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Clinical Case: Acute Tubulointerstitial Nephritis

📋 Clinical Presentation

Patient: 54-year-old woman Setting: Outpatient nephrology referral

Chief Complaint: "I've been running a low-grade fever for two weeks and my kidneys feel sore."

History of Present Illness: Mrs. R.M. was started on omeprazole 20 mg daily approximately 3 weeks ago for a new diagnosis of gastroesophageal reflux disease. Ten days after starting the medication, she noticed fatigue, a low-grade fever (38.1 °C), and bilateral flank discomfort. She developed nocturia (3–4 times per night), increased thirst, and noted her urine appeared slightly cloudy. She denies dysuria, urinary frequency, rigors, or recent upper respiratory infection. No recent NSAIDs, antibiotics, or contrast dye exposure. No prior kidney disease.

Past Medical History:

Hypertension (controlled with amlodipine 5 mg)
GERD (newly diagnosed, 3 weeks ago)
No diabetes, no autoimmune disease history

Medications:

Omeprazole 20 mg PO daily (started 3 weeks ago)
Amlodipine 5 mg PO daily

Allergies: Sulfonamides (rash)

Social History: Non-smoker, occasional wine, teacher, no occupational exposures.

Review of Systems:

Mild skin rash on the trunk (maculopapular, appeared 1 week ago)
No joint pain, no eye symptoms, no dry mouth/eyes

🔬 Physical Examination

Parameter	Finding
Temperature	38.2 °C
Blood pressure	138/84 mmHg
Heart rate	88 bpm
SpO₂	98% on room air
BMI	26 kg/m²

General: Mildly ill-appearing, alert and oriented ×3
Skin: Diffuse maculopapular erythematous rash on trunk and upper arms
Abdomen: Soft, mild bilateral costovertebral angle (CVA) tenderness on deep palpation; no guarding or rebound
Cardiovascular / Pulmonary: Normal
Eyes: No redness, no photophobia

🧪 Laboratory Results

Complete Blood Count:

Test	Result	Reference
WBC	9.8 × 10³/µL	4.5–11
Eosinophils	12% (absolute: 1.18 × 10³/µL)	< 0.5 × 10³/µL ↑
Hemoglobin	12.1 g/dL	12–16
Platelets	228 × 10³/µL	150–400

Comprehensive Metabolic Panel:

Test	Result	Reference
Serum creatinine	3.1 mg/dL	0.6–1.1 mg/dL ↑
BUN	38 mg/dL	7–20 mg/dL ↑
eGFR (CKD-EPI)	21 mL/min/1.73m²	> 60
Sodium	138 mEq/L	136–145
Potassium	5.4 mEq/L	3.5–5.0 ↑
Bicarbonate	16 mEq/L	22–29 ↓
Chloride	112 mEq/L	98–107 ↑
Calcium	9.1 mg/dL	8.5–10.5
Glucose	94 mg/dL	70–99

Interpretation: Hyperchloremic metabolic acidosis (non-anion gap; AG = 138 − 112 − 16 = 10), consistent with type 4 or distal RTA pattern from tubular dysfunction.

Urinalysis:

Test	Result
Color	Pale yellow, slightly cloudy
Specific gravity	1.008 (↓ — impaired concentrating ability)
pH	6.5
Protein	1+ (trace, non-nephrotic)
Blood	1+
Leukocyte esterase	3+
Nitrites	Negative
Glucose	Negative

Urine Microscopy (cytocentrifuged, Giemsa-stained):

WBC casts present ✓
Eosinophiluria present (Hansel stain) ✓
RBCs (non-dysmorphic): 5–10/hpf
No bacteria

24-hour urine protein: 380 mg/day (mild proteinuria — not nephrotic range)

Urine β₂-microglobulin: Elevated (proximal tubular dysfunction marker)

Urine electrolytes / tubular function:

Fractional excretion of sodium (FeNa): 3.1% (intrinsic renal, not pre-renal)
Urine anion gap: positive (impaired NH₄⁺ excretion → distal tubular dysfunction)

Serology (to exclude other causes):

ANA, Anti-dsDNA: Negative
ANCA (p and c): Negative
Complement (C3, C4): Normal
Serum IgE: Elevated (2.4× upper limit of normal)
Blood cultures: Negative ×2
Urine culture: No growth

🔍 Imaging

Renal Ultrasound:

Bilateral kidneys normal in size (right 11.2 cm, left 11.0 cm)
Increased echogenicity of renal cortex bilaterally — consistent with interstitial edema and inflammation
No hydronephrosis, no nephrolithiasis, no masses
Normal resistive indices on Doppler

🧫 Renal Biopsy

Indication: Unexplained AKI with eGFR < 30 mL/min/1.73m², no improvement at 5 days after drug withdrawal.

