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What is the definition of glomerulonephritis?
Path: intraglomerular inflammation
Clinical: hematuria + dysmorphic RBC or RBC casts +/- subnephrotic proteinuria
often w/ renal failure, htn, edema
What is the different tempos of progression of glomerulonephritis?
acute GN: days
rapidly progressing GN (RPGN): weeks
chronic GN: months, asx hematuria
What are the categories of glomerulonephritis?
ANCA + vasculitis (pauci-immune/minimal staining) 40-45%
Anti-GBM Disease (linear staining) %15
Immune Complex Disease (granular staining) 40-45%
What are the types of ANCA+ Vasculitides that cause glomerulonephritis? And how do the present with granules, renal, pulm, ANCA type?
(1) Wegener's granulomatosis
+ Gran, 80% renal, 90% pulm (+ENT), c-ANCA (anti-PR3), +ANCA 90%
(2) Microscopic polyangiitis
90% renal, 50% pulm, p-ANCA(anti-MPO), 70% +ANCA
(3) Churg-Strauss Syndrome
+Gran, 45% renal, 70%pulm (asthma), p-ANCA, 50% +ANCA
What are the types of Ant-GBM diseases and how do the present?
-glomerulonephritis, pulmonary hemorrhage, +anti-GBM
(2) Anti-GBM disease
What are the types of immune complex diseases causing glomerulonephritis?
(1) Post-strep GN: (10-14d, +ASLO, dec C3)
(2) Membranoprolif GN (dec C3)
(3) Fibrillary GN (nl C3)
(4) IgA nephropathy (nl C3)
(1) SLE (+ANA, anti-dsDNA, dec C3, dec C4)
(2) Cryoglobulinemia (+cryocrit, +RF, HCV ab, dec C3, dec C4)
(3) Endocarditis (dec C3)
(4) Henoch-Schonlein purpur: (IgA Nephropathy + systemic vasculitis, nl C3)
How do you work up glomerular disease?
(1) Acute & rapidly progressing +/- lung hemorrhage are emergencies: early dx/tx
(2) ANCA, anti-GBM, complement
(3) hx-> ANA, Anti-streptolysin O, BCx, cryocrit, hepatitis serologies, skin bx (prn)
(4) Renal biopsy with immunofluresence (IF) +/- electron microscopy (EM)
What are GN mimics and how do they present?
(1) THROMBOTIC MICROANGIOPATHY
dec Hct & plt, schistocytes on smear, inc LDH
(2) CHOLESTEROL EMBOLI
purple toes, livedo, dec C3/C4, eos, prior cath
rash, new drug, urine WBC (inc eos) +/- WBC casts
anemia, hypercalcemia, lytic bone lesions, +SPEP/UPEP
How do you treat glomerular disease
ANCA+ or Anti-GBM
steroids ASAP + cyclophos +/- plasmapheresis
SLE nephritis: IV cyclophosphamide +steroids->azothioprine or MMF (or induction with MMF, no cyclophos)
Other IC disease
?steroids +/- alkylating agents, tx underlying systemic disease
What is the definition of aysmptomatic glomerual hematuria? ddx?
hematuria+/- proteinuria of glomerual origin
w/o renal insufficiency or systemic disease
ddx: any cause of GN, esp IgA. Alport's (X-linked, deafnes, renal failure) and thin basement membrane nephropathy (AD, benign)
What is the epi, presentation, prognosis, and tx of IgA Nephropathy?
epi: most common GN, more males, peak age 20-30s
present: wide range: asx hematuria (30-40%), gross hematouria 1-3 d after URI (30-40%), chronic GN (10%) nephtrotic syndrome (5%), RPGN (<5%)
-definitive dx with biopsy
prognosis: 25-30% willl reach ESRD w/in 20-25 yr of presentation
tx: ACEI/ARB +/- fish oils, steroids +/- cytotoxic therapy for crescentic GN & nephrotic sx, possibly progressive chronic GN
What is the definition of nephrotic syndrome?
albumin <3.5 mg/dL
What are the primary glomerular diseases that cause nephrotic syndrome?
(1) Focal segmental glomerulosclerosis 40%
(2) Membranous nephropathy 30%
(3) Minimal change disease 20% (more children)
(4) Membranoproliferative GN 5% (mixed nephrotic/nephritic)
(5) Fibrillary-immunotactoid glomerulopathy 1%
(6) Mesangial proliferative GN
What are some etiologies of focal segmental glomerulosclerosis?
HIV (collapsing variant)
hyperfiltration due to prior nephron loss
What are some etiologies of membranous nephropathy?
