Interstitial Nephritis: Detailed Notes

Definition

 Interstitial Nephritis: Inflammation of the renal interstitium leading to fibrosis and

tubular atrophy.
 Primarily affects the renal tubules and interstitium, with relative sparing of
the glomeruli and vasculature.
 Divided into acute interstitial nephritis (AIN) and chronic interstitial nephritis
(CIN).

Acute Tubulointerstitial Nephritis (AIN)

 Presentation:
o Often presents with acute kidney injury (AKI).
o Clinical Features:
 Tissue edema, tubular cell injury, and compromised flow.
 Obstruction by casts, debris, or crystals.
 Drug-induced AIN: Classical triad (fever, rash, eosinophilia) in <10% of
cases.
 Rise in creatinine: 7–10 days after starting the offending drug.
 May have flank pain due to renal capsule distension.
o Urinary Findings:
 Active sediment: Leukocytes, leukocyte casts.
 Hematuria and red cell casts are rare.
o Pathophysiology:
 Allergic AIN: Type I (IgE-mediated) and Type IV (T-cell mediated)
hypersensitivity to medications.
 Non-Allergic AIN: Triggered by infections or autoimmune diseases.
 Laboratory Features:
o Urine Analysis:
 Proteinuria (<1 g; exception: NSAID-induced nephropathy).
 Pyuria with leukocyte casts.
 Eosinophiluria (positive predictive value: 38%).
o Serum Chemistry:
 Elevated BUN and creatinine.
 Hyper/hypokalemia.
 Normal anion gap metabolic acidosis (suggests tubular injury).
 Fractional excretion of sodium >1%.
o CBC:
 Eosinophilia (especially in drug-induced AIN).
 Variable anemia.
Chronic Tubulointerstitial Nephritis (CIN)

 Presentation:
o Insidious onset with progressive azotemia.
o Clinical Features:
 Modest proteinuria due to impaired tubular reabsorption.
 Disorders of tubular function:
 Polyuria (impaired concentrating ability).
 Proximal tubular dysfunction: Glucosuria, phosphaturia,
aminoaciduria (Fanconi syndrome).
 Type II RTA (proximal bicarbonate loss).
 Type IV RTA (hyperkalemia, impaired ammoniagenesis).
 Non-anion gap metabolic acidosis.
 Imaging and Pathology:
o Renal Ultrasound:
 Increased renal parenchymal echogenicity.
 Loss of corticomedullary differentiation.
 Prominent renal pyramids, cortical scarring.
o Pathology:
 Interstitial fibrosis, mononuclear infiltration, tubular atrophy.
 Tubular basement membrane thickening.

Renal Tubular Acidosis (RTA)

 Type I (Distal RTA):

o Defect in H⁺ secretion.
o Urine pH >5.5, hypokalemia.
o Associated with: Sjögren syndrome, lupus, urinary obstruction.
o Complication: Nephrolithiasis (low urinary citrate).
 Type II (Proximal RTA):
o Defect in HCO₃⁻ reabsorption.
o Initial urine pH >5.5, later <5.5, hypokalemia.
o Associated with: Multiple myeloma, Fanconi syndrome.
 Type IV (Hyperkalemic RTA):
o Aldosterone deficiency/resistance.
o Urine pH <5.5, hyperkalemia.
o Associated with: Diabetes, spironolactone use.

Classification of Causes
 1. Acute Interstitial Nephritis (AIN):
o Therapeutic Agents:
 Antibiotics, NSAIDs, diuretics, anticonvulsants, PPIs.
o Infections:
 BK virus (common in kidney transplants).
o Autoimmune:
 Sjögren syndrome, lupus, granulomatosis.
o Obstruction:
 Light-chain cast nephropathy, phosphate nephropathy.
2. Chronic Interstitial Nephritis (CIN):
o Reflux nephropathy, sickle cell disease.
o Chronic exposure to toxins: NSAIDs, lithium, heavy metals.
o Metabolic: Hypercalcemia, hyperuricemia, hypokalemia, hyperoxaluria.
o Cystic/Hereditary:
 Polycystic kidney disease, medullary sponge kidney.

