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Acute tubulo-interstitial nephritis : clinical profile and pathogenic mechanisms

Elmedhem, Abdurrezagh Mansur (2010)
Ph.D. thesis, University of Birmingham.

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Acute tubulointerstitial nephritis (ATIN) is an important cause of renal morbidity. This study showed that it represents up to 8% of acute renal failure where biopsy material was available and accounted for 1% of all renal biopsy material. This study, which is believed to be the largest single retrospective study carried out to date, consists of 78 cases over nineteen years (1984-2002). Forty one cases were males and 37 were females. Acute tubulointerstitial nephritis (ATIN) was divided into three groups according to the cause: drug-induced ATIN, idiopathic ATIN and TINU syndrome. Drug-induced ATIN has come to dominate this area of medicine and in this study it represented 85% of all the cases of ATIN. Comparing the creatinine level at different time points among the the diagnosis groups shows that the creatinine level at presentation was high in patients with drug-induced ATIN compared to patients with TINU syndrome or idiopathic ATIN and the P value was 0.020. Comparison of clinical features investigations with the reversibility of renal function (cr level < 150μmol/l) shows that patients with fever, normal or high haemoglobin level, normal or low potassium level, and normal or low level of phosphate tended to have reversible renal function with P values of 0.021, 0.018, 0.002 and 0.03 respectively. Comparing the result of investigations between the different diagnosis groups showed that the lymphocyte count tended to be lower in drug induced ATIN and TINU syndrome than in idiopathic acute tubulointerstitial nephritis and this difference was statistically significant (P value = 0.026). By one year follow-up, 75% of patients had an improvement in renal function(creatinine level < 150 μmol/l). Comparing the outcome for renal function among the different diagnostic groups showed a significant statistical difference (P values 0.017-30.020). ATIN due to non steroidal anti-inflammatory drugs carried a bad prognosis in comparison to other groups. Histologically, sections of ATIN tissue biopsies showed a strong staining for CD3+ cells, CD4+ cells, CD8+ cells, CD68+ cells, eotaxin, CCR3, VCAM-1, IL-4 and eosinophil proteins. These results suggest that there is a Th 2 type of inflammatory and immune response in acute tubulointerstitial nephritis. Comparison between the infiltrating cells showed no significant difference (P values were between 0.549 and 1.00). Comparison between the infiltrating cells and the renal function outcome shows no relationship. On the other hand, there was a correlation between the CD68 positive cells and the creatinine level at presentation which indicated that there was a tendency for a greater CD68 positive cell infiltration to be associated with a higher creatinine level at presentation, and the P value was 0.003 (r =0.651). Comparison between the index of chronic damage and the reversibility of renal function shows a significant relationship at three months and one year time and the P values were 0.002 and 0.001 respectively (low index of chronic damage associated with low creatinine level). This study also showed no relationship between idiopathic acute tubulointerstitial nephritis and Epstein-Barr virus. This study confirms that ATIN remains an important cause of acute renal failure, that is predominantly drug-related, and that renal biopsy has diagnostic and prognostic significance. Immunological mechanisms are important in pathogenesis with macrophagedependent processes correlating with renal function at presentation. Prognosis is good providing diagnosis and therapeutic intervention occurs before irreversible chronic damage has developed.

Type of Work:Ph.D. thesis.
Supervisor(s):Savage, Caroline
School/Faculty:Colleges (2008 onwards) > College of Medical & Dental Sciences
Department:Department of Immunity and Infection
Subjects:RB Pathology
Institution:University of Birmingham
ID Code:570
This unpublished thesis/dissertation is copyright of the author and/or third parties. The intellectual property rights of the author or third parties in respect of this work are as defined by The Copyright Designs and Patents Act 1988 or as modified by any successor legislation. Any use made of information contained in this thesis/dissertation must be in accordance with that legislation and must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the permission of the copyright holder.
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