Idiopathic: (phospholipase A2 rec Abs)
infection (esp HBV, also HCV, syphilis)
autoimmune (esp SLE)
drugs (NSAID, penicillamine)
What are some etiologies of membranoproliferative GN?
infection (esp HCV +/- cryos, IE, HBV, other chronic infxn)
immune complex disease (SLE, cryos, Sjorgren's)
Type II (v. rare)
autoAb blacks inactivation of C3 convertase (C3 nephritic factor)
What are systemic diseases that cause nephrotic syndrome?
Diabetes mellitus (nodular glomerulosclerosis-Kimmelstiel-Wilson lesion: large kidneys hyperfiltration-> microalbuminuria-> dipstick+ ->nephrotc range (10-15yr) w/ concommittant prolif retinopathy seen in 90% of type I, 60% of type II)
SLE: usually membranous nephropathy
Cryogrobulinemia: typically w/ membranoproliferative GN
How do you work up nephrotic syndrome?
Urine sediment (benign w/o nephritis +/- oval fat bodies, Maltese crosses)
Proteinuria: 24hr or prot/Cr ratio (not accurate in AKI)
R/o secondary causes
-HbA1c + retinopathy
-ANA, anti-ds DNA, C3, C4
-fat pad bx
-cryocrit, HBV, HCV
-phospholipase A2, receptor Ab
How do you treat nephrotic syndrome
GENERAL: protein supplement, diuretics for edema, treat HLD, Na restriction, watch for malnutrtion, thrombosis (loss of anticoag), infection (esp encapsulated org b/c loss of Ig)
ACEI/ARB (dec proteinuria, slow immune progression)
if primary glomerular dz: Steroids +/- cytotoxic therapy
if membranous neph - ca screen
secondary causes- tx
Urine Dipstick: What is the significance and uses of specific gravity?
use to est Uosm (each 0.001 above 1 is 30 osm)
SG and Uosm useful to eval AKA, dysnatremias, polyuria heavy substances (glc, contrast) increase SG more than Uosm
Urine Dipstick: What is the significance and uses of pH?
range 4.5-8.5; useful to eval stones and RTAs, infection
Urine Dipstick: What is the significance and uses of Protein?
detects albumin (marker of glomerular dysfuxn), ddx for proteinuria
Urine Dipstick: What is the significance and uses of RBC?
detects hemoglobin and myoglobin (rhabdomyolosis), ddx for hematuria
Urine Dipstick: What is the significance and uses of WBC?
suggests inflammation (UTI, interstitial nephritis, GN)
Urine Dipstick: What is the significance and uses of ketones?
detectes aceoacetate (ie ketoacidosis) but not beta-hydroxybutyrate
Urine Dipstick: What is the significance and uses of nitrite?
suggests presence of enterobacteriaceae
Urine Dipstick: What is the significance and uses of glucose?
+ in hyperglycemia (>180 mg/dL), pregnancy, Fanconi's syndrome
What are the type of cells that can show up in urine sediment, what should you look for re: them, and what do they indicate?
(1) RBCs: look for amt & morphology (many dysmorphic -> glomerular)
(2) WBC: PMNs (UTI) vs. eosinophils (AIN, may require special stain)
(3) Epithelial cells: tubular (ATN), transitional (bladder, or ureters), squamous
What are the type of casts that can show up in urine sediment, what should you look for re: them, and what do they indicate?
(1) RBC-> GN
(2) WBC -> AIN, pyelonephritis, GN
(3) Granular ("muddy brown"): degenerating (4) cellular casts -> ATN
(5) Tubular Cell -> ATN
(6) Hyaline: Tamm-Horsfall protein (nonspecific)
(7) Waxy and Broad->adv chronic kidney disease
What are the type of crystals that can show up in urine sediment, what are their shpaes, and what do they indicate?
(1) Calcium oxalate monohydrate: spindle, oval, or dumbbell shaped (stones)
(2) calcium oxalate dihydrate: envelope shaped or octahedral (stones)
(3) uric acid: variable shape, polychromatic under polarized light (5-10% of stones, indicate increased uric acid, eg. gout)
(4) cystine: hexagon shaped, from inherited defects of tubular amino acid absorption
(5) struvite: coffin-lid shaed, seen in chornic UTI w/ urea splitting organisms (e.g. proteus, Klebsiella) (aka 'triple phosphate, Mg ammonium phosphate)
How do you interpret Urine Dipstick?
Depends on SG (more conc, less inc)
1+ 30 mg/dL
2+ 100 mg/dL
3+ 300 mg/dL
Not Se for micoralbuminuria and myeloma light chains
What does spot urine measure?
protein/creatinine (each mg/dL), est grams/day of proteinuria
can measure myeloma light chains.
