TINU syndrome: review of the literature and case report

Marcelo A. Pinheiro Matheus B. C. Rocha Beatriz Oliveira Neri Isabelle Oliveira Parahyba Luis A.R. Moura Claudia Maria Costa de Oliveira Marcos Kubrusly About the authors

Resumo

Introdução:

A síndrome nefrite tubulointersticial e uveíte (síndrome TINU) é uma entidade clínica incomum e a maioria dos pacientes são adolescentes e mulheres jovens. O caso relatado a seguir refere-se a uma paciente idosa com manifestações oftalmológicas que antecederam às renais, sendo provavelmente o primeiro caso descrito no Brasil.

Relato de Caso:

Paciente feminina, 60 anos, procurou atendimento médico por queixa de "olhos vermelhos". Três meses após o primeiro episódio do quadro ocular, a paciente cursou com sintomas sistêmicos e disfunção renal. A biópsia renal evidenciou nefrite tubulointersticial com sinais de atividade.

Discussão:

A fisiopatologia da síndrome TINU permanece pouco entendida, provavelmente envolvendo a imunidade celular e humoral. Essa síndrome pode ser diferenciada de condições sistêmicas associadas à uveíte e à nefrite, sendo necessária a exclusão de outras doenças antes de se confirmar seu diagnóstico, especialmente na presença de achados oftalmológicos.

Conclusão:

A suspeição clínica e o conhecimento do manejo desta patologia por nefrologistas, internistas e oftalmologistas são mandatórios no tratamento do paciente com Síndrome TINU.

Palavras-chave:
doenças autoimunes; lesão renal aguda; nefrite intersticial; uveíte

Abstract

Introduction:

Tubulointerstitial nephritis and uveitis syndrome (TINU Syndrome) is an uncommon clinical entity, and the majority of patients are adolescents and young women. The case reported refers to an elderly patient with ophthalmologic symptoms detected earlier than kidney manifestations, being probably the first case described in Brazil.

Case Report:

Female patient, 60 years-old, sought medical attention for complaints of "red eye". Three months after the first episode of eye manifestation, the patient presented with systemic symptoms and renal dysfunction. Renal biopsy showed tubulointerstitial nephritis with signs of activity.

Discussion:

The pathophysiology of TINU Syndrome remains poorly understood, probably involving both cellular and humoral immunity. This syndrome can be differentiated from systemic conditions associated with nephritis and uveitis, and prior exclusion of other diseases is necessary to confirm diagnosis, especially in the presence of ophthalmologic findings.

Conclusion:

The clinical suspicion and the knowledge of the management of the disease by nephrologists, internists and ophthalmologists is mandatory in the treatment of patients with TINU Syndrome.

Keywords:
acute kidney injury; autoimmune diseases; interstitial; nephritis; uveitis

Introduction

Tubulointerstitial nephritis (TIN) is a significant cause of kidney failure in children and adults, and it is characterized by renal histological and functional abnormalities.11 Jahnukainen T, Ala-Houhala M, Karikoski R, Kataja J, Saarela V, Nuutinen M. Clinical outcome and occurrence of uveitis in children with idiopathic tubulointerstitial nephritis. Pediatr Nephrol 2011;26:291-9. DOI:http://dx.doi.org/10.1007/s00467-010-1698-4
http://dx.doi.org/10.1007/s00467-010-169...

TIN is rarely accompanied by uveal inflammation, an uncommon clinical entity,22 Mandeville JT, Levinson RD, Holland GN. The tubulointerstitial nephritis and uveitis syndrome. Surv Ophthalmol 2001;46:195-208. PMID: 11738428 DOI: http://dx.doi.org/10.1016/S0039-6257(01)00261-2
http://dx.doi.org/10.1016/S0039-6257(01)...

3 Helms E, Servilla KS, Hartshorne MF, Harris A, Nichols MJ, Tzamaloukas AH. Tubulointerstitial nephritis and uveitis syndrome: use of gallium scintigraphy in its diagnosis and treatment. Int Urol Nephrol 2005;37:119-22. PMID: 16132773DOI: http://dx.doi.org/10.1007/s11255-004-2356-1
http://dx.doi.org/10.1007/s11255-004-235...