Treatment

1. Acute Interstitial Nephritis (AIN):

o Initial:
 Withdraw offending agents.
 Supportive care: Correct electrolytes, avoid nephrotoxins.
o Steroids:
 Indicated for drug-induced AIN with severe injury or rapid progression.
 Use if no improvement after 1 week.
o Immunosuppressives:
 For autoimmune causes or granulomatous nephritis.
2. Chronic Interstitial Nephritis (CIN):
o Supportive:
 Address underlying cause.
 Manage complications (e.g., acidosis, hyperkalemia).
o Advanced Disease:
 Dialysis for end-stage kidney disease.

Entity-Specific Particularities

1. Allergic AIN:
o 15% of kidney biopsies for unexplained AKI.
o Clinical triad: Fever, rash, eosinophilia (rare).
o Treatment: Discontinue drug, glucocorticoids for severe cases.
2. Sjögren Syndrome:
o Dry eyes/mouth, lymphocytic infiltration.
 oAssociated with RTA and nephrogenic diabetes insipidus.
oTreatment: Steroids ± azathioprine/mycophenolate.
3. Tubulointerstitial Nephritis with Uveitis (TINU):
o Female > male (3:1), median age: 15 years.
o Symptoms: Anterior uveitis, sterile pyuria, mild proteinuria.
o Treatment: Glucocorticoids ± immunosuppressives.
4. Lupus Nephritis:
o Tubulointerstitial involvement with immune complex deposits.
o Associated with azotemia and RTA.
o Treatment: Steroids and disease-specific therapy.

Key Takeaways

 AIN is often reversible with early intervention.

 CIN progresses slowly and often leads to CKD.
 Diagnosis relies on clinical history, laboratory, imaging, and biopsy (in select cases).
 Individualized treatment based on etiology and disease severity.

Crystalline Nephropathy

Definition & Types

Crystalline nephropathy involves kidney injury due to crystal deposition, leading to tubular
obstruction, inflammation, and chronic kidney disease (CKD) if unrecognized early.

Key Examples

1. Acute Uric Acid Nephropathy:

o Cause: Uric acid crystal obstruction, often secondary to tumor lysis syndrome
(TLS) in hematological malignancies treated with cytotoxic agents.
o Pathophysiology:
 Crystals block tubules, collecting ducts, renal pelvis, or ureters.
 Severe hyperuricemia can occur even before treatment.
o Clinical Features:
 Hematuria: Microscopic or gross.
 Urine: Dense birefringent uric acid crystals.
o Management:
 Prophylaxis: Allopurinol to reduce hyperuricemia.
 Treatment: Alkalinization of urine, hydration, rasburicase (urate oxidase),
or emergent hemodialysis.
2. Calcium Oxalate Nephropathy:
o Causes:
 Enteric hyperoxaluria: Seen in malabsorptive conditions like ileal
resection or bypass surgery.
 Hereditary hyperoxaluria.

Acute oxalate intoxication (e.g., ethylene glycol poisoning).

o Outcome: Crystal deposition in tubules can cause permanent kidney dysfunction.
3. Acute Phosphate Nephropathy:
o Cause: Calcium phosphate crystal deposition from phosphate-based bowel
preparation (e.g., oral phospho-soda).
o Risk Factors: Chronic kidney disease (CKD), hypovolemia.
o Prevention: Avoid phosphate-based preparations in CKD patients.

Myeloma Kidney (Light Chain Cast Nephropathy)

Definition

Renal injury from monoclonal immunoglobulin light chain deposition in tubules, commonly seen
in multiple myeloma.

Pathophysiology

 Tubular Obstruction: Light chains aggregate with Tamm-Horsfall protein to form casts
in distal tubules.
 Inflammation & Fibrosis: Triggers giant cell reaction and interstitial fibrosis.

Clinical Features

 Presentation: Acute kidney injury (AKI), especially in elderly patients with unexplained
AKI or persistent AKI after correcting hypovolemia or hypercalcemia.
 Diagnosis:
o Spot urine test showing high protein with negative dipstick (detects albumin, not
light chains).
o Serum and urine electrophoresis for monoclonal bands.

Histology

 Atrophic tubules filled with eosinophilic casts surrounded by inflammatory cells.

