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HY Renal – by Dr Mike Mehlman Afferent vs efferent regulation

- Go to the kidney.
- Patency maintained by vasodilating prostaglandins.
Basic HY Renal lab values you must know for USMLE - NSAIDs inhibit prostaglandin synthesis à ¯ dilation of afferent arterioles à ¯ renal
Afferent arterioles
- Should be <20 mg/dL. blood flow.
- High urea nitrogen in the blood is called azotemia. - NSAIDs don’t actively constrict the afferent arterioles. This is incorrect wording.
Blood urea nitrogen They just merely ¯ vasodilation / ¯ diameter of the afferent arterioles.
- “Uremia” technically means “urea in the blood,” but is used to refer to patients
(BUN)
who have symptomatic renal failure with poor lab values. This has absolutely zero - Leave the kidney.
to do with hyperuricemia (gout) and is sometimes confused by students. - Angiotensin II normally constricts these.
- 0.7-1.2 mg/dL - ACEi/ARBs therefore ­ diameter of the efferent arterioles. They are not dilating
Creatinine (Cr)
- Once you’ve hit a creatinine of 2, you’ve lost ~90% of your renal function. them; they are merely ¯ constriction of them. As mentioned above, prostaglandins
Efferent arterioles
- 3.5-5.0 mEq/L. will actively dilate the afferent arterioles.
- Will always be elevated in renal failure on USMLE. - Some students might say, “Well doesn’t AT II act on the afferent arterioles as well?”
Potassium (K+) - This is because the kidney normally secretes (i.e., excretes through tubular walls In theory, a very minor amount, but on USMLE, this will get you questions wrong. You
into the urine) K+ in the cortical collecting duct under the action of aldosterone. So want to think:
if the kidney is fucked up, we can’t do that, so serum K+ rises. AT II = constricts efferent;
- 135-145 mEq/L. ACEi/ARBs = ¯ constriction of efferent (­ diameter).
Summary
- Can be variable in renal failure as per my observation on NBMEs. Prostaglandins = dilate afferent;
- Aldosterone normally reabsorbs sodium in the cortical collecting duct in exchange NSAIDs = ¯ dilation of afferent (¯ diameter).
Sodium (Na+)
for potassium being secreted, so one might think it should automatically be low if
the kidney can’t reabsorb it. But the kidney has a multitude of sodium regulation
mechanisms (i.e., vasopressin), so Na+ can be normal.
- Always ¯ in renal failure. This is due to 2 reasons:
1) Ca2+ is normally reabsorbed in the late-distal convoluted tubule (DCT), Pre-, intra-, and post-renal azotemias
so if we can’t do that, serum Ca2+ falls. - BUN/Cr = Blood urea nitrogen to creatinine ratio.
2) Proximal convoluted tubule (PCT) of the kidney is normally where 1a- - FENa = fractional excretion of sodium (i.e., amount of sodium in the urine).
hydroxylase, under the action of PTH, activates inactive 25-OH-D3 into - There’s no “normal” range you should be looking for here for either of these.
Calcium (Ca2+) - What matters is that when there is an actual kidney problem, we look at the values to help
active 1,25(OH)2-D3. The latter then goes to the small bowel, where it ­
absorption of Ca2+. So if we can’t do that, serum Ca2+ falls. us figure out what the diagnosis is. But we never actually say, “Oh the BUN/Cr or FENa is out
of the normal range.”
- Low serum Ca2+ means ¯ negative feedback at the Ca2+-sensing receptors at the
parathyroid glands à PTH goes up. We call this secondary hyperparathyroidism, BUN/Cr,
- BUN/Cr >20 and FENa <1% mean pre-renal azotemia.
which means PTH is high due to a cause external to the parathyroid glands FENa
- BUN/Cr <20 and FENa >1% just simply mean “not pre-renal.”
themselves. You need to know secondary hyperthyroidism is due to renal failure.
- Always ­ in renal failure.
- The notion of intra- vs post-renal having slightly different ranges is nonsense for USMLE.
- This is for 2 reasons:
- Also, what I’ve come to learn from NBME Qs is that only ~9/10 times the BUN/Cr will be
1) The kidney cannot filter it out sufficiently. Lots of phosphate is normally
what we expect. There are a couple 2CK NBME Qs that give BUN/Cr <20 for pre-renal
filtered by healthy kidneys.
azotemia and >20 for acute tubular necrosis. If the NBME ever “breaks the rules” this way,
Phosphate (PO43-) 2) PTH normally acts to ¯ phosphate reabsorption in the PCT via the vignette will be overwhelmingly obvious what the diagnosis is anyway.
downregulation of 3 different types of phosphate pumps. Since the
- Pre-renal azotemia means there is renal pathology because of reduced renal blood flow
function of PTH is impaired, the kidney reabsorbs too much phosphate, so
over the sub-acute to chronic time frame. The kidney will do everything it can to ­ retention
serum levels rise.
of fluid (because it thinks blood volume is low). The way it accomplishes this is by ­
- Combo of ¯ Ca2+ and ­ PO43- in renal failure = secondary hyperparathyroidism.
reabsorption of urea and sodium, since water will follow. This is why blood urea nitrogen is
- Always ¯ in renal failure. high (i.e., BUN/Cr >20) and sodium in the urine is low (FENa <1%).
- This is for 2 reasons: - Notice above I stress sub-acute to chronic time frame (i.e., days-months), since one of the
1) The kidney cannot reabsorb bicarb in the PCT as well, so ­ bicarb in the highest yield points you need to know for USMLE is that acute ¯ perfusion (i.e., seconds to
urine à ¯ bicarb in serum à metabolic acidosis. minutes) to the kidney from blood loss, acute heart failure exacerbation, or arrhythmia (i.e.,
Bicarbonate (HCO3-) Pre-renal
2) The kidney cannot secrete protons (H+) in the cortical collecting duct as VFib for 30 seconds before resusc) causes acute tubular necrosis, not pre-renal.
readily à retention of H+ mops up HCO3- à ¯ serum bicarb. - This is all over the NBME exams. For example, if they say a guy loses lots of blood during
- Renal failure = Uremia = the U in MUDPILES for high anion-gap metabolic surgery and receives 20 packs of RBCs, then two days later while recovering in hospital he
acidoses. (If you need help on the acid-base stuff, do my HY Arrows PDF). gets oliguria + deterioration of renal function, the answer is acute tubular necrosis, not pre-
renal. Student says, “Wait, but there was ¯ renal perfusion though, so how does that make
any sense. Isn’t pre-renal caused by ¯ perfusion?” à The PCT of the kidney is the most
susceptible to anoxic/hypoxic injury due to the ­ concentration of ATPase transporters. So
acute ¯ drop in blood flow à acute hypoxia à PCT sheds.

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- There is a 2CK NBME Q where they mention a guy post-op who had not lost any blood Nephritic vs Nephrotic syndromes
during surgery + had not experienced any episodes of low BP + was started on ketorolac (an - Nephritic conditions have blood in the urine; nephrotic syndromes don’t.
NSAID) for pain post-op + now has oliguria and ­ creatinine à answer = “hypoperfusion” as - You need to memorize for USMLE which HY conditions are nephritic vs nephrotic. Don’t worry, I keep
cause; this is example of where NSAIDs, not ATN, can cause post-op oliguria from pre-renal. things real clean and concise in the tables below without the bullshit nonsense of other resources.
- HY causes of pre-renal for USMLE are NSAID or diuretic use, chronic left heart failure, or - There are four main points you should memorize as being part of each syndrome type.
dehydration from days of vomiting/diarrhea.
- USMLE will give patient who’s been on an NSAID (e.g., naproxen) for several weeks, or who Nephritic syndromes:
was commenced on furosemide (loop diuretic) a few days ago. 1) Hematuria (blood in the urine).
- Vignette can give patient who is on an NSAID + now has peripheral edema + they ask why 2) Oliguria (¯ urinary output; the definition is <400 mL/day, but USMLE won’t assess that number).
there’s edema à answer = “¯ renal excretion of sodium.” This is because the PCT ­ 3) Azotemia (­ blood urea nitrogen; this is because urinary output is ¯).
reabsorption of sodium in pre-renal (FENa <1%). They will also sometimes give NSAID + 4) Hypertension (­ RAAS due to inflammation of renal microvasculature).
edema + ask what you do, and the answer is just “discontinuation of ibuprofen.”
- Essentially synonymous with acute tubular necrosis on USMLE. Nephrotic syndromes:
- The kidney can’t reabsorb urea and sodium as easily, so BUN is lower (i.e., BUN/Cr is <20) 1) Proteinuria (nephrotic level by definition is >3.5g/day, but USMLE won’t assess that number).
and sodium is higher in the urine (i.e., FENa is >1%). 2) Hypoalbuminemia (due to the proteinuria; will be <3.5 g/dL, but USMLE doesn’t care about the #).
Intra-renal - I discuss acute tubular necrosis in more detail in its own table below, but as I mentioned 3) Peripheral edema (due to the hypoalbuminemia à ¯ serum oncotic pressure à transudation of
above in red font, the most important point for USMLE is that you remember acute drop in fluid into interstitial spaces; severe can present with ascites; if the stem says “pre-sacral edema,”
perfusion to the kidney causes acute tubular necrosis, not pre-renal. I need to be an asshole this is nephrotic syndrome till proven otherwise on USMLE).
and inculcate that. 4) Hyperlipidemia (liver pumps out apolipoproteins in an attempt to preserve serum osmolality /
- Almost always due to BPH on USMLE, but can also be due to ovarian or cervical cancer oncotic pressure).
impingement on the ureter(s).
- What you need to know is: old dude + high creatinine = BPH till proven otherwise. - Should be noted that nephritic syndromes often have proteinuria, just usually not at nephrotic levels.
- The answer on USMLE is often just “increased Bowman capsule hydrostatic pressure.” Students sometimes erroneously think nephritic syndromes don’t have proteinuria because it’s not part of
- Next best step is “insertion of catheter” to relieve the urinary retention, even if the patient the 4-point categorization above.
has bacteriuria (i.e., choose catheter insertion over antibiotics). - You don’t have to worry about the notion of which conditions are “both nephritic and nephrotic.” What is
- Another 2CK Q has “check post-void volume” as answer in elderly male with high Cr. most important is: simply know which conditions have hematuria and which ones don’t (via tables below).
USMLE won’t force you to choose between catheter insertion of checking post-void volume. - Nephrotic syndromes can ­ risk of DVT, renal vein thrombosis, and varicocele due to loss of antithrombin
- Normal post-void volume is <50ish mL. If the USMLE wants overflow incontinence, they’ll III in the urine à hypercoagulable state. This is because nephrotic syndrome usually entails non-specific
give post-void volume ~300-400+ mL. massive protein loss due to loss of size and charge barrier, and antithrombin is a protein. The step 1 NBME
- Diabetic neurogenic bladder (i.e., hypotonic bladder from neuropathy to the detrusor wants you to know left renal vein thrombus accretion from hypercoagulable state can cause varicocele.
muscle) can also lead to overflow incontinence and post-renal azotemia, but as I said, most
Qs on USMLE will focus on the old dude with BPH.
- Hydronephrosis can be seen as large, dilated kidneys in patients with obstruction, but this
is rare diagnosis.
HY Nephritic syndromes
- Post-streptococcal glomerulonephritis; aka “proliferative glomerulonephritis”; the
Post-renal
latter is asked on NBME, where they give vignette of PSGN, and answer is just
“proliferative glomerulonephritis.” Student is like what the hell?
- Answer can sometimes be written by NBME as just “acute glomerulonephritis.”
- The answer on USMLE for red urine 1-3 weeks following a sore throat caused by
Group A Strep (Strep pyogenes). This is in contrast to IgA nephropathy (which I discuss
in detail below), which is red urine 1-3 days following a sore throat.
- PSGN can be caused by skin infections. This can be impetigo (school sores), cellulitis,
or erysipelas (I discuss these in detail in my HY Derm PDF). For example, the Q might
say a 10-year-old has yellow crusties on his arm for the past 7 days (impetigo) + now
PSGN has red urine à answer = “acute glomerulonephritis.”
- Type III hypersensitivity (antigen-antibody complexes that form in blood and deposit
in the kidney). Don’t confuse with rheumatic heart disease, which is a type II HS.
- Serum complement protein C3 can be ¯ (can also be ¯ in SLE, but unrelated).
- Streptolysin O or A titers will be ­.
- PANDAS is tested on Psych forms for 2CK à Pediatric Autoimmune Neuropsychiatric
- Step 1 wants you to know above gross specimen post-nephrectomy in patient with Hx of Disorder Associated with Streptococci à presents as new-onset tic/Tourette, OCD, or
hydronephrosis. They can give, e.g., kid with chronic ureteral obstruction + show above pic. ADHD within weeks of Group A Strep infection.
- Descriptors such as subepithelial deposits or “lumpy bumpy” appearance on electron
microscopy (EM), etc., have been parroted across resources over the years but are
essentially garbage for USMLE.

