Nephrology-Glomerular Dz, UA, Stones

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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?

(1) Goodpasture
-glomerulonephritis, pulmonary hemorrhage, +anti-GBM

(2) Anti-GBM disease
-glomerulonephritis, +anti-GBM

What are the types of immune complex diseases causing glomerulonephritis?

RENAL
(1) Post-strep GN: (10-14d, +ASLO, dec C3)
(2) Membranoprolif GN (dec C3)
(3) Fibrillary GN (nl C3)
(4) IgA nephropathy (nl C3)

SYSTEMIC
(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
(3) AIN
rash, new drug, urine WBC (inc eos) +/- WBC casts
(4) MYELOMA
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?

proteinuria >3.5g/d
albumin <3.5 mg/dL
edema
inc cholesterol

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?

idiopathic
HIV (collapsing variant)
pamidornate
heroin
congenital
hyperfiltration due to prior nephron loss
obesity
vesicoureteral reflux

What are some etiologies of membranous nephropathy?

Idiopathic: (phospholipase A2 rec Abs)
infection (esp HBV, also HCV, syphilis)
autoimmune (esp SLE)
carcinomas
drugs (NSAID, penicillamine)

What are some etiologies of membranoproliferative GN?

Type I
infection (esp HCV +/- cryos, IE, HBV, other chronic infxn)
immune complex disease (SLE, cryos, Sjorgren's)
lymphoproliferative disorders
idiopathic

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)

Amyloidosis

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
-SPEP/UPEP
-fat pad bx
-cryocrit, HBV, HCV
-HIV, RPR
-phospholipase A2, receptor Ab

Renal biopsy

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 bilirubin?

inc in biliary or hepatic disease

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
4+ >2g/dL

Not Se for micoralbuminuria and myeloma light chains
FP w/contrast

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
(1) Nephrolithiasis
(2) Neoplasm (transitional cell, prostate)
(3) Infection (cystitis, urethritis, prostitis)
(4) Folate trauma
(5) BPH
(6) Schistosoma haematobium (trematode causing schistosomiasis

What are the intrarenal etiologies of Hematuria?

(1) Nephrolithiasis or crystalluria
(2) Neoplasm
(3) Trauma/exercise
(4) Vascular (renal infarcts, renal vein thrombosis, sickle cell disease and trait)
(5) Glomerular disease (IgA, thin BM> others)
(6) OKD

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

Urine sediment:
dysmorphic RBC or RBC casts-> GN -> consider renal biopsy

If no e/o GN
-r/o UTI
-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
- GN
- Nephrotic syndrome

(2) Tubulointerstitial (1-2g/d): dec reabs of freely filtered proteins->use globulins
-ATN
-AIN
-Fanconi

(3) Overflow: inc production of freely filtered proteins
-multiple myeloma
-myoglobinuria

(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)
(4) Cystine

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

RF:
-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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