Renal Approach to Proteinuria and Polyuria Flashcards
What are the three layers of the glomerular filtration barrier?
1) fenestrated capillary endothelium 2) Glomerular Basement membrane 3) Podocytes
what is the function of the fenestrated capillary endothelium?
keeps out cells
what is the function of the glomerular basement membrane?
it keeps out large plasma proteins (eg albumin)
what is the function of the podocytes?
it keeps out large plasma proteins (eg albumin)
so what things get through the glomerular filtration barrier?
low molecular weight proteins, solutes and small molecules
what are 2 examples of low molecular weight proteins that get through the glomerular filtration barrier?
beta-2 macroglobulin and light chains
what happens to the low molecular weight proteins that get through the glomerular filtration barrier?
they get filtered and then reabsorbed in the proximal tubule
what are some examples of solutes and small molecules that get through the glomerular filtration barrier?
Na, K, and glucose
What makes up normal urine protein?
low-molecular weight proteins that pass through glomerular filtration barrier and don’t get reabsorbed; also includes Tamm-Horsfall protein produced by the renal tubule
what is the normal daily protein excretion (both protein and albumin)?
protein: less than 150; albumin: less than 30
what are the three different types of proteinuria?
glomerular, overflow, and tubulointerstitial
what occurs in glomerular proteinuria?
there is damage to the glomerular filtration barrier–> albuminuria
what occurs in overflow proteinuria?
the filtered low-molecular weight protein load is greater than the reabsorptive capacity of the kidney (eg. light chains in multiple myeloma)
what occurs in tubulointerstitial proteinuria?
tubular damage leading to impaired reabsorption of low-molecular weight proteins (eg acute tubular necrosis)
there are four different tests that can be ordered to test for proteinuria; what are they?
urinalysis, spot urine albumin/creatinine ratio, spot urine protein/creatinine ratio, and 24 hour urine protein
what are the pros of urinalysis?
cheap and easy; can detect other urine abnormalities
what are the cons of urinalysis?
it only detects albumin; low sensitivity (only detects >300 mg protein)
what are the pros of the spot urine albumin/creatinine ratio?
it can detect small amounts of albumin (this is important in recognizing early diabetic nephropathy)
what are the cons of the spot urine albumin/creatinine ratio?
it only detects albumin
what are the pros of the spot urine protein/creatinine ratio?
detects all proteins (albumin, light chains, beta-2-macroglobulin)
what are the cons of the spot urine protein/creatinine ratio?
it is not as well validated in diabetic nephropathy patients
what is the gold standard test for measuring proteinuria? but what is the con to this test?
24 hour urine protein; it is inconvenient
if you have a patient with known diabetic nephropathy, what tool used for measuring proteinuria would be best to use?
spot urine albumin/creatine ratio
what might the findings be on a spot urine albumin/creatinine ratio test in a patient with a light chain nephropathy (due to multiple myeloma)?
it may falsely show “no protein”- YOU NEED A SPOT URINE PROTEIN/CREATININE RATIO TO DETECT LIGHT CHAIN PROTEINURIA
what are two specific conditions that cause glomerular proteinuria?
nephrotic and nephritic syndrome
how does the urine appear in cases of nephrotic syndrome?
frothy
losing albumin in the urine creates other problems throughout the body such as what?
peripheral edema and periorbital edema
besides albumin, what is another protein that may be lost in cases of nephrotic syndrome?
antithrombin III
what happens if a patient loses antithrombin III in cases of nephrotic syndrome?
it is an anticoagulant- so if you lose it, you are going to create a hypercoagulable state which can create a higher risk for blood clots like DVTs, PEs, and renal vein thrombosis
which specific diseases do we most commonly see a hypercoagulable state?
membranous nephroapthy
what is the effect of nephrotic syndrome on the liver?
the liver tends to ramp up production of lipoproteins and this can lead to hyperlipidemia
the edema seen in nephrotic syndrome can be contributed to two different theories- what are they?
low intravascular oncotic pressure (underfill theory) and renal sodium retention (overfill theory)
what are the 5 main features of nephrotic syndrome?
proteinuria (>3.5/day), ede,a, hyperlipidemia, hypoalbuminemia, hypercoagulability
how does hyperlipidemia present in cases of nephrotic syndrome?
fatty cases and Xanthelasmas
What are 5 examples of nephrotic syndromes?
diabetic nephropathy, minimal change disorder, focal segmental slomerulosclerosis, membranous nephropathy, amyloidosis
what is the most common cause of nephrotic syndrome in children?
minimal change disorder
what is focal segmental glomerulosclerosis associated with?
