Tubulointerstitial Disease II Flashcards
What qualifies as acute kidney injury?
• over a period of: 6hrs, 48 hrs, 7 days?
6 hrs:
• less than 0.5 mL/Kg per hour for 6 hours
48 hrs:
•0.3 mg/dL over a 48 hour period
7 days:
• 1.5 times the baseline
What are the 3 major things to look for to determine whether damage is Pre-Renal or Post-Renal?
• subcategories?
ABILITY TO CONCENTRATE URINE:
Fractional Excretion of Na+
• less than 1% = Pre-Renal
• more than 2% = ATN
Urine Na+ concentration
• less than 20 = Pre-renal
• greater than 40 = ATN
Urine Specific Gravity
• greater than 1.018 = pre-renal
• Less than ~1.010 = ATN
GFR:
BUN/Creatinine
• Greater than 20 = pre-renal
• Less than 10-15 = ATN
UNINARY SEDIMENT:
Pre-renal = hyaline casts
ATN = Muddy Brown Granular Casts
What is a good way of determining where injury has occurred Tubular Dysfunction?
• See what is being peed out or what you lack in the serum
What would you expect to see in the urine in proximal tubular injury?
- AMINO ACIDS
- HCO3-
- GLUCOSE
- Protein
- Uric acid
What problems would result from distal tubular injury?
- Potassium
* Hydrogen (acidosis)
What effect does low GFR have on sodium balance?
• Low GFR = POSITIVE Na+ balance because
Acute Intersitial Nephritis
• cells mediating?
• Dose Dependence?
• Recurrence risk?
Cells:
• Immune Mediated Reaction
Dose Dependence:
• NOT DOSE DEPENDENT
Recurrence Risk:
• WILL recur on Re-Exposure
What proteins provide the antigenic stimulus for Acute Interstitial Nephritis?
- Tubular Basement Membrane
- Secreted Tubular Proteins
- Non Renal Proteins (immune complexes)
What causes the immune system to become activated against Tubular Basement Membrane, Secreted Tubular Proteins, and Non-renal proteins in Acute tubular NEHPRITIS?
Drugs or Infectious agents may act:
• as antigens themselves
• as haptens to modify immunogenicity of native renal proteins
• Molecular Mimickery
• Circulating Immune complex precipitation
What Immune Cells are the predominant mediators of Acute Interstitial NEPHRITIS?
• cytokines that play a major role?
• MONONUCLEAR cells, mostly T-CELLS
Cytokines:
• TGF-ß = major cytokine
How do people typically present with ACUTE TUBULAR NEPHRITIS?
• Vignette?
• Signs?
Vignette:
• Started a NEW DRUG 3 wks ago, with a SUDDEN ONSET of renal insufficiency
Signs:
• Hematuria, Sterile Pyuria, Eosinophiluria
Hemolysis and hepatitis may also be present
What drugs are common causative agents in acute drug-induced interstitial Nephritis?
- SYNTHETIC PENICILLINS
- NSAIDs
- PROTON PUMP INHIBITORS
(NSAIDs and H+ inhibitors don’t cause disease in a great percentage of pts., but there wide use makes this rxn common)
Others:
• Rifampin, ciprofloxacin, Diuretics - THIAZIDES, Allopurinol, Cimetidine
What sign should tip you off than an NSAID caused the Acute Interstitial Nephritis?
• who is this most common in?
- PROTEINURIA - this is b/c NSAIDs cause glomerular damage
- Elderly Population experiences this
***Note: you would expect to see an inability to concentrate urine, along with evidence of protein to imply glomerular damage.
What is the most common infectious cause of Acute Interstitial Nephritis?
• Viral Infections
pretty much any bacteria of infectious agent can cause this
AMINOGLYCOSIDE NEPHROTOXICITY
• how does the mechanism of toxicity differ from toxicity of Penicillins, NSAIDs, and Proton pump inhibitors?
• How does it gain access to the area that is causes pathology in?
How does it differ:
• Penicillins, NSAIDs, H+ pump blockers are all toxic to the interstitium
• Aminoglycosides DIRECTLY affect the PROXIMAL TUBULE
Hoes does it get access:
• Megalin pump transports the CATIONIC A.G. into the Tubular cells
What key labs would tell you that aminoglycosides have caused tubular damage and not some other process?
- Glucosuria
- Drop in GFR with HYPOkalemia
This can be explained by the fact that it acts on the PROXIMAL tubule preventing glucose and Na+ reabsorptionFailure to reabsorb Na+ means more gets to the distal tubule and more K+ is excreted via POMK
T or F: like the penicillins and NSAIDs the Aminoglycosides cause injury that is dose independent.