Treatment

 Correct precipitating factors (e.g., hypercalcemia, nephrotoxic drugs).

 Treat underlying myeloma.
 Dialysis may be of limited benefit in cast nephropathy.

Chronic Interstitial Nephritis

Etiologies

1. Heavy Metal Exposure: Rare due to improved regulations.

2. Analgesic Nephropathy: From over-the-counter phenacetin-containing analgesics.
3. Renal Ischemia: Secondary to primary glomerular disease.
4. Inherited Conditions: Reflux nephropathy, sickle cell nephropathy.

Management

 Treat underlying causes.

 Control hypertension with ACE inhibitors or ARBs to prevent progression.

Reflux Nephropathy

Cause

 Retrograde urine flow from bladder to ureters/kidneys due to incompetent ureter valves.

Pathophysiology

 Scarring and tubular atrophy lead to hypertrophy of residual glomeruli and secondary
FSGS.

Clinical Features

 May present asymptomatically, or with childhood UTIs, hypertension, and mild

proteinuria.
 Kidney ultrasound: Asymmetric small kidneys with irregular outlines.

Management

1. Prevent Scarring: Maintain sterile urine.

2. Surgical Reimplantation: Indicated in persistent high-grade reflux in children.
3. Control Hypertension: ACE inhibitors or ARBs to reduce proteinuria and preserve
function.

Sickle Cell Nephropathy

Manifestations

1. Tubular Injury: Polyuria (reduced concentrating ability), renal tubular acidosis (type
IV).
 2. FSGS: Secondary to nephron loss; treat with ACE inhibitors.
3. Papillary Necrosis: Ischemia from sickling in the hypoxic medullary vasculature,
leading to gross hematuria and obstruction by sloughed papillae.

Lithium-Associated Nephropathy

Pathophysiology

 Lithium accumulates in principal cells of collecting ducts, interfering with vasopressin-

regulated aquaporins.

Clinical Features

1. Nephrogenic Diabetes Insipidus: Polyuria and polydipsia.

2. Chronic Interstitial Nephritis: Presents as slowly progressive CKD.

Treatment

 Regular monitoring of lithium levels.

 Amiloride to reduce lithium entry into cells.
 Consider discontinuation of lithium if nephropathy develops.

Calcineurin Inhibitor (CNI) Nephrotoxicity

Acute Injury

 Vasoconstriction or thrombotic microangiopathy.

Chronic Injury

 Seen in solid organ transplant recipients.

 Histology: Patchy interstitial fibrosis, tubular atrophy, and FSGS.

Clinical Management

 Monitor kidney function.

 Dose adjustment to prevent progression to CKD.

Aristolochic Acid Nephropathy

Epidemiology

 First described as Balkan endemic nephropathy, later linked to Chinese herbal

medicine.

Pathophysiology

 Interstitial fibrosis with minimal inflammation; DNA damage leads to urothelial cancer.

Diagnosis

1. Characteristic histology.
2. History of aristolochic acid exposure.
3. Detection of DNA adducts.

Management

 Surveillance for urothelial cancer.

 Consider nephrectomy if ESRD is reached.

Analgesic Nephropathy

Clinical Features

 CKD with papillary necrosis and scarring.

 Increased risk of urothelial malignancy.

Imaging

 Small kidneys with papillary calcifications.

Management

 Avoid nephrotoxic analgesics.

 Monitor for malignancy.

……………………….

 Interstitial nephritis involves inflammation or fibrosis of the renal interstitium and

atrophy of the tubular compartment.
 It is a group of disorders primarily affecting tubules and interstitium, with relative
sparing of glomeruli and renal vessels. Divided into:
o Acute tubulointerstitial nephritis (TIN)
o Chronic tubulointerstitial nephritis
  Commonly secondary to diseases targeting glomeruli or vasculature.

Acute Interstitial Nephritis (AIN)

Presentation

 Typically presents with acute kidney injury (AKI).

 Caused by:
o Aggressive inflammatory infiltrates → tissue edema, tubular injury,
compromised tubular flow.
o Obstruction of tubules → casts, cellular debris, or crystals.
 Classical triad (fever, rash, eosinophilia):
o Seen in <10% of patients.
o Creatinine elevation usually occurs 7-10 days post-drug exposure.
 Symptoms:
o Flank pain (due to renal capsule distention).
o Active urinary sediment: leukocytes, cellular casts.

