EFFICACY OF CORTICOSTEROIDS IN ACUTE INTERSTITIAL NEPHRITIS AND THE IMPACT OF HISTOPATHOLOGICAL CHRONICITY: A SINGLE-CENTRE RESTROSPECTIVE OBSERVATIONAL STUDY IN THE UK

Acute interstitial nephritis (AIN) is a significant and potentially reversible cause of acute kidney injury (AKI), characterized by an inflammatory infiltrate within the renal interstitium and tubules. AIN, though often underdiagnosed due to nonspecific symptoms, makes up about 15–27% of biopsy-confirmed AKI cases. Hypersensitivity reactions to medications, infections, or autoimmune diseases usually precipitate this condition. Drug-induced AIN, particularly from antibiotics, proton pump inhibitors, and non-steroidal anti-inflammatory drugs (NSAIDs), remains the most common aetiology. The potential reversibility of AIN offers hope for effective treatment and recovery.

The diagnosis of AIN is frequently supported by renal biopsy, which reveals interstitial inflammation, oedema, and varying degrees of tubular damage. Ancillary findings such as sterile pyuria, white blood cell casts, and low-grade proteinuria further support the diagnosis, although these are not universally present. If left untreated, AIN can lead to chronic kidney disease and end-stage renal disease. Treatment usually includes stopping the causative agent and starting corticosteroids, mainly prednisolone. The benefits must be weighed against potential side effects, including hyperglycaemia, hypertension, weight gain, infections, and osteoporosis. However, there remains variability in the initiation timing, dosage, tapering schedules, and cumulative steroid exposure, with limited consensus on the optimal treatment protocol.

We retrospectively identified 173 patients at Birmingham Heartlands Hospital diagnosed with Acute Interstitial Nephritis (AIN) via native kidney biopsy between 2002 and 2024. The study focused on patients diagnosed between 2012 and 2024 due to the availability of more comprehensive and reliable patient data. The histopathology reports of the remaining patients were reviewed. Patients who exhibited symptoms of chronic interstitial nephritis were excluded, so only those with acute disease were part of the study. As a result, 81 patients with biopsy-proven acute interstitial nephritis were selected, of which 70 patients were included in this study's data set for analysis after excluding six patients who were not started on steroids and five patients who died before 12 months of follow-up; none of those deaths were related to kidney problems.

This comprehensive study aims to evaluate the precipitating factors and response to steroids in patients diagnosed with AIN. Key considerations include initial dose, taper duration, total dose, side effects, and potential need for restarting or escalating to dialysis. Additionally, this study examines the renal trajectory through changes in serum creatinine and estimated glomerular filtration rate (eGFR) from baseline, at diagnosis, and throughout treatment. Clinical outcomes in patients are associated with biopsy findings such as interstitial fibrosis, tubular atrophy, and glomerular sclerosis. The albumin-to-creatinine ratio (ACR) and protein-to-creatinine ratio (PCR) are urine biomarkers monitored over time to assess their effectiveness in evaluating treatment response.    

Glomerular sclerosis classification is based on the number of glomeruli sclerosed out of the number of glomeruli seen in the biopsy. The classification is as follows: grade 1 indicates no glomerular sclerosis, grade 2 covers cases with less than 10%, grade 3 includes 10% to 25%, grade 4 ranges from 25% to 50%, grade 5 applies to 50% to 75%, and grade 6 refers to 75% to 100% glomerular sclerosis.  No IFTA as grade 0, Mild IFTA as grade 1, and Moderate IFTA as grade 2. Chronicity was categorised as none, mild, or moderate.

The results were evaluated 12 months after prednisolone treatment began. The primary outcome was improved serum creatinine at the time of diagnosis and at the end of 12 months after the steroid treatment. Complete recovery was considered when serum creatinine levels returned to within 25% of the baseline value, whereas partial recovery referred to improvement within 50% of the baseline.   Secondary outcomes included age, sex, underlying cause, initial steroid dose, total cumulative steroid dose, biopsy results relating to renal function recovery, and whether dialysis was required.

