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Flashcards in Renal Deck (113):

Potter Sequence (Syndrome)

Oligohydramnios (too little amniotic fluid) leads to compression of developing fetus leading to limb deformities, facial anomalies (low-set ears and retrognathia), compression of chest and lack of amniotic fluid aspiration into fetal lungs.

This leads to pulmonary hypoplasia (cause of death)

Causes ARPKD, obstructive uropathy (posterior urethral valves), bilateral renal agensis.

Babies who can't P in utero develop Potter Sequence

P = Pulmonary hypoplasia
O = Oligohydramnios (trigger)
T = Twisted Face
T = Twisted Skin
E = Extremity defects
R = Renal failure (in utero)


Kidney embryo

1) Pronephros - week 4; then degenerates

2) Mesonephros - functions as interim kidney for 1st trimester; later contributes to male genital system

3) Metanephros - permanent; first appears in 5th week of gestation; nephrogenesis continues through 32-36 weeks of gestation.

- Ureteric Bud - derived from caudal end of mesonephric duct; gives rise to ureter, pelvises, calyces, collecting duct; fully canalized by 10th week

- Metanephric mesenchyme - ureteric bud interacts with this tissue; interaction induces differentiation and formation of glomerulus through to distal convoluted tubule (DCT)

- Aberrant interaction btw these 2 tissues may result in several congenital malformations of the kidney

4) Ureteropelvic junction - last to canalize. Most common site of obstruction (hydronephrosis) in fetus.


Horseshoe kidney

Inferior poles of both kidneys fuse. As they ascend from pelvis during fetal development, horseshoe kidneys get trapped under inferior mesenteric artery and remain low in the abdomen.

Kidneys function normally.

Associated with ureteropelvic junction obstruction, hydronephrosis, renal stones, infection, chromosomal aneuploidy syndromes (Edwards, Down, Patau, Turner), and rarely renal cancer.


Multicystic dysplastic kidney

Due to abnormal interaction between ureteric bud and metanephric mesenchyme.

Leads to a nonfunctional kidney consisting of cysts and connective tissue.

If unilateral (most common), generally asymptomatic with compensatory hypertrophy of contralateral kidney.

Often diagnosed prenatally via ultrasound


Duplex collecting system

Bifurcation of ureteric bud before it enters metanephric blastema creates Y-shaped bifid ureter.

Can alternatively occur when 2 ureteric buds reach and interact with metanephric blastema.

Strongly associated with vesicoureteral reflux and/or ureteral obstruction, higher risk of UTIs.


Which kidney is taken from donor before transplant?


It has a longer renal vein.


Ureters - course

Ureters pass under uterine artery and under ductus deferens (retroperitoneal)

Gyn procedures involving ligation of uterine vessels traveling in cardinal ligament may damage ureter leading to ureteral obstruction or leak.


Fluid compartments

HIKIN - High K intracellularly

60-40-20 rule (% of body weight for avg person):

60% total body water
40% ICF
20% ECF

Plasma volume measured by radiolabeled albumin

Extracellular volume measured by inulin

Osmolality = 285-295 mOsm/kg H2O


Normal fluid volumes

Normal person is 70kg (70L)

.6 (70) = 42L of total body water
.4 (70) = 28L of non water mass

Of the 42L water mass - 1/3 is extracellular, 2/3 is intracellular

OR 20% of overall = ECF, 40% of overall = ICF

.33 (42) or .2 (70) = 14 L ECF
.67 (42) or .4 (70) = 28 L ICF

Extracellular = Interstitial fluid + plasma
Intracellular includes RBC volume

Blood volume is about 6 L. Of these 6L, 45% is hematocrit (RBC). .45 (6) = 2.8 L of RBC (intracellular) and 3.2 L is plasma (extracellular)


Glomerular filtration barrier

Responsible for filtration of plasma according to size and net charge.

Composed of:
1) Fenestrated capillary endothelium (size barrier)
2) Fused basement membrane with heparan sulfate (negative charge barrier)
3) Epithelial layer consisting of podocyte foot processes

Charge barrier is lost in nephrotic syndrome leading to albuminuria, hypoproteinemia, generalized edema, hyperlipidemia


Renal Clearance

Cx = UxV/Px = volume of plasma from which the substance is completely cleared per unit time.

Cx = Clearance of X (mL/min)
Ux = Urine concentration of X (mg/mL)
Px = Plasma concentration of X (mg/mL)
V = urine flow rate (mL/min)



Net tubular reabsorption of X


Cx > GFR

Net tubular secretion of X


Cx = GFR

No net secretion or reabsorption


Glomerular Filtration Rate

Inulin clearance can be used to calculated GFR bc it is freely filtered and is neither reabsorbed nor secreted

UV/P for inulin:

GFR = (U inulin)V/(P inulin) = C inulin

GFR = Kf [(Pgc - Pbs) - (pi gc - pi bs)]
gc = glomerular capillary
bs = bowman space
Pi bs normally = 0

Normal GFR = 100 mL/min

Creatinine clearance is an approximate measure of GFR. Slightly overestimates GFR bc creatinine is moderately secreted by renal tubules.

