Chronic Interstitial Nephritis (CIN)

How to Cite This Chapter: To KC-Y, Czekalski S, Pawlaczyk K, Drabczyk R. Chronic Interstitial Nephritis (CIN). McMaster Textbook of Internal Medicine. Kraków: Medycyna Praktyczna. Accessed May 24, 2024.
Last Updated: February 13, 2022
Last Reviewed: February 13, 2022
Chapter Information

Definition, Etiology, Pathogenesis Top

Chronic interstitial nephritis (CIN), sometimes also referred to as chronic tubulointerstitial nephritis (CTIN), is a common description referring to a number of various nephropathies characterized by chronic inflammation that originates in the renal interstitium. It is associated with a progressive loss of glomerular filtration rate (GFR) over time and commonly also with tubular dysfunction.

Classification of CIN based on etiology:

1) Drug-induced: Analgesics (phenacetin and acetaminophen [INN paracetamol], either alone or in combination with acetylsalicylic acid [ASA] and caffeine, nonsteroidal anti-inflammatory drugs [NSAIDs]), lithium, calcineurin inhibitors (cyclosporine [INN ciclosporin], tacrolimus), 5-aminosalicylic acid.

2) Toxic: Lead, cadmium, mercury.

3) Chronic pyelonephritis.

4) Renal tuberculosis.

5) Metabolic diseases: Gout, hypercalcemia, hypokalemia.

6) Immune-mediated: Sjögren syndrome, systemic lupus erythematosus, anti–glomerular basement membrane disease, antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, chronic rejection of kidney transplant.

7) Hematologic/malignant: Sickle cell disease, light-chain diseases, lymphoproliferative disorders, multiple myeloma.

8) Vascular diseases: Ischemic nephropathy due to atherosclerosis of the renal arteries.

9) Structural abnormalities of the urinary tract: Obstructive nephropathy, reflux nephropathy.

10) Hereditary: Polycystic kidney disease, Autosomal dominant tubulointerstitial kidney disease, cystinosis, Dent disease, primary hyperoxaluria.

11) Other: Balkan endemic nephropathy, aristolochic acid nephropathy, radiation nephropathy.

Clinical Features and Natural History Top

CIN can remain asymptomatic for a long time, and the early clinical signs suggestive of kidney damage are often neglected by patients and physicians. Clinical features of chronic kidney disease develop gradually, along with a progressive impairment of GFR. A particular complication of some forms of CIN is papillary necrosis, which may be asymptomatic or manifest as renal colic. Common etiologies and features of CIN: Table 1.

Diagnosis Top

Diagnosis is usually established on the basis of clinical manifestations and noninvasive diagnostic tests.

Diagnostic Tests

1. Urinalysis: Specific gravity <1.02 (frequently close to 1.01), proteinuria (<1-2 g/d), leukocyturia of varying severity, sometimes white blood cell casts, less commonly microscopic hematuria.

2. Blood tests: Normocytic anemia, often disproportionately severe for the actual degree of GFR reduction; increased serum creatinine levels and other abnormalities typical for patients with a low GFR; various electrolyte disturbances (hypokalemia or hyperkalemia, hypocalcemia, hypomagnesemia, hyponatremia) and a non–anion gap metabolic acidosis due to renal tubular acidosis, which results from renal tubular dysfunction.

3. Imaging studies: Ultrasonography typically reveals a decreased kidney size and increased echogenicity, sometimes with irregular outlines and scarring.

4. Kidney biopsy is not performed routinely and is reserved for cases of diagnostic uncertainty. Isolation of mycobacterial DNA confirms the diagnosis of tuberculosis.

The demonstration of granuloma and etiologic agents such as acid-fast bacilli and fungal elements provides a clue to the diagnosis. An area of focal cortical necrosis, fragmented irregular broad fungal hyphae within the cytoplasm of giant cells and in the interstitium, associated with dense mixed inflammation and angioinvasion with Zygomycetes have been observed and should be considered in immunocompromised patients.

Treatment Top

1. Elimination of the cause: In early disease this may lead to a significant improvement or even to normalization of renal function (in patients with no interstitial fibrosis and glomerular atrophy).

2. Treatment of CKD: see Chronic Kidney Disease.

Prognosis Top

Prognosis depends on the degree of renal dysfunction (GFR reduction) at the time of diagnosis as well as on treatment options for the underlying condition.