4 Eyileten T, Dede F, Yenicesu M, Celebi G, Vural A. Idiopathic tubulointerstitial nephritis and uveitis-'TINU syndrome'. Nephrol Dial Transplant 2008;23:771-2. DOI: http://dx.doi.org/10.1093/ndt/gfm624
http://dx.doi.org/10.1093/ndt/gfm624...
-55 Liakopoulos V, Ioannidis I, Zengos N, Karabatsas CH, Karasavvidou F, Salmas M, et al. Tubulointerstitial nephritis and uveitis (TINU) syndrome in a 52-year-old female: a case report and review of the literature. Ren Fail 2006;28:355-9. DOI: http://dx.doi.org/10.1080/08860220600577775
http://dx.doi.org/10.1080/08860220600577...
first described in 1975 by Dobrin et al.,66 Dobrin RS, Vernier RL, Fish AL. Acute eosinophilic interstitial nephritis and renal failure with bone marrow-lymph node granulomas and anterior uveitis. A new syndrome. Am J Med 1975;59:325-33. PMID: 1163543 DOI:http://dx.doi.org/10.1016/0002-9343(75)90390-3
http://dx.doi.org/10.1016/0002-9343(75)9...
receiving the name tubulointerstitial nephritis and uveitis syndrome (TINU syndrome).77 Weinstein O, Tovbin D, Rogachev B, Basok A, Vorobiov M, Kratz A, et al. Clinical manifestations of adult tubulointerstitial nephritis and uveitis (TINU) syndrome. Int Ophthalmol 2010;30:621-8. DOI:http://dx.doi.org/10.1007/s10792-010-9369-9
http://dx.doi.org/10.10077 /s10792-010-9...
TINU is characterized by favorable acute tubulointerstitial nephritis and recurrent chronic uveitis.88 Timmermans SA, Huitema JJ, Wirtz JJ. Keep an eye out for tubulo-interstitial nephritis. Neth J Med 2013;71:523-5.

There are about 200 cases reported in the literature,99 Han JM, Lee YJ, Woo SJ. A case of tubulointerstitial nephritis and uveitis syndrome in an elderly patient. Korean J Ophthalmol 2012;26:398-401. DOI: http://dx.doi.org/10.3341/kjo.2012.26.5.398
http://dx.doi.org/10.3341/kjo.2012.26.5....
and most of the TINU patients are adolescents and young women.1010 Abed L, Merouani A, Haddad E, Benoit G, Oligny LL, Sartelet H. Presence of autoantibodies against tubular and uveal cells in a patient with tubulointerstitial nephritis and uveitis (TINU) syndrome. Nephrol Dial Transplant 2008;23:1452-5. DOI: http://dx.doi.org/10.1093/ndt/gfm890
http://dx.doi.org/1010. 1093/ndt/gfm890...
Its etiology is unknown, with several possible triggers that can start it, such as infections and drug use.22 Mandeville JT, Levinson RD, Holland GN. The tubulointerstitial nephritis and uveitis syndrome. Surv Ophthalmol 2001;46:195-208. PMID: 11738428 DOI: http://dx.doi.org/10.1016/S0039-6257(01)00261-2
http://dx.doi.org/10.1016/S0039-6257(01)...
,1111 Fried T. Acute interstitial nephritis. Why do the kidneys suddenly fail? Postgrad Med 1993;93:105-6.