Pathophysiology

 Allergic Reaction:
o Hypersensitivity reaction (type I & IV) to medications (e.g., penicillin).
o Medications act as haptens, inducing immune responses.
 Non-Allergic Reaction:
o Triggered by infections or autoimmune diseases.

Chronic Interstitial Nephritis (CIN)

Presentation

 Indolent progression with:

o Tubular dysfunction: polyuria, Fanconi syndrome (glycosuria, phosphaturia,
aminoaciduria).
o Acidosis:
 Non-anion gap metabolic acidosis.
 Type IV RTA (hyperkalemia, impaired ammoniagenesis).
o Azotemia.
o Proteinuria: modest (<2 g/day) or nephrotic range (due to secondary FSGS).
 Ultrasound findings:
o Increased renal parenchyma echogenicity.
 o Loss of corticomedullary differentiation, cortical scarring.
o Prominent renal pyramids.

Pathology

 Interstitial fibrosis, patchy mononuclear cell infiltration, tubular atrophy, and

thickened tubular basement membranes.
 Diagnosis:
o Relies on clinical history, drug/toxin exposure, symptoms, and imaging, as
histopathology is nonspecific.

Classification of Tubulointerstitial Diseases

1. Acute Interstitial Nephritis
2. Chronic Interstitial Nephritis
3. Metabolic Disturbances
4. Cystic and Hereditary Disorders
5. Miscellaneous Causes

Causes
1. Acute Interstitial Nephritis

 Therapeutic Agents: Antibiotics (β-lactams), NSAIDs, diuretics, anticonvulsants, PPIs,

H2 blockers.
 Infections:
o Bacteria: Streptococcus, Staphylococcus.
o Viruses: EBV, CMV, HIV.
o Miscellaneous: Leptospira, Rickettsia.
 Autoimmune:
o TINU syndrome, Sjögren’s syndrome, lupus nephritis.
o IgG4-related disease, anti-brush border disease.
 Acute Obstructive Disorders: Light chain cast nephropathy.

2. Chronic Interstitial Nephritis

 Vesicoureteral reflux/reflux nephropathy.

 Chronic toxin exposure: Phenacetin, lithium, lead, aristolochic acid.
 Sickle cell disease.
 Calcineurin inhibitors (e.g., cyclosporine).
3. Metabolic Disturbances

 Hypercalcemia, hyperuricemia, hypokalemia, hyperoxaluria, cystinosis.

4. Cystic and Hereditary Disorders

 Polycystic kidney disease, nephronophthisis, medullary sponge kidney.

5. Miscellaneous

 Aging, ischemia, radiation nephritis, chronic urinary tract obstruction.

Treatment
Supportive Care

 Manage fluids, electrolytes, and symptomatic relief.

 Avoid nephrotoxins and adjust drug dosages.
 Dialysis: Indicated for severe azotemia, fluid derangements, or hyperkalemia.

Corticosteroids and Immunosuppressives

 Reserved for severe cases, particularly AIN unresponsive to drug discontinuation.

Particular Entities
1. Allergic Interstitial Nephritis

 Incidence: >15% of kidney biopsies in AKI.

 Clinical Features:
o Rash, fever, eosinophilia, oliguria (rarely all together).
o Proteinuria: typically mild, except with NSAIDs.
 Diagnosis:
o History of drug exposure, pyuria, WBC casts.
o Biopsy shows interstitial leukocytic infiltration.
 Treatment:
o Stop offending agent.
o Glucocorticoids for severe or unresolving cases.

2. Sjögren’s Syndrome
  Features:
o Lymphocytic TIN, distal RTA, nephrogenic diabetes insipidus.
 Diagnosis:
o Anti-Ro (SS-A) and Anti-La (SS-B) antibodies.
 Treatment:
o Glucocorticoids, azathioprine, or mycophenolate.

