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Flashcards in Renal Diseases Deck (66):


scarring/luminal narrowing in afferent arteriole that causes ischemia of the nephron, resulting in global glomerular sclerosis


IgA Nephropathy

aka Berger disease.
Underglycosylated IgA (from genetic defect) is made during course of an infection; IgA is able to get from circulation out into the mesangium (because it's not as negatively charged as it should be); phagocytosis of IgA by podocytes activates the podocytes and they produce more ECM, thickening the mesangial matrix.


Goodpasture syndrome

Antibodies are formed against GBM and are deposited in the subendothelium. They circulate before being deposited so they can be removed via plasmapharesis.


Membranous nephropathy

Either antibodies attack antigens in podocytes (PLA2R or NEP), or cationic ICs deposit in subendothelial space.
This leads to thickening of GBM: spike and dome and granular on IF. Treatment depends on degree of proteinuria - 4g control BP and use cytotoxic agents (CIs)


Post-streptococcal/infectious glomerulonephritis (PIGN)

antibodies formed against exotoxin B from strep pyogenes (~1-3wks post-skin/throat infection) are then deposited on antigens that are planted in the basement membrane; forms subepithelial humps, lumpy-bumpy granular appearing deposits on IF stain, and NT infiltration/hypercellularity; treatment - control HTN and treat infection


Metabolic/diabetic glomerular injury

glycosylation of GBM proteins and plasma proteins that get deposited in the GBM damages it; some glycosylations are metabolized to "Advanced Glycated End-products", or AGE which leads to accelerated aging of organs. Will also get NADPH oxidase activation (by advanced oxidation protein products (AOPPs), RAAS, TGF-beta, and ROS) which leads to mesangial activation/matrix production and podocyte injury/apoptosis, and proteinuria. Start with sclerosis of efferent, raise GFR --> hyper filtration, microalbuminemia at first, then continued damage. Treat with ACEi's.


Membranoproliferative glomerulonephritis

membrano = GBM expansion
proliferative = hypercellular (proliferating native glomerulus cells as well as inflammatory infiltration)
glomerulonephritis = inflammation of the glomerulus


Malignant Hypertension

hypertension that causes end-organ damage - from thickening of the artery intima and basement membrane, ultimately cutting off blood supply to the downstream organ tissue


Nephrotic syndrome

glomerular disease that leaks protein; consists of 3 features:
1. thicker basal lamina but functionally leaky
2. hypoalbuminemia - because it's escaping through the leaky GBM
3. low oncotic pressure - results in edema


Focal Segmental Glomerulosclerosis (FSGS)

damaged adhesion proteins in podocytes degenerate, maybe due to sUPA-R, familial mutations in adhesion proteins (alpha-actinin-4, podocin, TRPC6), or drugs, infection (HIV/PVV), and nephron loss; highly associated with ApoL1 mutation; will see hyalinosis, perhaps adhesion to Bowman's and glomerular collapse.
Treat with GC and control HTN/HLD.


Minimal Change Disease (MCD)

suspected: T cells make a circulating factor (not an Ab because IF is negative) that causes podocyte damage and highly selective proteinuria (albuminuria); may be 2/2 Hodgkin's lymphoma or drugs. Treatment with HTN/HLD control, tx primary disease; usually great response to GCs



IGs, complement, and RF precipitate at cold temperatures and cause clinical sx of hyperviscosity and/or thrombosis; ICs deposit in endothelial, subendothelial, and mesangial layers--causing MPGN; treat underlying cause (Hep C, HIV, AI disease, MM, etc.)


HIV-associated nephropathy (HIVAN)

direct infection of podocytes by HIV (G1/2 ApoL1 mutation more susceptible); collapsing glomeruli with FSGS, microcystic tubular dilation, interstitial inflammation/fibrosis, and podocyte proliferation; can treat/reduce with anti-virals


Light Chain Disease (LCD)

non-amyloid monoclonal IG deposition/precipitation often associated with MM or other lymphoproliferative disease; causes nephrotic syndrome or RP-TIN; will see glomerulosclerosis with mesangial expansion. Congo red negative without fibrils.


Amyloidosis in kidney

deposition of mis-folded fibril proteins in the vessel wall, then interstitium, eventually organ infarction; non-proliferative, non-inflammatory glomerulopathy; tubular atrophy and interstitial fibrosis; “apple-green” on Congo red stain under polarized light; can treat with low dose melphalan and dexamethasone (AL)
eprodisate (AA)


Sickle cell nephropathy

vaso-occlusion of glomerulus, peritubular capillaries → infarction/necrosis, hemorrhage, glom. hyperfiltration, patient will have SCD, glomerular HTY and mesangial expansion, segmental sclerosis


Hereditary Renal Glycosuria

LOF mutation in SGLT2 (PT) that reduces glucose reabsorption, resulting in mild-moderate glycosuria. Can functionally occur when SGLT2 is saturated by the large amount of glucose, such as in diabetes.



