Dipstick Renal Pathology Flashcards
Specific
Gravity
•Specific gravity of plasma is 1.008-1.010
–urine SG 1.010 = water conserving
–Urine SG > 1.035 is non-physiologic (?X-ray dyes)
•Use to judge borderline results as 1+ protein (SG = 1.005) represents greater loss than 1+ (SG 1.030)
•In SIADH, USGwon’t increase with H2O deprivation
ph
- Metabolism produces acid, so kidney resorbs HCO3-(RTA type 1) and excretes acid in collecting tubules (RTA type 2)
- Kidney physiologic response to systemic metabolic changes and diet make urine pH difficult to interpret
Glucose
•all glucose filtered is resorbed in the proximal tubule until tubular threshold is exceeded at >180 mg/dL
•1+ dipstick ≈ 250 mg/dLplasma glucose
(normal
Proteins
- only albumin is measured
* normal excretion is
Proteins contd
- does not identify immunoglobulins (multiple myeloma)
- accurate measurement requires quantitative assays
- gold standard is 24 hour urine protein
- routine practice uses spot urine albumin to creatinine ratios
- typical urine excretion of creatinine = 1000 mg/day so that the spot urine albumin:creatinineratio = albumin excretion per day
- terms:
- 3.5 gm/day = nephrotic syndrome
- 40% daily variability and contaminating cells have protein
- test is for albumin and NOT globulins, including light chains
- protein = albumin by dipstick
- may be due to renal and non-renal causes
- physiologic: exercise, fever, standing
- pathologic: glomerular basement membrane damage
- follow-up with complete renal function testing:
- urine sediment morphology (blood, casts)
- Serum albumin (if low, then serious urine loss)
- quantitative measure of urine protein loss
- eGFR(corrects for age, sex and weight)
- imaging
Investigation of proteinuria rule out
Rule out transient proteinuria –fever, exercise
Rule out orthostatic proteinuria
Investigation of proteinuria urine sediment abnormal or normal?
1⁰vs 2⁰glomerular disease
- 300 mg/daymacroalbuminemia
Hematuria
•Ignore if female within 5 days of menstruation
•DDxof hematuria from hemaglobinuriaby centrifuging
–Myoglobin will also test positive
•DDxurology (infection, stones, tumor) from nephrology (“…nephritis”)
•Correlate to urine sediment morphology (? RBC casts, dysmorphic rbc’s)
centrifuge sediment red
hematuria
centrifuge supernatant red
dipstick heme negative
beeturia
phenazopyridine
porphyria
other
centrifuge supernatant red
dipstick heme positive either?
myoglobin or hemoglobin
centrifuge supernatant red
dipstick heme positive
plasma color clear
myglobinuria
centrifuge supernatant red
dipstick heme positive
plasma color red
hemoglobinuria
haptoglobin
binds to hemoglobin?
HEMATURIA
Non-hematologic
RBC Cast, dysmorphic RBC’s, protein >500 mg/24 hr
+
glomerulonephritis
Anti-GBM, ANCA, C’ levels, cryoglobulins, Hep B & C, VDRL, HIV, ASLO
renal biopsy
HEMATURIA
Non-hematologic
RBC Cast, dysmorphic RBC’s, protein >500 mg/24 hr
neg
pyuria wbc cast positive
culture eosinophils
tubulointersitial?
HEMATURIA
Non-hematologic
RBC Cast, dysmorphic RBC’s, protein >500 mg/24 hr
neg
Hb S, cytology, UA of family, 24 hour Ca+2/uric acid
tubulointerstitial
HEMATURIA
Non-hematologic
RBC Cast, dysmorphic RBC’s, protein >500 mg/24 hr
neg
Hb S, cytology, UA of family, 24 hour Ca+2/uric acid
imagin positive
cyst stone mass
HEMATURIA
Non-hematologic
RBC Cast, dysmorphic RBC’s, protein >500 mg/24 hr
neg
Hb S, cytology, UA of family, 24 hour Ca+2/uric acid
cytoscopy
urothelial neoplasm
hematuria upper tract - lower tract
- Stones2. Infection3. Neoplasm (urothelial)
The most reliable indicator of glomerular disease in hematuria without rbc casts is?