Light Microscopy (H&E):

H&E biopsy showing interstitial infiltrate with lymphocytes, plasma cells, eosinophils, and tubulitis in acute tubulointerstitial nephritis

Renal biopsy (H&E): Diffuse interstitial edema with a mixed inflammatory infiltrate — predominantly T lymphocytes and plasma cells with scattered eosinophils. Tubulitis is evident as lymphocytes disrupting tubular epithelium. Glomeruli appear relatively preserved (no proliferative or necrotizing lesions).

Findings:

Diffuse interstitial edema with mononuclear infiltrate (lymphocytes, macrophages, plasma cells)
Scattered eosinophils within the interstitium
Tubulitis: lymphocytes infiltrating tubular epithelium
Glomeruli: normal (no nephrotic or nephritic pattern)
No granulomas, no vasculitis, no immune deposits on IF
Immunofluorescence: Negative for IgG, IgA, IgM, C3, C1q

Conclusion: Acute hypersensitivity tubulointerstitial nephritis — consistent with drug-induced (PPI) etiology.

🩺 Differential Diagnosis

Diagnosis	Arguments For	Arguments Against
Acute TIN (drug-induced, PPI)	Temporal relation to omeprazole, eosinophilia, rash, fever, WBC casts, biopsy findings	—
Acute pyelonephritis	Pyuria, fever, CVA tenderness	Negative urine/blood culture, no nitrites, biopsy shows no bacteria
Acute tubular necrosis (ATN)	AKI, FeNa > 1%	No granular muddy casts, no hemodynamic insult, eosinophiluria, rash
ANCA-associated nephritis	AKI, hematuria	ANCA negative, no glomerular lesions on biopsy
Lupus nephritis (Class III/IV)	AKI, female patient	ANA/anti-dsDNA negative, no immune deposits on IF
Prerenal AKI	Creatinine elevation	FeNa 3.1%, no signs of volume depletion, no response to fluids

✅ Final Diagnosis

Acute Allergic Tubulointerstitial Nephritis (ATIN) secondary to Omeprazole (proton pump inhibitor)

💊 Management

1. Immediate

Discontinue omeprazole immediately — withdrawal of the offending agent is the cornerstone of treatment
Switch GERD management to an H₂-blocker (famotidine) — different class, no cross-reactivity
IV hydration (NS 0.9%) if volume-depleted; maintain adequate urine output

2. Corticosteroid Therapy

Given biopsy-confirmed ATIN with persistent AKI at 5 days after drug withdrawal:

Prednisone 1 mg/kg/day (max 60 mg/day) × 4 weeks, then taper over 4 weeks
Consider methylprednisolone IV pulse if creatinine continues to rise

3. Monitoring

Daily creatinine and electrolytes during acute phase
Bicarbonate supplementation for acidosis (target HCO₃⁻ ≥ 20 mEq/L)
Dietary potassium restriction while hyperkalemia persists
Monitor blood pressure closely (may worsen transiently with steroids)
Repeat creatinine at 4, 8, and 12 weeks

4. Outcome Counseling

Most patients recover with creatinine returning toward baseline over weeks to months
Older patients and those with delayed diagnosis are at higher risk for incomplete recovery
Avoid all PPI agents in future; document allergy/adverse drug reaction

📖 Pathophysiology Summary

Causes of acute tubulointerstitial nephritis — allergic, drug toxicity, immune, and infectious mechanisms

Figure: Etiologic categories of acute tubulointerstitial nephritis (Harrison's Principles of Internal Medicine, 22e).