What is orthostatic proteinuria?
inc protein excretion when upright, normal when supine. Usually in adolescents, 90% of young males with isolated proteinuria have this, typically resolves spontaneously.
What are the extrarenal etiologies of Hematuria?
extra renal is more common
(2) Neoplasm (transitional cell, prostate)
(3) Infection (cystitis, urethritis, prostitis)
(4) Folate trauma
(6) Schistosoma haematobium (trematode causing schistosomiasis
What are the intrarenal etiologies of Hematuria?
(1) Nephrolithiasis or crystalluria
(4) Vascular (renal infarcts, renal vein thrombosis, sickle cell disease and trait)
(5) Glomerular disease (IgA, thin BM> others)
What are some general rules of thumbs for ages and hematuria?
<20 yr old: GN, UTI, congenital
20-60 yr old: UTI, nephrolithiasis, cancer
>60 yr old (male): prostatitis, cancer, UTI
>60 yr old (Female): UTI, cancer
How do you work up Hematuria?
Urine dipstick: + if >3 RBC
+ dipstick and - sediment-> myo- or hemaglobinuria
dysmorphic RBC or RBC casts-> GN -> consider renal biopsy
If no e/o GN
-Urine cytology (se 70, sp 95, inc yild by checking am void x3)
-renal imaging: helical CT (r/o neophrolithiasis neoplasia of upper tract), cystoscopy (r/o bladder neloplasia, esp >50yo),
?U/S (r/o obstruction or parenchymal disease)
What are the etiologies of proteinuria?
(1) Glomerular (can be >3g/d): disruption of filtration barrier->lose alb
- Nephrotic syndrome
(2) Tubulointerstitial (1-2g/d): dec reabs of freely filtered proteins->use globulins
(3) Overflow: inc production of freely filtered proteins
(4) Isolated: asx, nl renal fx, sed, imaging, no h/o renal dz
- Functional (fever, exercise, CHF)
- Orthostatic (only when upright)
- Idiopathic (transient or persistent)
What are the types of kidney stones ?
(1) CALCIUM (70-90%)
(2) URIC ACID (5-10%)
(3) Mg Ammonium Phosphate (Struvite)
What are the Urine characteristics and risk factors of Ca kidney stones?
Ca oxalate> Ca phosphate
Urine characteristics: inc Ca, oxalate, urate, pH. dec citrate, volume
-secondary hypercalciuria (primary hyerparathyroidism, type 1 RTA, sarcoid)
- secondary hyperoxaluria (Crohn's, ileal disease w/ intact colon, gastric bypass)
- diet: inc animal protein, sucrose, Na or dec K, fluid, fruits & veggies
What are the characteristics and risk factors of uric acid kidney stones?
radiolucent on plain film
urine: inc uric acid (e.g. gout), dec pH (e.g. chronic diarrea)
What is the cause of struvite kidney stones?
chronic UTI with urea splitting organisms (e.g. Proteus, Kelbs)-> inc urine NH3 and pH
What are the clinical manifestations of nephrolithiasis?
sx/sx: Hematuria, flank pain, N/V, dysuria, frequency
Uretral obstruction (stones >5 mm don't pass)--> AKI if only one kidney
UTI: inc risk of infection proximal to stone, UA of distal urine may be normal
How do you work up nephrolithiasis?
- noncontrast helical CT scan (uretral dilation no stone suggest recent passage)
- strain urine for stone to analyze
- UA, UCx
- electrolytes, BUN/Cr, Ca, PO4, PTH,
- 24 hr Urine x 2 (>6 wk after acute setting) for Ca, PO4, UA, oxalate, citrate, Na, Cr
What is the acute treatment for nephrolithiasis?
(1) Analgesia (nsaid +/- opiate)
(2) aggressive PO/IV hydration
(3) Abx if UTI
(4) Consider CCB or alpha blocker for utertral relaxation
(5) Indications for immediate urological eval/hospitalization: obstruction (esp if only 1 kidney/transplant), urosepsis, intractable pain or vomiting, AKI
(6) Urological Rx: lithotripsy, cystoscopic stent, percutaneous nephrostomy, stone removal
What is chronic treatment for nephrolithiasis?
(1) Inc fluid intake for goal UOP >2L/d
(2) Ca Stones: 24 h urine ID specific urinary risk factors to treat
- dec Na and meat, thiazides, dec urine Ca
-dep on 24 h urineL K-citrate, dietary oxalate restriction, allopurional
-high dietary Ca is likely beneficial by dec oxalate abs (?supplements)
(3) Uric acid: urine alkalinization (K-citrate), allopurinol
(4) STruvite: Abx for UTI, urological-intervention
(5) Cystine: urine alkalinization, d-penicillamine, tipornin, captopril
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