Diagnosis is mainly clinical, proving the presence of TIN and uveitis with no evidence of other systemic or infectious diseases. Symptoms are mostly nonspecific, including fever, headache, fatigue and anorexia,11 Jahnukainen T, Ala-Houhala M, Karikoski R, Kataja J, Saarela V, Nuutinen M. Clinical outcome and occurrence of uveitis in children with idiopathic tubulointerstitial nephritis. Pediatr Nephrol 2011;26:291-9. DOI:http://dx.doi.org/10.1007/s00467-010-1698-4
http://dx.doi.org/10.1007/s00467-010-169...
,1212 Clarkson 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. DOI:http://dx.doi.org/10.1093/ndt/gfh485
http://dx.doi.org/10.1093/ndt/gfh485...
,1313 Baker RJ, Pusey CD. The changing profile of acute tubulointerstitial nephritis. Nephrol Dial Transplant 2004;19:8-11. DOI: http://dx.doi.org/10.1093/ndt/gfg464
http://dx.doi.org/10.1093/ndt/gfg464...
causing the clinical diagnosis to be difficult and often delaying treatment onset.11 Jahnukainen T, Ala-Houhala M, Karikoski R, Kataja J, Saarela V, Nuutinen M. Clinical outcome and occurrence of uveitis in children with idiopathic tubulointerstitial nephritis. Pediatr Nephrol 2011;26:291-9. DOI:http://dx.doi.org/10.1007/s00467-010-1698-4
http://dx.doi.org/10.1007/s00467-010-169...

The case described below was found in an elderly patient, with pre-nephritis ophthalmic manifestations, and it appears to be the first report of its kind from Brazil.

Case report

Female patient, 60 years old, with a past of systemic hypertension, sought medical treatment in September 2010, complaining of a "Red Eye" (Figure 1) of sudden onset, with pain on palpation and eye movement, associated with mild bilateral eyelid edema. She was diagnosed with non-bacterial conjunctivitis. Corticosteroid-based eye drops were prescribed for seven days, with symptom resolution. Seven days after interrupting the use of eye drops, the patient developed a new ophthalmic crisis, to which the prior approach was maintained, and symptoms subsided.

Figure 1
Anterior uveitis in patients with TINU syndrome.

Thirty days after the condition had started, the patient presented with low-intensity pain in her upper left quadrant, continuous, not ventilator-dependent, for 15 days, progressing to severe pain. A chest X-ray revealed mild pulmonary infiltrates in the left lung base. It was suggested the possibility of atelectasis secondary to pain or pneumonic disease, treated with clarithromycin for 7 days and 2 days with dexamethasone/indomethacin, to which she responded with clinical and radiological improvement. Thirty days after pain resolution, the patient had an episode similar to her initial ophthalmic condition. Three months after the first episode of her eye disease, she presented with systemic symptoms and lost 5 kg (7% of body weight) in one month without changes to her blood pressure.

Laboratory tests showed azotemia - creatinine: 2.5 mg/dL and urea: 75 mg/dl, while her baseline creatinine was 0.9 mg/dl. Urinalysis with urine glucose ++, without other changes; 24-hour proteinuria: 1,65g; Renal ultrasound: kidneys of normal size, slight increase in cortical echogenicity and good cortex-medulla differentiation. The other tests carried out are shown on Table 1. After admission, she was submitted to pulse therapy with methylprednisolone 500 mg for 3 days followed by prednisone 1 mg/kg/day for 1 month, and the medication was weaned during for 4 months, with progressive improvement in her tests. In January 2011 (post-pulse therapy), she was submitted to a renal biopsy, which showed glomeruli within normal limits (global sclerosis: 2/30), tubular epithelial degenerative changes with spotted atrophy and mild diffuse interstitial fibrosis and tubulointerstitial nephritis with signs of inflammatory activity. Direct immunofluorescence revealed no glomerular deposits and tubular cylinders with IgM and IgA (Figure 2).

Table 1
Laboratory tests from the patient of the case reported above

Figure 2
Kidney biopsy. A. Interstitial inflammation consisting of lymphoid cells that dissociate the tubular epithelium. (PAS - 400x); Renal biopsy B. Interstitial broadening by fibrosis and lymphocytic inflammatory infiltrate (Masson trichrome - 400x).

Three months after discontinuing the immunosuppressive medication, she had a new episode of anterior uveitis, and was started on corticosteroid eye drops and ketorolac. As a side effect, she had an increase in intraocular pressure, and was started on brinzolamide/timolol and brimonidine tartrate. We tried to wean her off the corticosteroid eye drops at times, but always with worsening of uveitis.