The mechanism in drug-induced ATIN involves the offending drug being secreted into the tubular lumen, where it covalently binds to tubular cell components, creating immunogenic neoantigens. This triggers both type I (IgE-mediated, explaining eosinophilia and rash) and type IV (T cell-mediated) hypersensitivity reactions. The resultant immune injury causes interstitial edema, inflammatory infiltration, tubular dysfunction, and — if unchecked — tubular atrophy and interstitial fibrosis. — Robbins & Kumar Basic Pathology (Robbins Pathology)

PPIs are now among the most common causes of ATIN, alongside NSAIDs, synthetic penicillins, fluoroquinolones, and cephalosporins. The classic triad of fever + rash + eosinophilia is present in fewer than one-third of cases and is atypical for NSAID- and PPI-induced ATIN specifically — making drug exposure history and biopsy central to diagnosis. — Harrison's Principles of Internal Medicine, 22e

Sources:

Harrison's Principles of Internal Medicine, 22e (2025), Chapter 319
Robbins & Kumar Basic Pathology (Robbins Pathology), Chapter 12
Robbins, Cotran & Kumar Pathologic Basis of Disease, Chapter 20

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Clinical Case: Acute Tubulointerstitial Nephritis (ATIN)

Patient Presentation

Patient: 67-year-old male, retired mechanic Setting: Emergency Department, referred from primary care

Chief Complaint: Progressive fatigue, decreased urine output, and flank discomfort for 10 days.

History of Present Illness

Mr. J.V. was diagnosed with Helicobacter pylori-associated peptic ulcer disease 4 weeks ago and was started on a triple therapy regimen including omeprazole 40 mg twice daily, amoxicillin, and clarithromycin. He completed the antibiotic course 2 weeks ago but continued on omeprazole. Approximately 12 days ago he noticed progressively worsening fatigue, bilateral flank aching, reduced urine output (no complete anuria), and new-onset nocturia (waking 3–4 times per night). He also reports a low-grade fever at home (~37.9 °C) and a pruritic, blotchy skin rash that appeared on his trunk and arms one week ago.

He denies dysuria, gross hematuria, recent vomiting, diarrhea, or changes in fluid intake. No recent contrast studies or nephrotoxic medications. No prior history of kidney disease.

Past Medical History:

Hypertension — well controlled on losartan 50 mg/day for 3 years
Dyslipidemia — rosuvastatin 10 mg/day
Peptic ulcer disease (new diagnosis, 4 weeks ago)
No diabetes, no autoimmune disease

Current Medications:

Losartan 50 mg PO daily
Rosuvastatin 10 mg PO nightly
Omeprazole 40 mg PO twice daily (started 4 weeks ago) ← offending agent
Amoxicillin + clarithromycin (completed 2 weeks ago)

Allergies: Penicillin (rash in childhood — documented)

Social History: Retired, non-smoker, rare alcohol use. No herbal supplements or OTC NSAID use.

Physical Examination

Parameter	Finding
Temperature	38.3 °C
Blood pressure	148/90 mmHg
Heart rate	94 bpm, regular
Respiratory rate	16/min
SpO₂	97% on room air
Weight	81 kg

General: Mildly ill-appearing, fatigued but alert and oriented ×3.

Skin: Diffuse maculopapular, erythematous rash covering the trunk, upper arms, and upper back. Non-vesicular, mildly pruritic.

Abdomen: Soft, non-distended. Bilateral costovertebral angle (CVA) tenderness on firm palpation. No peritoneal signs.

Cardiovascular: Regular rhythm, no murmurs. No signs of volume overload (no peripheral edema, no raised JVP).

Eyes: Clear, no conjunctival injection, no photophobia.

Lymph nodes: No lymphadenopathy.