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- PSGN usually self-resolves in kids without sequela. But USMLE wants you to know - Descriptors such as “dense deposits,” “C3 nephritic factor” and “duplication of
that ­ age is means worse prognosis, where chance of renal failure is ­ it if occurs in basement membranes” are all basically nonsense for USMLE.
adults. This is probably related to the more robust immune response resulting in more - Answer is “renal biopsy” as the next best step. This guides our management.
advanced renal damage. - A 2CK IM form has “heroin” as the answer (heroin-induced nephropathy) for patient
- Aka Berger disease; IgA deposition in renal mesangium. with protein and blood in the urine. In contrast, FSGS (discussed below) from heroin
- Red urine 1-3 days after a sore throat. This is in contrast to PSGN, which is red urine has no blood in the urine.
1-3 weeks after a sore throat. I just mentioned it above obviously. But students fuck - Diffuse proliferative glomerulonephritis.
this up despite the inculcation so I’m reiterating it like an asshole. - The answer on USMLE for red urine in a patient with SLE.
- Caused by viral infection, not Group A Strep. DPGN - Can sometimes be associated with “wire-looping of capillary walls.”
- Can sometimes be caused by GI infections, but USMLE usually avoids this etiology - Same as with MPGN, USMLE wants “renal biopsy” as the next best step, since this
unless including it in the Henoch-Schönlein purpura constellation. guides our management.
IgA nephropathy
- Henoch-Schönlein purpura is LY for Step 1 but HY for 2CK Peds. It’s a tetrad: - Rapidly progressive glomerulonephritis.
1) Palpable purpura (usually on buttocks/thighs). - Acute deterioration in renal function in the setting of a vasculitis (i.e., Wegener,
2) IgA nephropathy (red urine). microscopic polyangiitis) or Goodpasture syndrome. I discuss these conditions in detail
3) Arthralgias. later in this PDF, don’t worry.
4) Abdominal pain. - Characterized by fibrin crescents on biopsy.
- All 4 need not be present for HSP, but the abdo pain component here is presumably
viral gastroenteritis leading to IgA nephropathy.
- The answer on USMLE for a male 20s-40s with hematuria and hemoptysis. Similar to
Wegener and microscopic polyangiitis, can cause RPGN.
- Caused by anti-glomerular basement membrane antibodies (anti-GBM), which are
antibodies against collagen IV.
RPGN
- Renal biopsy will show linear immunofluorescence. USMLE likes showing the bright
green image for this.

Goodpasture
syndrome

HY Nephrotic syndromes
- The answer on USMLE for otherwise unexplained edema in a kid who doesn’t have
blood in the urine.
- Presents as peripheral edema, periorbital edema, and/or ascites.
- Do not confuse this with Alport syndrome, which is an XR condition caused by - Almost always this is pediatric. Very rarely it can be due to Hodgkin in adult.
mutations in collagen IV. - Classically post-viral (i.e., URTI), but ~50% of vignettes won’t mention that.
- X-linked disease; mutation in collagen IV gene. - In other words, textbook vignette is an 8-year-old who has the sniffles for 4 days,
- Do not confuse with Goodpasture syndrome, which is antibodies against type IV followed by peripheral and periorbital edema a week later, without blood in the
collagen. Minimal change urine. Once again though, the stem need not mention the viral infection.
- The answer on USMLE for a male who has red urine + an eye or ear problem (collagen disease - Called minimal change disease because light microscopy (LM) shows no
IV is present in basement membranes in the kidney, ear, and eyes). abnormalities. EM, however, shows effacement of the podocytes.
Alport syndrome
- The “eye problem” can be blurry vision/cataracts; the “ear problem” will be - Mechanism for nephrotic syndrome is “loss of size and charge barrier.”
neurosensory hearing loss (due to organ of Corti dysfunction). - Corticosteroids are the treatment and are highly effective.
- Some students have asked if it’s XR or XD. Literature appears to be varied, but USMLE - A 2CK Peds Q gives minimal change disease as etiology for spontaneous bacterial
doesn’t care. On offline NBME 18, however, it’s mentioned in a Q as XR. peritonitis (i.e., any cause of ascites can cause SBP; I discuss this stuff in the GIT PDF
- You can memorize “splitting of the lamina densa” as associated with Alport. in extensive detail).
- Membranoproliferative glomerulonephritis. - MCD is aka lipoid nephrosis (lipid droplets can be seen in urine on LM).
MPGN - The answer on USMLE for red urine in a patient with hepatitis C, heroin use, or Membranous - The answer on USMLE for nephrotic syndrome in patient who has:
malignancy. glomerulonephritis - Exposure to drugs: dapsone, gold salts, sulfonamides.
/ nephropathy - Infection: hepatitis B (Hep C can cause it too, but rare).

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- Visceral cancers, e.g., breast, pancreatic. 1) Hyperfiltration (­ glucose crossing the glomerular basement pulls water
- Autoimmune (primary): antibodies against phospholipase A2 receptor. with it à polyuria). Sometimes the Q can just simply give you diabetes +
- The LM image is important and shows highly eosinophilic (pink) and inflamed / they ask what’s most likely to be seen initially à answer = “­ glomerular
thickened capillary walls. filtration.” Over time, the kidney will fail and GFR will ¯.
2) Thickening of the glomerular basement membrane (non-enzymatic
glycosylation of the membrane à loss of size and charge barrier).
- Kimmelstiel-Wilson nodules are composed of hyaline and look like pink circles on
light microscopy. This image is very HY.

- Can cause “spike and dome” appearance of subepithelial deposits on EM.

- The answer on USMLE for nephrotic syndrome in multiple myeloma.
- Amyloidosis means protein depositing where it shouldn’t be depositing.
- Multiple myeloma = cancer of plasma cells that produce too much immunoglobulins
à high serum IgG kappa/lambda light chains. Immunoglobulins are proteins à these
fly through the kidney and cause Bence-Jones proteinuria; they also deposit in the - Hyaline arteriolosclerosis is deposition of hyaline (protein) in the walls of the renal
renal parenchyma, causing renal amyloidosis. vasculature. Although this can be due to many things, on USMLE, they want you to
- Biopsy shows classic apple-green birefringence with Congo red stain. know this is caused by diabetes.
- ACEi (e.g., lisinopril) or ARBs (e.g., valsartan) are the first drugs used in diabetes if
there is HTN (>130/80 in diabetes, not 140/90), proteinuria, or ­ creatinine or renin.
- AT-II normally constricts efferent arterioles leaving the kidney, causing a backup of
pressure at the glomerulus. This serves the purpose of maintaining GFR (i.e., filtration
through Bowman capsule) when renal blood flow has ¯.
- In other words, when renal perfusion ¯, RAAS goes ­, AT-II goes ­, and we get
constriction of efferent flow leaving the kidney à ­ filtration fraction (GFR/renal
Renal amyloidosis
plasma flow), where we have GFR staying the same despite ¯ perfusion.
- ACEi/ARBs ¯ constriction of efferent arterioles (they don’t “dilate”; this refers to the
action of prostaglandin on the afferent arterioles going to the kidney), thereby ¯
filtration fraction and reducing GFR. This might sound like a bad thing – i.e., “Why
would we want to ¯ GFR in diabetes if it’s the most common cause of chronic renal
failure?” à The answer is because the slightly reduced GFR and filtration fraction
early on ¯ the rate at which excess glucose is filtered across the glomerulus. Over
time, it is inevitable that the glomerular basement membrane will non-enzymatically
glycosylate and thicken, so ACEi/ARBs slow this process (i.e., slightly reduce GFR early
- For some magical reason, USMLE cares you know that the amyloid appears this way in order to prevent a massive decrease later).
because it is b-pleated sheets (i.e., answer on NBME; a-helices is wrong); makes - The answer on USMLE for nephrotic syndrome in sickle cell.
sense since the former are “flat” and can reflect light at different angles. - Can also be caused by heroin and HIV.
- An NBME Q has “renal parenchymal disease” as answer for kidney issue due to - Not as responsive to steroids as MCD.
Focal segmental
multiple myeloma. - FSGS literally means “some parts of some nephrons are affected.”
glomerulosclerosis
- Diabetes is the most common cause of chronic renal failure. - Focal = some glomeruli.
(FSGS)
Diabetic - Renal failure simply means ¯ glomerular filtration rate (GFR). - Diffuse = all glomeruli.
glomerulosclerosis - USMLE wants the first two changes that occur in the kidney due to diabetes as - Segmental = part of nephron.
follows: - Global = all of nephron.