Table 11.8-1. Etiology/types and features of chronic tubulointerstitial nephritis

Type or etiology

Causes/risk factors


Analgesic nephropathy

Excessive analgesic use >3 years in various combinations, including NSAIDs; more frequent in women

Hypertension, nocturia, sterile leukocyturia, hemolytic anemia; characteristic papillary calcifications on CT; small kidneys with irregular outlines, features of papillary necrosis; increased incidence of urinary system cancers

Lithium-associated nephropathy

Treatment with lithium for ~15 years

Proteinuria >1 g/d, hypertension, possibly NDI

Lead nephropathy

Long-term exposure to lead (lead smelters, paint or battery manufacturing/recycling plants, oil refineries)

Serum lead may not be elevated but urinary lead excretion (>0.6 mg/d after IV infusion of sodium versenate) is evidence of increased lead burden; high serum uric acid, gout (~50%)

Uric acid (gouty) nephropathy

Long-standing inconsistently treated hyperuricemia

Hypertension, proteinuria <1 g/d, decreased urinary concentrating ability, frequently uric acid nephrolithiasis

Hypercalcemic nephropathy

Chronic hypercalcemia

NDI (~20%), renal sodium loss, distal RTA; possible nephrocalcinosis and urolithiasis; acute hypercalcemia may be cause of AKI

Hypokalemic nephropathy

Chronic hypokalemia

Extrarenal symptoms of hypokalemia; NDI, renal cysts

Hyperoxaluric nephropathy

Congenital metabolic defect (primary hyperoxaluria); complication of extensive small bowel resection or gastric/bariatric bypass surgery or in patients with IBD

Nephrocalcinosis, nephrolithiasis

Sjögren syndrome


Symptoms of underlying condition (CIN develops within 2-4 y of disease onset); NDI (~10%), distal RTA (~5%), renal potassium loss

Radiation nephritis

Several years after exposure to cumulative radiation dose >23 Gy (2300 rad)

Hypertension, proteinuria, slow reduction in GFR

Aristolochic acid nephropathy (Chinese herbal nephropathy)

Chinese herbal preparations (made of Aristolochia plant, traditional Chinese names: Mu Tong, Fang Ji) that contain aristolochic acid (nephrotoxic alkaloid; used for weight loss or skin diseases)

Moderate proteinuria, glycosuria, no abnormalities of urinary sediment; severe anemia; diagnosis confirmed by detection of metabolites of aristolochic acid in DNA of renal cells; rapid GFR impairment, which may be partially inhibited by glucocorticoids; RRT necessary in >80% of patients within 2 years; urinary system cancers develop in 40%-50%

Balkan endemic nephropathy

Endemic along tributaries of the Danube River (Bulgaria, Romania, Bosnia and Herzegovina, Croatia, Serbia); long-term exposure to aristolochic acid contained in cereal products plus genetic predisposition

Progressive anemia and GFR reduction, rarely hypertension; ESRD develops within 15-20 years; ~100-fold increase in incidence of urinary system cancers

Hereditary interstitial kidney diseases

Include autosomal recessive disorders (nephronophthisis) diagnosed in children and autosomal dominant disorders (ADTKD) typically diagnosed in adulthood

– Nephronophthisis (form of ciliopathy); ESRD in teenagers to patients in their 20s, salt wasting, urinary concentrating defect, occasional medullary cysts on US, extrarenal involvement (CNS, liver)

– ADTKD: Slowly progressive kidney failure, bland urinalysis, unremarkable renal US; strong family history of ESRD in patients in their 30s-60s. More common mutations include UMOD gene encoding uromodulin (may present with history of gout), MUC1 gene encoding mucin 1, and REN gene encoding renin (may present with mild hypotension and hyperkalemia)

Papillary necrosis

Ischemic or toxic kidney damage (analgesics, NSAIDs); risk factors: diabetes, urinary obstruction, UTI, analgesics, NSAIDs

Polyuria, nocturia, renal colic; urinalysis: proteinuria, leukocyturia, microscopic hematuria; diagnosis: urography, antegrade pyelography

ADTKD, autosomal dominant tubulointerstitial kidney disease; AKI, acute kidney injury; CIN, chronic interstitial nephritis; CNS, central nervous system; CT, computed tomography; ESRD, end-stage renal disease; GFR, glomerular filtration rate; IBD, inflammatory bowel disease; NDI, nephrogenic diabetes insipidus; NSAID, nonsteroidal anti-inflammatory drug; RRT, renal replacement therapy; RTA, renal tubular acidosis; US, ultrasonography; UTI, urinary tract infection.

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