Currently, after 52 months of follow up, the patient remains in use of cyclosporine ophthalmic emulsion because of the failure in interrupting the medicine. Urinalysis is within the normal range, and urea and creatinine with values of 36 mg/dL and 1.0 mg/dL, respectively.

Discussion

The TINU syndrome has an approximate prevalence of 3.5 cases/million people and an incidence of 0.2 cases/million/year,33 Helms E, Servilla KS, Hartshorne MF, Harris A, Nichols MJ, Tzamaloukas AH. Tubulointerstitial nephritis and uveitis syndrome: use of gallium scintigraphy in its diagnosis and treatment. Int Urol Nephrol 2005;37:119-22. PMID: 16132773DOI: http://dx.doi.org/10.1007/s11255-004-2356-1
http://dx.doi.org/10.1007/s11255-004-235...
,77 Weinstein O, Tovbin D, Rogachev B, Basok A, Vorobiov M, Kratz A, et al. Clinical manifestations of adult tubulointerstitial nephritis and uveitis (TINU) syndrome. Int Ophthalmol 2010;30:621-8. DOI:http://dx.doi.org/10.1007/s10792-010-9369-9
http://dx.doi.org/10.10077 /s10792-010-9...
probably being underdiagnosed;1414 Tan Y, Yu F, Qu Z, Su T, Xing GQ, Wu LH, et al. Modified C-reactive protein might be a target autoantigen of TINU syndrome. Clin J Am Soc Nephrol 2011;6:93-100. DOI: http://dx.doi.org/10.2215/CJN.09051209
http://dx.doi.org/10.2215/CJN.09051209...
,1515 Thomassen VH, Ring T, Thaarup J, Baggesen K. Tubulointerstitial nephritis and uveitis (TINU) syndrome: a case report and review of the literature. Acta Ophthalmol 2009;87:676-9. PMID: 18700885 DOI:http://dx.doi.org/10.1111/j.1755-3768.2008.01302.x
http://dx.doi.org/10.1111/j.1755-3768.20...
without racial or ethnic predominance among the cases reported.1616 Parameswaran S, Mittal N, Joshi K, Rathi M, Kohli HS, Jha V, et al. Tubulointerstitial nephritis with uveitis syndrome: A case report and review of literature. Indian J Nephrol 2010;20:103-5. DOI: http://dx.doi.org/10.4103/0971-4065.65307
http://dx.doi.org/10.4103/0971-4065.6530...

There is a higher incidence among women,22 Mandeville JT, Levinson RD, Holland GN. The tubulointerstitial nephritis and uveitis syndrome. Surv Ophthalmol 2001;46:195-208. PMID: 11738428 DOI: http://dx.doi.org/10.1016/S0039-6257(01)00261-2
http://dx.doi.org/10.1016/S0039-6257(01)...
,99 Han JM, Lee YJ, Woo SJ. A case of tubulointerstitial nephritis and uveitis syndrome in an elderly patient. Korean J Ophthalmol 2012;26:398-401. DOI: http://dx.doi.org/10.3341/kjo.2012.26.5.398
http://dx.doi.org/10.3341/kjo.2012.26.5....
in the ratio of 3: 1 and, according to recent studies, the prevalence in men has increased.33 Helms E, Servilla KS, Hartshorne MF, Harris A, Nichols MJ, Tzamaloukas AH. Tubulointerstitial nephritis and uveitis syndrome: use of gallium scintigraphy in its diagnosis and treatment. Int Urol Nephrol 2005;37:119-22. PMID: 16132773DOI: http://dx.doi.org/10.1007/s11255-004-2356-1
http://dx.doi.org/10.1007/s11255-004-235...