proteinuria
- 3.5 gm/24 hr: nephrotic
Mimics of 1⁰ Hematuria
- menstruation
- pigments (eg beets)
- anticoagulation
bilirubin
- Does not filter as bound to albumin - circulating albumin bilirubin (unconjugated)
- Test is for conjugated bilirubin (circulating conjugated bilirubin)
- Urobilinogen is colorless (Urobilinogen)
- dipstick bilirubin is positive when direct (i.e. conjugated) bilirubin is increased (negative in hemolysis)
- may appear before clinical jaundice
- relatively insensitive for detecting liver disease
Ketones
•Energy is from fatty acid metabolism (diabetes, starvation)
Acetone, acetoacetate, hydroxybutyrate
urobilinogen
- water-soluble metabolic product of bilirubin absorbed from gut and filtered
- Increased in hemolytic anemia (↑production) and liver disease ( ↓metabolism)
- not seen with obstructive jaundice (no bilirubin to gut)
nitrites
- Nitrates from diet are metabolized to nitrites by bacteria
- sensitive to 105 organisms/ml
- most gram (-) (E. coli, Klebsiella) and some gram (+) (Staph)
- Specific for bacteruria, but not sensitive
wbc in urine is most telling sign of?
infection
leukocyte esterase
- Enzyme found in neutrophils
- specific for pyuria (≠infection), and sensitive for infection
stone can also cause this
In a setting of high prevalence, LE(+) and nitrite (+) has a high PPV(+) for?
uti
SUMMARY-key on 3 analytes in the dipstick:
1.Proteinuria: confirm with P/C ratio, sediment, eGFR
2.Hematuria: R/O menses , urology versus nephrology
3.Infection (LE/nitrite)
Use the Specific Gravity to judge degree of dilution of analytes
A 26 year old newly married woman presents a 1 day history of burning on urination, urgency and frequency •Urine sediment: 12 pmn/hpf, 3 rbc/hpf •Urine dipstick: Spec Gravity:1.020 pH6.4 Glucoseneg Protein1+ Bloodtrace BilirubinNeg KetonesNeg UrobilinogenNeg Nitrite3+ LeukEsterase3+
Acute cystitis
ecoli gram neg, from gi tract
A 32 year old single female presents with a 2 day history of burning on urination. •Urine sediment: 6 pmn/hpf •Urine dipstick: Spec Gravity:1.015 pH6.4 Glucoseneg Protein1+ BloodNeg BilirubinNeg KetonesNeg UrobilinogenNeg NitriteNeg LeukEsterase3+
Pyuria & dysuria from urethritis (not UTI)…? Maybe bacteria that does not react and is nitrite neg
A 24 year old afebrile female presents to your office with 3 day history of back pain after heavy lifting •Urine sediment: NDA •Urine dipstick: Spec Gravity:1.015 pH6.4 GlucoseNeg ProteinNeg BloodNeg BilirubinNeg KetonesNeg UrobilinogenNeg Nitrite3+ LeukEsteraseNeg
Bactururia from poor transport
so contaminated
A 52 year old male presents with a 3 hour onset of severe colicky right-sided flank pain radiating into his groin •Urine sediment: 5 rbc/hpf •Urine dipstick: Spec Gravity:1.025 pH6.4 GlucoseNeg Protein1+ Blood2+ BilirubinNeg KetonesNeg UrobilinogenNeg NitriteNeg LeukEsterase1+
calculus
A 28 year old man has been in the ICU for 2 weeks following a motorcycle accident. He has had an indwelling bladder catheter for the 2 weeks. Repeated urine cultures have been negative •Urine sediment: 4 PMN/hpf, 3 rbc/hpf •Urine dipstick: Spec Gravity:1.015 pH6.4 GlucoseNeg Protein1+ Blood1+ BilirubinNeg KetonesNeg UrobilinogenNeg NitriteNeg LeukEsterase2+
Pyuria/hematuria from mechanical cause
A 66 year old female with atrial fibrillation is seen in your office for routine follow-up of her Warfarin therapy (anti-coagulation). Prothrombin time = 68 sec (11-15) with INR 6X upper limit •Urine sediment: 6 rbc/hpf •Urine dipstick: Spec Gravity:1.020 pH6.4 GlucoseNeg Protein1+ Blood3+ BilirubinNeg KetonesNeg UrobilinogenNeg NitriteNeg LeukEsteraseNeg
Hematuria from coagulation defect
A 54 year old asymptomatic male comes to your office after a dipstick for an insurance physical revealed blood. •Urine sediment: 5 rbc/hpf •Urine dipstick: Spec Gravity:1.020 pH6.4 GlucoseNeg ProteinNeg Blood2+ BilirubinNeg KetonesNeg UrobilinogenNeg NitriteNeg LeukEsteraseNeg
bladder tumor
A 6 year old boy presents with an acute onset of shaking and chills, with marked change in the color of his urine •Urine sediment: whole thing is red after centrifugation -after centrifugation -no rbc's seen on microscopy •Urine dipstick: Spec Gravity:1.020 pH7.4 GlucoseNeg ProteinNeg Blood4+ BilirubinNeg KetonesNeg UrobilinogenNeg NitriteNeg LeukEsteraseNeg
HUS
hemolysis is happeneing in the vessels
myoglobin doesnt stain it red hemoglobin does
haptoglobin binds the hemoglobing in the blood so haptoglobin will go to 0 in the blood
hemoglobin is spilling into the urine
