Tubulointerstitial nephritis (TIN)
Soha Nageb
Lecturer of Internal Medicine
Internal Medicine Department
Faculty of Medicine
MUE
CASE SCENARIO
• A 19-year-old male was involved in a road traffic accident while driving his motorbike. He suffered a
penetrating wound of his left knee joint. There was no clinical suggestion of trauma to his kidneys or
lower urinary tract, and he continued to pass urine normally. Routine urine analysis was unremarka-
ble. Within 3 days, the left knee joint became swollen, painful and inflamed. The patient was febrile.
Pus was aspirated from the knee which grew a penicillin resistant staphylococcus pyogenes and paren-
teral methicillin therapy was commenced. The response to treatment was rapid but, after few days, he
developed a diffuse erythematous skin rash, fever and he became oliguric, serum creatinine, which
was 0.7mg/dl on admission had risen to 5mg/dl. There was no obvious fluid depletion. Examination of
his fluid balance and blood pressure charts were similarly unremarkable. The urine contained blood
and protein but no myoglobin. Serum potassium was 4.9mm/1, full blood count showed an eosino-
philia 10% of a total WBC count of 12.9 x 10³/1, abdominal sonography demonstrated anormal sized
kidneys, with no evidence of urinary tract obstruction.
1. What is the most likely diagnosis?
2. How should the patient be managed?
Definition: a group of Diseases primarily affects the tubules
and interstitium.
• Although the tubules and the interstitium are distinct
functional entities, they are intimately related.
• Injury involving one of them invariably results in damage
to the other.
• Types:
1- Acute tubulointerstitial nephritis (TIN) in
approximately 70% of the cases, acute TIN is due to a
hypersensitivity reaction to drugs, most commonly
drugs of the penicillin family and (NSAID)
2- Chronic tubulointerstitial nephritis.
Pathogenesis:
Tubular damage to the medullary area of the kidney
leads to defects in urine concentration and sodium
conservation with polyuria and salt wasting. Fibrosis
progressing into the cortex leads to loss of excretory
function and uremia.
Pathological picture:
1- Acute, or chronic inflammatory cellular
infiltration of the interstitium
2- Tubular atrophy
3- Interstitial edema or fibrosis.
4- Papillary necrosis in (analgesic abuse, diabetes
mellitus, sickle cell disease)
Reflux nephropathy
❖Vesicoureteral reflux is primarily a disorder of childhood. It is the second most
common cause of chronic tubulointerstitial disease.
❖It occurs because of an incompetent vesicoureteral sphincter
and occurs when urine passes retrograde from the bladder to the
kidneys during voiding.
❖Urine can extravasate into the interstitium, triggering an
inflammatory response that leads to fibrosis over time.
❖The inflammatory response is due to either bacteria or normal urinary components.
Analgesic nephropathy
Pathogenesis:
• Chronic consumption of large amounts of analgesics and NSAIDs leads to chronic
tubulointerstitial nephritis and papillary necrosis.
• These drugs also decrease medullary blood flow
• Ingestion of at least 1 g/day for 3 years is associated with chronic TIN
• Analgesic nephropathy is twice as common in women as in men and presents
typically in middle age.
Presentation; Drug-induced acute TIN. Patients present with fever, arthralgia, skin
rashes, and acute oliguria or non-oliguria kidney injury.
Diagnosis:
1- Many have eosinophilia and eosinophiluria.
2- Renal histology shows an intense interstitial cellular infiltrate, often including
eosinophils, with variable tubular necrosis.
3- Chronic analgesic nephropathy: is usually made on clinical grounds combined with
the non-pathognomonic appearance on imaging (such as ultrasonography or CT
scan), demonstrating small irregularly outlined kidneys.
Fate: Most patients make a good recovery in kidney function, but some may be left with
significant interstitial fibrosis and CKD.
Chinese herb nephropathy
Chinese herbal medicines have been increasingly used e.g. for slimming, and have caused
nephropathy.
Pathogenesis: The causal agent has been identified as aristolochic acid produced due to
fungal contamination of the herbal medicine.
The renal histology is similar to Balkan nephropathy
Clinical Course: is very aggressive. It is characterized by progression to ESKD and a
high incidence of uroepithelial tumors.
Hyperuricemic nephropathy
Pathogenesis: marked hyperuricemia that is usually due to lymphoproliferative or
myeloproliferative disorders. After chemotherapy or radiotherapy, there is rapid lysis of
malignant cells, with the release of large amounts of nucleoprotein and increased uric acid
production. Renal failure is due to intrarenal and extrarenal obstruction caused by the
deposition of uric acid crystals in the collecting ducts, pelvis, and ureters.
Diagnosis: 1- Plasma urate levels are high (hyperuricemia).
2- Ultrasound may demonstrate extrarenal obstruction due to stones, but a negative scan
does not exclude this where there is coexistent intrarenal obstruction.
Management:
1- Drugs lowering urate level:
• Allopurinol
• Febuxostat inhibitor of xanthine oxidase
2- Alkalization by the administration of sodium bicarbonate 600 mg four times daily
and acetazolamide 250 mg three times daily, since uric acid is more soluble in an
alkaline than in an acid medium.
3- In severely oliguric or anuric patients, dialysis is required to lower the plasma urate.
Clinical picture of chronic interstitial nephritis :
A.General Findings
1- Polyuria is common because tubular damage leads to
nephrogenic diabetes insipidus, possibly from vasopressin
insensitivity.
2- Volume depletion can also occur because of a salt-
wasting defect in some individuals.
3- Hyperkalemia: both because the GFR is lower and the distal tubules become
aldosterone resistant.
4- Renal tubular acidosis is common and develops through three possible mechanisms:
(1) reduced ammonia production in the proximal tubules,
(2) Inability to reabsorb bicarbonate in the proximal tubules
3) Decreased excretion of acids
5- oliguria or anuria
6- Increasing uremia.
7- Occasionally a sloughed papilla may cause ureteric colic or produce acute ureteric
obstruction. There may be flank pain or colic (sloughed papillary obstruction).
B. investigations:
1- Urinalysis:
❖Acute TIN, Sterile pyuria (WBCs, white cell cast, esinophiliuria).
❖Chronic TIN is often nonspecific
❖Microscopic or overt hematuria.
❖Sloughed papilla.
2- Proteinuria is typically less than 2 g/day, owing to the inability of the proximal
tubule to reabsorb freely filterable proteins.
3- Abdominal ultrasound
❖Obstructive uropathy: mass lesions, hydroureter, and hydronephrosis
❖Chronic nephritis, kidney is shrunken
4- Papillary necrosis can be detected by C.T. scan
Diagnosis: of all forms depends on a history of drug ingestion or industrial exposure to
nephrotoxins. In patients with unexplained renal impairment with normal-sized kidneys,
renal biopsy must always be undertaken to exclude a treatable tubulointerstitial nephritis
such as granulomatous TIN due to renal sarcoidosis, which may be the first presentation
of sarcoidosis Renal sarcoidosis generally responds rapidly to steroids.
Treatment
Treatment depends on
a- Identifying underlying etiology.
❖Hydronephrosis: obstruction should be promptly relieved to prevent further
tubular damage
❖surgical correction of reflux
❖Analgesic nephropathy requires withdrawal of all analgesics.
b- The degree of interstietial fibrosis on biopsy and likelihood of ESKD
progressesion.
c- Treatment options :
1- Treatment of risk factors for disease progression, such as hypertension and
proteinuria.
2- bicarbonate supplementation to treat metabolic acidosis
3- phosphorus and potassium restriction.
4- Volume repletion
5- Dialysis if needed