The disease manifests earlier in men, ranging from 9-52 years; while in women it involves those ranging from 10-74 years of age.22 Mandeville JT, Levinson RD, Holland GN. The tubulointerstitial nephritis and uveitis syndrome. Surv Ophthalmol 2001;46:195-208. PMID: 11738428 DOI: http://dx.doi.org/10.1016/S0039-6257(01)00261-2
http://dx.doi.org/10.1016/S0039-6257(01)...
,77 Weinstein O, Tovbin D, Rogachev B, Basok A, Vorobiov M, Kratz A, et al. Clinical manifestations of adult tubulointerstitial nephritis and uveitis (TINU) syndrome. Int Ophthalmol 2010;30:621-8. DOI:http://dx.doi.org/10.1007/s10792-010-9369-9
http://dx.doi.org/10.10077 /s10792-010-9...
,1010 Abed L, Merouani A, Haddad E, Benoit G, Oligny LL, Sartelet H. Presence of autoantibodies against tubular and uveal cells in a patient with tubulointerstitial nephritis and uveitis (TINU) syndrome. Nephrol Dial Transplant 2008;23:1452-5. DOI: http://dx.doi.org/10.1093/ndt/gfm890
http://dx.doi.org/1010. 1093/ndt/gfm890...
There are few cases described in the literature involving the elderly.77 Weinstein O, Tovbin D, Rogachev B, Basok A, Vorobiov M, Kratz A, et al. Clinical manifestations of adult tubulointerstitial nephritis and uveitis (TINU) syndrome. Int Ophthalmol 2010;30:621-8. DOI:http://dx.doi.org/10.1007/s10792-010-9369-9
http://dx.doi.org/10.10077 /s10792-010-9...
,99 Han JM, Lee YJ, Woo SJ. A case of tubulointerstitial nephritis and uveitis syndrome in an elderly patient. Korean J Ophthalmol 2012;26:398-401. DOI: http://dx.doi.org/10.3341/kjo.2012.26.5.398
http://dx.doi.org/10.3341/kjo.2012.26.5....

The main manifestations are nonspecific and associated with the renal disease, including, in decreasing order, fever, weight loss, fatigue and malaise, anorexia, abdominal pain, among others.11 Jahnukainen T, Ala-Houhala M, Karikoski R, Kataja J, Saarela V, Nuutinen M. Clinical outcome and occurrence of uveitis in children with idiopathic tubulointerstitial nephritis. Pediatr Nephrol 2011;26:291-9. DOI:http://dx.doi.org/10.1007/s00467-010-1698-4
http://dx.doi.org/10.1007/s00467-010-169...
,22 Mandeville JT, Levinson RD, Holland GN. The tubulointerstitial nephritis and uveitis syndrome. Surv Ophthalmol 2001;46:195-208. PMID: 11738428 DOI: http://dx.doi.org/10.1016/S0039-6257(01)00261-2
http://dx.doi.org/10.1016/S0039-6257(01)...
,77 Weinstein O, Tovbin D, Rogachev B, Basok A, Vorobiov M, Kratz A, et al. Clinical manifestations of adult tubulointerstitial nephritis and uveitis (TINU) syndrome. Int Ophthalmol 2010;30:621-8. DOI:http://dx.doi.org/10.1007/s10792-010-9369-9
http://dx.doi.org/10.10077 /s10792-010-9...
,99 Han JM, Lee YJ, Woo SJ. A case of tubulointerstitial nephritis and uveitis syndrome in an elderly patient. Korean J Ophthalmol 2012;26:398-401. DOI: http://dx.doi.org/10.3341/kjo.2012.26.5.398
http://dx.doi.org/10.3341/kjo.2012.26.5....
,1515 Thomassen VH, Ring T, Thaarup J, Baggesen K. Tubulointerstitial nephritis and uveitis (TINU) syndrome: a case report and review of the literature. Acta Ophthalmol 2009;87:676-9. PMID: 18700885 DOI:http://dx.doi.org/10.1111/j.1755-3768.2008.01302.x
http://dx.doi.org/10.1111/j.1755-3768.20...

16 Parameswaran S, Mittal N, Joshi K, Rathi M, Kohli HS, Jha V, et al. Tubulointerstitial nephritis with uveitis syndrome: A case report and review of literature. Indian J Nephrol 2010;20:103-5. DOI: http://dx.doi.org/10.4103/0971-4065.65307
http://dx.doi.org/10.4103/0971-4065.6530...
-1717 Onyekpe I, Shenoy M, Denley H, Riad H, Webb NJ. Recurrent tubulointerstitial nephritis and uveitis syndrome in a renal transplant recipient. Nephrol Dial Transplant 2011;26:3060-2. DOI: http://dx.doi.org/10.1093/ndt/gfr352
http://dx.doi.org/10.1093/ndt/gfr352...

