Saudi Journal of Kidney Diseases and Transplantation

ORIGINAL ARTICLE
Year
: 2020  |  Volume : 31  |  Issue : 2  |  Page : 335--341

Frequency and etiology of tubulo-interstitial nephritis in an adult renal biopsies in a tertiary renal care hospital: A single-center study


Ruqaya Qureshi, Salman Imtiaz, Murtaza Dhrolia, Aasim Ahmad 
 Department of Nephrology, The Kidney Centre Post Graduate Training Institute, Karachi, Pakistan

Correspondence Address:
Ruqaya Qureshi
Department of Nephrology, The Kidney Centre Post Graduate Training Institute, Karachi
Pakistan

Abstract

Tubulo-interstitial nephritis (TIN) is an important cause of acute renal failure which may progresses to chronic kidney disease (CKD). TIN is often under diagnosed with there are no specific signs and symptoms. As this entity has paramount importance, so we evaluated the frequency and etiological of TIN both acute TIN (ATIN) and chronic tububulo-interstitial nephritis (CTIN) in renal biopsies. This is a retrospective observational, descriptive study carried out in the Department of Nephrology at The Kidney Centre Post Graduate Training Institute from 2004 to 2016. A total of 1560 adult renal biopsies were done during this period with 125 biopsies of TIN, of which 70 (56%) cases were ATIN and 55 (44%), were CTIN. Thirty-eight (30%) patients had a history of taking proton-pump inhibitors, use of various antibiotics in 21 (16%) cases, and 11 (8%) patients had a history of taking Hakeemi (traditional healer using herbs and sometimes trace amounts of heavy metals) medications. The incidence of TIN is higher than suspected and can be caused by variety of etiological agents. Therefore, clinical awareness will help in the diagnosis and early identification of the disease.



How to cite this article:
Qureshi R, Imtiaz S, Dhrolia M, Ahmad A. Frequency and etiology of tubulo-interstitial nephritis in an adult renal biopsies in a tertiary renal care hospital: A single-center study.Saudi J Kidney Dis Transpl 2020;31:335-341


How to cite this URL:
Qureshi R, Imtiaz S, Dhrolia M, Ahmad A. Frequency and etiology of tubulo-interstitial nephritis in an adult renal biopsies in a tertiary renal care hospital: A single-center study. Saudi J Kidney Dis Transpl [serial online] 2020 [cited 2020 Jun 1 ];31:335-341
Available from: http://www.sjkdt.org/text.asp?2020/31/2/335/284007


Full Text



 Introduction



Tubules and interstitium make up about 80% of kidney volume[1] and combined termed as tubulo-interstitial compartment. Pathologies of kidneys can be broadly classified as glome- rular, vascular, and tubulo-interstitial. Tubulo- interstitial nephropathy (TIN) is an important cause of renal dysfunction and causes end-stage renal disease (ESRD) and lifelong renal replacement therapy may be needed in some patients.[2] TIN is associated with immune- mediated infiltration of interstitium of the kidneys by inflammatory cells which can lead to chronic changes and subsequently leads to fibrosis and chronic kidney disease (CKD). Between 1992 and 1995, the percentage of TIN in renal biopsies gradually increased from 2.3% to 16.3%.[3] The incidence of TIN among ESRD patients varies from 42.2% in Scotland,[4] 29% in Berlin,[5] and 27.5% in Delaware county, Pennsylvania in the USA[6] to 25.7% in North Carolina, USA[7] and the percentage of chronic TIN (CTIN) in ESRD in India[8] is 7% and in Pakistan[9] 17%.

TIN can be categorized on the history of duration into acute TIN (ATIN), CTIN or ATIN superimposed on pre-existing CTIN. The causes of TIN include, infections, systemic inflammatory conditions, i.e., tubulo-interstitial nephritis uveitis (TINU) syndrome, inflammatory bowel disease, autoimmune, genetic, and idiopathic. Drug-induced TIN is quite common.[10],[11] A variety of drugs are responsible for causing TIN, rifampicin,[12] penicillin, aminoglycosides, cloxacillin and methotrexate,[13],[14] proton-pump inhibitor (PPI),[15] and nonsteroidal antiinflammatory drugs (NSAIDs)[16] are found in literatures over the past many decades.

