TubuloInterstitial Disease and PCKD Flashcards
How does the protein loss associated with tubulointerstitial disease differ from the nephrotic protein loss?
TIN predominantly loses LMW proteins like B2-microglobulin instead of albumin
TIN can have isolated tubular defects and urinary concentrating defects. What would be the clinical presentations of those?
Tubular defects: glycosuria proteinuria aminoaciduria K wasting OR retention RTA
Urinary concentrating defects:
polyuria
nocturia
What is the effect of TIN on urinary Na, urine concentration and body volume?
It enhances Na wasting, the urine is dilute and the body volume is depleted
What metablic disorder is often associated with TIN?
NG metabolic acidosis due to defective ammoniagenesis in the tubules
You do a urinalysis and see RBC, RBC casts, proteinuria and granular casts. What is the likely cause of the disease : nephritic, nephrotic or interstitial?
Nephritic
You do urinalysis and see heavy proteinuria, fatty casts, oval bodies, and free fat droplets. Is this nephrotic, nephritic or interstitial?
Nephrotic
You do urinalysis and see WBC casts, sterile pyuria, eosinophiluria, low grade proteinuria, hematuria. Nephritic, nephrotic or interstitial?
Interstitial
Primary Na retention Low urinary Na hypertension CHF edema severe reduction in GFR
Nephritic, nephrotic, interstitial?
Nephritic
Secondary Na retention low urinary Na \+/- hypertension edema less severe reduction in GFR
Nephritic, nephrotic, interstitial?
nephrotic
impaired urine concentration
hyperkalemia
RTA (type IV)
Na wasting
Nephritic, Nephrotic, interstitial ?
Interstitial
What if Fanconi syndrome?
The clinical presentation of myeloma where there is disruption of the proximal tubule resulting in:
- RTA
- Glycosuria
- Phopsphate wasting, Uricosuria
What is the functional defect of a proximal tubule defect in Interstitial renal disease?
What is the syndrome?
Decreased reabsorption of HCO3, glucose, aminoacids, phosphate, uric acid
=
Fanconi syndrome
What are the functional defects of distal nephron interstitial renal disease?
decreased Na reabsorption, impaired K and H excretion –> RTA 4
What are the functional defects of the loop in interstitial renal disease?
- decreased Na reabsorption leading to salt wasting.
2. nephrogenic DI
What are the functional defects of the interstitium in TIN?
decreased epo—> anemia
decreased gradient so can’t concentrate urine
What is the most common cause of acute interstitial nephritis (non-infectious)?
How does it manifest?
Acute-Allergic drug reaction - a hypersensitivity reaction to a medication like antibiotic, NSAID, diuretic
The patient gets a rash, pruritis, eosinophilia and fever [ABSENT RESPONSE W NSAIDS]
What are indications for biopsy when acute allergic TIN is suspected?
- diagnostic uncertainty
- advanced kidney failure
- lack of spontaneous recovery after drug removal
How is acute allergic TIN treated?
- withdraw inciting medication
- corticosteroids if there is aggressive disease (worsening azotemia).
If biopsy shows acute inflammation in the absence of chronic damage, cortico will be more effective
What does the urinary sediment for acute allergic TIN show?
RBC, WBC, WBC casts
How does acute TIN from NSAIDs differ from TIN from antibiotics or diuretics?
NSAIDs will not have rash, fever etc but will have large amounts of proteinuria.
It looks like MCD with concurrent tubulointerstitial inflammation
What two renal syndromes are NSAIDs associated with?
- ATN when the patient has decreased EABV
2. TI renal disease with nephrotic proteinuria
What are clinical signs of chronic TIN?
What is seen in the urine?
It is a syndrome of CKD that progressed to ESKD where older women are at highest risk
- polyuria
- nocturia
Urine will have bland sediment, low urine protein (and the proteins will be LMW like b2 microglobulin, tamm-horsfall, and light chains)
What is seen on ultrasonography and biopsy for chronic TIN?
Ultrasonography- atrophic echogenic kidneys with CKD
Biopsy-
- lymphocytic infiltrate
- fibrosis in interstitium
- tubular atrophy
- arteriosclerosis
- global glomerulosclerosis
What drugs cause chronic TIN?
Chinese herbs, lithium, cyc A, ANALGESICS
What are the metabolic situations that can cause chronic TIN?
uric acid/oxalate deposition
chronic hypokalemia (which upregulates ammoniagenesis)
nephrocalcinosis
What immunologic situations cause chronic TIN?
Sjogrens, SLE
What are the two most prominent histologic features of analgesic nephropathy?
- vascular lesions
- papillary necrosis
Due to prolonged ingestion of analgesic mixtures (phenacetin and aspirin)
The findings of analgesic nephropathy are relatively non-specific. (they present like any other chronic TIN). So what are the frequent findings that point in this direction?
- women 30-70
- questioning of chronic back pain/ headaches
- soreness
What is the pathogenesis by which lead causes chronic TIN?
Lead is reabsorbed in the proximal tubule and accumulates in the proximal tubule cells.
The histological findings show intranuclear inclusion bodies with lead-protein complexes
A patient presents with classic symptoms of chronic TIN. (glycosuria, dilute urine, etc). However, they have hyperuricemia, hypertension and gout. what does this make you suspicious of?
Lead nephropathy because it is the only one with hyperuricemia
A patient presents with chronic TIN. They have type 1 RTA and nephrogenic diabetes insipidus. They have dry eyes and dry mouth. What is suspected?
Sjogren’s syndrome
What is myeloma kidney?
Cast nephropathy which refers to acute or chronic renal failure resulting from filtration of toxic light chains leading to tubular injury (direct) and intratubular cast formation (obstruction)
Why does volume depletion increase the likelihood of light chain nephropathy?
It is a TIN that damages tubules and forms intratubular casts.
If there is volume depletion, there will be slower flow allowing the concentration of light chain to increase promoting aggregation
What would you see in the interstitium in a patient with cast nephropathy?
Macrophages with formation of giant cells
What test confirms multiple myeloma?
SSA test will precipitate non-albumin proteins including light chains
Which part of the tubule is most -affected by myeloma-related kidney disorders?
Proximal—> fanconi syndrome
What gene is mutated in ADPKD1 and 2?
Which presents earlier/is more severe?
ADPKD1- mutated polycystin (plasma protein in most cystic epithelia) on chrom 16
ADPKD2 - mutated polycystin 2 (ca cell signaling)
ADPKD1 presents earlier
A patient presents with flank pain, abdominal mass, gross hematuria. they frequently present with UTIs and uric acid stones.
They are hypertensive. Their parent had kidney problems. What is a suspicion?
PKD
Where else can cysts form with ADPKD?
What is the effect on the heart?
What is the usual cause of death for a person with ADPKD?
Liver, pancreas spleen
Heart- hypertrophied LV, MVP
bursting berry aneurysm in the circle of willis
ARPKD presents at what age? Describe the cysts.
It presents early in childhood. There is a high rate of infant mortality
There are many oval cysts that run parallel to each other and perpendicular to the poles of the kidney
What two situations will have BUN/Cr ratios over 20?
- Pre-renal
2. Acute GN