Diagnostic Workup

Complete Blood Count

Test	Result	Reference Range
WBC	10.2 × 10³/µL	4.5–11.0
Eosinophils	14% → 1.43 × 10³/µL	< 0.5 × 10³/µL ↑
Hemoglobin	11.8 g/dL	13.5–17.5 ↓ (mild normocytic anemia)
MCV	87 fL	80–100
Platelets	214 × 10³/µL	150–400

Comprehensive Metabolic Panel

Test	Result	Reference Range
Serum Creatinine	4.2 mg/dL	0.7–1.3 mg/dL ↑↑
BUN	52 mg/dL	7–20 mg/dL ↑↑
eGFR (CKD-EPI)	14 mL/min/1.73 m²	>60
BUN/Creatinine ratio	12.4	(intrinsic renal pattern, not prerenal)
Sodium	136 mEq/L	136–145
Potassium	5.6 mEq/L	3.5–5.0 ↑
Bicarbonate	14 mEq/L	22–29 ↓
Chloride	110 mEq/L	98–107 ↑
Anion gap	136 − 110 − 14 = 12 mEq/L	(normal AG → hyperchloremic metabolic acidosis)
Calcium	9.3 mg/dL	8.5–10.5
Phosphorus	5.8 mg/dL	2.5–4.5 ↑
Albumin	3.6 g/dL	3.5–5.0
Total bilirubin	0.7 mg/dL	Normal
AST/ALT	Normal

Acid-base interpretation: Hyperchloremic, normal anion gap metabolic acidosis — consistent with impaired tubular H⁺ secretion (distal RTA pattern) and/or reduced ammoniagenesis due to tubular dysfunction.

Urinalysis

Test	Result
Color	Pale yellow, cloudy
Specific gravity	1.007 (↓ — impaired urinary concentrating ability)
pH	6.5
Protein	2+
Blood	1+
Leukocyte esterase	3+
Nitrites	Negative
Glucose	Negative (no glucosuria despite AKI)

Urine Microscopy (Giemsa-stained cytocentrifuged preparation)

Finding	Result
WBC casts	Present ✓
Eosinophiluria (Hansel stain)	Present ✓
Non-dysmorphic RBCs	8–12/hpf
Renal tubular epithelial cells	Present
Bacteria	Absent
Granular (muddy) casts	Absent

Additional Urine Studies

Test	Result	Interpretation
Spot urine protein/creatinine ratio	0.8 g/g	Moderate proteinuria — subnephrotic
Urine β₂-microglobulin	Elevated	Proximal tubular dysfunction
FeNa	2.8%	Intrinsic renal injury (not prerenal)
Urine anion gap	Positive (+12 mEq/L)	Impaired NH₄⁺ excretion — distal tubular dysfunction
Urine culture	No growth

Serologic Workup (to exclude secondary causes)

Test	Result
ANA	Negative
Anti-dsDNA	Negative
ANCA (c-ANCA, p-ANCA)	Negative
Anti-GBM antibody	Negative
Complement (C3, C4)	Normal
Serum IgE	Elevated (3× upper limit of normal)
Serum protein electrophoresis	No monoclonal band
HIV, Hepatitis B surface antigen, Anti-HCV	Negative
Blood cultures ×2	Negative

Imaging

Renal Ultrasound

Right kidney: 11.4 cm | Left kidney: 11.1 cm (mildly enlarged, consistent with edema)
Increased bilateral cortical echogenicity — reflects interstitial inflammation and edema
No hydronephrosis, no nephrolithiasis, no renal masses
Normal Doppler waveforms; resistive index mildly elevated (0.74)

Ultrasound findings are neither sensitive nor specific for ATIN but help exclude obstruction and structural causes. Renal volume can increase up to 100% in ATIN due to interstitial edema and inflammatory infiltration. — Brenner and Rector's The Kidney

Renal Biopsy

Indication: Unexplained AKI with eGFR 14 mL/min/1.73 m², no spontaneous improvement at 5 days after drug withdrawal, biopsy needed to confirm diagnosis and guide steroid therapy.

Light Microscopy (H&E stain)

Renal biopsy H&E: diffuse interstitial edema with mononuclear inflammatory infiltrate, scattered eosinophils, tubulitis with lymphocyte infiltration of tubular epithelium, and relatively preserved glomeruli — pattern of acute tubulointerstitial nephritis

Renal biopsy (H&E stain): Diffuse interstitial edema with a mononuclear inflammatory infiltrate comprising T lymphocytes, plasma cells, and macrophages, with scattered eosinophils. Tubulitis is evident as lymphocytes infiltrating tubular epithelium. Glomeruli appear relatively preserved with no proliferative or necrotizing lesions.

