AIN 1
List four clinical features that are characteristic of acute interstitial nephritis
What is fever, peripheral eosinophilia, rash, & (oliguric) renal failure ?
Also accept: WBC casts on microscopic analysis
Note: Acute interstitial nephritis, often used synonymously with allergic interstitial nephritis, refers to acute inflammation of the renal interstitial tissue, with relative sparing of the glomeruli and renal vessels.
The most common renal manifestation of Sjogren's syndrome
What is (acute) tubulointerstitial nephritis ?
Also accept: interstitial nephritis
Note: Autoimmune conditions can cause acute interstitial nephritis. Tubulointerstitial nephritis with a predominant lymphocytic infiltrate is the most common renal manifestation of Sjogren’s syndrome. Sjogren’s is also associated with RTA, nephrogenic DI, & moderate renal failure.
Abnormal retrograde urine flow from the bladder into one or both ureters & kidneys due to mislocated & incompetent ureterovesical valves
What is Vesicoureteral reflux (VUR) ?
Note: VUR may result in chronic interstitial nephritis via abnormal retrograde urine flow from the bladder into one or both ureters & kidneys due to mislocated & incompetent ureterovesical valves. High pressure reflux impairs normal growth of kidneys. End result is patchy interstitial scarring, tubular atrophy
Syndrome of defective proximal tubular reabsorption resulting in glycosuria, phosphaturia, aminoaciduria, hypokalemia, and type II RTA
What is Fanconi's syndrome ?
The anion gap is generally calculated using the values of these three molecules
What is sodium, chloride, and bicarbonate ?
Note: The two most important causes of metabolic acidosis with a normal anion gap are diarrhea & renal tubular acidosis. Anion gap = Na minus (chloride + bicarbonate). Anion gap normally 8-12 mEq. 3 major types of RTA - Type 1 RTA, Type 2 RTA, & Type 4 RTA.
Today, acute interstitial nephritis is most often due to this etiology
What is an allergic reaction to a medication ?
Note: AIN can be due to medications, infection, obstruction, & autoimmune conditions. Today, medications are the most common offender. It is believed that drugs act as haptens, which covalently bind to some cytoplasmic or extracellular component of tubular cells and become immunogenic. Resultant injury is due to IgE &/or cell-mediated immune reactions to tubular cells or their basement membranes.
Prophylactic use of this medication decreases the risk of acute urate nephropathy in the setting of myeloproliferative disorders with a high cell turnover or tumor lysis syndrome
What is allopurinol ?
Possibly accept: Rasburicase
Note: Uric acid crystallization in tubules/collecting system leads to obstruction of collecting ducts, renal pelvis, or ureter. Birefringent uric acid crystals found in urine often associated with microscopic or gross hematuria. Prophylactic allopurinol decreases risk of urate nephropathy. Once oliguria develops, emergent Tx with HD or rasburicase is usually required
Mood stabilizer used in the treatment of bipolar disorder and cause of chronic tubulointerstitial nephritis
What is lithium ?
Note: Lithium causes chronic tubulointerstitial nephritis with prolonged exposure. Bx shows interstitial fibrosis, tubular atrophy. Most cases are asymptomatic.
Medical term used to describe the inability to concentrate the urine
What is hyposthenuria ?
Medication associated with impaired bicarbonate reabsorption in the proximal tubule and an iatrogenic cause of renal tubular acidosis, type 2
What is acetazolamide ?
Note: RTA type 2 may be due to several etiologies including: autoimmune, drug-induced, infiltrative disorders. Wilson’s disease, galactosemia, amyloidosis, myeloma, fanconi’s syndrome, & acetazolamide.
The most accurate test for the diagnosis of acute interstitial nephritis
What is renal biopsy ?
Note: Biopsy proven AIN accounts for <15% of unexplained acute renal failure. Biopsy is generally not required but is considered the most accurate test. Biopsy reveals extensive interstitial & tubular infiltration of leukocytes (including eosinophils).
List one medication that can result in acute interstitial nephritis via crystal formation
What is acyclovir ?
Also accept: Sulfadiazine, indinavir
Note: Acute renal failure may occur when crystals get deposited in tubular cells/interstitium. Crystals obstruct tubules & cause oliguric acute renal failure. Tx via saline + drug withdrawal
Persistently low levels of this electrolyte, seen in the setting of laxative/diuretic abuse, surreptitious vomiting, and primary aldosteronism, can eventually result in tubular atrophy and interstitial fibrosis
What is hypokalemia ?