3. TINU Syndrome

 Definition:
o Systemic autoimmune disorder with TIN and uveitis.
 Features:
o Painful anterior uveitis, fever, arthralgia, anorexia.
 Diagnosis:
o Elevated ESR, sterile pyuria, Fanconi syndrome.
o Negative autoimmune serologies.
 Treatment:
o Glucocorticoids; maintenance therapy for relapsing cases.

4. Systemic Lupus Erythematosus

 Tubulointerstitial inflammation may predominate, manifesting with type IV RTA and

azotemia.

5. Granulomatous Interstitial Nephritis

 Features:
o Relapsing course with granulomas in biopsy.
 Differential:
o Tuberculosis, sarcoidosis.
 Treatment:
o Glucocorticoids; other agents for recurrent cases.

6. AIN Associated with the Use of Immune Checkpoint Inhibitors

 Background:
o Immune checkpoint inhibitors are critical in cancer therapy.
o They block checkpoint proteins to prevent the “off” signal that inhibits T cells,
allowing T cells to destroy cancer cells.
o These therapies can cause autoimmune phenomena as a side effect.
 Epidemiology:
o Renal involvement occurs in:
 2% of cases with monotherapy.
 5% with dual checkpoint inhibitor therapy.
 Clinical Features:
 o Acute rise in serum creatinine typically occurs within 15 weeks of therapy
initiation but can appear later or up to 2 months after the final dose.
 Histological Findings:
o Biopsy often reveals acute interstitial inflammation but may show glomerular
pathologies.
 Association with Drugs:
o Commonly co-administered medications like proton pump inhibitors
(PPIs) or NSAIDs may contribute.
 Management:
o Severe acute kidney injury treatment:
 Corticosteroids.
 Discontinuation of potential inciting medications.
 Avoidance of further immune checkpoint inhibitors until kidney function
recovers.

7. Idiopathic AIN

 Pathogenesis:
o Involves autoantibodies targeting antigens in the collecting duct or proximal
tubular brush border.
 Management:
o Responsive to glucocorticoid therapy.
o Relapsing cases may require maintenance immunosuppression.

8. Infection-Associated AIN

 Pathogenesis:
o Occurs as a local inflammatory reaction to microbial infection.
o Must be differentiated from acute bacterial pyelonephritis:
 Pyelonephritis rarely causes AKI unless it:
 Affects both kidneys.
 Leads to septic shock.
 Epidemiology:
o Common in immunocompromised patients, especially:
 Kidney transplant recipients with polyomavirus BK
(BKV) reactivation.

9. Crystal Deposition Disorders and Obstructive Tubulopathies

 Pathophysiology:
 o Crystals can:
 Deposit in tubular cells and interstitium.
 Obstruct tubules, causing AKI.
o Commonly associated with:
 Sulfadiazine (toxoplasmosis).
 Indinavir, atazanavir (HIV).
 Intravenous acyclovir (herpesvirus infections).
 Clinical Features:
o Flank pain due to tubular obstruction.
o Urinalysis findings:
 "Sheaf of wheat" sulfonamide crystals.
 Needle-shaped indinavir or acyclovir crystals.
 Red-green birefringent uric acid crystals.
 Management:
o Hypovolemia is the primary precipitant.
o Treatment:
 Saline volume repletion.
 Drug withdrawal.

Specific Conditions:

1. Intratubular Indinavir Crystals:

o Needle-shaped crystals in distal tubules and collecting ducts.
o Associated monocytic inflammatory infiltrate and giant-cell reaction on
histology.
o Early recognition is critical to prevent chronic kidney disease (CKD).
2. Acute Urate Nephropathy:
o Cause: Tumor lysis syndrome leading to severe hyperuricemia.
o Pathology: Uric acid crystallization in tubules and collecting system.
o Management:
 Prophylactic allopurinol reduces risk.
 Treatment for oliguria:
 Alkaline diuresis.
 Hemodialysis or rasburicase to lower uric acid rapidly.
3. Calcium Oxalate Crystal Deposition:
o Etiologies:
 Ethyleneglycol intoxication.
 Enteric hyperoxaluria (e.g., ileal resection).
 Hereditary hyperoxaluria.
o Can cause permanent kidney damage if untreated.
4. Acute Phosphate Nephropathy:
o Cause: Calcium phosphate crystal deposition.
o Risk factors:
 Use of oral Phosphosoda (laxative).
 Underlying kidney disease and hypovolemia.
o Avoid Phosphosoda in patients with CKD.
10. Light Chain Cast Nephropathy (Myeloma Kidney)