Uveitis may precede (21%), happen concurrently (15%) or succeed (65%) nephritis,99 Han JM, Lee YJ, Woo SJ. A case of tubulointerstitial nephritis and uveitis syndrome in an elderly patient. Korean J Ophthalmol 2012;26:398-401. DOI: http://dx.doi.org/10.3341/kjo.2012.26.5.398
http://dx.doi.org/10.3341/kjo.2012.26.5....
,1616 Parameswaran S, Mittal N, Joshi K, Rathi M, Kohli HS, Jha V, et al. Tubulointerstitial nephritis with uveitis syndrome: A case report and review of literature. Indian J Nephrol 2010;20:103-5. DOI: http://dx.doi.org/10.4103/0971-4065.65307
http://dx.doi.org/10.4103/0971-4065.6530...
,1818 Hinkle DM, Foster CS. Tubulointerstitial nephritis and uveitis syndrome. Int Ophthalmol Clin 2008;48:9-13. DOI:http://dx.doi.org/10.1097/IIO.0b013e3181694db9
http://dx.doi.org/10.1097/IIO.0b013e3181...
with eye symptoms starting, in average, one month after the systemic effects. The main ocular disease is anterior uveitis, which occurs in 80% of patients, and the most common symptoms are pain and redness.22 Mandeville JT, Levinson RD, Holland GN. The tubulointerstitial nephritis and uveitis syndrome. Surv Ophthalmol 2001;46:195-208. PMID: 11738428 DOI: http://dx.doi.org/10.1016/S0039-6257(01)00261-2
http://dx.doi.org/10.1016/S0039-6257(01)...

In our patient, the disease manifested initially by anterior uveitis, which happened three months before the renal involvement. After the onset of nephritis, there were new episodes of uveitis, showing a lack of temporality between the two events.

The pathophysiology of the TINU syndrome remains poorly understood, but reports suggest that it is the result of an autoimmune process that involves cellular and humoral immunity.88 Timmermans SA, Huitema JJ, Wirtz JJ. Keep an eye out for tubulo-interstitial nephritis. Neth J Med 2013;71:523-5. The renal and ocular injuries in the clinical course of TINU may suggest a common antigen to these two structures that could be the target of a crossed autoimmune reaction.1919 Khammassi N, Mohsen D, Ounissi M, Tougourti MN, Hamza M. TINU syndrome and lymphoid interstitial alveolitis: a new observation. Tunis Med 2011;89:210-2. PMID: 21308636

This syndrome can be differentiated from systemic conditions associated with uveitis and nephritis. TIN has a variety of etiologies and it would be no different with TINU syndrome. The role of infections and noninfectious causes is speculated in the immune response, leading to the development of the syndrome.11 Jahnukainen T, Ala-Houhala M, Karikoski R, Kataja J, Saarela V, Nuutinen M. Clinical outcome and occurrence of uveitis in children with idiopathic tubulointerstitial nephritis. Pediatr Nephrol 2011;26:291-9. DOI:http://dx.doi.org/10.1007/s00467-010-1698-4
http://dx.doi.org/10.1007/s00467-010-169...
,22 Mandeville JT, Levinson RD, Holland GN. The tubulointerstitial nephritis and uveitis syndrome. Surv Ophthalmol 2001;46:195-208. PMID: 11738428 DOI: http://dx.doi.org/10.1016/S0039-6257(01)00261-2
http://dx.doi.org/10.1016/S0039-6257(01)...
,88 Timmermans SA, Huitema JJ, Wirtz JJ. Keep an eye out for tubulo-interstitial nephritis. Neth J Med 2013;71:523-5.,99 Han JM, Lee YJ, Woo SJ. A case of tubulointerstitial nephritis and uveitis syndrome in an elderly patient. Korean J Ophthalmol 2012;26:398-401. DOI: http://dx.doi.org/10.3341/kjo.2012.26.5.398
http://dx.doi.org/10.3341/kjo.2012.26.5....
,1111 Fried T. Acute interstitial nephritis. Why do the kidneys suddenly fail? Postgrad Med 1993;93:105-6.,2020 Alon US. Tubulointerstitial nephritis. In: Avner ED, Harmon WE, Niaudet P, Yoshikawa N, eds. Pediatric Nephrology. 6th ed. Berlin and Heidelberg: Springer-Verlag; 2009. p.1081-98.,2121 Kim DH, Jang YS, Do WS, Oh DM, Kim SH, Kwak EK, et al. A case of tubulointerstitial nephritis and uveitis syndrome in an old age female. Korean J Nephrol 2010;29:250-5.