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Acute tubular necrosis the kidney causing pre-renal azotemia will be more subacute/chronic, such as due to
- Sloughing of PCT tubular epithelial cells due to chemical or ischemic insult. NSAID use, recent initiation of diuretic, or dehydration. There are rare Qs that are
- Only ~50% of Qs will mention “muddy brown granular casts,” or “dirty brown granular casts,” or “brown, exceptions, but that is the general principle.
pigmented casts.” - As mentioned earlier, USMLE will give a one-liner where they say, “Dude had
- The other ~50% of Qs will just mention oliguria or acutely worsening renal function in patient with classic surgery where he lost a lot of blood + received many packs of RBCs. 2 days later, he’s
ATN etiologies. now recovering in hospital + gets oliguria” (they don’t say anything about brown
Next best step in diagnosis (answer on Surg form 8) is “measurement of urine sodium and creatinine casts) à answer = ATN, not pre-renal.
concentrations.” We expect FENa >1% and BUN/Cr <20 almost always for ATN. - Likewise, they’ll say woman had surgery + had 30-second episode intra-operatively
Cause HY points where BP fell to 80/40 à answer = ATN, not pre-renal.
- Can be caused by drugs: aminoglycosides (gentamicin, tobramycin, amikacin); - Guy has an MI (cardiogenic shock) + new-onset oliguria à ATN, not pre-renal.
cisplatin (a chemo agent), or IV contrast. - Guy has burns covering 50% of his body + develops oliguria à ATN due to excessive
- Any of the above drugs + new-onset oliguria or ­ creatinine (there need not be fluid loss à acute ¯ perfusion to kidney.
mention of casts) = ATN. - Acute exacerbation of heart failure causing ATN is a difficult one since heart failure
- For instance, new Step 1 NBME simply tells you patient was given many drugs and is classically associated with pre-renal from chronic ¯ blood flow to the kidney. But in
now has creatinine of 2 (NR 0.1-1.2) + no mention of casts + they ask for what was acute exacerbation of heart failure, we have acute ¯¯ blood flow, leading to ATN (as
given à answer = gentamicin. Not hard. I said, it’s on Free 120).
Drugs
- Patient who’s recently been treated for endocarditis + now has new-onset oliguria =
ATN due to gentamicin (empiric Tx for endocarditis = gentamicin + vancomycin [new
literature suggests vancomycin is not reliably nephrotoxic]).
- Contrast nephropathy is exceedingly HY on 2CK, where they want you to know that
adequate hydration prior to IV contrast is the number-one way to prevent it. For Other renal conditions associated with ischemia
instance, they’ll say patient got a CT + now has ­ creatinine + they’ll ask how it could - Diffuse cortical necrosis is a term thrown around sometimes and causes
have been prevented à answer = “0.9% saline,” or just “IV hydration therapy.” confusion for students. I don’t think I’ve ever seen USMLE assess this. I’ve only
- Myoglobin is nephrotoxic. Big risk factors are alcoholism, falls, intense training seen it show up rarely as an incorrect answer choice.
Diffuse cortical necrosis
(e.g., marathon), McCardle syndrome, statins/fibrates. - DCN is simply considered an extension of ischemic ATN, where DCN can occur
- Rhabdo causes a false (+) blood on urine dipstick. They will say urinalysis shows 2+ in severe cases of ischemia (e.g., obstetric hemorrhages).
blood but only 1-2 RBCs/hpf. This is because the dipstick can’t differentiate between - You can be aware it exists, but don’t worry about it for USMLE.
free myoglobin and hemoglobin on RBCs. - Renal papillae = parts of kidney where the collecting ducts meet the ureters.
- One Surgery Q gives 3-4 RBCs/hpf as negative. I’ve seen this fool some students - The answer on USMLE for red/dark urine in a patient with sickle cell.
who were already aware of the false (+) blood point about rhabdo. If the Q wants (+) - In contrast, if a sickle cell patient has a renal condition + no blood in the urine,
RBCs, they’ll say like 10-20+/hpf. the answer = FSGS, as mentioned earlier.
- The other half of rhabdo vignettes won’t mention the false (+) urinalysis and will - RPN is loss of the renal medulla from ischemia, but unlike ATN, the etiology is
Rhabdomyolysis instead just say oliguria. You need to know that refers to ATN. usually more subacute or chronic. NSAIDs are a notable cause in this regard,
- For example, an NBME-favorite vignette is patient being found at bottom of stairs in Renal papillary necrosis where ¯ afferent blood flow due to ¯ vasodilating prostaglandins over weeks-
his/her house + has false (+) blood on urine dipstick and/or oliguria à answer = (RPN) months causes the medullar blood flow to be slowly choked off.
rhabdomyolysis. - RPN can occur more acutely in sickle crises, where sickling within
- They also like ­ K+ as part of rhabdo vignettes (makes sense if we have renal failure microvasculature feeding the medulla results in focal pockets of ischemia.
from ATN) and ­ serum creatine kinase (CK). - Pyelonephritis (discussed later) can also cause RPN due to inflammatory
compression of the medullar microvasculature. There’s one NBME Q I can recall
- Q can say 44-year-old guy found on bench in park has ­ K+, ­ CK, and oliguria à
where renal papillary necrosis is the answer due to infection. But I’d say, overall,
diagnosis = rhabdo. Or they’ll say just ­ CK + oliguria, and they ask what is most likely
the highest yield point is just remembering red/dark urine in sickle cell = RPN.
to be seen in this guy à answer = ­ K+.
- It’s to my observation acute ischemia is the highest yield cause of ATN on NBME
exams.
- Even though the medulla of the kidney technically receives less blood flow
compared to the cortex, as I mentioned earlier, the USMLE is obsessed with the PCT Interstitial nephritis
of the kidney as most susceptible to anoxic / hypoxic injury. This is due to the ­ - Exceedingly HY renal condition often confused with ATN.
concentration of PCT ATPase transporters, so acute ¯ drop in blood flow à acute - Aka interstitial nephropathy, or tubulointerstitial nephritis/-nephropathy.
hypoxia à PCT sheds. - Think of this as “an allergic reaction of the kidney.”
Acute ischemia - Step 1 Qs love cellular swelling as part of this mechanism – i.e., acute ischemia à ¯ - 4/5 Qs will be an NSAID, b-lactam, or cephalosporin, followed by getting a maculopapular rash and WBCs
activity of PCT ATPases à buildup of intracellular Na+ à water stays with sodium à (eosinophils) in the urine. This presentation is textbook/pass-level.
tubular cell swelling. Answer on NBME for why there’s swelling simply = ¯ ATPase - Only ~50% of vignettes will mention the maculopapular rash.
activity (this is similar mechanism for why we get swelling + hemolysis in pyruvate - The stem need not say “eosinophils” either. They can just say patient is on b-lactam + now has WBCs in
kinase deficiency). the urine + no mention of rash à answer = interstitial nephritis. If they say the rash, it’s even easier.
- Acute ischemia to the kidney can be due to loss of blood from trauma/surgery, - 1/5 Qs will just say a patient was on an NSAID, b-lactam, or cephalosporin and now has mild proteinuria
acute arrhythmia (e.g., 30 seconds of Vfib), MI, or acute exacerbation of heart failure and hematuria. They don’t mention a rash or WBCs in the urine.
(on 2CK Free 120). These conditions cause ATN, not pre-renal. Once again, ¯ flow to