 Epidemiology:
o Common in multiple myeloma, especially with:
 Hypovolemia.
 Hypercalcemia.
 Infection.
 NSAID or contrast media exposure.
 Pathophysiology:
o Filtered monoclonal light chains (Bence-Jones proteins):
 Form aggregates with Tamm-Horsfall protein in the distal tubule.
 Obstruct tubules and trigger a foreign-body reaction.
o Consequences:
 Tubular rupture.
 Interstitial fibrosis.
 Histologic Appearance:
o Eosinophilic casts surrounded by giant cell reactions.
 Clinical Spectrum:
o Also occurs in monoclonal gammopathy without overt myeloma.
o May cause:
 Renal tubular acidosis (RTA).
 Fanconi syndrome (proximal tubular dysfunction).
 Management:
o Correct precipitating factors (e.g., infection, hypovolemia).
o Monitor renal function in patients with known or suspected monoclonal
gammopathies.

hronic Interstitial Nephritis (CIN) and Related Entities

Diagnosis of Plasma Cell Dyscrasia-Related Kidney Injury:

1. Key Clinical Features:

o Anemia, bone pain, hypercalcemia.
o Narrow anion gap due to hypoalbuminemia and hypergammaglobulinemia.
2. Urine and Protein Electrophoresis:
o Urinary Dipstick: Detects albumin but not immunoglobulin light chains.
o Increased protein in urine + negative dipstick = possible Bence-Jones protein.
o Serum/Urine Tests: Perform protein electrophoresis and immunofixation to
detect monoclonal bands.
o Sensitive methods available for free light chain detection.
3. Treatment:
o Correct precipitating factors (e.g., hypovolemia, hypercalcemia).
o Discontinue nephrotoxic agents.
o Treat underlying plasma cell dyscrasia.
 o Plasmapheresis for light chain removal is of questionable benefit.

CIN: Particularities

1. Epidemiology:
o Decline in heavy metal and phenacetin-related nephritis in North America.
o Common causes: renal ischemia, primary glomerular disease, developmental
anomalies, and inherited diseases (e.g., reflux nephropathy, sickle cell
nephropathy).
2. Management:
o Prevention of further damage through control of glomerular hypertension
(ACEI/ARB).
o Early detection to prevent ESRD.

Specific Entities

1. Vesicoureteral Reflux (VUR) and Reflux Nephropathy:

 Pathophysiology: Retrograde urine flow → interstitial scarring and tubular atrophy.

 Symptoms: Hypertension, mild proteinuria, kidney injury, history of UTIs/bed-wetting.
 Diagnosis:
o Ultrasound: Asymmetric kidneys, irregular outlines, compensatory hypertrophy.
 Treatment:
o Maintain sterile urine in childhood to limit scarring.
o Surgical reimplantation of ureters in young children.
o ACEI/ARB to reduce proteinuria and delay CK

SUMMARY ALL ABOVE

 Interstitial Nephritis: Inflammation or fibrosis of the renal interstitium, primarily

affecting the renal tubules with relative sparing of glomeruli and vasculature.
 Divided into:
o Acute Interstitial Nephritis (AIN)
o Chronic Interstitial Nephritis (CIN)

Acute Interstitial Nephritis (AIN)

Presentation
  Typically presents as acute kidney injury (AKI).
 Clinical Features:
o Tissue Edema, tubular injury, impaired blood flow.
o Obstruction by casts, debris, or crystals.
o Drug-induced AIN: Classical triad (fever, rash, eosinophilia) in <10% of cases.
o Creatinine rise: 7–10 days after drug exposure.
o May cause flank pain due to renal capsule distension.

Urinary Findings

 Active sediment: Leukocytes, leukocyte casts.

 Rare: Hematuria, red cell casts.

Pathophysiology

1. Allergic AIN:
o Type I hypersensitivity: IgE-mediated.
o Type IV hypersensitivity: T-cell mediated.
2. Non-Allergic AIN:
o Triggered by infections or autoimmune diseases.

