AKI Flashcards
Role of kidneys
maintain ECF, produce erythropoietin/renin, activate vitamin D
What are normal GFR numbers?
- ## 140 in men, 126 in women
How to calculate urinary clearance? What is an ideal urinary clearance measure? Why is 24h CrCl not used?
UV/PT (urinary conc. x urine volume/ plasma conc. x time of urine collection)
- inulin is gold standard but serum creatinine measured clinically (constant, small, freely filtered)
- it overestimates GFR especially at low values - as kidney function decreases more creatinine is secreted by the kidney tubules
Failings of serum creatinine measurement?
- people have different muscle mass, meat diet, etc.
-insensitive to GFR decreases, especially in early stages as nephrons are initially hyperfiltrating
Which GFR equation is used? Limitations?
- CKD-EPI –> more accurate for normal GFR >60
- less accurate for extremes of age and body size, para/quadripelegia, amputation, skeletal muscle diseases, pregnancy, CANNOT USE IF AKI
CKD Categories (CGA)
Stage 1,2,3a,3b,4,5 based on GFR (1 is above 90 and 5 is below 15)
Stage A1/2/3 based on albuminuria (ACR)
- normal/ mild is under 30 (mg/g) or 3 (mg/mmol)
- moderate is 30-300, 3-30
- severe is 300+, 30+
What could cause a transient increase in albuminuria?
- fever, inflammation, exercise, meds, hyperglycemia
If a man has to secrete 600mosm/day of solute, how much urine should he secrete if
- in the desert
- force fed water
- 600/1200 = 0.5L (as concentrated as possible)
- 600/50 = 12L (as dilute as possible)
*normal urine concentration is between 50-1200mosm/kg
Definition of AKI (Stage 1/2/3)
An acute (48h) rise in creatinine –> over 26umol/L increase or 1.5x baseline.
Can also include urine output, though less definitive (kidneys can produce normal amounts of urine despite dysfunction).
1 –> under 0.5ml/kg/h for 6-12 hours
2 –> under 0.5ml/kg/h for 12+ hours
3 –> under 0.3ml/kg/h for over 24 hours OR anuria for 12 hours
Post-Renal AKI
How do you test for it?
Treatment?
- Anything that impairs urinary outflow –> back up of urine leads to hydronephrosis/ distended renal pelvises and calyces –> can lead to chronic obstructive nephropathy
Intraluminal –> stones, clots, tumors, abscesses
Extra luminal –> tumors, abscesses, fluid, LNs, vessels
- i.e. prostate hypertrophy, urethral stricture/ stenosis
- Rule out with foley catheter (lower) or nephrostomy tube (upper) and renal U/S
- Decompression before dialysis
Pre-Renal AKI
Treatment?
- Anything that impairs renal perfusion
- Absolute Decreased ECF –> diarrhea/vomiting, poor oral intake, diuretics, blood loss
- low JVP and hypotension
- Effective Decreased ECF –> impaired CO, shock, altered hepatorenal flow (i.e Hep C leading to vasodilation, fluid moving to interstitial space, and renal constriction) NSAIDs and ACEis that decrease intra-glomerular pressure
- edema, high JVP, and ascites
- solve the underlying problem (stop NSAIDs, five fluids)
Intrinsic AKI
- An anomaly inside the kidney (vascular, glomerular, intersitital, tubes)
- Most commonly acute tubular necrosis (ATN) –> decreased flow and O2 leads to PGs/NO/TGF/etc.
Ischemic ATN –> sepsis, shock, meds, lower BP, ischemia, up to 3 months
Toxic ATN –> contrast, antimicrobials, chemotherapeutics, myoglobin from rhabdomyolysis, uric acid
- typically non-oliguric, days
What can lead to oliguria?
decreased flow, increased intratubular pressure, increased Na distally (all decrease GFR)
Indications for dialysis
- persistence of severe AKI consequences despite treatment, OR toxic ingestion/ decreased LOC
- pulmonary edema (respiratory failure), acidemia (cardiac standstill), hyperkalemia (lethal arrythmias i.e. peaked T, wide QRS, Vfib), pericarditis, encephalopathy/ seizures
What do you give to a hyperkalemic patient experiencing arrythmias?