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- There is also a singular NBME Q where they just say a patient has simple peripheral edema due to an Other renal conditions
NSAID, with no mention of anything else, and the answer is interstitial nephropathy. This is more unusual, - Lysis of tumor cells (especially leukemic) by chemoradiotherapy leads to release
since “NSAIDs + edema” classically = pre-renal, but I’ve seen the NBME assess interstitial nephropathy for of uric acid and phosphate that can overwhelm the kidneys and cause crystals,
this as well. namely from uric acid.
- NBME also can give you simple vignette of interstitial nephritis, and then ask for the location in the kidney - USMLE loves asking what can be given to prevent renal failure in patient
that’s affected (e.g., efferent arterioles, etc.) à answer = “renal tubule.” Tumor lysis syndrome undergoing chemo à answer = “allopurinol.”
- For example, 40M + treated with nafcillin for 6 weeks for MSSA endocarditis + now has maculopapular - Or they’ll ask for MOA of drug that can prevent renal failure à answer =
rash and eosinophils in the urine; diagnosis? à interstitial nephritis. “xanthine oxidase.”
- 60F + using naproxen (an NSAID) for 6 weeks for her osteoarthritis + has peripheral edema à answer = - The arrows USMLE wants for what will be seen in the blood in tumor lysis
interstitial nephropathy. syndrome is same as renal failure except we also have ­ uric acid.
- 35F + just recently finished 10-day course of cephalexin + has mild proteinuria and hematuria à answer = - Inability of the PCT to reabsorb “lots of stuff.”
interstitial nephropathy. - Shows up on NBME as an arrow Q, where they ask about the reabsorption of
- 35F + taking ibuprofen + has maculopapular rash and eosinophils in the urine; Q asks where in the kidney amino acids, glucose, bicarbonate, and phosphate, and the answer is a ¯ for all of
is fucked up à answer = “renal tubule.” Student says, “But don’t NSAIDs affect the afferent arteriole?” à them.
Yes, but this particular presentation is clearly tubulointerstitial nephropathy. I haven’t seen them be - Since bicarb reabsorption is impaired, this can lead to RTA type II, but USMLE
ambiguous here with “NSAID + peripheral edema alone,” where you have to debate whether it’s interstitial doesn’t really give a fuck. The key point is the ¯ for the reabsorption of the above
nephropathy or pre-renal. They’ll either ask one or the other. Fanconi syndrome
substrates.
- For whatever magical reason, an important cause of Fanconi syndrome is
consumption of expired tetracyclines.
- Don’t confuse Fanconi syndrome with Fanconi anemia. The latter is an
autosomal recessive aplastic anemia with hypoplastic thumbs/radii (I’ve made
Renal tubular acidosis
YouTube clips discussing this).
Quick notes before discussing RTA:
- Inability of the PCT to reabsorb tryptophan.
- Can cause niacin (B3) deficiency in theory, since tryptophan is a precursor in
MUDPILES = mnemonic for high anion-gap metabolic acidoses = Methanol, Uremia (renal failure), DKA,
niacin synthesis.
Phenformin (a drug you don’t have to worry about), Iron/Isoniazid, Lactic acidosis, Ethylene glycol, Hartnup disease
- This is more just textbook masturbation to be honest that’s been parroted over
Salicylates (aspirin).
the years. Can’t say I’ve seen this ever assessed once. Just mentioning it here
otherwise I’ll get some umbrageous student popping into my DMs about it.
Anion-gap is calculated as Na+ - (Cl- + HCO3-). Normal range is 8-12. High anion-gap = 13 or greater.
- Cystine stones (hexagonal) can occur in young adult due to an inability to
- USMLE really doesn’t give a fuck that you know the specifics of types I, II, and IV.
reabsorb the COLA (dibasic) amino acids à Cysteine, Ornithine, Lysine, Arginine.
- The way they assess this is by you knowing this is a type of normal anion-gap metabolic acidosis (i.e., it is Cystinuria
- Cystine is two cysteines put together.
not part of MUDPILES).
- Cystinuria can be diagnosed with cyanide-nitroprusside test.
- For example, you’ll get a 15-line massive paragraph + tons of lab values + have no idea what’s going on,
- Nonsense diagnosis on USMLE that will sometimes show up as an incorrect /
but then you calculate the anion gap as 12 (NR 8-12), so you can eliminate all of the MUDPILES answer
distractor answer choice.
choices, such as lactic acidosis, DKA, and ethylene glycol poisoning, and you’re left with, e.g., Crohn disease
Hepatorenal syndrome - Apparently liver failure can sometimes cause renal failure via obscure
or renal tubular acidosis. Then you just say, “Well this clearly ain’t Crohn, so it must be RTA.” That is how I
mechanisms.
would say 4/5 RTA Qs show up.
- Renal biopsy will be normal almost always.
Thin glomerular - Benign familial condition where patient can have mild hematuria.
- RTA type I = ¯ ability to secrete H+ in the cortical collecting duct.
basement membrane - Thin basement membranes allow for passage of small amounts of RBCs.
- RTA type II = ¯ ability to reabsorb HCO3- in the PCT.
disease - No treatment necessary.
- RTA type IV = renal resistance to aldosterone, or hyporeninemic hypoaldosteronism.

- Type IV presents with hyperkalemia. The others do not. Type III apparently is hyper-rare.
- Type IV will be a patient who has Addisonian-like picture (i.e., ¯ Na+, ­ K+, ¯ HCO3-), but the vignette will
present in a patient who has chronic renal failure. Renovascular hypertension
- Type II can be caused by Fanconi syndrome (discussed more in table below). - Narrowing of one or both renal arteries due to atherosclerosis that causes ­
- Type I can apparently have renal parenchymal stones (i.e., stones in the actual tissue of the kidney, rather renin-angiotensin-aldosterone system (RAAS) and ­ BP.
than within the tubular lumina as with traditional nephrolithiasis). - Q will be patient over the age of 50 with cardiovascular disease risk factors,
- As I said, the key point is you just know RTA is normal anion-gap / not part of MUDPILES. That’ll cover you such as diabetes, HTN, and/or smoking.
like 4/5 times. Renal artery stenosis - Patients who have pre-existing HTN causing atherosclerosis leading to RAS will
(RAS) often have 10-20 years of background HTN that then becomes accelerated over
a few-month to 2-year period. What this means is: the slowly developing
atherosclerosis in the renal arteries finally reaches a point at which the kidney is
unable to maintain autoregulation, and the RAS is now clinical (i.e., accelerated
HTN of ­­ BP within, e.g., 3 months).

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- Another way USMLE will give RAS is by giving ­ BP in patient with significant
evidence of atherosclerotic disease (i.e., Hx of coronary artery bypass grafting,
intermittent claudication), and then ask for the most likely cause à RAS. You
have to say, “Well he clearly has atherosclerosis in his coronaries and aortoiliac
vessels, so that means he’ll have it in the renal arteries too.”
- Q can say older patient with carotid bruit has recent ­­ in BP and then ask for
diagnosis à answer = RAS. Similar to above, if the patient has atherosclerosis in
one location (i.e., the carotids), then he/she will have it elsewhere too.
- HY factoid about RAS is that ACEi or ARBs will cause renin and/or creatinine
to go up. This is a HY point that is often overlooked and is asked on NBMEs. I
have not seen NBME care whether it’s uni- or bilateral in this case. à Kidney
can autoregulate across flux in perfusion. Patients with already-compromised
renal blood flow are more sensitive to the subtle ¯ in filtration fraction that
occurs secondary to ACEi/ARB use, so renin/creatinine ­.
- If USMLE gives you unilateral RAS, renin is only ­ from that kidney. The other
kidney will not produce ­ renin.
- After renin and aldosterone levels are obtained, MR angiography of the renal
vessels is what USMLE wants for the next best step in diagnosis.
- The answer on USMLE for narrowing of the renal arteries in a woman 20s-40s.
- Not the same as renal artery stenosis, and not caused by atherosclerosis.
- If you broadly say “renal artery stenosis,” that specifically refers to
atherosclerosis of the renal arteries in patient >50 with CVD. Angiogram of PAN shows pearls that are more distal in the renal vasculature;
- FMD is tunica media hyperplasia (not dysplasia, despite the name) that results FMD, in contrast, shows more proximal beading, with the termini not as
in a “string of beads” appearance on renal angiogram. conspicuously involved.

- There is an NBME Q where they list both PAN and FMD as answer choices and
it relies on you knowing the angiogram to get it right. They don’t mention
hepatitis B, but answer is PAN. That’s why I’m harping on this here.
- Causes fibrinoid necrosis.
- Can be caused by hepatitis B.
Fibromuscular dysplasia - Spares the pulmonary vasculature.
(FMD) - The answer on USMLE for hypertension in a neonate following umbilical artery
catheterization. USMLE simply wants “­ renin, ­ aldosterone” as the answer.
- Sounds weird, but you need to know umbilical artery catheterization is a major
risk factor for renal artery thrombosis in neonates.
Renal artery thrombosis - 2CK NBME Q gives brief umbilical artery catheter insertion in kid born 26
weeks’ gestation in order to monitor blood pressure for a pneumonia. 3 weeks
later, he has ­ BP (128/86) à answer = “­ renin, ­ aldosterone” as answer.
- BP in term neonates should be ~60/40. In a preemie 29 weeks’ gestation, it
should be ~50/30 according to Google.
- MR angiography is answer on NBME for diagnostic modality.
- Can affect the carotid vessels. A 2CK Surg Q gives FMD vignette and also says
there is 25% occlusion of one of the carotids.
- As discussed in the cardio PDF, this is a medium-vessel vasculitis that causes a
HY Vasculitides affecting the kidney
“string of pearls” appearance of the renal vessels. This can be confused with
Polyarteritis nodosa FMD, but note the difference in the imaging. FMD shows more beading along - Vasculitides is a fancy word that is pleural for vasculitis.
(PAN) the larger/proximal arterial sections, whereas PAN shows pearls more at the - Formerly known as Wegener granulomatosis.
vascular termini, with the more proximal parts more likely to be spared. - Answer on USMLE for adult with triad of 1) hematuria, 2) hemoptysis, and 3)
“head-itis” – i.e., any problem with the head, such as nasal septal perforation,
Granulomatosis with
mastoiditis, sinusitis, otitis.
polyangiitis
- Associated with cANCA and anti-proteinase 3 (anti-PR3) antibodies.
- Causes “necrotizing glomerulonephritis” that can lead to rapidly progressive
glomerulonephritis (RPGN).
- Will just present as hematuria in a patient who is pANCA / anti-MPO (+).
Microscopic polyangiitis
- Similar to Wegener, can cause RPGN.

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- The above conditions can be associated with a weird neuropathy called mononeuritis multiplex, which - Thiazides can be used to prevent recurrent stones by ¯ urinary calcium. NBME has a Q
means neuropathy of “one large nerve in many locations” – e.g., wrist drop + foot drop in same patient. that asks why à answer = ­ reabsorption of calcium.
- You don’t need to worry about the fancy term “mononeuritis multiplex,” but what I do want you to be - In theory, alkalinization of the urine can help treat oxalate stones, and acidification of the
aware of is that neuropathy will sometimes show up in these vasculitis vignettes, so don’t be confused urine can help treat phosphate stones.
about it. - Composed of ammonium magnesium phosphate.
- Eosinophilic granulomatosis with polyangiitis (formerly known as Churg-Strauss) less commonly has renal - Formed in ­ pH in the presence of urease (+) bacteria.
involvement compared to Wegener and MP. I discuss many vasculitides in more detail in the HY Cardio PDF. - Klebsiella, Serratia, and Proteus are HY causes.
- These stones are large, ram-horn like. The image is HY.