LOF mutation of (PT) amino acid transporter, normally reabsorbs cystine, ornithine, lysine, and arginine; can lead to cystine stones (hexagons)


Defective Phosphate reabsorption

normally: PHEX inhibits FGF-23 which inhibits P reabsorption.
1. LOF in FGF-23 or GOF in PHEX: too much P reabsorption; hyperphosphatemia
2. GOF in FGF-23 or LOF in PHEX: too much inhibition of P reabsorption; hypophosphatemia (rickets)


X-linked hypophosphatemia

(think pheX = X-linked)


AD hypophosphatemic rickets

GOF in FGF-23


AR hypophosphatemic rickets

several mutations that add up to too much FGF-23, OR defect in Na/P co-transporter


Oncogenic hypophosphatemic Osteomalacia

increased FGF-23 production by some tumors



softening of the bones - when you have too little phosphorous (as in rickets or FGF-23 overproduction) then you reduce PTH (because PTH decreases P reabsorption) which prevents Ca reabsorption; softens bones
*this condition is called rickets in children


Hartnup disease

SLC 6A19 defect - transporter for neutral amino acids; symptoms are failure to thrive, photosensitivity, intermittent ataxia, nystagmus, tremor


Vitamin D dependent rickets - type I

defect in 1-alpha-hydroxylase (PT) preventing VitD activation; results in hypophosphatemia


Defects in uric acid handling

- defective reabsorption, leads to hypouricemia and uric acid stones
- defective secretion, leads to hyperuricemia and gout


Fanconi syndrome

generalized PT dysfunction, from different things (like impaired Na binding to transport proteins or mitochondrial dysfunction/little ATP); most commonly acquired (tenofovir, MM, heavy metals but genetic causes include lysosomal storage disorders (cystinosis), mitochondrial disorders, etc.; results in electrolyte wasting, polyuria/polydypsia, hypovolemia, metabolic acidosis, arrhythmias


Dilutional Hyponatremia

plasma is diluted because more water has moved into it because there are more osmotically active solutes there, e.g. increased glucose without insulin, or administered mannitol


True Hyponatremia

impaired urine dilution mechanisms - water retained and plasma is diluted; may be due to:
-decreased GFR
-thiazide diuretics blocks NaCl reabsorption in DCT and since water can only leave after that, it can't get any more dilute, so you lose more Na than H2O
-too much ADH/AQPs, reabsorb to much water



gain of Na into circulation (hypernatremia); causes include:
-Hyperaldosteronism/Cushing's: ALD upregulates ENaC and NaCl co-transporter
-renal water losses, such as in DI (doesn't respond to ADH) and osmotic diuresis (mannitol)
-extrarenal water losses


Nephrogenic DI

kidney-level resistance to ADH/vasopressin/AVP; causes include:
-X-linked V2R mutation (LOF)
-AQP2 mutation
-can't generate medullary gradient
-defective cAMP generation
-AQP2 downregulation
-pregnancy (placental synthesis of vasopresinase)


Kidney stones - precipitating factors

1. increased filtered load - such as in increased salt intake
2. decreased reabsorption of filtered load - such as in congenital reabsorption defects
3. increased reabsorption of water - such as in dehydration
4. decreased urine solubility - pH can affect, as can lack of stone inhibitors, like citrate (prevents Ca stones), Tamm-Horsfall mucoprotein (aka uromodulin), nephrocalcin, and uropontin.
*stones also tend to form around foreign bodies, like around bacteria or around uric acid nidus (Ca stones especially)


Calcium oxalate stones

- 60% - most common
- look like envelopes or squares with 4-sided stars
- caused by hypercalcemia - could be exogenous (too much Ca intake, loop diuretics, or malabsorption of oxalate) or endogenous (inc. PTH, sarcoid, idiopathic)
- pH independent
- treatment: don't take Ca supplements, but don't limit Ca intake, inc. water intake, limit animal protein, may try thiazides or K citrate


Uric acid stones

- 10%
- look like diamonds/rhombi and are radiolucent (not visible)
- caused by hyperuricemia - exogenous (dietary purines, gout) or endogenous (cell turnover/TLS, enzyme defects, or transporter defects)
- acidic urine - more likely to form
- treatment: increase water intake, decrease animal protein, allopurinol, K citrate


