Tubulointristitial Nephritis

Dr.boshra hasanzamani

• Primary tubulointerstitial diseases

• Secondary tubulointerstitial disease

Primary tubulointerstitial diseases

• histologic and functional abnormalities that involve the tubules and interstitium to a greater degree than the glomeruli and renal vasculature.

Secondary tubulointerstitial disease

• occurs as a consequence of progressive glomerular or vascular injury.

Laboratory Manifestions

• Acute rise in plasma creatinine concentration

• Eosinophilia and eosinophiluria

• Urine sediment: wbcs, rbcs, white cell casts

• Proteinuria (< 1 g/day)

• Signs of tubulointerstitial damage

Interstitial Nephritis

• Acute

• Chronic

Acute Interstitial Nephritis

• interstitial edema

• cortical and medullary infiltration by both mononuclear cells and polymorphonuclear leukocytes

• patchy areas of tubule cell necrosis

Acute Interstitial Nephritis

Therapeutic agents

Infection

AutoimmuneAcute obstructive disorders

Therapeutic agents

1.Antibiotics (-lactams, sulfonamides, quinolones, vancomycin, erythromycin, minocycline, rifampin, ethambutol, acyclovir)

2.Nonsteroidal anti-inflammatory drugs, COX-2 inhibitors

3.Diuretics (rarely thiazides, loop diuretics, triamterene)

4.Anticonvulsants (phenytoin, valproate, carbamazepine, phenobarbital)

5.Miscellaneous (proton pump inhibitors, H2 blockers, captopril, mesalazine, indinavir, allopurinol)

Infection

Bacteria (Streptococcus, Staphylococcus, Legionella, Salmonella, Brucella, Yersinia, Corynebacterium diphtheriae) 

Viruses (EBV, CMV, hantavirus, polyomavirus, HIV)

Miscellaneous (Leptospira, Rickettsia, Mycoplasma) 

Autoimmune

1.Tubulointerstitial nephritis with uveitis (TINU)

 2.Sjögren's syndrome

3.Systemic lupus erythematosus

4.Granulomatous interstitial nephritis

5.IgG4-related systemic disease

 6.Idiopathic autoimmune interstitial nephritis

Acute obstructive disorders

1.Light chain cast nephropathy ("myeloma kidney")

2.Acute phosphate nephropathy

3.Acute urate nephropathy

Allergic Interstitial Nephritis

Clinical Features

• classic presentation :

- fever, rash, peripheral eosinophilia, and

oliguric renal failure

• occurring after 7–10 days of treatment with methicillin or another -lactam antibiotic

• Atypical reactions :

-nonsteroidal anti-inflammatory drug

(NSAID)-induced AIN, in which fever,

rash and eosinophilia are rare, but acute

renal failure with heavy proteinuria is

common

Diagnosis

• unexplained renal failure with or without oliguria and exposure to a potentially offending agent

• Peripheral blood eosinophilia adds supporting evidence

• Urinalysis reveals pyuria with white blood cell casts and hematuria

• Urinary eosinophils are neither sensitive nor specific for AIN

• Renal biopsy is generally not required for diagnosis

Crystal Deposition Disorders and Obstructive Tubulopathies

• in patients treated with :

- sulfadiazine for toxoplasmosis

-indinavir for HIV

-intravenous acyclovir for severe herpesvirus infections

• Oliguric acute renal failure, often accompanied by flank pain

Acute Uric Acid Nephropathy

• tumor lysis syndrome • deposition of uric acid crystals in the kidneys and their

collecting systems, leading to partial or complete obstruction of collecting ducts, renal pelvis, or ureter.

• acute renal failure• In the early phase uric acid crystals can be found in urine• microscopic or gross hematuria• Hyperuricemia • urine uric acid/creatinine ratio >1 mg/mg (0.7 mol/mol)

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Light Chain Cast Nephropathy

• Patients with multiple myeloma may develop acute renal failure in the setting of :

- hypovolemia, infection, or hypercalcemia or after exposure to NSAIDs or

radiographic contrast media

• The diagnosis of light chain cast nephropathy (LCCN)—commonly known as myeloma kidney—should be considered in :

- patients who fail to recover when the precipitating factor is corrected

- in any elderly patient with otherwise unexplained

acute renal failure

Light Chain Cast Nephropathy

• filtered monoclonal immunoglobulin light chains (Bence-Jones proteins) form :

- intratubular aggregates

- giant cell or foreign body reaction

- direct toxicity to proximal tubular cells

- intracellular crystal formation

Diagnosis

• Clinical clues to the diagnosis include anemia, bone pain, hypercalcemia

• Serum and urine should both be sent for protein electrophoresis

Histologic appearance of myeloma cast nephropathy

Chronic Tubulointerstitial Diseases

Chronic Tubulointerstitial Diseases

• interstitial fibrosis

• inflammatory cells are typically mononuclear

• abnormalities of the tubules tend to be more widespread, as evidenced by atrophy, luminal dilatation, and thickening of tubule basement membranes.