Incremental reductions in GFR define the stages of chronic kidney disease.


Effective Renal Plasma Flow

eRPF can be estimated using para-aminohippuric acid (PAH) clearance bc it is both filtered and secreted in the proximal collecting tubule, resulting in near 100% excretion of all PAH entering kidney

eRPF = U pah V / P pah = C pah

RBF = RPF / (1 - Hct)

eRPF underestimates true renal plasma flow (RPF) by about 10%



Filtration fraction (FF) = GFR/RPF

Normal FF = 20%

Filtered load (mg/min) = GFR (mL/min) x Plasma concentration (mg/mL)

GFR can be estimated with creatinine clearance. RPF is best estimated with PAH clearance.


Changes in glomerular dynamics

1) Afferent arteriole constriction:
Lower GFR, Lower RPF, no change FF (GFR/RPF)

2) Efferent arteriole constriction:
Higher GFR, Lower RPF, Higher FF

3) Higher plasma protein concentration:
Lower GFR, Flat RPF, Lower FF

4) Lower plasma protein concentration:
Higher GFR, Flat RPF, Higher FF

5) Constriction of ureter:
Lower GFR, Flat RPF, Lower FF


Prostaglandin effects on glomerulus

Preferentially dilates afferent arteriole (higher RPF, higher GFR, flat FF)

NSAIDs inhibit this


Angiotensin II effects on glomerulus

Preferentially constricts efferent arteriole (Lower RPF, Higher GFR, Higher FF)

ACE Inhibitors inhibit this


Calculation of reabsorption and secretion rate

Filtered Load = (GFR) (Px)
Excretion rate = (V)(Ux)

Reabsorption = filtered - excreted
Secretion = excreted - filtered


Glucose clearance

Glucose at a normal plasma level is completely reabsorbed in PCT by Na/Glucose cotransport

At plasma glucose of 200, glucosuria begins (threshold).

At 375, all transporters are fully saturated (Tm)

Glucosuria is an important clinical clue to diabetes mellitus

Normal pregnancy may decrease ability of PCT to reabsorb glucose and amino acids leading to glucosuria and aminoaciduria.


Amino acid clearance

Na-dependent transporters in PCT reabsorb amino acids


Hartnup Disease

Auto recessive

Deficiency of neutral amino acid (like tryptophan) transporters in proximal renal tubular cells and on enterocytes leads to neutral aminoaciduria and lower absoprtion from the gut.

This lowers tryptophan for conversion to niacin leading to pellagra-like symptoms.

Treat with high protein diet and nicotinic acid


List the Renal Tubular Defects (5)

The kidneys put out FABulous Glittering LiquidS.

FA = Fanconi Syndrome is the 1st defect (PCT)
B = Bartter Syndrome is next (Thick Ascending loop)
G = Gitelman Syndrome is after Bartter (DCT)
L = Liddle Syndrome is last (collecting tubule)
S = Syndrome of apparent mineralocorticoid excess (collecting tubule)


Fanconi Syndrome

Generalized reabsorptive defect in PCT

Associated with higher excretion of nearly all amino acids, glucose, Bicarb, Phosphate.

May result in metabolic acidosis (prox renal tubular acidosis)

Causes include:
1) hereditary defects (Wilson disease, tyrosinemia, glycogen storage disease)

2) Ischemia

3) Multiple myeloma

4) Nephrotoxins/drugs (expired tetracyclines, tenofovir), lead poisoning


Bartter Syndrome

Reabsorptive defect in thick ascending loop of Henle.

Autosomal recessive

Affects Na/K/2Cl cotransporter

Results in hypokalemia and metabolic acidosis with hypercalciuria


Gitelman Syndrome

Reabsorptive defect of NaCl in DCT

Auto recessive

Less severe than Bartter. Leads to hypokalemia, hypomagnesemia, metabolic alkalosis, hypocalciuria


Liddle Syndrome

Gain of function mutation leading to higher Na reabsorption in collecting tubules (increased activity of epithelial Na channel)

Auto Dominant

Results in HTN, hypokalemia, metabolic alkalosis, lower aldosterone

Tx = Amiloride


Syndrome of apparent mineralocorticoid excess

Hereditary deficiency of 11B-hydroxysteroid dehydrogenase, which normally converts cortisol into cortisone in mineralocorticoid receptor-containing cells before cortisol can act on the mineralocorticoid receptors

Excess cortisol in these cells from enzyme deficiency leads to increased mineralocorticoid receptor activity.

This leads to HTN, hypokalemia, metabolic alkalosis.