An 18 year old high school athlete presents for evaluation for an endurance event. She is mid-cycle. •Urine dipstick: Spec Gravity:1.020 pH6.4 GlucoseNeg ProteinNeg Blood1+ BilirubinNeg KetonesNeg UrobilinogenNeg NitriteNeg LeukEsteraseNeg Reference ranges cp. normal plasma: SG = 1.005-1.010, pH = 6.9-7.1 •Urine sediment: 4 rbc/hpf (normal
Thin basement membrane disease
A 32 year old, previously well male presents complaining of swelling of his face in the morning and swelling of his legs in the afternoon. •Urine dipstick: Spec Gravity:1.030 pH6.4 GlucoseNeg Protein4+ BloodNeg BilirubinNeg KetonesNeg UrobilinogenNeg NitriteNeg LeukEsteraseNeg Reference ranges cp. normal plasma: SG = 1.005-1.010, pH = 6.9-7.1 •Urine sediment: waxy casts, oval fat bodies
3+ protein approximates 3 g/day, oval fat bodies from lipoproteins into tubules, absorbed by tubular cells which end up in urine, urine protein : urine creatinine > 2 g/g = 3 g/day loss,
diabetic nephropathy
could be in esrd already?
Average age for nephrotic syndrome
congenital nephrosis minimal change foacal glomerulosclerosis diabetic type 1 nephropathy minimal change membranous nephropathy diabetic type 2 amyloidosis paraneoplastic
congenital nephrosis - 0 minimal change - 5 foacal glomerulosclerosis - 8 diabetic type 1 nephropathy - 30 minimal change - 40 membranous nephropathy - 50 diabetic type 2 - 60 amyloidosis - 70 paraneoplastic - 70
A 64 year old insulin-dependent diabetic is in for routine monitoring. He has had the disease for 2 decades •Urine dipstick: Spec Gravity:1.005 pH6.4 GlucoseNeg Proteintrace BloodNeg BilirubinNeg KetonesNeg UrobilinogenNeg NitriteNeg LeukEsteraseNeg Reference ranges cp. normal plasma: SG = 1.005-1.010, pH = 6.9-7.1
Diabetic nephropathy: note urine is not concentrated (isothenuria)
Definitions of microalbuminuria
Urine dipstick: 1+ equals a concentration of 30 mg/dL( so at 1 L/day = 300mg/day)
> 30 mg urine albumin/gm urine creatinine is proteinuria
24 hour urine protein
30-300
mg protein/24hours
Spot urine albumin/urine creatinine ratio
Diabetes diffuse and nodular glomerulosclerosis
Basement Membrane Thickening
PAS + Nodules
Kimmelstiel -Wilsonlesion
CD2AP, CD2-associated protein
proteins of the
glomerular slit diaphragm
dvanced glycation products in vascular pathology
This diagram depicts some of the key points discussed in the text on the role of AGE products in microangiopathy as well as in macroangiopathy.
It is well known that the main features in diabetic glomerulopathy are proteinuria, mesangial expansion, and focal sclerosis. How do AGE contribute to this? AGE formation on laminin (a key structural protein of the ECM) causes reduction in polymer self-assembly and decreased binding of the other major components of the molecular scaffolding of the basement membrane, namely type IV collagen and heparan sulfate proteoglycan. Heparan sulfate proteoglycan (HSPG) which provides the negative charge of glomerular basement membrane (GBM) is per se the key factor impairing the leaking of plasma proteins and the resultant proteinuria. As we depict in Figure 4, diabetes-induced loss of matrix-bound heparan sulfate proteoglycan, secondary to AGE modification of glomerular basement membrane proteins, could prompt protein leaking and stimulate a compensatory overproduction of other matrix components in the vessel wall. This provides a strong molecular support to diabetic Kimmelstiel-Wilson nephropathy. On the other hand, these AGE-induced abnormalities alter the structure and function of microvessels other than the renal microcirculation.
AGEs also form on cell proteins in vivo. More so, they also form on DNA in vitro. The formation of AGEs is now also known to result from the action of various metabolites other than glucose, which are primarily located intracellularly and participate in the Maillard reaction at a much faster rate, such as fructose, trioses and dicarbonyl compounds, such as methylglyoxal and deoxyglucosone.
If AGEs also form on DNA in vivo, deleterious effects on gene expression may occur and intracellular AGE formation on cell proteins may thus, in turn, affect DNA function. Histones from the liver of rats after only one month of hyperglycemia showed AGE levels three-fold higher than those of their age-matched controls, and accumulation of AGEs on histones increased with the duration of the disease. This suggests a possible role for intracellular glycation in the increased teratogeny associated with diabetes mellitus.
