three risk factors for preeclampsia?
First pregnancy, twins, molar pregnancy
What is the pathophysiology of preeclampsia?
High circulating levels of sFlt1 (soluble VEGF receptor 1) that binds VEGF and reduces its activity, resulting in hypertension, damage to glomerular endothelium, and other vascular beds resulting in thrombi formation
What is the treatment for preeclampsia?
Delivering the baby, MgSO4 for neurologic symptoms, blood pressure control
What are the side-effects of anti-VEGF drugs?
Hypertension, kidney injury with glomerular endotheliosis, platelet-rich thrombi
What are ant-VEGF drugs used for?
Treatment for diabetic retinopathy