Our study involved a total of 70 adult patients diagnosed with acute interstitial nephritis through renal biopsy. This group comprised 32 men (45.7%) and 38 women (54.3%), with a mean age of 61.6 and a median age of 65. Most patients fell within the age group of 50-70 (41.4%), followed by the age group of 70-90 (35.7%).

The most common cause of interstitial nephritis is drugs, 65.6% (47), of which Proton pump inhibitors are 34.3% (24), non-steroidal anti-inflammatory drugs are 15.7% (11), and antibiotics are 11.4% (8), followed by unknown cause, 19.8% (14), and infection, 10% (7)

Of the 70 patients, 72.9% (51) responded positively to treatment, with 55.7% (39) achieving complete recovery and 17.1% (12) experiencing partial recovery. However, 18.6% (13) required dialysis, and 8.5% (6) became dialysis dependent. 

Our findings demonstrate the effectiveness of steroid dosing in treating acute interstitial nephritis. Patients responded well to different doses, with 100% (1/1) responding to prednisolone 20mg once daily, 60% (12/20) to 30 mg once daily, 78.8% (26/33) to 40 mg once daily, 100% (2/2) to 50 mg once daily, and 80% (8/10) to 60 mg once daily. Even when high-dose steroids needed to be restarted, 50% (3/6) of patients responded to treatment.

90.5% (38/42) of nil IFTA responded to treatment, 52.3% (11/21) of mild IFTA responded to treatment, and 28.6% (2/7) of moderate IFTA responded to treatment. 82.7% (43/52) of no chronicity responded to treatment, 62.5% (5/8) of mild chronicity responded to treatment, and only 30% (3/10) of moderate chronicity responded to treatment. 83.8% (31/37) of no glomerulosclerosis responded to treatment, 66.7% (4/6) of less than 10% glomerulosclerosis responded to treatment, 66.7% (10/15) of 10% to 25% glomerulosclerosis responded to treatment, 55.5% (5/9) of 25% to 50% glomerulosclerosis responded to treatment, 50% (1/2) of 50% to 75% glomerulosclerosis responded to treatment, and 0% (0/1) of 75% to 100% glomerulosclerosis responded to treatment.

To our knowledge, this is the first single-centred retrospective study on acute interstitial nephritis in the UK. This study, which investigated patients' histopathological and laboratory findings and measured outcomes at the end of 12 months after starting prednisolone treatment, is significant as it provides unique insights into the management of this condition. The primary outcome of this retrospective observational study has proven the benefit of corticosteroid treatment in improving kidney function in 72.8% (51/70).

The treatment regimen typically commenced with a high dose of prednisolone—commonly 40mg, occasionally 60mg once daily for specific patients—and was usually tapered over two weeks. Notably, females exhibited a slightly higher response to prednisolone than males (81.5% vs 62.5%), with a p-value of 0.074. Drugs were identified as the most common cause of AIN, with a response rate of 65.6% (47). From an aetiological perspective, NSAIDS responded to treatment in 54.5% (6/11) of cases, PPIs in 83.3% (20/24), antibiotic-related AIN in 87.5% (7/8), and infection-related AIN in 85.7% (6/7).

Patients with no or mild evidence of interstitial fibrosis, tubular atrophy, and glomerulosclerosis in renal biopsy have responded well to prednisolone with acute interstitial nephritis. 53.8% (7/13) of patients who commenced haemodialysis have made a remarkable recovery from acute interstitial nephritis and no longer rely on dialysis. This promising outcome instills hope and optimism. However, it's crucial to note that patients with albuminuria of more than 1 g face a high risk of progression to CKD.

Our study underscores the critical importance of early biopsy and prompt treatment with high-dose steroids for acute interstitial nephritis. This approach has been shown to significantly enhance kidney function, thereby mitigating the progressive decline of renal function and reducing the burden of chronic kidney disease and dialysis in the community.