TIN accounts for 2% of native renal biop- sies[17] and up to 27% of cases, in whom renal biopsy was performed due to unexplained kidney failure in young patients.[18]

Clinical features of TIN usually vary from nonspecific symptoms such as generalized weak-ness, anorexia, nausea, and low-grade fever. Together with clinical signs and symptoms, the history is very valuable in these patients because it may reveal some important clues which can help in reaching the diagnosis. Enquiry should be about medication history and place of living as water pollution and other factors might help in reaching the diagnosis. Sometimes, an etiological culprit may not be found and renal biopsy reveals CTIN, this entity is labeled as CTIN of unknown etiology. The aim of this study was to determine the main causes and frequency of TIN in renal biopsies performed in our institute.

 Material and Methods



This was an observational, descriptive study carried out in the Department of Nephrology on biopsies performed from 2004 to 2016. Exemption was obtained from Ethical Review Committee of The Kidney Centre Post Graduate Training Institute.

The inclusion criteria were all those biopsies that revealed ATIN or CTIN in in the duration of 12 years. Patients who were <18 years of age and who had other histo-pathological diagnosis in their renal biopsy were excluded from the study.

We reviewed a total of 1560 renal biopsies and 125 biopsies had a diagnosis of TIN.

ATIN was confirmed by the presence of inflammatory cells within the interstitium and CTIN was diagnosed by the presence of interstitial fibrosis with varying degree of chronic inflammatory cells and tubular atrophy.

We divided the duration of various drugs taken by patients for various reasons into several groups, i.e., Group A included those patients which were taken the drugs for <1 week, Group B: between one and two weeks, Group C: between two and four weeks, Group D: one to three months and Group D: who are taking the drugs for >6 months.

Of the southernmost province of Sindh has following districts, Hyderabad, Larkana, Bhanbhor, Shaheed Benazirabad, Sukkur, Mirpurkhas, and Karachi which is further subdivide into Central, EastWest, South, Malir, and Korangi.

 Statistical Analysis



Data analysis was performed using software IBM SPSS Statistics version 21.0 (IBM Corp., Armonk, NY, USA). Categorical variables were described in frequency with percentages. Mean ± standard deviation was used for continuous normally distributed data, while for skewed data, median with interquartile range was used.

 Results



Total number of 125 patients was included in our study, in which 65(52%) were male while 60 (48%) were female. Seventy (56%) cases were ATIN and 55 (44%), were CTIN. Their demographic variables and clinical symptoms of patients are shown in [Table 1] and [Table 2]. In our study, 88 (70%) patients had hypertension (HTN), whereas 46 (36%) were diabetic. Use of PPI was found in 38 (30.4%) and use of antibiotics in 16 (12.8%) [Table 3]. Laboratory parameters at the time of presentation are described in [Table 4]. We divided the duration of various drugs causing ATIN or CTIN into different groups, but we did not found an effective risk factor between the duration and drug group, further characterization is shown in [Table 5].{Table 1}{Table 2}{Table 3}{Table 4}{Table 5}

In our study, patients residing in district Korangi (home to 2,457,019 residents it is the second-largest industrial zone of Karachi and it has dozens of slums) of Karachi had more findings of ATIN [n =18 (25.7%)] and CTIN [n =12 (21.8%)] in their renal biopsies, further description is shown in [Table 5]. The diagnosis of ATIN and CTIN is associated with tubular atrophy and interstitial fibrosis, however mild tubular atrophy is more common in ATIN [17 (24.3%)], whereas moderate and severe were more usual in CTIN [28 (50.9%) and 19 (34.5%], respectively. Similarly, mild interstitial fibrosis is more prevalent is in ATIN as compared to moderate and severe interstitial fibrosis which were more frequent in CTIN [Table 6].{Table 6}

 Discussion



The renal tubulo-interstitium is an often underappreciated compartment of the kidneys but of great importance in acute kidney injury and CKD. TIN is characterized by rapid onset of inflammation of renal tubules that compromises its function, when acute changes to the tubulo-interstitium are not reversible, and then fibrosis occurs which progress the disease toward chronicity and eventually end stage.

