Chronic Interstitial Nephritis (CIN)

Definition, Etiology, PathogenesisTop

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, IgG4-related disease.

8) Renal sarcoidosis.

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

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

11) Hereditary: Polycystic kidney disease, autosomal dominant tubulointerstitial kidney disease, cystinosis, Dent disease, primary hyperoxaluria.

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

Clinical Features and Natural HistoryTop

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.

DiagnosisTop

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.

TreatmentTop

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.

PrognosisTop

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.

TablesTop