Histologic Findings Summary

Compartment	Finding
Interstitium	Diffuse edema; dense mononuclear infiltrate (lymphocytes, macrophages, plasma cells)
Eosinophils	Scattered within interstitium ✓
Tubulitis	Lymphocytes breaching and disrupting tubular epithelium ✓
Glomeruli	Normal — no crescents, no endocapillary proliferation, no necrosis
Vessels	No vasculitis
Granulomas	Absent

Immunofluorescence

Negative for IgG, IgA, IgM, C3, C1q, fibrin — no immune complex deposits

Electron Microscopy

No dense deposits
Foot process effacement absent (no concurrent minimal change disease)

Histologic hallmarks of ATIN: interstitial inflammatory cellular infiltrate, variable tubular injury, interstitial edema, and tubulitis. — Brenner and Rector's The Kidney

Etiology Classification

Etiologic classification of acute tubulointerstitial nephritis: allergic (antibiotics, allopurinol, PPIs), drug toxicity (NSAIDs, checkpoint inhibitors, lithium), immune-mediated (SLE, Sjögren's, sarcoid), and infectious causes

Figure 319-2: Etiologic categories of acute tubulointerstitial nephritis. — Harrison's Principles of Internal Medicine, 22e

Differential Diagnosis

Diagnosis	Evidence For	Evidence Against
ATIN — drug-induced (omeprazole/clarithromycin) ✓	Temporal drug exposure, fever, rash, eosinophilia, WBC casts, eosinophiluria, biopsy findings, elevated IgE	—
Acute pyelonephritis	Fever, pyuria, CVA tenderness	Negative urine/blood cultures, no nitrites, no bacteria on microscopy, biopsy non-purulent
Acute tubular necrosis (ATN)	AKI, FeNa > 1%	No hemodynamic insult, no granular casts, eosinophiluria and rash present, biopsy shows mononuclear infiltrate not tubular necrosis
ANCA-associated interstitial nephritis	AKI, hematuria	ANCA negative, no glomerular crescents on biopsy
Lupus nephritis	AKI, female excluded but considered	ANA/anti-dsDNA negative, no immune deposits on IF, complement normal
Multiple myeloma / cast nephropathy	Elderly male, AKI	Normal SPEP, no monoclonal casts on biopsy
Prerenal AKI	Reduced urine output	FeNa 2.8%, BUN/Cr ratio 12.4, no volume depletion on exam

Diagnosis

Acute Allergic Tubulointerstitial Nephritis (ATIN), drug-induced — most likely attributable to omeprazole (proton pump inhibitor)

The clinical triad of fever, rash, and eosinophilia — present in this patient — occurs in only approximately 5–10% of unselected ATIN cases and should not be relied upon as a required criterion. Most patients present with subacute kidney function decline with or without this triad. — Brenner and Rector's The Kidney

Pathophysiology

Drugs secreted into the tubular lumen can covalently bind to tubular cell cytoplasmic or extracellular components, creating immunogenic neoantigens. The resultant immune injury is mediated by:

Type I hypersensitivity (IgE-mediated): explains eosinophilia, elevated serum IgE, and skin rash
Type IV hypersensitivity (T cell–mediated): drives the mononuclear interstitial infiltrate, tubulitis, and tubular injury

The idiosyncratic nature of the reaction (not dose-dependent), the latent period of 1–4 weeks from exposure, and recurrence on re-exposure are hallmarks of an immune-mediated mechanism. — Robbins & Kumar Basic Pathology

Management

Step 1 — Remove the Offending Agent (Immediate)

Discontinue omeprazole immediately. Drug withdrawal is the cornerstone of treatment and can be sufficient for mild cases.
Switch acid suppression to famotidine (H₂-blocker) — different drug class, no cross-reactivity with PPI-induced ATIN.
Document omeprazole (and class) as an adverse drug reaction in the medical record.

