AIN. Decline in renal function characterized by an inflammatory infiltrate in the kidney interstitium

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2 AIN Decline in renal function characterized by an inflammatory infiltrate in the kidney interstitium Present in up to 27% of AKI biopsies 10% over 60yr olds Incidence increasing? Presentation Allergic type: Rash (15%), fever (27%), eosinophillia (23%) Arthralgia (50%) Asymptomatic Oliguria (51%) Systemic disease signs Diagnosis Peripheral eosiniphillia Eosiniphiluria, white cell casts Haematuria Low grade proteinuria Renal biopsy- interstitial inflam infiltrate IF and TA

3 Sarcoidisis SLE SS IgG4-related disease AIN causes Systemic diseases, 10% (Previously Methicillin) Penicillins Cephalosporins Rifampicin Co-trimoxazole Ciprofloxacin Legionella CMV TB EBV E coli Adenovirus TINU, 10% Infections, 10% Other Drugs, 35% Antibiotic Induced, 35% Are steroids effective in AIN?? NSAIDS (proteinuria) PPIs Loop diuretics Thiazide diuretics Cimetidine Allopurinol 5-ASAs

4 Methods AIN renal biopsies over 14 year period Interstitial inflam cell infiltrate Non-atrophic tubules Tubulitis in absence of bacterial infection Retrospective analysis of medical records Age, gender, ethnicity Biopsy features egfr (placed into 4 groups) RRT requirement Drug induced AIN if clearly defined (drug identified and discontinued) Exclusion Criteria Maintenance steroids Co-exisiting glomerular disease on Bx <3 month f/up or missing data

5 Treatments and outcomes Divided into those Rx with steroids and those not (Dose, Rx duration clinician choice) Response to steroids assessed by ΔeGFR from baseline or change in egfr group 1, 3, 6, 12, 24 month and last documented f/up RRT dependence and mortality data collated DI-AIN and TB-AIN analysed separately

6 Statistics Mann Whitney U continuous variables Chi-squared for different proportions between groups Kaplan-Meir survival analyses Matched group analysis Attempt to control for confounding factors Diabetic status, egfr group at biopsy, age (determined by propensity analysis)

7 Results 238/3983 biopsies had AIN (6%) 40 or 60mg po pred 3 pts had prior IV MP Median duration steroids 6/12 (1 week-5 years) 51 excluded: (187 left) 28 insuff data 11 co-existing GN 4 on steroids 8 f/up<3/12

8 Results Steroid Rx group had sig better egfr at 6,12,24 and final f/up Same pattern observed with matched group but n/s Less RRT dependence in steroid Rx group 3.2% vs 20.6% at 6/12 (p<0.001) 5.1% vs 24.1% at 24/12 (p<0.001) 9.4% vs 34.4% at final f/up Less deaths at 3yrs in steroid Rx group 6.9% vs 27.6% (p=0.003)

9 Subgroup analyses DI-AIN v other aetiologies TB-AIN v other aetiologies 48 (27%) of total cases Abx, NSAIDS, PPIs most common culprits More of DI-AIN patients were Rx with steroids (93.8% vs 81.4%, n/s) Worse egfr category at time of Bx in DI group, but higher egfr at all other timepoints ( demonstrating a better response to Rx ) Steroid Rx DI-AIN showed better improvements in SCr by 12 months 5/6 RRT patients in DI-AIN Rx with steroids regained independent RF 26 (15%) of total cases! All Rx with full dose anti-tb Rx for minimum 6/ % had granulomatous IN No e/o AFB on renal Bx 20 patient Rx with steroids, 8 not Rx Rx group were younger (38.4yrs vs 55yrs), had higher egfr (25 vs 19) at time of Bx Rx group had higher egfr at all timepoints and less RRT (5% vs 33% at 6/12)

10 Discussion Discussion This study: Steroids= improved RF and less RRT Benefit more pronounced in DI-AIN g TB-AIN had poorer prognosis vs all o suggestion that steroids beneficial Suggest po pred 1mg/kg to max 8-12/52

11 Critique (STROBE statement for casecontrol observational studies) Valid and important topic addressed Clear inclusion and exclusion criteria Attempt made to select a matched control group, selection bias acknowledged Reasonable patient numbers cf other publications Decent f/up period (median 39 months) Didn t attempt to statistically analyse small group subanalyses Impressive numbers of TB-AIN Some limitations acknowledged Details lacking; Baseline egfr not described, timing of steroid therapy, weaning regime used Selection bias; vast majority of patients were Rx with steroids (29 not treated) Propensity analysis poorly detailed KM survival unadjusted Insufficient statistical evidence to suggest Rx with steroids for TB- AIN Insufficient evidence presented to suggest 1mg/kg pred for 8-12 weeks

12 Dream RCT (Ukidney.com) Multicentre trial All patients with suspected AIN would need a Bx AIN features graded and verified by 2 independent pathologists Randomised 1:1 steroid 1mg/kg (up to 60mg max) for 2 weeks, tapered over further 2 months Primary outcome: RRT need at 3/12 Secondary outcome: ΔSCr/eGFR at 3/12 Assuming a 10% reduction in dialysis dependence (15% to 5%) and a 10% drop-out rate, the total number of patients required in each group would be 204 for a total of 408 individuals.