Low serum aldosterone levels

Can acquire disorder from glycyrrhetic acid (present in licorice), which blocks activity of 11B-hydroxysteroid dehydrogenase


Renin-Angiotensin-Aldosterone System


1) Lower BP (JG Cells)
2) Low Na delivery (Macula Densa Cells)
3) Higher sympathetic tone (B1 receptors)

What happens?

These triggers increase secretion of Renin

Renin converts Angiotensinogen (from liver) to Angiotensin I

AT I is converted to Angiotensin II via ACE (from lungs and kidney). NOTE!!! ACE also breaks down bradykinins

AT II acts at a lot of places:

1) Acts at AT II receptor type 1 on vascular smooth muscle.
- This leads to vasoconstriction leading to increased BP

2) It constricts efferent arterioles of glomerulus.
- This leads to higher FF to preserve renal function (GFR) in low volume states (i.e. when RBF falls)

3) It triggers aldosterone release from adrenal gland.
- This increases Na channel and Na/K pump insertion in principal cells
- Enhances K and H excretion by way of principal cell K channels and alpha-intercalated cell H ATPases
- All this creates a favorable Na gradient for Na and H2O reabsorption

4) Triggers release of ADH from posterior pituitary
- Increases aquaporin insertion in principal cells (these dudes are in the collecting ducts)
- Leads to H2O reabsoprtion

5) Increases PCT Na/H activity
- leads to Na, Bicarb, H2O reabsorption (can permit contraction alkalosis)

6) Stimulates hypothalamus
- stimulates thirst


Angiotensin II

Affects baroreceptor function; limits reflex bradycardia, which would normally accompany its pressor effects. Helps maintain blood volume and blood pressure.

AT II acts at a lot of places:

1) Acts at AT II receptor type 1 on vascular smooth muscle.
- This leads to vasoconstriction leading to increased BP

2) It constricts efferent arterioles of glomerulus.
- This leads to higher FF to preserve renal function (GFR) in low volume states (i.e. when RBF falls)

3) It triggers aldosterone release from adrenal gland.
- This increases Na channel and Na/K pump insertion in principal cells
- Enhances K and H excretion by way of principal cell K channels and alpha-intercalated cell H ATPases
- All this creates a favorable Na gradient for Na and H2O reabsorption

4) Triggers release of ADH from posterior pituitary
- Increases aquaporin insertion in principal cells (these dudes are in the collecting ducts)
- Leads to H2O reabsoprtion

5) Increases PCT Na/H activity
- leads to Na, Bicarb, H2O reabsorption (can permit contraction alkalosis)

6) Stimulates hypothalamus
- stimulates thirst



Released from atria (ANP) and ventricles (BNP) in response to an increase in volume

May act as a "check" on renin-angiotensin-aldosterone system

Relaxes vascular smooth muscle via cGMP leading to an increased GFR, and lower renin



Primarily regulates osmolarity; also responds to low blood volume states

- Increases aquaporin insertion in principal cells (these dudes are in the collecting ducts)
- Leads to H2O reabsoprtion



Primarily regulates ECF volume and Na content; responds to low blood volume states

- This increases Na channel and Na/K pump insertion in principal cells
- Enhances K and H excretion by way of principal cell K channels and alpha-intercalated cell H ATPases
- All this creates a favorable Na gradient for Na and H2O reabsorption


Juxtaglomerular apparatus

Consists of mesangial cells, JG Cells (modified smooth muscle of afferent arteriole) and the macula densa (NaCl sensor, part of DCT)

JG cells secrete renin in response to decreased renal blood pressure and increased sympathetic tone (B1)

Macula densa cells sense reduced NaCl delivery to DCT leading to adenosine release which causes vasoconstriction.

JGA maintains GFR via renin-angiotensin-aldosterone system

B-Blockers can decrease BP by inhibiting B1-receptors of the JGA leading to decreased renin release


Substances released by the Kidney (Kidney endocrine function)

1) Erythropoietin
2) 1,25-(OH)2D3
3) Renin
4) Prostaglandins



Released by interstitial cells in peritubular capillary bed in response to hypoxia



PCT cells convert 25-OH vitamin D to 1,25-(OH)2 Vitamin D (active form)

The enzyme that does this is 1alpha-hydroxylase

This enzyme is inhibited by PTH



Secreted by JG Cells in response to lower renal arterial pressure and increased renal sympathetic tone (B1 effect)



Paracrine secretion vasodilates the afferent arterioles to increase RBF

NSAIDs block renal-protective prostaglandin synthesis leading to constriction of afferent arteriole and lower GFR

This may result in acute renal failure


What causes a shift of K out of cells leading to hyperkalemia?

1) Digitalis
2) HyperOsmolarity
3) Lysis of cells (crush injury, rhabdomyolysis, cancer)
4) Acidosis
5) B-blocker
6) high blood Sugar (insulin deficiency)

trick = "DO LABS" on patients with hyperkalemia


What causes a shift of K into cells leading to hypokalemia?