Glycation and the other 3 pathways linked to hyperglycemia-induced damage may be linked in a unifying hypothesis put forward by Brownlee. This hypothesis suggests these biochemical pathways all arise from a single hyperglycemia-induced process, the overproduction of toxic “free radicals” produced by mitochondria acting on glyceraldehydes-3-phosphate dehydrogenase. Normalizing the levels of these excess free radicals inhibits the pathways through which cell damage occurs, and that all of these pathways can be activated, even in the presence of normal glucose levels, simply by using molecular genetic techniques to shut down the key enzyme that high glucose turns off.
A 24 year old male presents with gross hematuria 72 hours after the onset of acute pharyngitis •Urine dipstick: Spec Gravity:1.025 pH7.4 GlucoseNeg Protein3+ Blood4+ BilirubinNeg KetonesNeg UrobilinogenNeg NitriteNeg LeukEsteraseNeg Reference ranges cp. normal plasma: SG = 1.005-1.010, pH = 6.9-7.1 •Urine sediment: rbc: TNTC, rbc casts
GN (Berger d)
abnormal glycosylatio of iga hinge and so an autoantibody is made for it and they are deposited and caught in the glomerulus
goes on slowly to esrd and still hapeens with transplant so they are low on the list
Evaluation of glomerulonephritis
•Urine spot urine albumin/urine creatinine ratio –(>30mg/g is proteinuria) •eGFR •Kidney biopsy IF: mesangial IgA
Mesangial proliferation
Prognosis of Glomerulonephritis:Progression to ESRD at 10 years
•IgA nephropathy10% •Lupus nephritis20% •Membranous nephritis25% •Membranoproliferative40% •Focal and segmental80% Rate of progression is slowed by ACE inhibitors
A 76 year old female with known IgG kappa multiple myeloma presents with progressive renal failure •Urine dipstick: Spec Gravity:1.035 pH6.4 GlucoseNeg ProteinNeg BloodNeg BilirubinNeg KetonesNeg UrobilinogenNeg NitriteNeg LeukEsteraseNeg Reference ranges cp. normal plasma: SG = 1.005-1.010, pH = 6.9-7.1 •Urine sediment: waxy casts
Light chain nephropathy
A 7 year old male with recurrent episodes of E. Coli cystitis presents with fever and right CVA pain •Urine sediment: 9 wbc/hpf, •Urine dipstick: Spec Gravity:1.025 pH7.4 GlucoseNeg Protein1+ BloodNeg BilirubinNeg Ketones1+ UrobilinogenNeg Nitrite2+ LeukEsterase2+ Reference ranges cp. normal plasma: SG = 1.005-1.010, pH = 6.9-7.1
White blood Cell Casts
Acute pyelonephritis secondary to ureteric reflux
Ethylene glycol poisoning
anti-freeze/brake fluid Calcium oxalate Cystals in tubular lumens Calcium oxalate crystals urine Kids-tastes sweet-green
Uremia
untreated
Chronic Renal Failure
↑creatinine (azotemia=↑↑BUN)
eGFR
ESKD (end-stage kidney disease)
Oliguria
out-patient
Acute Renal Failure
Non-oliguria
in-patient
Acute Renal Failure
↑creatinine
Fractional excretion of Na+
AKI
hematuria
Nephritic Syndrome
RBC cast Proteinuria
edema
Nephrotic Syndrome
Proteinuria > 3.5 gm/day
Renal Biopsy (Not minimal Δ or Diabetes > 5 yrs)
Glomerulopathy
Fever, CVA pain
Infection
WBC cast, dipstick
Urine culture
Pyelonephritis
Pain (colicky)
Stones
Imaging & Hematuria
Stone analysis
Renal calculus
↑Blood pressure
♀50
Renovascular hypertension
Imaging (angio… or vascular…)
Renal vein renins
Renal Artery Steno
Malaise
Isolated lab abnormality
↑Creatinine
eGFR
Chronic RenalFailure
Fatigue
Anemia
EPO
hyrdonephrosis
obstruction
small kidneys
-sediment
isothenuria
protein
chronic renal failure
abnormal UA
bacteria
WBC, casts, eosinophils
RBC’s
RBC, casts ↑protein
bacteria - pyelonephritis
WBC, casts, eosinophils - interstitial nephritis
RBC’s - vascular occlusion
RBC, casts ↑protein - glomerular, vasculitis
normal ua
FeNa500
prerenal azotemia
normal ua
FeNa>1%
Uosm
acute tubular necrosis (AKI)