Struvite stones

- 15%
- look like coffin lids
- caused by too much ammonia, commonly with infection of UUT with urease-producing bacteria (commonly proteus, klebsiella) because urease breaks urea down into ammonia + CO2
- alkaline pH promotes stone formation
- treatment: clear the infection, increased fluid intake


Cystine stones

- rare - 1%
- look like hexagons
- caused by inherited defect in PT cystine transporter, so increased cystine wasting, and cystine is not very soluble
- alkaline pH promotes cystine solubility
- treatment: K citrate to make urine more alklaline


Clinical presentation of kidneys stones

- usually men in the summer
- flank pain that radiates into groin or moves down over a few hours, pt may be writhing in pain
- may be accompanied by N/V, feeling of urinary urgency, usually gross hematuria, may also have crystals in urine
- STONE score: sex, timing, origin, nausea, erythrocytes
- CTs good for seeing stones but have disadvantages; will see hydronephrosis on US


General treatment for kidney stones

- if non-infectious: don't usually need to treat beyond drink lots of water; try to catch stones for analysis
- NSAIDs good for pain
- 7mm may need intervention
- can also give Alpha-1 antagonists/CCBs to relax bladder
- want to avoid complications of obstruction and infection (together = medical emergency)


Urinalysis characteristics of:
- nephrotic syndrome
- nephritic syndrome
- mixed nephrotic/nephritic syndrome
- tubular injury
- mesangial

- nephrotic syndrome = heavy proteinuria and lipiduria
- nephritic syndrome = hematuria, often RBC casts (w/wo proteinuria, but not much)
- mixed nephrotic/nephritic syndrome = hematuria (w/wo RBC casts) and heavy proteinuria
- tubular injury = hematuria (from peritubular capillaries) and granular casts (renal tubular epithelial cells), dilute urine (tubules can't concentrate it)


What does specific gravity of 1.010 mean?

it means the osmolarity of urine is about 300mOsm, which is about the same as plasma, indicating the urine was neither concentrated nor diluted, so there's tubular dysfunction
*maximum dilute urine has SG of 1.002 (~50mOsm), maximum concentrated urine has SG of 1.030 (~1200mOsm)


Types of tubular injury

1. non-inflammatory - no pyuria, due to ischemia/ATN or aminoglycosides
2. inflammatory - sterile pyuria from inflammatory cell infiltration, such as in allergic interstitial nephritis
3. pyelonephritis - pyuria from infected tubules
4. obstructive uropathy - tubule cell injury, tubular urine w/wo RBC (depending on +/- tumor/trauma)


Presence of nitrites and leukocyte esterase in urine means what?

- we normally excrete nitrates, but if bacteria are present in the urinary tract they can reduce the nitrates to nitrites
- we don't normally have any leukocyte esterase, a NT specific enzyme, because we don't normally have any NTs in urine, but we do in UTI


Glomerular vs. Tubular proteinuria

*protein usually very low in urine
- nephrotic range proteinuria = 3+-4+ and indicates glomerular dysfunction (will usually see albumin)
- LMW proteins in urine indicates either: PT dysfunction (supposed to reabsorb little proteins that get through) or excess protein production (overwhelmed the reabsorption capacity, such as in MM, LCD)--here will see positive sulfosalicylic acid test when light chains precipitate


Renal vs. Extra-renal origin of hematuria

- renal - means that RBCs are getting through the glomerulus, so will see dysmorphic RBCs, casts, and proteinuria
- extra-renal - means that RBCs are coming from lower in the urinary tract, so will see in tact RBCs, no casts, and maybe some clots but not likely proteinuria


Maltese crosses associated with

accompanied by proteinuria


Muddy brown granular casts associated with

ATN!!; made of degenerated renal tubular epithelial cells that were sloughed off after ATN; in this case may also see the renal tubular epithelial cells, looks like hard-boiled egg cut in half


Acute Kidney Injury

rise in blood Creatinine in hours-days; first decide if pre-renal, intrinsic, or post-renal
Pre-renal: high urine osmolarity and spec. gravity; low urine Na and low FeNa; BUN:Cre >20; hyaline casts (not specific)
Intrinsic: low urine osmolarity and spec. gravity; high urine Na; BUN:Cre


3 specific types of pre-renal AKI

1. hepatorenal syndrome - portal HTN causes inc. RAAS and Na retention --> high ECFV but low BP
2. RAS in combination with ACEi/ARBs - these drugs prevent efferent constriction so kidney can't compensate to raise GFR
3. drugs that impair autoregulation, such as NSAIDs - they prevent PG synthesis, which would normally dilate afferent arteriole