1) Hypo-osmolarity
2) Alkalosis
3) B-adrenergic agonist (increases Na/K ATPase)
4) Insulin (Increases Na/K ATPase)

"IN"sulin shifts K "IN"to cells


Angiotensin II - where does it act? what does it do? Part 2

Made in response to lower BP

Causes efferent arteriole constriction leading to increased GFR and increased FF but with compensatory Na reabsoprtion in proximal and distal nephron

Net effect: preservation of renal function (higher FF) in low-volume state with simultaneous Na reabsoprtion (both proximal and distal) to maintain circulating volume


Parathyroid hormone

Secreted in response to:
1) lower plasma Ca
2) high plasma PO4
3) low plasma 1,25-(OH)2D3

Causes/leads to:
1) increased Ca reabsorption (DCT)
2) lower PO4 reabsorption (PCT)
3) higher 1,25-(OH)2D3 production (higher Ca and PO4 absorption from gut via vitamin D)


ANP - part 2

Atrial Natriuretic Peptide - it's in the name!

Secreted in response to increased atrial pressure.

Causes increased GFR and increased Na filtration WITH NO COMPENSATORY NA REABSORPTION in distal nephron

Net effect: Na loss and volume loss.

Acts at afferent arteriole and DCT


Aldosterone - again part 2

Secreted in response to low blood volume (via AT II) and high plasma K

Causes more K secretion and more H secretion

Acts at collecting duct


ADH - again part 2


Secreted in response to high plasma osmolarity and low blood volume.

Binds to receptors on principal cells

Causes more aquaporins to increase H2O reabsorption

Acts at collecting duct


Na imbalances

Nausea and maliase, stupor, coma, seziures

Irritability, stupor, coma


K imbalances

U waves on ECG, flattened T waves, arrhythmias, muscle spasm

Wide QRS and peaked T waves, arrhythmias, muscle weakness


Ca imbalances

Tetany, seizures, QT prolonged

Stones (renal)
Bones (pain)
Groans (abdominal pain)
Thrones (higher urinary frequency)
Psychiatric Overtones (anxiety, altered mental status)

Not necessarily calciuria


Mg imbalances

Tetany, torsades de pointes, hypokalemia

Lower DTRs, lethargy, bradycardia, hypotension, cardiac arrest, hypocalcemia


PO4 imbalances

Bone loss, osteomalacia (adults), rickets (children)

Renal stones, metastatic calcifications, hypocalcemia


Acid-Base physiology - Intro

* = primary disturbance
** = compensatory response

1) Metabolic acidosis
- Low pH**
- Low P CO2**
- Low bicarb*
Compensatory response: Hyperventilation (immediate)

2) Metabolic alkalosis
- High pH**
- High P CO2**
- High Bicarb*
Compensatory response: Hypoventilation (immediate)

3) Respiratory acidosis
- Low pH**
- High P CO2*
- High Bicarb**
Compensatory response: Increased renal Bicarb reabsorption (delayed)

4) Respiratory alkalosis
- High pH**
- Low P CO2*
- Low Bicarb**
Compensatory response: Reduced renal bicarb reabsorption (delayed)


Henderson-Hasselbach Equation

pH = 6.1 + log [HCO3] / (0.3 P CO2)


Winters Formula

P CO2 = 1.5 [HCO3] + 8 +/- 2

Predicted respiratory compensation for a simple metabolic acidosis can be calculated with this formula. If measured P CO2 significantly differs from predicted P CO2, then a mixed acid-base disorder is likely present.


Renal tubular acidosis

Disorder of the renal tubules that leads to normal anion gap (hyperchloremic) metabolic acidosis


Presence of casts in urine

Presence of casts indicates that hematuria/pyuria is of glomerular or renal tubular origin.

For example,

Bladder cancer, kidney stones lead to hematuria (no casts)

Acute cystitis leads to pyuria (no casts)


RBC casts

1) Glomerulonephritis
2) Malignant HTN


WBC casts

1) Tubulointerstitial inflammation
2) Acute pyelonephritis
3) Transplant rejection


Fatty casts ("oval fat bodies")

Nephrotic syndrome


Granular ("muddy brown") casts

Acute tubular necrosis


Waxy casts

End-stage renal disease/chronic renal failure


Hyaline casts

Nonspecific - can be a normal finding, often seen in concentrated urine samples


Diffuse glomerular disorders

> 50% of glomerulus is involved

Diffuse proliferative glomerulonephritis


Proliferative glomerular disorders

Hypercellular glomeruli

Membranoproliferative glomerulonephritis


Membranous glomerular disorders

Thickening of glomerular basement membrane (GBM)

Membranous nephropathy


Primary glomerular disease

A primary disease of the kidney specifically impacting the glomeruli

Minimal Change Disease


Secondary glomerular disease

A systemic disease or disease of another organ system that also impacts the glomeruli

SLE, diabetic nephropathy


Nephritic Syndrome

Due to GBM disruption.