Calcium gluconate
Urinalysis signs of glomerulonephritis
red cells, red cell casts, protein
Indications for kidney biopsy
- unexplained progressive AKI
- evidence of glomerular or systemic disease
- potential genetic cause (Alport’s)
Proper collection technique for a urine sample?
First thing in the morning, midstream, clean and sterile container, analyze within 1-2 hours
What can different colours of urine indicate? What does frothy urine indicate?
Black –> Hgb, Mgb, homogenistic acid
White –> pyuria, propofol
Green/ Blue –> pseudomonas, methylene blue, propofol
Purple –> bacturia w catheters
Orange/red –> phenazopyridine
Pink/red/brown –> blood, Hgb, Mgb, beets, rifampin
frothy urine indicates proteins
What is normal urine pH?
- 4.5-8
- can be more acidic if protein, acidosis
- can be more basic if vegetarian, citrus, UTI, alkalosis
What is specific gravity? What could high or low values indicate?
- ratio of urine density: equal volume of H20 (measures concentrating ability)
- 1.003 (dilute) to 1.035 (concentrated)
Low –> increased fluids, diuretics, DI
High –> dehydration, SIADH
Fixed –> severe renal disease
What is measured on urine macroscopy (dipstick)?
pH, specific gravity, blood (peroxidase activity of RBCs/Hgb/Mgb, need confirmation with microscopy), protein, glucose, ketones, nitrite, leukocyte esterase
Measuring protein in urine - what exactly are you measuring?
- mostly sensitive to albumin, not senstitive enough to detect microalbuminuria
- graded negative to 4+
- dilute urine may underestimate proteinuria (and vv)
Why would you see glucose in urine? Ketones? Leukocyte esterase?
Glucose –> filtered load exceeds resorptive capacity of tubules (over 10mM) OR defect in resorption (under 10 mM)
Ketones –> diabetes, starvation, alcoholic ketoacidosis (does not detect B-hydoxybutyrate which is 80% of ketones)
Leukocyte esterase –> enzyme in neutrophils/ macrophages, see if intact/lysed WBCs (infxn, inflamm, malignancy, stones, glomerunephritis)
What would cause a false (+) vs false (-) nitrite?
False (+) –> bacteria (especially enterobacter), delayed, bad storage
False (-) –> low nitrite diet, ABX
RBC and WBC findings on urine microscopy
- normal values
- what can cause them to be increased
RBC –> normal is under 3
- can be more if exercise, trauma, stones, infxns, malignancies, glomnephritis
WBC –> normal is under 5
- can be more if infxn, inflamm
Renal tubular epithelial cells
Transitional epithelial cells
Squamous epithetial cells
Normal values? What can cause them to be increased?
Renal tubular –> normal is under 2
- can be more if ATN, nephritis, etc.
Transitional Epithelial –> a few is normal
- SUPERFICIAL (large, circular, small nucleus) common with UTI
- DEEP (small, oval, large nucleus) common with bladder cancer and stones
Squamous –> insignificant! genital contamination
Oval fat bodies
Bacteria
Yeast
Free lipid droplets
Oval fat bodies –> nephrotic syndrome
Bacteria –> infection or contamination, normally <10
Yeast –> infection or contamination
Free lipid –> nephrotic syndrome, trauma, contamination
What are casts? What can different types of casts indicate?
Hyaline, granular, waxy, broad, RBC, WBC, RTE, fatty
- Tamm-Horsfall mucoproteins and trapped elements
- Hyaline - no cells only mucoproteins, non-specific
- granular/ waxy - non-specific
Broad - diluted renal tubules (advanced CKD, ESRD) - RBC - glomerulonephritis
- WBC - pyelonephritis, acute interstitial nephritis, glomerulonephritis
- RTE - ATN, nephrotoxins, transplant rejection
- Fatty - nephrotic syndrome
What are crystals? What are examples of pathological crystals?
- formed when urine is supersaturated
Cystine - cystinuria (defect in proximal tubules)
Cholesterol - nephrotic syndrome
Bilirubin - severe liver disease
Drug - overdose, dehydration, hypoalbuminemia
Overflow vs Post-renal vs Tubular proteinuria?