HY Uremia points
- As mentioned earlier, “uremia” means “urea in the blood,” but is used to refer to patients who have
symptomatic renal failure with poor lab values.
- On USMLE, uremic patients will have: ­ K+, ¯ HCO3-, ¯ Ca2+, ­ PO43-. Na+ is variable.
- Friction rub in patient with ­ BUN and Cr.
Uremic pericarditis
- Answer = hemodialysis.
- Mental status change in patient with ­ BUN and Cr. Struvite
Uremic encephalopathy
- Answer = hemodialysis.
- Nosebleeds and/or petechiae in patient with renal failure.
- Qualitative, not quantitative, platelet problem. In other words, bleeding
time is ­, but platelet count is normal.
- Mechanism is ­ BUN causing impairment of platelet function.
Uremic platelet dysfunction - Answer on USMLE can be written as “acquired platelet dysfunction.”
- Treatment = hemodialysis.
- On 2CK NBME 10, Surg Q wants “initiation of dialysis” as answer in uremic
patient pre-op. Improving RFTs will ¯ peri-op morbidity/mortality + ¯ risk of
intra-op bleeding due to uremic platelet dysfunction.
- Yellow skin sometimes seen in severe renal failure due to ¯ ability to
excrete urea. Excess is excreted in sweat, precipitating out as white - Apart from adequate hydration, Tx is acidification of urine with NH4Cl + surgery.
Uremic frost
crystalline deposits (frost). - Seen in patients who have gout. Not complicated.
- Can be associated with itchy skin (uremic pruritis). - First-line Tx for chronic gout is xanthine oxidase inhibitors (i.e., allopurinol or febuxostat).
They are preferred over uricosurics (meaning ­ urinary excretion of uric acid) like
probenecid and sulfinpyrazone because the latter agents ­ risk of uric acid stones.
- Probenecid and sulfinpyrazone inhibit organic anion transporter (OAT), which normally
Urolithiasis Uric acid functions to ­ absorption of uric acid.
- Urolithiasis is broad, umbrella term that refers to both nephrolithiasis and ureterolithiasis. - Weird factoid about probenecid is that it can help maintain serum b-lactam levels, since
- Diagnosed with non-contrast CT of abdomen and pelvis. the latter are excreted by OAT. There’s an NBME Q around somewhere that asks about
- KUB (X-ray of kidney, ureters, bladder) can be done but isn’t as sensitive (although below I show an X-ray). this. Sometimes old-school docs will put a patient on a b-lactam and probenecid. Don’t be
Stone type HY points confused by this. The patient doesn’t have gout. It’s just a way of ¯ renal excretion of the
- Most common type of stone. Can be calcium oxalate or calcium phosphate, although I’ve b-lactam.
never seen USMLE once assess or give a fuck about phosphate stones. - As mentioned earlier, cystine is two cysteines put together.
- Most young adults with idiopathic kidney stones will have “normocalcemia and - Cystine stones (hexagonal) can occur in young adult due to an inability to reabsorb the
Cystine
hypercalciuria” – i.e., normal serum calcium but elevated urinary calcium. COLA (dibasic) amino acids à Cysteine, Ornithine, Lysine, Arginine.
- USMLE will give you healthy male in his 20s with sharp pain in the flank or groin + RBCs in - Cystinuria can be diagnosed with cyanide-nitroprusside test.
the urine à answer = urolithiasis. - Acyclovir (for HSV and shingles) and indinavir (for HIV) can cause crystal nephropathy.
Miscellaneous
- Crohn disease and disorders causing fat malabsorption increase the risk for calcium Not particularly HY, but worthy of 1-2 lines here.
Calcium oxalate stones (­ fat retained in GI tract à ­ chelation with calcium in GI tract à ¯
calcium available to bind oxalate à ­ oxalate absorption by GI tract à ­ urinary oxalate).
- Primary hyperparathyroidism and malignancy causing hypercalcemia are HY etiologies.
- Milk-alkali syndrome: ­ calcium + ­ bicarb + calcium stones. Textbook scenario is a
patient taking too many antacids, but vignette will usually not mention this and it will
simply be a diagnosis of exclusion (i.e., you eliminate to get there).
- Ethylene glycol (Anti-Freeze) and hypervitaminosis C can cause oxalate stones.
- First step in prevention and treatment of stones is “adequate hydration.”

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Cystic kidneys - Obstructed outflow ­ risk for UTIs, cystitis, and pyelonephritis.
- Autosomal dominant polycystic kidney disease; chromosome 16. - Apart from knowing this diagnosis, highest yield point is that we do
- The answer on USMLE if disease starts as an adult (i.e., 30s-40s). ultrasound followed by voiding cystourethrogram to diagnose.
- Cysts are technically present early in life, but only become clinical as adult (i.e., ­ BP and - NBME Qs might already mention negative ultrasound in the vignette, or
­ RFTs). might omit it altogether, where you just select “voiding cystourethrogram.”
- Congenital abnormality in which urine from the bladder can go back up into
the ureter toward the kidney.
- This ­­ risk for recurrent acute pyelonephritis à chronic pyelonephritis (as I
discuss below).
Vesicoureteral reflux - Can also occur in pregnancy due to 2 reasons: 1) larger uterus in 3rd trimester
can compress the ureters; 2) progesterone ¯ ureteral peristalsis.
- This is why pregnant women can get pyelonephritis, and also why we always
treat asymptomatic bacteriuria in pregnancy, whereas we don’t treat it if
woman is not pregnant.
- Bit of a weird one, but not me being fancy. It’s on NBME.
- “Failure of canalization of proximal ureter” will be the answer if they tell you
the renal collecting duct system is dilated, but the ureters are not dilated.
- Sounds obvious, but I see students get this wrong a lot.
ADPKD Ureteral atresia - You need to simply know: kidneys à ureters à bladder à urethra, and if we
have a congenital obstruction at any point, that could be referred to as
“failure of canalization.”
- “Congenital ureteral obstruction” is an answer on one of the NBMEs for
chronic pyelonephritis causing tubular atrophy (once again, discussed below).
- These patients have ­ BP due to ­ RAAS (compression of microvasculature of kidney due
to enlarging cysts).
- Can cause saccular (berry) aneurysms of the circle of Willis à risk for subarachnoid
hemorrhage.
- Highest yield point is that serial blood pressure checks are correct over circle of Willis Genitourinary infection-related stuff
MR angiogram screening. Latter is wrong answer on USMLE. MR angiogram screening of - For all of the STD/STI-related stuff, I cover that in the Repro/Obyn PDF. I’m keeping this small table more
circle of Willis is only done when there is (+) family Hx of SAH or saccular aneurysms. limited to kidney/bladder stuff.
- Step 1 NBME gives easy vignette of ADPKD, and then the answer is just “polycystin” as - Infection of the kidney. “Pyelo” means kidney.
the protein that’s fucked up. Sounds obvious, but it’s asked so I’m mentioning it. - 9/10 questions will mention fever + costovertebral angle (CVA) tenderness,
- Cystic kidneys are part of “ciliopathies,” which is obscure term that refers to conditions which is pain with percussion of the flank.
where cilia are abnormal. Polycystin is a protein required for cilia function on renal - “Granular casts” can be seen. Do not confuse this with acute tubular necrosis.
epithelium. “General granular casts” can sometimes be seen in pyelonephritis and
- Most common extra-renal location for cysts is the liver (85% by age 30). dehydration. It’s on one of the 2CK IM forms, where students say, “Wait, but they
- Autosomal recessive polycystic kidney disease; chromosome 6. say granular casts; how is this not ATN?”
ARPKD - The answer on USMLE for cystic kidneys in pediatrics. - Major risk factors are vesicoureteral reflux (especially in pregnancy) and
- Can be associated with hepatic fibrosis. posterior urethral valves.
- Just be aware renal cysts can occasionally develop in other conditions, such as chronic - Most common organism is E. coli. Other organisms, i.e., Klebsiella, Serratia, and
Miscellaneous dialysis patients. Proteus cause struvite stones.
- Conditions such as medullary sponge kidney are garbage for USMLE. Waste of time. - Neutrophilic infiltration will show up as lots of blue/purple (basophilic) cells on
Acute pyelonephritis histo. USMLE likes this image.

HY anatomic abnormalities
- Exceedingly HY for Peds for 2CK; also shows up on Step 1 NBME.
- Most common genitourinary abnormality in neonatal males.
- Urethra has abnormal presence of valves at the posterior (prostatic) urethra,
preventing the outflow of urine.
Posterior urethral valves - USMLE will give Qs of varying severity.
(PUV) - Most severe is in utero oligohydramnios.
- Can present as 12-hour-old neonate who hasn’t yet urinated + has
suprapubic mass (i.e., full bladder).
- Can also present as 6-week-old boy who has full bladder (i.e., possibly slower
accumulation due to only partially obstructed outflow).