HIV, heroin use, and chronic reflux
what is associated with membranous nephropathy?
hep b, hep c, syphilis, solid tumors, and SLE
if you suspect a patient has nephrotic syndrome, what should their workup be?
serum creatinine with eGFR, urinalysis with microscopy, urine albumin to creatinine ratio and urine protein to creatinine ratio; additional labs: HIV, hep b/c serologies, SPEP, lipid panel, A1c
how do you manage nephrotic syndrome, specifically the proteinuria aspect?
blood pressure control, ACE/ARB may be renoprotective
what are the 4 main features of nephritic syndrome?
heamturia, proteinuria (<3.5), new-onset hypertension, AKI/oliguria
what are the three broad categories that nephritic syndromes can be grouped into?
- immune complex 2. anti-GBM 3. ANCA-associated
how can the immune-complex associated nephritic syndromes further be broken down?
low complement levels and normal complement levels
what are the causes of immune complex associated nephritic syndromes with low complement levels?
post-strep, SLE
what are the causes of immune complex nephritic syndromes with normal complement levels?
IgA nephropathy
how can SLE nephritis present?
with other systemic findings (butterfly rash, polyarticular arthritis); or it could present with rapidly progressive glomerulonephritis
what is the most common nephritic syndrome?
IgA nephropathy
what are the pulmonary-renal nephritic syndromes?
anti-glomerular basement membrane (anti-GBM), GPA, MPA, and EGPA
how does GPA present?
upper respiratory symptoms (saddle nose deformity, chronic sinusitis), lower respiratory symptoms (hemoptysis), renal symptoms (hematuria with severe AKI)
what is microscopic polyangitis (MPA)?
think GPA without the upper respiratory symptoms
how does EGPA present?
adult onset asthma, eosinophilia, palpable purpura, hematuria and AKI
if you have a patient present with symptoms of a nephritic syndrome, what should their workup be?
serum creatinine with eGFR, urinalysis with microscopy, urine albumin to creatinine ratio and urine protein to creatinine ratio; additional labs: ANCA, anti-GBM, ANA, complements
what is the urine sediment like in nephritic syndrome?
“active”: hematuria, dysmorphic RBCs, RBC casts, WBCs; non-nephrotic range proteinuria
what is the urine sediment like in nephrotic syndrome?
“bland”: see heavy proteinuria but few cells
what is the definition of polyuria?
production of more than 3 L of urine in 24 hours
what are the 2 mechanisms in place to help the body regulate serum osmolality?
AND release and thirst
how does ADH release work?
the hypothalamus has osmoreceptors that sense osmolality- ADH is going to go down the pituitary stalk and then travel to the kidneys where it binds to AVPR2
what happens when ADH binds to AVPR2?
it causes aquaporins to move over to the apical surface of the cells, which allows water to move from the tubular lumen back into the blood
what are the 4 causes of polyuria that we talked about?
osmotic diuresis, central diabetes insipidus, nephrogenic diabetes insipidus, primary polydipsia
what is the mechanism of osmotic diuresis?
excess solute (glucose or mannitol) draws water into the renal tubules–> diuresis
what is the mechanism of central diabetes insipidus?
lack of ADH–> inability to concentrate urine
what is the mechanism of nephrogenic diabetes insipidus?
kidneys don’t respond to ADH
what is the mechanism of primary polydipsia?
patient drinking excess H2O
what are the key features of osmotic diuresis?
UA with glucosuria (if solute= glucose) and Uosm is >300
what are 4 causes of central DI?
head trauma, brain tumor, congenital malformation, idiopathic
what are the key features of central DI?
Uosm less than 300, urine osmolality does not increase with water deprivation, urine osmolality increases with administration of desmopressin (synthetic ADH)
what is a common cause of nephrogenic DI?
medications such as lithium
what are the key features of nephrogenic DI?
Uosm <300, urine osmolality does not increase with water deprivation, urine osmolality does not increase with the administration of desmopressin (synthetic ADH)
does DI lead to hypernatremia?
if thirst mechanism is intact, then it won’t; patient compensates for ADH inactivity by drinking more water; if thirst mechanism is lost or patient lacks access to water, we can see hypernatremia
what is primary polydipsia?
patient drinking excess water; commonly seen with psychiatric disorders including psychosis and OCD
what are the key features associated primary polydipsia?
Uosm is less than 300, urine osmolality increases with overnight water deprivation
how do you treat central diabetes insipidus?
drink more water; desmopressin