Overflow –> excess proteins in serum that exceeds resorptive capacities (Mgb suggests rhabdo, Hgb suggests hemolysis, Ig light chains suggests multiple myeloma)
Post-renal –> infxn/ inflammation/ stones/ tumours of the lower tract
Tubular –> interference with proximal tubule reabsorption
ACR
- urine albumin to creatinine ratio
- useful for prognosis, Dx of diabetic nephropathy, CKD staging
Spot vs 24h urine
Spot –> dipstick, ACR, PCR (protein), urine protein electrophoresis (for MM), 1ST LINE
24h –> albumin and protein excretion rate, urine protein electrophoresis
Urine findings for:
- Glomerulonephritis
- Nephrotic syndrome
- Acute Pyelonephritis
- Lower UTI
- ATN
- DM
- Carcinoma
Glom - turbid, blood/protein, RBC (casts), WBC (casts), RTE casts
Nephrotic - frothy, lots of protein, fatty casts, oval bodies, cholesterol crystals
Pyelonephritis - turbid, nitrite, leukocyte esterase, WBC (casts), bacteria
Lower UTI - same as pyelonephritis + transitional epithelial cells and NO casts
ATN - isotonic urine (fixed specific gravity) in a hypotensive patient
DM - glucosuria, ketonuria, nocturia, dehydration
Carcinoma - atypical urothelial cells and RBCs
Glomerular filtration barrier
- fenestrated endothelial cells, glomerular basement membrane, podocytes (slit diaphragm)
- prevent filtration of larger (-) proteins
Glomerulonephritis
- cause
- dx/tx
- etiology
- immune injury to glomerulus
- dx: kidney biopsy
- tx: immumnosuppresives
- either NEPHROTIC (isolated barrier injury) or NEPHRITIC (diffuse inflammation)
Nephrotic Syndrome
- signs?
- most common cause?
- a lot of protein in the urine (>3.5)
- hypoalbuminemia, hypercholesterolemia
- peripheral edema (loss of oncotic pressure)
- hypercoaguability (VTE), infection (loss of Ig),
- AKI (proteinuria damage, interstitial edema)
- Lipiduria (oval bodies, fatty casts
- most common cause is diabetic nephropathy
- can also be caused by membranous nephropathy (MN), FSGS, MCD, etc.
Nephritic Syndrome
- signs?
- causes?
- RBCs, RBC casts, dysmorphic RBCs
- proteinuria and edema is less severe than in nephrotic, but GFR will decrease faster and earlier on than nephrotic
Based on direct IgG immunofluorescence staining…
Pauci-immune –> ANCA vasculitis
Linear staining –> Goodpasture’s (anti-GBM Ab)
Granular immune complex –> SLE, IgA, autoimmune
Immune mediated glomerular injury
- 3 main mechanisms
- subendothelial vs subepithelial vs mesangial
- Ag-Ab immune complexes
1. Circulating IC (passive deposition in glomerulus)
2. Circulating Ag (in-situ Ab binding)
3. Ab targets self-AG in the glomerulus
Subendothelial (most inflamm) > mesangial > subepithelial (little inflamm as no access to circulation)
Non-immune mediated glomerular injury
- glomerular sclerosis and interstitial fibrosis
- remaining healthy nephrons must increase their GFR
- angiotensin II causes vasoconstriction of the EA>AA, this helps maintain GFR initially but long term leads to glomerular damage
Pyelonephritis vs cystitis
Colonization vs ascension
- infection of the kidney/ renal parenchyma (upper) vs infexion of the bladder (lower)
- movement from urethra to bladder vs. movement from ureter to kidney (via fimbria attaching to uroepithelium)
UTI Risk factors
indwelling catheter, ABX, spermicides, voiding disfunction, female (shorter urethra), sex, pregnancy, vesicouretal reflux (urinary retention)
UTI Sx
dysuria, frequency, hematuria, suprapubic tenderness, chills/fever, flank pain and CVA tenderness
*malodorous/ cloudy urine or mental status change is NOT specific to UTI
* leukocyte esterase/nitrite also poor Sn/Sp
Which pathogen most commonly causes UTIs?