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- For above image, you say, “Mike I feel weird. Idk what I’m looking at.” The blue - E. coli most common cause. HY for USMLE you know fimbriae and pilus proteins
cells are neutrophils infiltrating the kidney in acute pyelo. The USMLE will show facilitate E. coli’s attachment to urothelium.
images basically identical to this for a variety of infections, e.g., prostatitis, where - Will have bacteria and WBCs in the urine (i.e., bacteriuria + pyuria).
the bigger picture concept is, “Oh that’s acute inflammation. Those purple cells - Urinary nitrites and leukocyte esterase can be positive. These just reflect
are neutrophils.” That’s what USMLE wants you to know. For instance, a nearly bacterial infections. Some students get pedantic about which organisms result in
identical image of prostate histo in old dude with prostate pain and fever à which combo of (+) or (-) findings here, but that’s low-yield for USMLE.
you’d know immediately it’s prostatitis. - Can be caused by suprapubic catheters (on 2CK IM and Surg).
- It’s to my observation bacteria can be few in the urine in acute pyelo. This - Nitrofurantoin is HY drug to treat cystitis on USMLE.
confuses some students. But it’s typically what I see on NBME forms. If the - Not an infection.
infection is further down, i.e., UTI in the urethra, then bacteria are more copious. - This is >6 weeks of suprapubic tenderness + dysuria (pain with urination) that is
- Treatment for pyelo is ciprofloxacin or ceftriaxone. USMLE is known to ask unexplained, where laboratory and urinary findings are negative.
Chronic interstitial
these. - They can mention anterior vaginal wall pain (bladder is anterior to vagina).
cystitis
- Persistent fever despite Abx Tx à do ultrasound to look for perinephric abscess. - USMLE wants you to know you don’t treat. Steroids are wrong answer.
- For example, old dude + high Cr (caused by post-renal from BPH) + treated for “Treatment” is standard placating placebo nonsense such as “education,” “self-
pyelo à now gets sore ankle à was treated with cipro (causes tendonopathy). care” and “physiotherapy.”
- 2CK form has ceftriaxone as an answer in pyelo Q where cipro isn’t listed. But - Classically E. coli infection of the urethra.
cipro is classic Tx. It’s to my observation that ceftriaxone is HY drug on 2CK for - Common in women due to shorter urethras.
community-acquired “general sepsis” or “general complicated/severe infections” - As mentioned above for cystitis, fimbriae and pilus proteins facilitate E. coli’s
– i.e., it is hard-hitting and covers wide array of community organisms. attachment to urothelium.
- There is one 2CK Q where they mention pyelo is treated with amp + gent in the - Inoculation of the urethra following sexual activity is most common mechanism.
stem, but I’ve never seen this assessed as an answer you need to choose. I’ve only - Can be caused by catheters. You need to know dysuria + Hx of catheter = UTI.
ever seen ciprofloxacin or ceftriaxone as actual NBME answers for pyelo. - Tangentially, this is also HY for general sepsis, where if they mention Hx of IV
- Due to recurrent acute pyelonephritis. line/catheter, USMLE wants you to be able to say, “Got it. That’s the cause.”
- Almost always pediatric, where they give a 4-year-old who has a small, shrunken - Trimethoprim, trimethoprim/sulfamethoxazole (TMP/SMX), or nitrofurantoin
kidney with tubular atrophy and blunting and scarring of the renal calyces. are standard treatments for UTI.
General UTI - For prevention, post-coital voiding confers ¯ risk of recurrence.
- If post-coital voiding doesn’t work, “post-coital nitrofurantoin therapy” is
answer on 2CK NBME form.
- If post-coital nitrofurantoin therapy doesn’t work, “daily TMP/SMX prophylaxis”
is the answer. Sounds absurdly wrong / like a bad idea, but it’s an answer a
couple times on Obgyn assessments.
- There’s also a Q where they say a girl was treated successfully in the past with
TMP/SMX for a UTI + ask how to prevent recurrent UTIs now, and they just jump
straight to “daily TMP/SMX prophylaxis.”
- If patient is treated for a UTI and dysuria persists, the next best step is testing
for Chlamydia and Gonorrhea.

Chronic pyelonephritis
HY Bladder incontinences
- The answer for loss of urine with ­ intra-abdominal pressure from laughing, sneezing,
coughing.
- Stereotypical risk factor is grand multiparity (i.e., Hx of many childbirths) leading to
Kidney appears to show loss of architecture + scarring.
weakened pelvic floor muscles.
- I’d say only ~50% of Qs will mention Hx of pregnancy. The other ~50% are idiopathic.
- USMLE will show you kidney that looks similar to the above in a child with
- Buzzy vignette descriptors and answer choices are: “downward mobility of the
recurrent UTIs, and then the answer is just “tubular atrophy” for what is most
vesicourethral junction,” “urethral hypermobility,” and “urethral atrophy with loss of
likely to be seen on microscopic examination.
urethrovesical angle.”
- Another Q shows the same image and the answer is “congenital ureteral Stress
- Treatment is pelvic floor (Kegel) exercises. These notably strengthen levator ani,
obstruction” as the cause.
pubococcygeus, and the external urethral sphincter.
- “Thyroidization of the kidney” is a buzzy phrase that has been applied to chronic
- USMLE is known to ask which muscle is not strengthened by Kegel exercises, which
pyelo over the years, but USMLE doesn’t so much care about this. What they
sounds obscure, since any muscle could theoretically be the answer (“Well the deltoid
really like is the tubular atrophy and scarring / loss of architecture of the calyces.
isn’t strengthened.”). But a favorite answer here is internal urethral sphincter. The
- Chronic pyelo doesn’t present with cellular infiltration the way acute pyelo does.
way you know this is the answer is because internal sphincters are under sympathetic
It refers to the kidney being destroyed/shrunken from repeated prior infections.
(i.e., involuntary; autonomic) control, which means it’s impossible to strengthen it via a
Cystitis - Suprapubic tenderness in female. Patient need not have fever.
voluntary (i.e., somatic) exercise. USMLE doesn’t expect you to be an obstetrician. The

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bigger picture concept is simply knowing internal sphincter control is involuntary. It is Urinary retention diagnoses
external sphincter control that is voluntary (somatic). - Lack of coordination between bladder sphincters and detrusor muscle.
- Do not give medications for stress incontinence on USMLE. - HY cause is spinal cord injury, which can cause either inability to void or
- If Kegel exercises fail, patients can get a mid-urethral sling (LY; asked once). urinary incontinence.
Bladder neck dyssynergia
- The answer on USMLE for patient who has an “urge” (NBME will literally say that - MS is another theoretical cause, which is where “overflow incontinence”
word and I’ve seen students get the Q wrong) to void 6-12+ times daily unrelated to as a result of MS has been asked by students, but once again, I’ve only
sneezing, coughing, laughing, etc. (otherwise stress incontinence). ever seen urge incontinence for MS on NBME exams. Qbank ¹ NBMEs.
- Ultra-HY for multiple sclerosis. I’ve had students ask whether MS is urge or overflow. - Acute urethral obstruction due to catheter removal is HY on Surg forms.
It shows up repeatedly on the NBMEs as urge; I’ve never seen it associated with - They’ll say patient has anuria (i.e., no urinary output at all) following
overflow. I’d say ~1/3 of urge incontinence vignettes on NBME forms are MS. removal of a catheter.
Bladder outflow obstruction
- Other vignettes will be peri-menopausal women, or idiopathic in old women. - “Acute urethral obstruction” or “bladder outflow obstruction” is the
- Mechanism is “detrusor hyperactivity,” or “detrusor instability.” answer.
- Vignette can mention woman has urge to void when stepping out of her car, or when - Treatment on NBME is “re-insertion of urinary catheter.”
sticking her key in the car/front door of her house. Sounds weird, but these are - Will present as leg pain + urinary retention on USMLE.
Urge important Qs to ask when attempting to diagnose urge incontinence. - Can be idiopathic, from disc herniation, or other trauma.
- UTIs can present similarly to urge incontinence. Some students have asked, “Well - Metastases is HY cause (i.e., random guy over 50; or female with Hx of
isn’t that because UTIs are a cause of urge incontinence?” Not really. It just happens to mastectomy 5 years ago).
be that UTIs can sometimes cause transient urinary urgency. For example, if they give a Cauda equina syndrome - “Saddle anesthesia” is an overrated detail and doesn’t show up in the
Q where they say patient had Hx of urinary catheter + now has dysuria and urinary vast majority of NBME Qs, as per my observation.
urgency, answer = “urinary tract infection” on NBME; “detrusor hyperactivity” is wrong - Cauda equina is the collection of nerves at the end of the spinal cord.
answer. Impingement on these nerves is what causes the syndrome. I cover this
- Treatment is oxybutynin (muscarinic receptor antagonist); this ¯ activity of the stuff in more detail in my HY Neuroanatomy PDF.
detrusor muscle of the bladder.
- Some students get hysterical about mirabegron (b3-agonist), but I’ve never seen
NBME forms assess this.
- Will be due to either BPH or diabetes on USMLE.
- Will have ­ post-void volume. Normal is < ~50 mL. On USMLE for overflow, they’ll HY Genitourinary injuries (2CK)
give you 300-400 mL as post-void volume. - Always presents with blood at the urethral meatus.
- As I talked about earlier for BPH, they will give old dude + high creatinine (post-renal - 3 ways this presents on USMLE:
azotemia). Next best step is “insertion of catheter” to relieve the obstruction. If they 1) Blood at urethral meatus + saddle injury (dude falls on balance beam).
Urethral injury
don’t have this listed, “measurement of post-void volume” can be an answer. We then 2) Blood at urethral meatus + pelvic fracture/instability.
treat the BPH with finasteride (5a-reductase inhibitor) or an a1-blocker (tamsulosin, 3) Blood at urethral meatus + “prostate not palpable.”
terazosin). - Next best step is retrograde urethrogram.
Overflow - Answer on USMLE for blunt force trauma to abdomen + exquisite suprapubic
- For diabetes, the mechanism is neuropathy to the bladder causing “neurogenic
bladder,” or “hypotonic bladder,” or “hypocontractile bladder/detrusor muscle.” tenderness + catheter insertion yields 10-30 mL of dark bloody fluid.
Bladder injury
- For neurogenic bladder causing overflow incontinence +­ post-void volume, - Next best step is retrograde cystourethrogram. Do not confuse with voiding
remember that USMLE is first obsessed with “measure post-void volume” and cystourethrogram, which is for posterior urethral valves.
“insertion of catheter” if they are listed. They will not force you to choose between the - Just be aware this is USMLE-favorite injury in Obgyn for any surgery done in the
two. But they like these answers prior to giving medications. gynecologic area.
Ureteral injury
- Give bethanechol (muscarinic receptor agonist); this stimulates the detrusor muscle. - Diagnosis is with retrograde pyelogram or CT urogram, although I haven’t seen the
- Making sure you don’t confuse oxybutynin and bethanechol is pass-level for USMLE. USMLE give a fuck. Any ureter injury Q I’ve seen just has “ureter” as answer.
- Patient who has “wet, wobbly, wacky” presentation (i.e., urinary incontinence, ataxia, - Exceedingly HY on both IM and Surg forms on 2CK.
cognitive changes) +/- Parkinsonism (e.g., short-steppage gait). - Will present as bruising or pain over a flank following accident.
Normal pressure - Blood in the urine is highly sensitive, meaning if it’s not there, we can rule-out.
- Caused by failure of reabsorption of CSF by the arachnoid granulations, resulting in
hydrocephalus - First step in diagnosis: “Is there gross blood in the urine?” If yes à do CT of the
impingement on the zona radiata and “failure to inhibit the voiding reflex” (answer on
(NPH) abdomen with contrast to diagnose (sounds wrong, since we’re worried about kidney
NBME). Renal injury
- Enlargement of the lateral ventricles on head CT. injury, so student says, “Why would we use contrast?” But it’s what USMLE wants.
AIDS complex - Presents similar to NPH – i.e., “wet, wobbly, wacky” in AIDS patient. Ultrasound is wrong answer).
dementia - If patient does not have gross blood in the urine, next best step is urinalysis looking
for microscopic blood. If present à answer = CT of the abdomen with contrast. If
negative à “no further diagnostic studies indicated.”