Causes of ATN

1. drugs - aminoglycosides (accumulation/inhibition in lysosomes), amphotericin B
2. IV contrast - directly tubulotoxic, and vasoconstricts afferents


Acute interstitial nephritis (AIN)

- allergic reaction to: abx (penicillins, cephalosporins, sulfas)/NSAIDs which act as haptens and set off immune response; components of the interstitium (tubular BM, tubular secretions, or immune complexes); molecular mimicry to infectious agents; or transplant rejection
- damage to/necrosis of tubular cells exposes interstitium resulting in inflammation/infiltration of granulocytes (esp. NTs & eosinophils) causing pyuria/hematuria and decreased renal function (inc. Cre)
- presenting with classic triad of fever, rash, and eosinophilia; may also see proteinuria (little)


Causes of chronic interstitial nephritis (CIN)

long-term analgesic use causing chronic interstitial nephropathy and hematuria; aristolochic acid (as in exposure in contaminated chinese herbs); Balkan endemic (very similar, thought related to aristolochic acid - may also represent uroepithelial tumor)


Cystic renal disease

Including PKD and nephronophthisis
- AD (adult) PKD mutated polycystin-1 or -2, resulting in ciliopathy: defective cell adhesion and mechanosensing of urine; slow-growing cysts causing ischemic atrophy; 2nd hit needed for cyst
- AR (childhood) PKD: mutated fibrocystin (cilia protein, unknown function); cysts replace fetal tissue; usually fatal because lungs fail at birth
- Nephronophthisis: AR due to ≥9 mutations for cilia components, leads to medullary cysts and ESRD in kids


Myeloma kidney

associated with MM; many eosinophilic often fractured casts in medullary distal nephron; also causes MPs/giant cells and interstitial inflammation, fibrosis, tubular atrophy, crystalline inclusions


Rapidly Progressive Glomerulonephritis

It's what other kidneys problems can develop into in a matter of weeks to months; it makes crescents in bowmans space--made of fibrin and macrophages.


Aminoglycosides and nephrotoxicity

these abx cause direct toxicity to the interstitium as well as tubular cell necrosis; will see increased Cre and hypokalemia (unique to this drug/TIN)


Bartter's syndrome

AR LOF mutation in either: NKCC, Cl channel, or ROMK in TAL cell; causes increased delivery to DT and hypokalemia, high renin/ALD, and Na wasting, low Mg


Gitelman's syndrome

LOF mutation in NaCl co-transporter in DT; causes Na wasting but not as much as in bartter's syndrome, hypokalemia, high renin/ALD, HYPERCALCEMIA, low Cl and Mg


Liddle's syndrome

ENaC is always open; get hypernatremia, negative lumen, and hypokalemia/metabolic acidosis, low renin/ALD; treat with triamterene/amiloride


RTA Type 4

hypoaldosteronism: either adrenal gland doesn't produce it, or the kidneys are insensitive to it; results in urine pH


RTA Type 1

can't secrete protons in the DT (problem with alpha cells) so have pH >5.5 and hypokalemia; basic urine increases risk of Ca-P stones; associated with Amphotericin and analgesic use, as well as MM


RTA Type 2

can't reabsorb bicarbonate in the PT, so get acidemia; urine pH can stay about normal; often associated with poor phosphate reabsorption as well (Rickets) and Fanconi syndrome


Gordon's syndrome

normal pathway: Wnk1 --| Wnk 4 --| NaCl co-transporter
GOF in Wnk 1 or LOF in Wnk 4 = too much NaCl reabsorption, resembles Liddle's Syndrome or hyeraldosteronism (hence Gordon's is a pseudo-hyperaldosteronism)


Pathophysiology of HTN secondary to hyperaldosteronism

- ALD excess
- GC excess, as in Cushing's
- 11-BHD deficient or overwhelmed
All of the above make the CD principal cells react as they would to lots of ALD, which increases the amount of ENaC, ROMK, and Cl channels. Increased Na reabsorption raises the BP. Can treat with triamterene/amiloride.


Acute Tubular Necrosis (ATN)

- muddy brown granular casts in urine from dead tubular cells
- will also see lots of Na in urine because it can't be reabsorbed; also oliguria because body will decrease GFR to prevent Na/H2O wasting
- MCC is ischemia or toxic agent (drug, heavy metals)
- treat by restoring perfusion, removing toxin, and supportive care


Causes of hyperphosphatemia

- in CKD, GFR is decreased, but it takes a while for P reabsorption to also decrease and catch up to new (lower) GFR, so for a while you get hyperphosphatemia
- increased reabsorption of P can also be caused by low PTH (inhibited by high calcitriol), high PHEX, low FGF-23