- E. coli
- things like pseudomonas and enterobacter are more likely if hospital-acquired
When should you order a blood culture for UTI?
When should you collect urine?
- only collect blood if sepsis/ shock/ fever/ immunocompromised
- DO NOT collect urine/culture unless symptomatic UNLESS pregnant/ instrumented (also do not give ABX in this scenario)
Treatment for Cystitis vs pyelonephritis
Cystitis –> nitrofurantoin (5 days) or fosfomycin (1 dose)
Pyleonephritis –> IV ceftriaxone or gentamicin
–> oral cefixime or amox-clav or TMP-SMX
–> if ER/ septic, ceftriaxone or gentamicin
*shortest duration possible, change to oral ASAP, remove catheter ASAP, hydrate
Role of:
Proximal tubule
Loop of Henle
Distal tubule
Collecting tubule
Proximal –> reabsorbs 65% NaCl/H20/K, 90% HCO3-, glucose and amino acids
LOH –> reabsorbs 35% NaCl/H20 (countercurrent multiplier), 25% K in ascending loop
Distal Tubule –> reabsorbs 5% NaCl, almost no H20
Collecting Tubule –> principal cells reabsorb Na+ and Cl- and secrete K+ via aldosterone
- intercalated cells reabsorb K+ and secrete H+
- will reabsorb more water in the presence of ADH
What is normal serum K? Where is it located? What is it needed for? How is it excreted/ managed?
- 3.5-5
- most abundant intracellular cation, important for nerve conduction and muscle contraction
- whatever is ingested must be excreted, mainly excreted in urine. Controlled by SECRETION, not by reabsorption.
- kidney however cannot handle minute to minute, so Na/K ATPase on principal cells and EVERY cell in the body modulates small changes in ECF potassium
How do insulin and B-adrenergic catecholamines affect potassium?
- they stimulate the pump to drive K intracellularly
- done after a meal to avoid hyperkalemia
Where is the main site of K+ secretion?
What is K reabsorption dependent on?
- Main site of secretion is the CCD (influenced by aldosterone/ flow/ Na/ pH)
- reabsorption is linked to Na (i.e. water absorption driven by Na, NaK2Cl cotransporter in LOH)
Effect of Aldosterone
- what stimulates it?
- increases Na reabsorption and K secretion
- released from adrenal gland due to hyperkalemia and hypovolemia
- activates ENaC and new ENaC production (brings Na into cells so ATPase can work)
- increases Na/K ATPase activity
- more (-) lumen which increases secretion of K into the lumen
- stimulates ROMK channels on luminal membrane (secretes K into the lumen to be excreted)
Effect alkalosis has on potassium?
low H+ causes shift of H out of principal cells and K into principal cells which results in increased K secretion (hypokalemia)
Effect a full ECV has on potassium?
- increased flow rate allows for delivery of more Na distally, which increases Na reabsorption and thus K secretion
- lower flow in the CCD would result in less K excreted
Definition of hyperkalemia
Sx
Causes
Tx
- K over 5, dangerous if over 6
- weakness, nausea, paresthesias, peaked T waves, wide PR and QRS, Vfib, etc.
- Increased intake - usually not the only reason
- Shift/Redistribution - decreased insulin, B-blockers, metabolic acidosis, digoxin toxicity, cell breakdown (rhabdo, hemolysis, tumors)
- Decreased Excretion - low GFR, low ECV, hypoaldosteronism (ACEis, ARBs, heparin, spironolactone)
Tx –> calcium gluconate, calcium chloride, insulin, B-agonists, bicarbonate, Kayexalate, diuertics, dialysis
Defintion of hypokalemia
Sx
Causes
Tx
- K under 3.5, dangerous if under 2.5
- weakness, cramping, ileus, U waves, VT/VF
- Decreased intake
- Shift - B-agonists, insulin, anabolism, metabolic alkalosis
- Increased loss - diarrhea, laxatives, ileostomy, hyperaldosteronism (cushings, HTN, liver failure), hypomagnesia (releases inhibition of ROMK), loop/thiazide diuretics, aminoglycosides
Tx –> replace ORALLY (IV is hard), assess Mg/PO4 and consider replacing (Mg inhibits ROMK)
*SERUM potassium is not a reliable index for deficit!