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Urothelial malignancies - Rare as fuck. 0-3% of renal malignancies. But shows up on Step 1 NBME.
- Aka “clear cell carcinoma”; this is most common variant of RCC.
- Classic Q is a smoker over 50 with red urine and a painful flank mass.
- Q need not mention smoking, but it is biggest risk factor.
- USMLE likes the histo for this, which will show you large clear cells.

Collecting duct carcinoma

Renal cell carcinoma

(RCC)

- Offline NBME Q shows some pic of a kidney split open like this and then the
answer is just “naphthylamine” (moth balls) as the causative agent.
- Most common bladder cancer.
- Classic vignette is hematuria in smoker without a painful flank mass or
polycythemia/hypercalcemia (otherwise RCC).
- Can cause polycythemia due to ­ EPO and hypercalcemia due to PTHrp - USMLE wants you to know smoking is most common risk factor, but aniline
secretion (correct, same as squamous cell carcinoma of the lung). dyes (industrial clothing dyes) and naphthylamine are important causes.
- For example, they say 55-year-old male + red urine + polycythemia + - 2CK Surg Q gives Stage 0 bladder cancer vignette; answer is just “endoscopic
hypercalcemia + show you above image; they ask for the source of the resection.”
malignancy à answer “kidney,” not lung. Squamous cell carcinoma of the - I’ve never seen BCG vaccine as correct answer on NBME. I’ve only seen it as a
lung won’t cause hematuria, nor does it metastasize to the kidney. distractor. For whatever reason, some studies in the past have suggested
- The answer for painless flank mass in a kid age 2-4 years. intra-cystic instillation of the TB vaccine can help with bladder cancer. But this
- Does not present in newborns. If they give you a 12-hour-old male, for is wrong on USMLE.
instance, with a midline mass, that is posterior urethral valves causing a full
bladder (let alone the fact they say “midline,” not flank). I’ve seen tons of Transitional cell carcinoma
students select Wilms for this, and I’m like, is the kidney in your midline? of the bladder
- If they give you a kid 2-4 years with a midline mass, that is neuroblastoma.
- For whatever magical reason, you need to know Wilms tumor is sometimes
caused by mutations on chromosome 11. They ask this factoid on 2CK as well.
There are various Wilms tumor syndromes you need to be aware of:
- Beckwith-Wiedemann syndrome
- Wilms tumor + macrosomia (big baby >4,000g) + hemi-hypertrophy
(half of the body is bigger than the other) + macroglossia +
Wilms tumor omphalocele + hypoglycemia.
(Nephroblastoma) - Hard 2CK Peds Q gives newborn with macrosomia + hemi-
hypertrophy + macroglossia + omphalocele; they don’t mention a
Wilms tumor (makes sense, since we said we won’t see it in Can have papillary structure on histo.
newborns); they ask for what else could be seen in this patient à
answer = “hypoglycemia.” I say hard Q because Wilms plays no role.
- Can be caused by Schistosoma hematobium (a trematode or fluke, which is a
- WAGR syndrome type of helminth).
- Wilms tumor, Aniridia (iris abnormalities), Genitourinary anomalies, - S. hematobium lays its eggs in the bladder wall and cystic veins draining the
Retardation. Squamous cell carcinoma
bladder.
- Usually an easy Q, where they mention “aniridia” straight up in the of the bladder
- Vignette will be young guy who has red urine months after returning from
vignette and then the answer is just “Wilms tumor” for what the kid Africa where he went swimming in a lake à answer is just Schistosomiasis. Or
can go on to develop.
they ask what he’s at ­ risk of à answer = squamous cell carcinoma.
- Denys-Drash syndrome
- Ambiguous genitalia + Wilms tumor.

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SIADH vs DI vs PP - After we determine that the urine is staying dilute + the serum is staying concentrated, the
- Syndrome of Inappropriate Anti-Diuretic Hormone secretion à means too much ADH next best step is desmopressin (analogue of vasopressin). If the urine gets more concentrated,
(vasopressin secretion). (i.e., if the drug works), we know central DI is the diagnosis and we’re merely deficient in ADH.
- ADH is produced by supraoptic nucleus of hypothalamus à stored in posterior pituitary. - If desmopressin doesn’t work, we know we have nephrogenic DI. I should point out that even
- ADH ­ free water reabsorption by the medullary collecting duct (MCD) of the kidney by in nephrogenic DI, desmopressin might work but only very little, whereas with central DI,
causing aquaporin insertion. administration will ­­ urinary osmolality robustly. It will be obvious on USMLE. But my point is,
- Central SIADH à follows head trauma, meningitis, brain cancer, and pain (latter on 2CK Surg). don’t say, “Oh well desmopressin worked like 5% so we can’t have nephrogenic DI here.”
- Ectopic SIADH à small cell lung cancer secreting ADH. - Treatment for central DI is therefore desmopressin.
- Drug-induced ADH à ultra-rare on USMLE, but carbamazepine can do it. - Treatment for nephrogenic DI is NSAID + a thiazide. Sounds weird, but ¯ Na+ reabsorption
induced by thiazides in the early-DCT promote compensatory ­ Na+ reabsorption in the PCT,
- Patient will have dilute serum and concentrated urine: where water follows Na+ and our net loss of fluid is less than without the thiazide. In healthy
- ¯ serum sodium, ¯ serum osmolality, ¯ serum specific gravity. individuals, however, they will lose more net fluid with the thiazide. The NSAID presumably ¯
- ­ urinary osmolality, ­ urinary specific gravity. renal blood flow, which will ¯ GFR and ¯ net fluid loss.
- You must know serum sodium is normally 135-145 mEq/L. So in SIADH, it’s <135. - There is difficult 2CK NBME Q where they say patient is on lithium + has ­ urinary output, and
- Serum vs urinary osmolalities will be all over the place and you do not need to fluid restriction is wrong answer to this question (I say hard because 9/10 times, fluid restriction
memorize values. They might say serum osmolality is 250 and urinary is 750, and then is correct when it’s listed); answer = NSAID + thiazide diuretic. The implication is, if it’s obvious
you say, “Well I can tell serum is dilute compared to urine, which sounds like SIADH.” what the patient’s diagnosis is already nephrogenic DI, going straight to Tx is acceptable.
SIADH - Specific gravity will be 1.000-1.030 on USMLE. Sounds obscure, but it shows up quite - Psychogenic polydipsia means the patient is simply drinking too much.
a bit, particularly on 2CK Qs. It’s to my observation that values 1.000-1.006ish are - Both the urine and serum will be dilute.
“dilute”; 1.024-1.030 are “concentrated.” For 9/10 Qs, values will be what you expect. - Serum vs urinary values are the opposite of SIADH:
- ¯ serum sodium (<135 mEq/L), ¯ serum osmolality, ¯ serum specific gravity.
- As I talk about in detail in my HY Arrows PDF, only the medullary collecting duct osmolality will - ¯ urinary osmolality, ¯ urinary specific gravity.
change in response to ADH. The USMLE will ask you for the osmolality of the urine at different PP
- I’d say 3/4 Qs on USMLE are obvious and will say some psych patient is drinking lots to “clear
nephron locations in comparison to serum, and the combo is: PCT isotonic; juxtaglomerular himself from evil spirits,” etc.
apparatus (JGA) hypotonic; MCD hypertonic. à The PCT is always isotonic no matter what; the - Probably 1/4 Qs won’t be an obvious psych vignette, but will just show you the lab values
JGA (at top of thick ascending limb of loop of Henle) is always hypotonic no matter what; the where you have to say, “The urine and serum are both dilute, so this is psychogenic polydipsia.”
MCD is clearly hypertonic in SIADH since we’re pulling free water out of the urine. - First step in diagnosis is fluid restriction in order to see how urinary/serum values change.
- “Fluid restriction” is first answer in diagnosis on 2CK. We want to see how serum/urinary
values change in response.
- Demeclocycline is answer on 2CK offline NBME 8 for treatment of SIADH. Demeclocycine is
technically a tetracycline antibiotic but isn’t used because it can cause insensitivity to ADH at
the kidney (i.e., nephrogenic diabetes insipidus). So we essentially cause a 2nd problem that Obscure miscellaneous conditions
cancels out the 1st problem. - Disease that presents as though patient is on loop diuretic.
Bartter syndrome
- Conivaptan and tolvaptan are ADH receptor antagonists that can be used for SIADH. - For whatever magical reason, is associated with juxtaglomerular cell hyperplasia.
- Central diabetes insipidus à means not enough ADH secretion by hypothalamus, or the Gitelman syndrome - Disease that presents as though patient is on thiazide diuretic.
posterior pituitary is unable to release it properly.
- Nephrogenic DI à insensitivity to ADH at the kidney (serum ADH is ­).
- Similar to central SIADH, central DI can be caused by head trauma, meningitis, and cancer.
- Nephrogenic DI is caused by lithium, demeclocycline, hypercalcemia, and NSAIDs.
Hyper-terse summary of drugs causing HY renal conditions
- There is an NBME Q that asks about a patient’s response to ADH who is on chronic NSAIDs,
- Discussed all this stuff earlier. But students confuse this stuff a lot. So the summary is warranted.
and the answer is “« Response to ADH” and “« urinary osmolality” (meaning no change).
- Aminoglycosides (gentamicin, tobramycin, amikacin).
- 2CK Q gives patient with primary hyperparathyroidism and ­­ serum calcium + nephrogenic Acute tubular necrosis
- Cisplatin.
DI; Q asks cause of the DI à answer = hypercalcemia. High calcium can cause renal insensitivity
to vasopressin. Interstitial nephritis - NSAIDs, b-lactams, cephalosporins.
DI Membranous glomerulonephropathy - Dapsone, gold salts, sulfonamides.
- Serum vs urinary values are the opposite of SIADH:
- ­ serum sodium (>145 mEq/L), ­ serum osmolality, ­ serum specific gravity.
- ¯ urinary osmolality, ¯ urinary specific gravity.