In a report from Italy, in which of 14,607 renal biopsies, (of which 89.9% were from native kidneys) TIN was found to be 5.3%.[19] Study done by Rajeev in 2014 revealed that in a period of 10 years, of 3165 renal biopsies, 240 (6.4%) were diagnosed with TIN either acute [n =150 (62%)] or chronic [n = 90 (38%)].[20] In our study, TIN was found in 8% of all biopsies, in which 70 cases (56%) were found to be ATIN and 55 (44%) were found to be CTIN.

The clinical features of TIN may be nonspecific and it is difficult to differentiate with other kidney diseases. HTN was prevalent in our patients as 70% of the patients had a history of HTN, as shown in other study.[21]

In terms of patient’s demography, area of living plays an important role in disease causation because in this era water pollution has a strong contribution toward interstitial nephritis.[22] People are exposed to various potentially toxic agents and conditions in their natural environment. In our study, we divided the population into various districts where they are living, so we found that in the district of Korangi, there was more prevalence of ATIN and CTIN. Low- and middle-income countries have an alarming rise in CKD over the past 20 years much of this may be attributed to TIN.[23] Drugs and herbal medicines[24] are the most common cause of TIN, similar to our study which accounted for 50% for the history of NSAIDs and 38% for PPI and 10% and 11% for homeopathic and Hakeem medications, respectively. Analgesics are widely prescribed drugs worldwide. Study done by Pommer et al confirmed the role of NSAIDs in causation of TIN.[5] Contrary to this Murray et al studied 527 patients from dialysis center and did not find significant relation between nonsteroidal anti- inflammatory drugs and TIN causing ESRD.[25] Besides NSAIDs several antibiotics are also involved in causation of TIN,[26],[27] Richet et al did a study on 976 patients with acute kidney injury, noted that 14% of 218 renal biopsies TIN and these patients had strong history had of taking antibiotics.[28] In our study, over 17% of patients had a history of taking different antibiotics.

In the past in the Chinese population an increased incidence of TIN was found in renal biopsies and reported a strong association between herbal medicines and TIN.[29] The perception of many patients is that herbal/ homeopathic medications are safe and they do not cause harm or side effects and that is why many times in history patient fail to mention these medications which they may betaking for different ailments. Some herbal medications contain heavy metals which may predispose the patient to develop kidney injury.[30]

Kidney biopsy most often show mononuclear and frequently eosinophilic cellular infiltration of the interstitium with sparing of the glome- ruli mostly in ATIN, interstitial changes such as fibrosis and atrophy are also present mostly in CTIN, but tubular atrophy and interstitial fibrosis can be found in ATIN also. In our study, severe interstitial fibrosis was found in 36.4% in CTIN and 10% in ATIN, often the findings are nonspecific and the etiology is not discernible from the biopsy.

 Conclusion



TIN is an important cause of renal dysfunction, it has variety of etiological factors with many associated components. A thorough history and identification of causative agent might lead to cessation of the disease process and prevent the disease to progress into severe form.

Conflict of interest: None declared.