Inflammatory process. When it involves glomeruli, it leads to hematuria and RBC casts in urine.

Associated with HTN (from salt retention), High BUN, High Creatinine, Oliguria (low urine output), hematuria, RBC casts in urine, azotemia.

Proteinuria often in subnephrotic range (


Nephrotic Syndrome

Massive proteinuria (> 3.5 g/day) with hypoalbuminemia, resulting edema, hyperlipidemia.

Frothy urine with fatty casts.

Due to podocyte damage disrupting glomerular filtration charge barrier.

May be primary (direct sclerosis of podocytes) or secondary (systemic process like diabetes secondarily damages podocytes)

Severe nephritic syndrome may present with nephrotic syndrome features (nephritic-nephrotic syndrome) if damage to GBM is severe enough to damage charge barrier.

Associated with a hypercoagulable state/thromboembolism (it causes the state) due to antithrombin (AT) III loss in urine and a higher risk of infection (due to loss of immunoglobulins in urine and soft tissue compromise by edema)

1) Focal segmental glomerulosclerosis (primary or secondary)
2) Minimal change disease (primary or secondary)
3) Membranous nephropathy (prim or second)
4) Amyloidosis (secondary only)
5) Diabetic glomerulonephropathy (secondary only)


Nephritic-Nephrotic Syndrome

Severe nephritic syndrome with profound GBM damage that damages the glomerular filtration charge barrier.

This leads to nephrotic-range proteinuria (> 3.5 g/day) and concomitant features of nephrotic syndrome. Can occur with any form of nephritic syndrome, but most commonly seen with:

1) Diffuse proliferative glomerulonephritis
2) Membranoprolifereative glomerulonephritis


Acute poststreptococcal glomerulonephritis

A nephritic syndrome

LM - glomeruli enlarged and hypercellular
ImmunoF - ("starry sky") granular appearance ("lumpy bumpy") due to IgG, IgM, and C3 deposition along GBM and mesangium
EM - Subepithelial immune complex (IC) humps

Most often seen in children. Occurs about 2 weeks after GAS infection of pharynx OR skin.

Resolves spontaneously

Type 3 hypersensitivity rxn

Presents with peripheral and periorbital edema, cola-colored urine, HTN

High anti-DNase B titers, Low complement levels


Rapidly Progressive (Crescentic) Glomerulonephritis (RPGN)

A nephritic syndrome

LM and IF - crescent moon shape. Crescents consist of fibrin and plasma proteins (C3b) with glomerular parietal cells, monocytes, macrophages

Poor prognosis. Rapidly deteriorating renal function (days - weeks)

Several disease processes may result in this pattern, in particular:

1) Goodpasture Syndrome - Type 2 hypersensitivity; antibodies to GBM and alveolar basement membrane leads to linear Immunofluorescence (IF)


Tx = emergent plasmapheresis

2) Granulomatosis with polyangiitis (Wegener)


3) Microscopic polyangiitis



Diffuse proliferative glomerulonephritis (DPGN)

A nephritic syndrome

Due to SLE or membranoproliferative glomerulonephritis

LM - wire looping of capillaries
EM - subendothelial and sometimes intramembranous IgG-based ICs often with C3 deposition
IF - granular

Most common cause of death in SLE (think "wire lupus")

DPGN and MPGN often present as nephrotic syndrome and nephritic syndrome concurrently.


IgA nephropathy (Berger Disease)

A nephritic syndrome

LM - mesangial proliferation
EM - mesengial IC deposits
IF - IgA based IC deposits in mesangium.

Renal pathology of Henoch-Schonlein purpura

Often presents with renal insufficiency or acute gastroenteritis. Episodic hematuria with RBC casts. Not to be confused with Buerger Disease (thromboangiitis obliterans)


Alport Syndrome

A nephritic syndrome

Mutation in type 4 collagen leads to thinning and splitting of glomerular basement membrane

Most commonly X linked

Eye problems (retinopathy, lens discoloration), glomerulonephritis, sensorineural deafness

"cant see, cant pee, cant hear a buzzing bee"

"Basket-weave" appearance on EM


Membranoproliferative glomerulonephritis (MPGN)

A nephritic syndrome

Type 1 - subendothelial immune complex (IC) deposits with granular IF; "tram track" appearance on PAS stain and H&E stain due to GBM splitting caused by mesangial ingrowth

Type 2 - intramembranous IC deposits; "dense deposits"

MPGN is a nephritic syndrome that often copresents with nephrotic syndrome.

Type 1 may be secondary to Hep B or C infection. May also be idiopathic.