Step 2 — Corticosteroid Therapy

Given persistent AKI (eGFR 14 mL/min/1.73 m²) and biopsy confirmation with no spontaneous improvement at 5 days:

Prednisone 1 mg/kg/day (max 60 mg/day) orally for 4 weeks
Taper over an additional 4 weeks (total 8-week course)
Corticosteroids are supported by immunologic rationale and observational data; the extensive T-cell inflammatory infiltrate on biopsy is the basis for immunosuppressive therapy — Brenner and Rector's The Kidney

Step 3 — Supportive Care

Problem	Intervention
Hyperkalemia (K⁺ 5.6 mEq/L)	Low-potassium diet; patiromer or kayexalate if persistent
Metabolic acidosis (HCO₃⁻ 14)	Oral sodium bicarbonate supplementation (target HCO₃⁻ ≥ 20)
Hypertension (148/90 on losartan)	Continue losartan with close monitoring of K⁺ and creatinine
Hyperphosphatemia	Dietary phosphate restriction; consider binder if persistent
Volume status	Careful IV NS if clinically hypovolemic; avoid overhydration

Step 4 — Monitoring and Follow-up

Daily creatinine, electrolytes, and urine output during acute hospitalization
Weekly creatinine for 4 weeks after discharge
Creatinine targets: return toward baseline within 4–12 weeks in responsive patients
Ophthalmology referral not needed in this case (no ocular symptoms), but note: bilateral red eyes + AKI should prompt evaluation for TINU syndrome (tubulointerstitial nephritis and uveitis)
Avoid all PPI agents permanently; document allergy/ADR

Prognosis

Most patients with drug-induced ATIN recover kidney function following drug withdrawal, though recovery may take several months. Older patients and those with delayed diagnosis carry higher risk of incomplete recovery. Persistent tubular dysfunction (impaired concentrating ability, tubular acidosis) may outlast the acute phase. — Harrison's Principles of Internal Medicine, 22e; Robbins & Kumar Basic Pathology

Teaching Points

The classic triad (fever + rash + eosinophilia) is present in fewer than 10% of ATIN cases — its absence does not exclude the diagnosis.
PPIs are now among the most common causes of drug-induced ATIN, alongside NSAIDs, synthetic penicillins, fluoroquinolones, and cephalosporins.
WBC casts and eosinophiluria on urine microscopy are highly suggestive; a cytocentrifuged, Giemsa-stained preparation optimally demonstrates T lymphocytes, eosinophils, and plasma cells.
Kidney biopsy is the gold standard for diagnosis and guides the decision to initiate corticosteroids.
FeNa > 1% in the setting of oliguria points to intrinsic renal injury (not prerenal), narrowing the differential.
Hyperchloremic normal anion gap metabolic acidosis reflects tubular dysfunction (impaired H⁺/NH₄⁺ secretion) — a key distinguishing feature from glomerular disease.
Immunofluorescence negative distinguishes ATIN from immune complex glomerulonephritis.

Sources:

Harrison's Principles of Internal Medicine, 22e (2025), Chapter 319
Brenner and Rector's The Kidney, Chapter 35
Robbins & Kumar Basic Pathology, Chapter 12

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Here is the condensed version of the clinical case:

Clinical Case: Acute Tubulointerstitial Nephritis (ATIN)

Patient Presentation

Patient: 67-year-old male, retired mechanic Setting: Emergency Department

Chief Complaint: Progressive fatigue, decreased urine output, and bilateral flank discomfort for 10 days.

History of Present Illness

Mr. J.V. was diagnosed with H. pylori-associated peptic ulcer disease 4 weeks ago and started on triple therapy (omeprazole 40 mg twice daily, amoxicillin, clarithromycin). He completed antibiotics 2 weeks ago but continued omeprazole. Twelve days ago he developed fatigue, bilateral flank aching, reduced urine output, nocturia (3–4×/night), low-grade fever (~37.9 °C), and a pruritic maculopapular rash on the trunk and arms.

He denies dysuria, gross hematuria, recent NSAID use, or prior kidney disease.