- PCT isotonic; JGA hypotonic; MCD hypotonic. à The PCT is always isotonic no matter what;
the JGA is always hypotonic no matter what; the MCD is clearly hypotonic in DI since we’re not
pulling free water out of the urine.
- When we are trying to first diagnose DI, the first thing we do is fluid restriction, same as with
SIADH. We want to see how serum/urinary values change first.

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Diuretics / Renal-related drugs - Answer on USMLE for patient with heart failure who has ¯ O2 sats who “refuses
to lie supine/back on the gurney” because he/she can’t breathe. Q might say CXR or
exam shows fluid 2/3 up the lung fields.
- Application of loops can be confused by students with ACEi/ARB. For instance, the
latter are used first-line to ­ EF in heart failure even if O2 sats are low (¯ AT-II
constrictive effect on arterioles à ¯ afterload à heart pumps easier), but loops
are first-line if the vignette specifically emphasizes the dyspnea and low O2 sats of
the patient as the focus.
- HY point is that they can cause hypokalemia. What USMLE loves to do is tell you a
patient is initiated on furosemide but it is insufficient + now needs a second
diuretic à answer = anything that is potassium-sparing (i.e., ENaC inhibitor such as
amiloride or triamterene; or aldosterone receptor antagonist such as
spironolactone or eplerenone).
- Can also cause ototoxicity (tinnitus, vertigo).
- Loops ­ urinary calcium. This is in contrast to thiazides, which ¯ it.
- Ethacrynic acid is another loop you can be aware of. It is used in patients with
- Osmotic diuretic that ­ osmolality of urine, thereby retaining free water within sulfa allergies, since furosemide is a sulfa drug. It is also ototoxic.
the PCT and descending limb of loop of Henle. - Hydrochlorothiazide (HCTZ) is HY example; chlorthalidone is “thiazide-like.”
- Can be used as Tx for ­ intracranial pressure after patient has been intubated + - Inhibit the Na+/Cl- symporter on the apical membrane of the early-DCT.
hyperventilated (¯ CO2 à ¯ cerebral perfusion). - ­ calcium reabsorption in the DCT of the kidney. Used to ¯ recurrence of calcium
- Avoid in heart failure (transient ­ in serum osmolality prior to renal excretion à ­ stones by promoting ­ reabsorption of urinary calcium. In turn, they can
retention of free water within vascular space à transient ­ preload on heart). sometimes cause hypercalcemia. There is an NBME Q where they ask for MOA of
- USMLE asks about mannitol’s effect on serum osmolality and ADH. This is a Q HCTZ, where Na+/Cl- symporter inhibition isn’t listed; answer is just “­ calcium
repeated twice on the NBMEs. They will show a graph same as below and ask what reabsorption.”
change will be expected with mannitol administration: - Thiazides and dihydropyridine calcium channel blockers are used first-line for HTN
in patients without any renal or cardiovascular issues. If patient has proteinuria, ­
Thiazides
in creatinine or renin, or pre-diabetes or diabetes, ACEi or ARBs are used first.
- Can be used in heart failure in patients with diabetic nephropathy who are already
Mannitol on ACEi and b-blocker. Sounds specific, but there’s a new 2CK Q that has thiazide as
correct over spironolactone in a diabetic. Spironolactone can cause hyperkalemia in
patients who have worrisome kidney function.
- Thiazides can cause gout (i.e., contraindicated in gout).
- Offline NBME 20 wants you to know thiazides can cause galactorrhea (milky
discharge from the nipples) via some obscure mechanism. Literature search shows
it accounts for ~0.2% of adverse effects of thiazides, but count on NBME to ask it.
- ENaC inhibitors à block apical sodium channel in cortical collecting duct à ¯ Na+
reabsorption à ¯ water reabsorption.
- These are potassium-sparing, which means they do not ¯ serum K+. This is
because by inhibiting the apical ENaC channel, they indirectly inhibit the basolateral
Answer = C; serum osmolality goes ­, which then causes ADH to go ­ (this is Na+/K+ ATPase à ¯ Na+ reabsorption + ¯ K+ secretion.
because ADH normally ­ free water reabsorption in setting of ­ serum osmolality). Amiloride, - The answer on USMLE for a second diuretic given in a patient already on
- Carbonic anhydrase inhibitor (enzyme that enables H2CO3 « HCO3- + H+) that acts Triamterene furosemide who needs additional fluid unloading. Be careful however. I’ve seen
within the tubular cells of the PCT. one Q where the patient is on furosemide, but the point of the Q is he/she needs
- Classic use is altitude sickness à causes ¯ reabsorption of HCO3- in the PCT à HTN control, and the answer is a thiazide, not the ENaC inhibitor. You want to
Acetazolamide results in ­ urinary pH and volume + ¯ serum pH and volume. In altitude sickness, select an ENaC inhibitor specifically if the Q says, “We have a patient who has
patients hyperventilate (¯ CO2 à ­ pH) to take in more O2, but it takes a minimum peripheral/pulmonary edema due to X cause + is already on furosemide; what do
of 12-24 hours for the kidney to ¯ HCO3- reabsorption, so acetazolamide forces the we do now?” à answer = amiloride or triamterene.
¯ reabsorption by causing metabolic acidosis. - Aldosterone receptor antagonists.
- Can cause Fanconi syndrome (¯ ability of PCT to reabsorb amino acids, glucose, - By blocking aldosterone receptor, they ¯ activity of the basolateral Na+/K+ ATPase
Expired tetracyclines à leads to indirect ¯ activity of apical ENaC à ¯ Na+ reabsorption à ¯ water
bicarb, and phosphate).
- Classic loop diuretic that inhibits the apical Na+/K+/2Cl- ATPase symporter on the reabsorption.
Spironolactone,
thick ascending limb. Apical means side of urine. Basolateral means side of blood. - Potassium-sparing. Same as with ENaC inhibitors, used for fluid unloading in
Furosemide Eplerenone
- Most efficacious diuretic at enabling fluid unloading for pulmonary and peripheral patients who are already on furosemide in whom we worry about dropping their K+
edema. Do not decrease mortality in cardiac patients. too much.
- Used in heart failure up the hierarchy of meds – i.e., ACEi/ARB first-line, followed
by adding b-blocker, followed by spironolactone (but if patient is diabetic with poor

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renal function, don’t add spironolactone here; give thiazide instead as per new 2CK
NBME).
- Can be for aldosteronoma (Conn syndrome) prior to surgery.
- Spironolactone can cause gynecomastia (anti-androgenic effect by blocking
androgen receptors).
- Eplerenone has ¯ risk of gynecomastia compared to spironolactone.
- USMLE-favorite ACE inhibitor.
- Prevents conversion of AT-I into AT-II in the lungs.
- Used for HTN in patients with pre-diabetes, diabetes, atherosclerotic disease, or
renal disease (I talk about this in HY Risk Factors PDF in more detail).
Lisinopril - Can cause dry cough (ACE is aka bradykininase, so ACEi cause ¯ breakdown of
bradykinin in lungs à cough).
- Can ­ serum K+, since ¯ aldosterone synthesis. Aldosterone normally secretes K+
in the distal kidney).
- Avoid in hereditary angioedema.
- Angiotensin II receptor blocker (ARB).
- Use-cases are identical on USMLE to ACEi (i.e., if you see both as answer choices
Valsartan
to a question, they’re usually both wrong because they’re the “same”).
- Doesn’t cause dry cough the way ACEi do.
- ADH receptor antagonists at V2 receptor in the medullary collecting duct.
Tolvaptan,
- Can be used for SIADH.
Conivaptan
- Remember, however, that demeclocycline is also answer on 2CK NBME for SIADH.

- 27M + dilated renal pelvis and collecting system + ureters not dilated; Dx? à USMLE wants

“incomplete recanalization of proximal ureter.”

- Student says: “I can never remember which conditions are subepithelial deposits vs subendothelial.”

à Cool. Well you ready for something epic? à If the renal condition has “proliferative” in the name,

it has subendothelial deposits. If it doesn’t have “proliferative” in the name, it must not be

subendothelial. So for instance, membranoproliferative glomerulonephritis (MPGN) and diffuse

proliferative glomerulonephritis (DPGN); what would you see on biopsy? à USMLE answer =

subendothelial deposits. Yeah, I know. As I said, epic.

- Four classic findings you see in nephrotic syndrome?

o Proteinuria (usually high, i.e., >3g/24 hours)

o Hypoalbuminemia (because of the proteinuria)

o Peripheral edema (due to decreased intravascular oncotic pressure because of the

hypoalbuminemia)

o Hyperlipidemia (liver exports more apolipoproteins in an attempt to compensate for the low

serum albumin)

- Four classic findings you see in nephritic syndrome?

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