In HYPOkalemia what would a transtubular protein gradient of over 7 vs under 3 mean?
over 7 –> renal loss
under 3 –> extrarenal loss (GI)
What are complications of dialysis?
- hypotension, arrythmias, thrombosis, sepsis, bleeding (especially if on heparin)
- more and earlier is not necessarily better
What are biomarkers of AKI? How can you differentiate between AKI and CKD?
- NGA1, KIM-1, Il-18, Cystatin C
- only a kidney biopsy can differentiate
What is the most common cause of AKI in hospital? Outpatient?
Hospital –> ATN
Outpatient –> pre-renal
What urinalysis finding should always be seen by urology?
Gross hematuria (visibly red urine)
*gross PAINLESS hematuria is malignancy until proven otherwise
Most common cause of AKI by age
0-20
20-40
40-60
60+
0-20: glomerulonephritis
20-40: UTI
40-60: bladder tumor (or UTI if female)
60+: prostate hyperplasia
Risks for urothelial tumors?
Dx
Most common bladder cancer?
Tx
- SMOKING #1, aniline dyes (painter, hairdresser), radiation, chronic cystitis (catheters, infxns)
- Dx –> cystoscopy and biopsy (lesion and detrusor muscle for staging –> TIS, TA, T1 non-invasive, T2-T4 if invasive, T4 has spread to other organs)
- most common is urothelial (transitional cell)
- if non-muscle invasive –> transurethral resection, mitomycin C, chemo if high grade/ in-situ/ many lesions/ rapid recurrence
- if muscle invasive –> radical cystectomy, chemo
U/S
CT IVP
Cystoscopy
pros and cons
U/S - good for renal tumors/stones and hydronephrosis
- may miss ureter stones, smaller tumors, may just be a blood clot, no function
CT IVP - most sensitive for GU pathology, can see fluid and filling defects
- expensive, contrast, radiation (cannot give if pregnant, MM, renal dysfxn)
Cystoscopy - lower tract imaging, telescope, good for urothelial carcinomas
Renal Mass
- signs
- labs to order
- most common malignant finding and its treatment
- triad of flank pain, hematuria, and palpable mass (rare)
- alkaline phosphatase (bone metastases), liver function, calcium (bone metastases or parneoplastic syndrome if also weight loss/fever/anemia/HTN)
- most common malignant finding is renal cell carcinoma (clear cell)
- Tx –> nephrectomy, chemo, targeted therapy with TK inhibitors
Difference between pseudo-tumours and tumours on DMSA scan?
Tumors will have decreased uptake
Renal Colic
- what are potential life threatening causes?
- imaging?
- when to refer?
- abdominal aortic dissection/ aneurysm, appendicitis, ectopic pregnancy, septic stone
- plain film KUB/ CT-KUB –> stones will be radiopaque
- refer if fever, WBC, bacturia, only onekidney, CHF, pregnancy, etc.
Stones
- what can you give to help pass
- different kinds?
- will likely pass spontaneously if small, non-obstructive stones should not cause pain
- can give tamsulosin (flomax)
Ca Oxalate –> most common, chocolate/ nuts/ tea/ hypercalciuria
Ca phosphate –> primary hyperparathyroidism, tubular acidosis, malignancy, sarcoidosis
Uric acid –> acidic urine, gout, meat, chemo
Struvite (staghorn) –> pH > 8, infection, Mg/ammonium/ PO4/ Ca
Treatment options for stones
- hydration, NSAIDs, and Flomax (tamsulosin) IF no renal impairment, vomiting, infection
Ureter stent (double J stents)
Shockwave lithotripsy if under 2cm
Ureteroscopy and laser if bigger
Percutaneous nephrolithotomy if large and risk of bleed
Common sites for stone formation?
- ureto-pelvic junction
- ureto-vesical junction
- crossing of iliac artery