Medication class associated with chronic renal injury in transplant recipients
What is calcineurin inhibitors ?
Medication used in the treatment of systemic mycotic infections and known to result in renal tubular acidosis, type 1
What is amphotericin B ?
Note: Sjogren's syndrome and SLE are other secondary causes of RTA, Type 1.
Most effective management strategy of acute interstitial nephritis (AIN)
What is discontinue the offending medication ?
Also accept: Treat the underlying disorder
Note: AIN is an inflammatory disorder of the renal interstitium. It has several etiologies including medications, infection, obstruction, and autoimmune conditions. The most common etiology is an allergic reaction to a medication. Therefore, the most effective treatment is discontinuing the offending medication. When AIN is secondary to another etiology, the most effective strategy would be to treat the underlying disorder.
Upon aggregation with this protein & resultant cast formation, immunoglobulin light chains may obstruct tubular flow & incite a giant cell or foreign body reaction that can lead to tubular rupture or interstitial fibrosis
What is Tamm - Horsfall protein ?
Note: In those with plasma cell dyscrasias (i.e. myeloma), filtered monoclonal immunoglobulin light chains (bence jones proteins) form intratubular aggregates with Tamm Horsfall protein in the tubules. Casts obstruct tubular flow & incite a giant cell or foreign body reaction that can lead to tubular rupture or interstitial fibrosis.
Triad of saturnine gout, hypertension, & renal insufficiency should prompt evaluation for toxicity with this substance
What is lead ?
Condition suggested by hypercalcemia, renal insufficiency, anemia, and bone disease
What is multiple myeloma ?
In the autosomal recessive form of RTA type 1, patients cannot acidify their urine due to defective hydrogen ion secretion because of dysfunction of this cortical collecting duct cell
What is the intercalated cell ?
Note: RTA type 1 occurs as a primary disorder or due to a secondary condition. Primary RTA has two forms - AR & AD. The AR form is characterized by dysfunction of the intercalated cell in the cortical collecting duct. Mutations affect H-ATPase proton pump on luminal surface. Results in impaired hydrogen ion secretion.Pts cannot acidify their urine which results in a metabolic acidosis. In the AD form, mutations involve chloride bicarbonate exchanger on the basolateral membrane at the cortical collecting duct. End result is bicarbonate loss in the urine.
Classic stain utilized for the detection of eosinophils on renal biopsy and useful for the diagnosis of acute interstitial nephritis
What is the Hansel stain ?
Also accept: the Wright stain
Autoimmune condition accounting for <5% of AIN cases, characterized by a lymphocytic predominant interstitial nephritis with painful anterior uveitis, increased creatinine & ESR, sterile pyuria, mild proteinuria, and features of Fanconi's syndrome
What is tubulointerstitial nephritis with uveitis (TINU) ?
Causative agent resulting in a progressive tubulointerstitial disease seen in Eastern Europeans who live along the Danube river & those in the Far East taking certain herbal remedies
What is aristolochic acid ?
Note: Balkan nephropathy is seen in Serbian, Bulgarian, Croatian, Romanian, Hungarian, & Slovakians who live by the Danube river & Asians taking aristolochic acid (supplement in some herbal remedies). A progressive tubulointerstitial disease. Aristolochic acid causes renal interstitial fibrosis w/ a paucity of cellular infiltrates. Urine sediment is bland w/ rare leukocytes, mild proteinuria. Associated w/ increased risk of bladder, ureteral malignancy.
In the past, this substance was commonly added to analgesic medications for it's antipyretic effect, but has been banned in several countries due to its association with renal papillary necrosis and chronic tubulointerstitial nephritis
What is phenacetin ?
The only RTA subtype that results in metabolic acidosis, normal anion gap, and hyperkalemia
What is renal tubular acidosis, Type 4 ?
Note: RTA IV should be thought of as relative aldosterone deficiency. Only RTA that produces hyperkalemia. Only RTA to have a normal, acidic urine pH. If hyperkalemia is extreme, arrhythmia/ECG changes can occur. Etiologies of RTA 4 include: DM nephropathy, ACE Is, NSAIDs, TMP-SMX. Obstructive uropathy, aldosterone deficiency states, interstitial nephritis, heparin, sickle cell disease.