Kim et al. consider that the main causes of concomitant nephritis and uveitis, which can be mistaken for the TINU syndrome are: sarcoidosis, Sjogren's syndrome,2121 Kim DH, Jang YS, Do WS, Oh DM, Kim SH, Kwak EK, et al. A case of tubulointerstitial nephritis and uveitis syndrome in an old age female. Korean J Nephrol 2010;29:250-5. lupus, Wegener's granulomatosis, Behcet's disease,2222 Lee G, Ashfaq A. Tubulointerstitial nephritis and uveitis (TINU syndrome). 2014 [cited 2014 Ago 3]. Available from: http://www.uptodate.com/contents/tubulointerstitial-nephritis-and-uveitis-tinu-syndrome?source=search_result&search=tinu&selectedtitle=1~6#h14
http://www.uptodate.com/contents/tubuloi...
and it is imperative to order tests to rule these out.

In 2001, Mandeville et al.22 Mandeville JT, Levinson RD, Holland GN. The tubulointerstitial nephritis and uveitis syndrome. Surv Ophthalmol 2001;46:195-208. PMID: 11738428 DOI: http://dx.doi.org/10.1016/S0039-6257(01)00261-2
http://dx.doi.org/10.1016/S0039-6257(01)...
published the TINU syndrome diagnostic criteria, requiring the presence of acute interstitial nephritis and uveitis, with no other systemic disease as a cause, in addition to completing the 3 following criteria: 1. abnormal kidney function; 2. abnormal urinalysis; and 3. Systemic disease lasting ≥ 2 weeks.

Laboratory tests in the evaluation of TINU syndrome are not typical. Moreover, the ANCA, antinuclear antibody, anticardiolipin antibodies, anti-DNA antibody and rheumatoid factor may be positive and may be hypocomplementemia, and polyclonal hypergammaglobulinemia and circulating immune complexes.22 Mandeville JT, Levinson RD, Holland GN. The tubulointerstitial nephritis and uveitis syndrome. Surv Ophthalmol 2001;46:195-208. PMID: 11738428 DOI: http://dx.doi.org/10.1016/S0039-6257(01)00261-2
http://dx.doi.org/10.1016/S0039-6257(01)...
,2323 Goda C, Kotake S, Ichiishi A, Namba K, Kitaichi N, Ohno S. Clinical features in tubulointerstitial nephritis and uveitis (TINU) syndrome. Am J Ophthalmol 2005;140:637-41. PMID: 16226516 DOI: http://dx.doi.org/10.1016/j.ajo.2005.04.019
http://dx.doi.org/10.1016/j.ajo.2005.04....
,2424 Paladini A, Venturoli V, Mosconi G, Zambianchi L, Serra L, Valletta E. Tubulointerstitial nephritis and uveitis syndrome in a twelve-year-old girl. Case Rep Pediatr 2013;2013:652043. DOI: http://dx.doi.org/10.1155/2013/652043
http://dx.doi.org/10.1155/2013/652043...

The patient had mild anemia, elevated inflammatory markers, azotemia and increased proteinuria. C4 was high (60.8 mg/dL), and C3 dosage was normal (154 mg/dL). C-ANCA, P-ANCA and FAN were negative.