Medications:

Losartan 50 mg/day (hypertension, 3 years)
Rosuvastatin 10 mg/night
Omeprazole 40 mg PO twice daily — started 4 weeks ago ← offending agent

Allergies: Penicillin (childhood rash)

Physical Examination

Parameter	Finding
Temperature	38.3 °C
Blood pressure	148/90 mmHg
Heart rate	94 bpm
SpO₂	97% room air

Skin: Diffuse maculopapular erythematous rash — trunk and upper arms
Abdomen: Soft; bilateral CVA tenderness on deep palpation
Eyes: Clear; no photophobia or conjunctival injection

Laboratory Results

Complete Blood Count

Test	Result	Reference
WBC	10.2 × 10³/µL	4.5–11.0
Eosinophils	14% → 1.43 × 10³/µL	< 0.5 ↑
Hemoglobin	11.8 g/dL	13.5–17.5 ↓

Metabolic Panel

Test	Result	Reference
Serum Creatinine	4.2 mg/dL	0.7–1.3 ↑↑
BUN	52 mg/dL	7–20 ↑↑
eGFR	14 mL/min/1.73 m²	>60
Potassium	5.6 mEq/L	3.5–5.0 ↑
Bicarbonate	14 mEq/L	22–29 ↓
Chloride	110 mEq/L	98–107 ↑
Anion gap	12 mEq/L	(normal)

Hyperchloremic normal anion gap metabolic acidosis → reflects distal tubular dysfunction (impaired H⁺/NH₄⁺ secretion).

Urinalysis & Urine Microscopy

Test	Result
Specific gravity	1.007 ↓ (impaired concentrating ability)
Protein	2+
Leukocyte esterase	3+
Nitrites	Negative
WBC casts	Present ✓
Eosinophiluria (Hansel stain)	Present ✓
Bacteria	Absent
Urine culture	No growth

A cytocentrifuged, Giemsa-stained urine preparation best demonstrates T lymphocytes, eosinophils, and plasma cells — the most characteristic cell types in ATIN. — Harrison's Principles of Internal Medicine, 22e

FeNa: 2.8% (intrinsic renal injury, not prerenal) | Urine β₂-microglobulin: elevated (proximal tubular dysfunction)

Serology

ANA, anti-dsDNA, ANCA, anti-GBM — all negative. Complement normal. Serum IgE elevated (3× ULN). Blood cultures ×2 negative.

Imaging — Renal Ultrasound

Bilateral kidneys mildly enlarged (right 11.4 cm, left 11.1 cm)
Increased cortical echogenicity bilaterally — consistent with interstitial edema
No hydronephrosis, no stones, no masses

Renal volume can increase up to 100% in ATIN due to inflammatory infiltration and interstitial edema; imaging findings are not specific but exclude obstruction. — Brenner and Rector's The Kidney

Renal Biopsy

Indication: Confirmed AKI with eGFR 14 mL/min/1.73 m²; no spontaneous improvement at 5 days after drug withdrawal.

Histology (H&E)

Renal biopsy H&E: diffuse interstitial edema with mononuclear inflammatory infiltrate, scattered eosinophils, tubulitis, and preserved glomeruli — acute tubulointerstitial nephritis

Compartment	Finding
Interstitium	Diffuse edema; dense infiltrate of lymphocytes, macrophages, plasma cells
Eosinophils	Scattered within interstitium ✓
Tubulitis	Lymphocytes infiltrating and disrupting tubular epithelium ✓
Glomeruli	Normal — no crescents, no necrosis
Immunofluorescence	Negative (IgG, IgA, IgM, C3, C1q)

ATIN is characterized by interstitial inflammatory infiltrate, variable tubular injury, interstitial edema, and tubulitis. — Brenner and Rector's The Kidney

Differential Diagnosis

Diagnosis	For	Against
Drug-induced ATIN (omeprazole) ✓	Drug exposure, fever, rash, eosinophilia, WBC casts, biopsy	—
Acute pyelonephritis	Fever, pyuria, CVA tenderness	Negative cultures, no bacteria on biopsy
Acute tubular necrosis	AKI, FeNa > 1%	No hemodynamic insult, no granular casts, eosinophiluria present
ANCA-associated nephritis	AKI, hematuria	ANCA negative, no crescents on biopsy
Prerenal AKI	Oliguria	FeNa 2.8%, no volume depletion

Diagnosis

Acute Allergic Tubulointerstitial Nephritis — drug-induced, attributed to omeprazole (proton pump inhibitor)