Laboratory Features

 Urine Analysis:
o Proteinuria (<1 g, except NSAID-induced nephropathy).
o Pyuria with leukocyte casts.
o Eosinophiluria: Positive predictive value ~38%.
 Serum Chemistry:
o Elevated BUN and creatinine.
o Electrolyte imbalances: Hyper/hypokalemia.
o Normal anion gap metabolic acidosis (tubular dysfunction).
o Fractional excretion of sodium >1%.
 CBC:
o Eosinophilia, especially in drug-induced AIN.
o Variable anemia.

Chronic Interstitial Nephritis (CIN)

Presentation

 Insidious onset with progressive azotemia.

  Clinical Features:
o Modest proteinuria due to impaired tubular reabsorption.
o Tubular dysfunction:
 Polyuria: Reduced concentrating ability.
 Proximal tubular dysfunction: Glucosuria, phosphaturia, aminoaciduria
(Fanconi syndrome).
 Type II RTA: Bicarbonate loss.
 Type IV RTA: Hyperkalemia, impaired ammoniagenesis.
o Non-anion gap metabolic acidosis.

Imaging and Pathology

 Renal Ultrasound:
o Increased parenchymal echogenicity.
o Loss of corticomedullary differentiation.
o Cortical scarring, prominent renal pyramids.
 Pathology:
o Interstitial fibrosis, mononuclear infiltration, tubular atrophy.
o Tubular basement membrane thickening.

Classification of Causes
1. Acute Interstitial Nephritis (AIN)

 Therapeutic Agents:
o Antibiotics, NSAIDs, diuretics, anticonvulsants, PPIs.
 Infections:
o BK virus (common in transplants).
 Autoimmune:
o Sjögren syndrome, lupus, granulomatosis.
 Obstruction:
o Light-chain cast nephropathy, phosphate nephropathy.

2. Chronic Interstitial Nephritis (CIN)

 Reflux nephropathy, sickle cell disease.

 Chronic toxin exposure: NSAIDs, lithium, heavy metals.
 Metabolic: Hypercalcemia, hyperuricemia, hypokalemia, hyperoxaluria.
 Cystic/Hereditary:
o Polycystic kidney disease, medullary sponge kidney.
Specific Conditions
1. Allergic AIN

 15% of kidney biopsies for unexplained AKI.

 Classical triad: Fever, rash, eosinophilia (rare).
 Treatment: Discontinue offending drug, glucocorticoids for severe cases.

2. Tubulointerstitial Nephritis with Uveitis (TINU)

 Affects predominantly females (3:1), median age 15 years.

 Symptoms: Anterior uveitis, sterile pyuria, mild proteinuria.
 Treatment: Glucocorticoids ± immunosuppressives.

Renal Tubular Acidosis (RTA)

 Type I (Distal RTA):
o Defect in H⁺ secretion.
o Urine pH >5.5, hypokalemia.
o Associated with Sjögren syndrome, lupus.
o Complication: Nephrolithiasis (low urinary citrate).
 Type II (Proximal RTA):
o Defect in HCO₃⁻ reabsorption.
o Initial urine pH >5.5, later <5.5, hypokalemia.
 Type IV (Hyperkalemic RTA):
o Aldosterone deficiency/resistance.
o Urine pH <5.5, hyperkalemia.
o Associated with diabetes, spironolactone use.

Treatment
Acute Interstitial Nephritis (AIN)

1. Initial:
o Withdraw offending agents.
o Correct electrolytes, avoid nephrotoxins.
2. Steroids:
o For severe drug-induced AIN or rapid progression.
 3. Immunosuppressives:
o For autoimmune causes or granulomatous nephritis.

Chronic Interstitial Nephritis (CIN)

1. Supportive:
o Address underlying cause.
o Manage complications (e.g., acidosis, hyperkalemia).
2. Advanced Disease:
o Dialysis for end-stage kidney disease.

Key Takeaways
 AIN is reversible with early intervention; CIN progresses to CKD.
 Diagnosis integrates clinical history, labs, imaging, and biopsy.
 Treatment targets the underlying cause and disease severity.