Type 2 is associated with C3 nephritic factor (Stabilizes C3 convertase leading to lower C3 levels in serum)


Focal segmental glomerulosclerosis

A nephrotic syndrome

LM - segmented sclerosis and hyalinosis
IF - nonspecific for focal deposits of IgM, C3, C1
EM - Effacement of foot process similar to minimal change disease

Most common cause of nephrotic syndrome in blacks and Hispanics.

Can be primary (idiopathic) or secondary to other conditions (HIV, sickle cell, heroin abuse, massive obesity, interferon treatment, chronic kidney disease due to congenital malformations)

Primary disease has inconsistent response to steroids. May progress to chronic renal disease


Minimal Change Disease (Lipid Nephrosis)

A nephrotic syndrome

LM - normal glomeruli (lipid may be seen in PCT cells)
IF - negative
EM - effacement (fusion) of foot processes

Most common cause of nephrotic syndrome in children.

Often primary (idiopathic) and may be triggered by recent infection, immunization, immune stimulus.

Rarely, may be secondary to lymphoma (cytokine-mediated damage).

Primary disease has excellent response to corticosteroids


Membranous nephropathy

A nephrotic syndrome

LM - Diffuse capillary and GBM thickening
IF - granular as a result of immune complex deposition. Nephrotic presentation of SLE.
EM - "spike and dome" appearance with subepithelial deposits

Most common cause of primary nephrotic syndrome in white adults.

Can be primary (idiopathic) or secondary to other conditions [antibodies to phospholipase A2 receptor, drugs (NSAIDs and penicillamine), infections (HBV and HCV), SLE, solid tumors]

Primary disease has poor response to steroids. May progress to chronic renal disease.



A nephrotic syndrome

LM - Congo red stain shows apple-green birefringence under polarized light.

Kidney is most commonly involved organ (systemic amyloidosis).

Associated with chronic conditions (multiple myeloma, TB, RA)


Diabetic glomerulo-nephropathy

A nephrotic syndrme

LM - mesangial expansion, GBM thickening, eosinophilic nodular glomerulosclerosis (Kimmelstiel-Wilson lesions)

Nonenzymatic glycosylation of GBM leads to higher permeability and thickening of efferent arterioles. This leads to higher GFR and mesangial expansion.


Kidney stones

Can lead to severe complications, such as hydronephrosis, pyelonephritis.

Presents with unilateral flank tenderness, colicky pain radiating to groin, hematuria.

Treat and prevent by encouraging fluid intake.


Calcium stones


Precipitates at high pH (calcium phosphate)
Precipitates at low pH (calcium oxalate)

XR = radiopaque

Urine crystal = Envelope-or dumbell-shaped calcium oxalate

Oxalate crystals can result from ethylene glycol (antifreeze) ingestion, vitamin C abuse, hypocitraturia, malabsorption (Crohn Disease).

Most common kidney stone presentation: Calcium oxalate stone in patient with hypercalciuria and normocalcemia

Tx = hydration, thiazides, citrate


Ammonium magnesium phosphate stones


Precipitates at high pH

XR = radiopaque

Urine crystal = Coffin Lid

Also known as struvite. Caused by infections with urease (+) bugs - Proteus, Klebsiella, Staph sapro

These bugs hydrolyze urea to ammonia leading to urine alkalinization

Commonly form staghorn calculi

Tx = eradication of underlying infection, surgical removal of stone


Uric acid stones


Precipitates at low pH

XR = radiolucent

Urine crystal = Rhomboid or rosettes

Risk factors: low urine volume, arid climates, acidic pH

Visible on CT and US, but not XR.

Strong association with hyperuricemia (gout)

Often seen in diseases with high cell turnover, like leukemia

Tx = alkalinization of urine, allopurinol


Cystine stones

1 %

Precipitates at low pH

XR = radiolucent

Urine crystal = hexagonal

Hereditary (auto recess) condition in which cysteine-reabsorbing PCT transporter loses function, causing cystinuria.

Cystine is poorly soluble, thus stones form in urine. Mostly seen in children. Can form staghorn calculi.

Sodium cyanide nitroprusside test (+)

SIXtine stones have SIX sides

Tx = alkalinization of urine



Distention/dilation of renal pelvis and calyces

Usually caused by urinary tract obstruction (renal stones, BPH, cervical cancer, injury to ureter)

Other causes include retroperitoneal fibrosis, vesicoureteral reflux

Dilation occurs proximal to site of pathology.

Serum creatinine becomes elevated ONLY if obstruction is bilateral or if patient has only one kidney.

Leads to compression and possible atrophy of renal cortex and medulla


Renal cell carcinoma

Originates from PCT cells going to polygonal clear cells filled with accumulated lipids and carbs.

Most common in men 50-70 years old. Increased incidence with smoking and obesity.

Manifests clinically with hematuria, palpable mass, secondary polycythemia, flank pain, fever, weight loss.