References

1Lemley KV, Kriz W. Anatomy of the renal interstitium. Kidney Int 1991;39:370-81
2Alper AB. Tubulointerstitial Nephritis. Medscape Website; 23 January, 2015
3Chiang PC, Yang CS, Ferng SH, Peng SJ, Hsu HC. Increasing Incidence of Tubulointerstitial Nephritis in Adult Nephropathy. Taipei, Taiwan: Taiwan Society of Nephrology Members Symposium; 1996. p. 67
4Pendreigh DM, Howitt LF, Macdougall AJ, Robson JS, Heasman MA, Kennedy AC, et al. Survey of chronic renal failure in Scotland. Lancet 1972;1:304-7
5Pommer W, Bronder E, Greiser E, Helmert U, Jesdinsky HJ, Klimpel A, et al. Regular analgesic intake and the risk of end-stage renal failure. Am J Nephrol 1989;9:403-12
6Murray TG, Stolley PD, Anthony JC, Schinnar R, Hepler-Smith E, Jeffreys JL. Epidemiologic study of regular analgesic use and end-stage renal disease. Arch Intern Med 1983;143: 1687-93
7Gonwa TA, Hamilton RW, Buckalew VM Jr. Chronic renal failure and end-stage renal disease in Northwest North Carolina. Importance of analgesic-associated nephropathy. Arch Intern Med 1981;141:462-5
8Rajapurkar MM, John GT, Kirpalani AL, Abraham G, Agarwal SK, Almeida AF, et al. What do we know about chronic kidney disease in India: First report of the Indian CKD registry. BMC Nephrol 2012;13:10
9Jeloka TK, Upase S, Chitikeshi S. Monthly cost of three exchanges a day peritoneal dialysis is same as of thrice a week hemodialysis in self-paying Indian patients. Indian J Nephrol 2012;22:39-41
10Andreoli SP. Acute kidney injury in children. Pediatr Nephrol 2009;24:253-63
11Perazella MA, Markowitz GS. Drug-induced acute interstitial nephritis. Nat Rev Nephrol 2010;6:461-70
12Muthukumar T, Jayakumar M, Fernando EM, Muthusethupathi MA. Acute renal failure due to rifampicin: A study of 25 patients. Am J Kidney Dis 2002;40:690-6
13Solomon R, Dauerman HL. Contrast-induced acute kidney injury. Circulation 2010;122: 2451-5
14Widemann BC, Adamson PC. Understanding and managing methotrexate nephrotoxicity. Oncologist 2006;11:694-703
15Torpey N, Barker T, Ross C. Drug-induced tubulo-interstitial nephritis secondary to proton pump inhibitors: Experience from a single UK renal unit. Nephrol Dial Transplant 2004;19: 1441-6
16Michel DM, Kelly CJ. Acute interstitial nephritis. J Am Soc Nephrol 1998;9:506-15
17Clarkson MR, Giblin L, O’Connell FP, O’Kelly P, Walshe JJ, Conlon P, et al. Acute interstitial nephritis: Clinical features and response to corticosteroid therapy. Nephrol Dial Transplant 2004;19:2778-83
18Baker RJ, Pusey CD. The changing profile of acute tubulointerstitial nephritis. Nephrol Dial Transplant 2004;19:8-11
19Gesualdo L, Di Palma AM, Morrone LF, Strippoli GF, Schena FP; Italian Immuno- pathology Group, Italian Society of Nephrology. The Italian experience of the national registry of renal biopsies. Kidney Int 2004;66:890-4
20Raghavan R, Eknoyan G. Acute interstitial nephritis - A reappraisal and update. Clin Nephrol 2014;82:149-62
21Nachman PH, Glassock RJ. Tubulointerstitial diseases: Acute and chronic interstitial nephritis Neph SAP 2012;11:216-17
22Soderland P, Lovekar S, Weiner DE, Brooks DR, Kaufman JS. Chronic kidney disease associated with environmental toxins and exposures. Adv Chronic Kidney Dis 2010;17: 254-64
23Mills KT, Xu Y, Zhang W, Bundy JD, Chen CS, Kelly TN, et al. A systematic analysis of worldwide population-based data on the global burden of chronic kidney disease in 2010. Kidney Int 2015;88:950-7
24Chang CH, Wang YM, Yang AH, Chiang SS. Rapidly progressive interstitial renal fibrosis associated with Chinese herbal medications. Am J Nephrol 2001;21:441-8
25Dubach UC, Rosner B, Pfister E. Epidemio- logic study of abuse of analgesics containing phenacetin. Renal morbidity and mortality (1968-1979). N Engl J Med 1983;308:357-62
26Buysen JG, Houthoff HJ, Krediet RT, Arisz L. Acute interstitial nephritis: A clinical and morphological study in 27 patients. Nephrol Dial Transplant 1990;5:94-9
27Greising J, Trachtman H, Gauthier B, Valderrama E. Acute interstitial nephritis in adolescents and young adults. Child Nephrol Urol 1990;10:189-95
28Richet G, Sraer JD, Kourilsky O, et al. Role of renal biopsy in acute renal failure in ICU setting. Ann Med Intern 1978;129:445-7
29Lin CH, Yang CS. Chinese herbs nephropathy. J Intern Med Taiwan 2002;13:276-81
30Isnard Bagnis C, Deray G, Baumelou A, Le Quintrec M, Vanherweghem JL. Herbs and the kidney. Am J Kidney Dis 2004;44:1-1.