FALSE, toxicity due to aminoglycosides is DOSE DEPENDENT
This is b/c the drug is directly attacking the tubule in aminoglycoside toxicity, in NSAIDs and Penicillins your IMMUNE system is doing the damage
Is Aminoglycoside Toxicity or Penicillin toxicity more associated with the following:
• Inflammation
• Granular Casts
Inflammation is associated with Penicillins. AMINOGLYCOSIDES cause NON-INFLAMMATORY damage
Granular Casts: present in aminoglycoside toxicity
T or F: only IV contrast is toxic
TRUE
Contrast Induced Nephrotoxicity: • Mechanism of Toxicity? • Dose depenent? • Inflammatory or Non-inflammatory? • When does it occur? • Urinalysis
Mechanism of Toxicity:
• Causes TRANSIENT vasocontriction followed by DIRECT TUBULAR toxicity
Dose Dependence:
• Like Aminoglycosides it IS DOSE DEPENDENT
Inflammatory vs. Non-Inflammatory:
• NON-INFLAMMATORY condition
When does it occur:
• HAPPENS IN PEOPLE WITH CKD or DIABETES most often
Urinalysis:
• Granular Casts
What are some causes of Papillary Necrosis?
SODA • Sickle Cell Disease • Obstructive Pyelonephritis • Diabetes • Analgesic Nephropathy
What common analgesic may cause kidney injury?
• mechanism of toxicity?
Analgesic = TYLENOL and Asprin
MOT:
• Drug accumulates and is concentrated in the medullary interstitium to alter vasomotor tone leading to ischemia
This is SLOWLY progressing and often seen in working class ppl. who take lots of Tylenol to stay on the job`
If someone experience Hematuria with Analgesic use WHAT SHOULD YOU ASSUME?
Assume Uro-epitheilial Cancer until proven otherwise
What kidney condition is caused by Aristolochic Acid?
• proteinuria?
- Chronic Interstitial Nephritis - BALKAN Nephropathy
* Low Proteinuria b/c its a nephritis, less than 1 g/day
What is the relationship between Balkan Nephropathy, Chinese Herbs nephropathy, and Aristolochic Acid?
• explain the disease characterisitics.
• significance of gross hematuria?
Aristolochic Acid is believed to be the cause of Chinese Herbs Nephropathy that resembles Balkan Nephropathy.
Disease Characteristics:
• Slowly Progressive Renal insufficiency with Low Proteinuria (less than 1g/day), HYPERTENSION in some pts.
Gross Hematuria:
• Sign of Uroepithelial tumor
Type of Nephropathy cause by TUMOR LYSIS SYNDROME?
• earliest sign that this has caused kidney dysfunction.
URATE Nephropathy - often this is an OBSTRUCTIVE nephropathy because of STONE formation
What characterizes a hypercalcemic Nephropathy?
Hypercalcemic Nephropathy:
• Presents like Nephrogenic Diabetes Incipidis (i.e. an inability to concentrate urine)
Acute Phosphate Nephropathy:
• when is it often seen?
• problem?
When:
• COLONOSCOPY Preparations contain high does of oral Phosphate Solutions
Problem:
• Precipitation of Calcium Phosphate may present as renal insufficiency weeks after exposure
Polycystic Kidney Disease
• Inheritance?
• Penetrance
• Gene?
Inheritance:
• Autosomal Dominant or Recessive
Autosomal Dominant = HIGH penetrance
Gene = ADPKD1 and ADPKD2 = polycistins = proteins used in cilia to aid in absorption in the tubule
T or F: polycystic kidney disease is often associated with HTN and heavy proteinuria.
FALSE, HTN is common and Proteinuria is minimal
What is the most common genetic disorder leading to end-stage kidney disease?
• Adult Polycystic Kidney Disease
**What disease is a common Fanconi Syndrome look alike?
• why is this?
**MULTIPLE MYELOMA = Fanconi Look Alike b/c proximal tubule will be defective from over reabsorption of Light Chains
**What will standard urinanlysis show in Multiple Myeloma?
Multiple Myeloma:
• Negative Urinalysis because urinalysis only looks at 24 hour urine
**What are the two main pathogenetic mechanisms leading to MYELOMA KIDNEY?
- Intra-tubular Cast Formation with Tamm-Horsfall Protein
2. Direct Tubular Toxicity by light chains
**Why might you get glomerular damage in addition to tubular damage in multiple myeloma?
• NEPHROTIC syndrome may result from AMYLOIDSOSIS
