URINARY BIOMARKERS FOR NON INVASIVE DIAGNOSIS OF ACUTE INTERSTITIAL NEPHRITIS

Introduction:

Acute interstitial nephritis has been found in 5-15% of hospitalized patients with AKI.[1] AIN is not frequently reported due to diagnostic hurdles as a kidney biopsy is required to establish a definitive diagnosis and etiology.[2]Kidney biopsies are deemed too aggressive a procedure and empirical treatments (drug withdrawal, corticosteroids) are recommended. The aging kidneys, on the other hand, may be more susceptible to the development of chronic kidney disease (CKD) when the diagnosis and treatment of AIN are delayed. Hence it is useful to develop non invasive urinary biomarkers like MCP-1 and TNF-alpha.[2]This study was conducted to investigate the utility of urinary biomarkers in the non invasive diagnosis of acute interstitial nephritis.

Methods:

 After obtaining approval from IEC, the study was performed for 20 months. All the hospitalized patients with unexplained renal failure were included in the study and  urinary MCP-1 and TNF alpha levels were estimated in them.25 controls in whom urinary tract infection had been ruled out by urine routine examination and culture were also tested. Urinary MCP-1 levels and TNF alpha were measured by ELISA (R and D systems and Abbkine respectively). Urine MCP-1 and TNF alpha levels were standardized to urinary creatinine measured in the same spot urine.

Results:

In total, 800 AKI patients were screened of which 65 patients had unidentified etiology and urinary markers were estimated in them. Out of the 65 patients, 27 patients had undergone kidney biopsy and  10 patients had AIN, 13 patients had glomerular disease and 4 patients had ATN. The urinary levels of inflammatory markers were compared in patients with a biopsy proven diagnosis. Only AIN patients had elevated levels and all other patients (biopsy proven ATN or glomerulonephritis or other diagnoses) had substantially lower levels. Hence it is very likely that patients with elevated urinary TNF alpha levels and/or urinary MCP-1 levels (more than 90th percentile of normal values) have AIN. In our study, the average urinary MCP-1 was 893.6 ng/mmol Cr and average urinary TNF alpha was 116.2 ng/mmol Cr, both well above the levels seen in other diseases and controls (Figure 1). This validates the results from previous studies[3] [4]  that Urinary TNF alpha and urinary MCP-1 levels can discriminate AIN well from the other causes of acute kidney injury.

Figure 1: Box and plot diagram comparing urinary tumor necrosis factor alpha and monocyte chemoattractant protein-1 levels among various etiological subgroups and controls. AIN: Acute interstitial nephritis, GN: Glomerulonephritis, CGN: Chronic glomerulonephritis, ATN: Acute tubular necrosis

Conclusions:

Either urinary MCP-1 or urinary TNF alpha can be useful for the non-invasive diagnosis of acute interstitial nephritis.

References:

1.   Sathick IJ, Zand L, Kamal AN, Norby SM, Garovic VD. Acute Interstitial Nephritis: Etiology, Pathogenesis, Diagnosis, Treatment and Prognosis. Nephrol Res Rev 2013;5(1):13–20.

2.   Nussbaum EZ, Perazella MA. Diagnosing acute interstitial nephritis: considerations for clinicians. Clin Kidney J 2019;sfz080.

3.   Wu Y, Yang L, Su T, Wang C, Liu G, Li X mei. Pathological significance of a panel of urinary biomarkers in patients with drug-induced tubulointerstitial nephritis. Clin J Am Soc Nephrol CJASN 2010;5(11):1954–9.

4.   Moledina DG, Parikh CR. Differentiating Acute Interstitial Nephritis from Acute Tubular Injury: A Challenge for Clinicians. Nephron 2019;143(3):211–6.

I have no potential conflict of interest to disclose.

I did not use generative AI and AI-assisted technologies in the writing process.