The classic triad of fever + rash + eosinophilia occurs in only 5–10% of unselected ATIN cases and should not be required for diagnosis. — Brenner and Rector's The Kidney

Pathophysiology

Omeprazole is secreted into the tubular lumen, where it covalently binds to tubular cell components creating immunogenic neoantigens. Resultant injury involves:

Type I (IgE-mediated): eosinophilia, elevated IgE, skin rash
Type IV (T cell–mediated): mononuclear interstitial infiltrate and tubulitis

The reaction is idiosyncratic (not dose-dependent), with a latent period of 1–4 weeks from exposure. — Robbins & Kumar Basic Pathology

Etiologic categories of ATIN: allergic (antibiotics, PPIs, allopurinol), drug toxicity (NSAIDs, checkpoint inhibitors, lithium), immune-mediated (SLE, Sjögren's, sarcoid), and infections

Figure 319-2: Etiologic categories of acute tubulointerstitial nephritis. — Harrison's Principles of Internal Medicine, 22e

Management

1. Remove the offending agent — Discontinue omeprazole immediately. Switch to famotidine (H₂-blocker, no cross-reactivity). Document as ADR.

2. Corticosteroids — Given biopsy-confirmed ATIN with no improvement at 5 days after withdrawal:

Prednisone 1 mg/kg/day (max 60 mg/day) × 4 weeks, then taper over 4 weeks
Rationale: the extensive T-cell interstitial infiltrate supports immunosuppressive therapy — Brenner and Rector's The Kidney

3. Supportive care:

Problem	Intervention
Hyperkalemia (K⁺ 5.6)	Low-K⁺ diet; patiromer if persistent
Metabolic acidosis (HCO₃⁻ 14)	Oral sodium bicarbonate (target ≥ 20 mEq/L)
Hyperphosphatemia	Dietary restriction; phosphate binder if needed
Hypertension	Continue losartan; monitor K⁺ closely

4. Monitoring: Daily creatinine/electrolytes during admission; weekly creatinine for 4 weeks post-discharge. Most patients recover kidney function following drug withdrawal, though recovery may take several months. Older patients and those with delayed diagnosis are at higher risk for incomplete recovery. — Harrison's Principles of Internal Medicine, 22e; Robbins & Kumar Basic Pathology

Key Teaching Points

The classic triad (fever + rash + eosinophilia) is present in < 10% of ATIN cases — do not rely on it.
PPIs are among the most common causes of drug-induced ATIN today.
WBC casts + eosinophiluria on cytocentrifuged Giemsa-stained urine are the most suggestive urinary findings.
Normal anion gap metabolic acidosis signals tubular dysfunction, distinguishing ATIN from glomerular disease.
Negative IF on biopsy excludes immune complex glomerulonephritis.
Kidney biopsy is the gold standard and guides the decision to initiate corticosteroids.

Sources:

Harrison's Principles of Internal Medicine, 22e (2025), Chapter 319
Brenner and Rector's The Kidney, Chapter 35
Robbins & Kumar Basic Pathology, Chapter 12

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Acute Tubulointerstitial Nephritis

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The presentation contains 12 slides with a dark navy + teal clinical theme:

#	Slide
1	Title Slide — Clinical case cover
2	Patient Presentation — Demographics, HPI, medications (offending drug highlighted)
3	Physical Examination — Vital signs cards + findings
4	Laboratory Results — CBC & Metabolic Panel with color-coded abnormal values
5	Urinalysis & Tubular Function — WBC casts, eosinophiluria, FeNa, β₂-microglobulin, serology
6	Imaging — Renal ultrasound findings
7	Renal Biopsy — Embedded H&E histology image + findings table
8	Etiology & Final Diagnosis — Embedded etiology diagram from Harrison's + diagnosis callout
9	Differential Diagnosis — Table with evidence for/against each dx
10	Pathophysiology — 5-step mechanism (tubular secretion → neoantigen → Type I/IV hypersensitivity → tubular dysfunction)
11	Management — Drug withdrawal → corticosteroids → supportive care → prognosis
12	Key Teaching Points — 6 numbered highlights

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