• nonspecific nature

• The urine sediment is also unlikely to be diagnostic, except in allergic forms of acute tubulointerstitial disease in which eosinophils may predominate in the urinary sediment

• Defects in renal function • Proteinuria ( predominantly of low-molecular-weight proteins, is

usually modest, rarely > 2 g/d )• Defects in urinary acidification and concentrating ability Hyperchloremic metabolic acidosis nocturia and polyuria. • Proximal tubule dysfunction (fanconi syndrome) hypokalemia, aminoaciduria, glycosuria, phosphaturia, uricosuria, bicarbonaturia(RTA)

Chronic Tubulointerstitial Diseases

Vesicoureteral reflux Sickle cell diseaseChronic exposure to toxins

Metabolic Disturbances 

Cystic and Hereditary Disorders Miscellaneous 

Vesicoureteral Reflux and Reflux Nephropathy

• urologic anomalies in early childhood

• recurrent urinary tract infections

• high-pressure sterile reflux may impair normal growth of the kidneys + recurrent UTIs

• patchy interstitial scarring and tubular atrophy

Vesicoureteral Reflux

• function of the ureterovesical junction is impaired

• voiding cystourethrography may be required for definitive diagnosis

• Substantial proteinuria is often present

TOXINS

• Exogenous Toxins

Analgesic Nephropathy

Lead Nephropathy

• Metabolic Toxins

Chronic Uric Acid Nephropathy

Gouty Nephropathy

Hypercalcemic Nephropathy

Analgesic Nephropathy

• renal function usually declines gradually • papillary necrosis (hematuria -renal colic). • sterile pyuria• unable to generate maximally concentrated urine• Distal RTA and nephrocalcinosis • anemia • the kidneys usually appear bilaterally shrunken on intravenous

pyelography, and the calyces are deformed. • "ring sign" on the pyelogram is pathognomonic of papillary necrosis• CT may reveal papillary calcifications surrounding the central sinus

complex in a "garland" pattern• Transitional cell carcinoma may develop in the urinary pelvis or

ureters as a late complication of analgesic abuse.

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Lead Nephropathy

• occupational exposure • accumulation of lead within renal cells • proximal tubule dysfunction• kidneys become atrophic • Urinary excretion of lead may be increased• hyperuricemi• Acute gouty arthritis (so-called saturnine gout) develops in about 50%

of patients with lead nephropathy• Hypertension• triad of "saturnine gout," hypertension, and renal insufficiency

• Therefore, in any patient with:

slowly progressive renal failure

atrophic kidneys

gout

hypertension

the diagnosis of lead intoxication should be considered

• measuring urinary lead after infusion of a chelating agent or by radiographic fluoroscopy of bone

Gouty Nephropathy

• Patients with less severe but prolonged forms of hyperuricemia

• presence of crystalline deposits of uric acid and monosodium urate salts in kidney parenchyma.

• proteinuria• diminished urinary concentrating ability• Early in its course, GFR may be near normal,

Hypercalcemic Nephropathy

• Chronic hypercalcemia is seen in

Hyperparathyroidism

Sarcoidosis

Multiple myeloma

Vitamin D toxicity

Metastasis bone disease

• Hypercalcemia decrease GFR through renal vasoconstriction

• Calcium deposition in distal nephron and interstitial that leads to mononeuclear cell infiltration and tubular necrosis

• Defective concentration ability, poliuria, nocturia

• Nephrocalcinosis & nephrolitiasis

Radiation Nephritis

• if 23 Gy (2300 rad) of x-ray irradiation is administered to both kidneys.

• acutely or chronically renal failure• moderate to malignant hypertension• anemia• proteinuria that may reach the nephrotic range• Malignant hypertension without renal failure may

follow unilateral renal irradiation and resolve with ipsilateral nephrectomy

WBC Casts

Cells in the cast have nuclei(unlike RBC casts)

Pathognomonic for Acute Interstitial Nephritis

Question

• 1. 65 year old with H/o HTN, ventricular arrythmias controlled on Amiodarone, OA on NSAIds presents with puffiness on face on waking up. Has bilateral pitting dema. UA 3+ prot, 3 RBC., 15-20 WBC

• 24 h prot – 4 g/day

• BUN/creat 80/5

• Serum albumin 2.8, TSH normal. The most likely diagnosis?

• A) amiodarone induced hypothyroidism

• B) RPGN

• C) NSAIDs induced nephrotic sdr and interstitial nephritis

Match:

• 1. hyaline casts

• 2. muddy brown casts

• 3. RBCs

• 4. RBC casts

• 5. Oval fat bodies

• 6. eosinophils

• A. ATN

• B. prerenal azotemia

• C. glomerulonephritis

• D. nephrolithiasis

• E. interstitial disease

• F. nephrotic syndrome

Match:

• 1. hyaline casts

• 2. muddy brown casts

• 3. RBCs

• 4. RBC casts

• 5. Oval fat bodies

• 6. eosinophils

• A. ATN

• B. prerenal azotemia

• C. glomerulonephritis

• D. nephrolithiasis

• E. interstitial disease

• F. nephrotic syndrome