Invases renal vein then IVC and spreads hematogenously; metastasizes to lung and bone.

Tx = resection if localized disease. Immunotherapy or targeted therapy for advanced/metastatic disease. Resistant to chemotherapy and radiation therapy.

Most common primary renal malignancy

Associated with gene deletion on chromosome 3 (sporadic or inherited as von-Hippel-Lindau syndrome)

RCC = 3 letters = chromosome 3

Associated with paraneoplastic syndromes (ectopic EPO, ACTH, PTHrP)

"Silent" cancer bc commonly presents as a metastatic neoplasm


Renal oncocytoma

Benign epithelial cell tumor

Large eosinophilic cells with abundant mitochondria without perinuclear clearing (vs Chromophobe renal cell carcnoma)

Presents with painless hematuria, flank pain, abdominal mass

Often resected to exclude malignancy (eg RCC)


Wilms Tumor (Nephroblastoma)

Most common renal malignancy of early childhood (age 2-4)

Contains embryonic glomerular structures

Presents with large, palpable, unilateral flank mass and/or hematuria. Loss of function mutations of tumor suppressor genes WT1 or WT2 on chromosome 11.

May be part of Beckwith-Wiedmann syndrome (Wilms tumor + macroglossia + organomegaly + hemihypertrophy)

OR WAGR complex (Wilms + Aniridia + GU malformation + retardation)


Transitional Cell Carcinoma

Most common tumor of urinary tract system (can occur in renal calyces, renal pelvis, ureters, and bladder)

Painless hematuria (no casts) suggests bladder cancer

Associated with problems in your Pee SAC: Phenacetin (an analgesic drug), Smoking, Aniline dyes, and Cyclophosphamide


Squamous cell carcinoma of the bladder

Chronic irritation of urinary bladder leads to squamous metaplasia leading to dysplasia and squamous cell carcinoma

Risk factors include Schistosoma haemotobium infection (middle east), chronic cystitis, smoking, chronic nephrolithiasis

Presents with painless hematuria


Urinary tract infection (acute bacterial cystitis)

Inflammation of urinary bladder

Presents as suprapubic pain, dysuria, urinary frequency, urgency.

Systemic signs (high fever, chills) are usually absent

Risk factors include female gender (short urethra), sexual intercourse (honeymoon cystitis), indwelling catheter, diabetes mellitus, impaired bladder emptying


1) E Coli (#1)
2) Staph sapro - seen in sexually active young women (E coli is still more common in this group tho)
3) Klebsiella
4) Proteus - urine has ammonia scent

Lab findings:
(+) leukocyte esterase
(+) nitrites for gram (-) organisms (esp E Coli)

Sterile pyuria and (-) urine cultures suggest urethritis by N. Gonorrhae or Chlamydia


Acute Pyelonephritis

Neutrophils infiltrate renal interstitium. Affects cortex with relative sparing of glomeruli/vessels.

Presents with fevers, flank pain (CVA tenderness)

Causes include ascending UTI (E Coli most common), hematogenous spread to kidney.

Presents with WBCs in urine +/- WBC casts. CT shows striated parenchymal enhancement

Risk factors: Indwelling catheter, urinary tract obstruction, vesicoureteral reflux, diabetes mellitus, pregnancy

Complications include chronic pyelonephritis, renal papillary necrosis, perinephric abscess, urosepsis

Tx = antibiotics


Chronic Pyelonephritis

The result of recurrent episodes of acute pyelonephritis.

Typically requires predisposition to infections such as vesicoureteral reflux or chronically obstructing kidney stones

Coarse, asymmetric corticomedullary scarring, blunted calyx. Tubules can contain eosinophilic casts resembling thyroid tissue (thyroidization of kidney)


Drug-induced interstitial nephritis (tubulointerstitial nephritis)

Acute interstitial renal inflammation. Pyuria (classically eosinophils) and azotemia occurring after administration of drugs that act as haptens, including hypersensitivity.

Nephritis usually occurs 1-2 weeks after certain drugs (diuretics, penicillin derivatives, proton pump inhibitors, sulfonamides, rifampin), but can occur months after starting NSAIDs

Associated with fever, rash, hematuria, and CVA tenderness, but can be asymptomatic


Diffuse cortical necrosis

Acute generalized cortical infarction of both kidneys. Likely due to a combination of vasospasm and DIC

Associated with obstetric catastrophes (abruptio placentae), septic shock


Acute tubular necrosis

Most common cause of acute kidney injury in hospitalized patients. Can be fatal, especially during initial oliguric phase. Increased FENa

Key finding*** = granular ("muddy brown") casts

3 stages

1) Inciting event
2) Maintenance phase - oliguric; lasts 1-3 weeks; risk of hyperkalemia, metabolic acidosis, uremia
3) Recovery phase - polyuric; BUN and serum creatinine fall; risk of hypokalemia

Can be caused by ischemic or nephrotoxic injury

1) Ischemic - secondary to lower renal blow flow (hypotension, shock, sepsis, hemorrhage, HF). Results in death of tubular cells that may slough into tubular lumen (PCT and thick ascending limb are highly susceptible to injury)

2) Nephrotoxic - secondary to injury resulting from toxic substances (aminoglycosides, radiocontrast agents, lead, cisplatin), crush injury (myoglobinuria), hemoglobinuria. PCT is particularly susceptible to injury


Renal papillary necrosis

Sloughing of necrotic renal papillae leads to gross hematuria and proteinuria. May be triggered by recent infection or immune stimulus. Associated with sickle cell disease or trait, acute pyelonephritis, NSAIDs, diabetes mellitus

SAAD papa with papillary necrosis

S= Sickle Cell disease or trait
A = Acute pyelonephritis
A = Analgesics (NSAIDs)
D = Diabetes mellitus


Acute Kidney Injury (Acute Renal Failure)

Acute kidney injury is defined as an abrupt decline in renal function as measured by increased creatinine and increased BUN


Prerenal azotemia

Due to lower RBF (hypotension)

This leads to lower GFR

Na/H2O and BUN retained by kidney in an attempt to conserve volume. This leads to increased BUN/creatinine ratio (BUN is reabsorbed, creatinine is not) and lower FENa


Intrinsic renal failure

Generally due to acute tubular necrosis (ATN) or ischemia/toxins; less commonly due to acute glomerulonephritis (e.g. RPGN, hemolytic uremic syndrome).

In ATN, patchy necrosis leads to debris obstructing tubule and fluid backflow across necrotic tubule leading to lower GFR.

Urine has epithelial/granular casts

BUN reabsorption is impaired leading to lower BUN/Creatinine ratio.


Postrenal azotemia

Due to outflow obstruction (stones, BPH, neoplasia, congenital anomalies)

Develops only with bilateral obstruction


Acute renal failure table

1) Prerenal
- Urine osmolality > 500
- Urine Na 20

2) Intrinsic Renal
- Urine osmolality 40
- FENa > 2%
- Serum BUN/Cr 40
- FENa > 1% (mild), > 2% (severe)
- Serum BUN/Cr varies


Consequences of renal failure

Inability to make urine and excrete nitrogenous wastes.

Consequences (MAD HUNGER)
MA = Metabolic Acidosis
D = Dyslipidemia (esp high TGs)
H = Hyperkalemia
U = Uremia - clinical syndrome marked by:
High BUN
- Nausea and anorexia
- Pericarditis
- Asterixis
- Encephalopathy
- Platelet dysfunction
N = Na/H2O retention (HF, pulmonary edema, HTN)
G = growth retardation and developmental delay
E = Erythropoietin failure (anemia)
R = Renal osteodystrophy

2 forms of renal failure: acute (ATN) and chronic (HTN, diabetes mellitus, congenital anomalies)


Renal osteodystrophy

Failure of vitamin D hydroxylation, hypocalcemia, and hyperphosphatemia leading to secondary hyperparathyroidism.

Hyperphosphatemia also independently lowers serum Ca by causing tissue calcifications, whereas low 1,25-(OH)2D3 leads to lower intestinal Ca absorption.

Causes subperiosteal thinning of bones


List the Renal cyst disorders

3) Medullary cystic disease



Formerly adult polycystic kidney disease. Numerous cysts causing bilateral enlarged kidneys ultimately destroy kidney parenchyma. Presents with flank pain, hematuria, HTN, urinary infection, progressive renal failure

Autosomal Dominant (AD for ADPKD)

Mutation in PKD1 (85% of cases, chromosome 16) or PKD2 (15% of cases, chromosome 4).

Death from complications of chronic kidney disease or HTN (caused by higher renin production).

Associated with berry aneurysms, mitral valve prolapse, benign hepatic cysts.



Formerly infantile polycystic kidney disease. Presents in infancy. Auto recessive (AR for ARPKD)

Associated with congenital hepatic fibrosis. Significant oliguric renal failure in utero can lead to Potter Sequence. Concerns beyond neonatal period include systemic HTN, progressive renal insufficiency, and portal HTN from congenital hepatic fibrosis


Medullary cystic disease

Inherited disease causing tubulointerstitial fibrosis and progressive renal insufficiency with inability to concentrate urine.

Medullary cysts usually not visualized; shrunken kidneys on ultrasound

Poor prognosis


Simple vs Complex renal cysts

Simple cysts are filled with ultrafiltrate (anechoic on ultrasound - black). Very common and accounts for majority of all renal masses. Found incidentally and typically asymptomatic.

Complex cysts, including those that are septated, enhanced, or have solid components on imaging require follow-up or removal due to risk of RCC.