Histological evidence of TIN should be sought for the definitive diagnosis of the syndrome. However, an invasive procedure such as a kidney biopsy may not be suitable for all patients, and should be considered in a case-by-case basis.33 Helms E, Servilla KS, Hartshorne MF, Harris A, Nichols MJ, Tzamaloukas AH. Tubulointerstitial nephritis and uveitis syndrome: use of gallium scintigraphy in its diagnosis and treatment. Int Urol Nephrol 2005;37:119-22. PMID: 16132773DOI: http://dx.doi.org/10.1007/s11255-004-2356-1
http://dx.doi.org/10.1007/s11255-004-235...

TIN may resolve spontaneously, but the treatment of patients with progressive renal failure include the use of corticosteroids. The nephropathy becomes chronic in 11% of cases and only 5% of patients require dialysis.1818 Hinkle DM, Foster CS. Tubulointerstitial nephritis and uveitis syndrome. Int Ophthalmol Clin 2008;48:9-13. DOI:http://dx.doi.org/10.1097/IIO.0b013e3181694db9
http://dx.doi.org/10.1097/IIO.0b013e3181...
In this case, after pulse therapy, the patient experienced a reduction in urea and creatinine levels.

Topical steroids associated with cycloplegic agents are commonly recommended as a treatment option for anterior uveitis.1616 Parameswaran S, Mittal N, Joshi K, Rathi M, Kohli HS, Jha V, et al. Tubulointerstitial nephritis with uveitis syndrome: A case report and review of literature. Indian J Nephrol 2010;20:103-5. DOI: http://dx.doi.org/10.4103/0971-4065.65307
http://dx.doi.org/10.4103/0971-4065.6530...
,2525 Gion N, Stavrou P, Foster CS. Immunomodulatory therapy for chronic tubulointerstitial nephritis-associated uveitis. Am J Ophthalmol 2000;129:764-8. PMID: 10926986 DOI: http://dx.doi.org/10.1016/S0002-9394(00)00482-7
http://dx.doi.org/10.1016/S0002-9394(00)...
If refractory, one should consider using oral steroids1515 Thomassen VH, Ring T, Thaarup J, Baggesen K. Tubulointerstitial nephritis and uveitis (TINU) syndrome: a case report and review of the literature. Acta Ophthalmol 2009;87:676-9. PMID: 18700885 DOI:http://dx.doi.org/10.1111/j.1755-3768.2008.01302.x
http://dx.doi.org/10.1111/j.1755-3768.20...
or immunosuppressive agents.55 Liakopoulos V, Ioannidis I, Zengos N, Karabatsas CH, Karasavvidou F, Salmas M, et al. Tubulointerstitial nephritis and uveitis (TINU) syndrome in a 52-year-old female: a case report and review of the literature. Ren Fail 2006;28:355-9. DOI: http://dx.doi.org/10.1080/08860220600577775
http://dx.doi.org/10.1080/08860220600577...
,99 Han JM, Lee YJ, Woo SJ. A case of tubulointerstitial nephritis and uveitis syndrome in an elderly patient. Korean J Ophthalmol 2012;26:398-401. DOI: http://dx.doi.org/10.3341/kjo.2012.26.5.398
http://dx.doi.org/10.3341/kjo.2012.26.5....
,1515 Thomassen VH, Ring T, Thaarup J, Baggesen K. Tubulointerstitial nephritis and uveitis (TINU) syndrome: a case report and review of the literature. Acta Ophthalmol 2009;87:676-9. PMID: 18700885 DOI:http://dx.doi.org/10.1111/j.1755-3768.2008.01302.x
http://dx.doi.org/10.1111/j.1755-3768.20...
,2525 Gion N, Stavrou P, Foster CS. Immunomodulatory therapy for chronic tubulointerstitial nephritis-associated uveitis. Am J Ophthalmol 2000;129:764-8. PMID: 10926986 DOI: http://dx.doi.org/10.1016/S0002-9394(00)00482-7
http://dx.doi.org/10.1016/S0002-9394(00)...
Reports indicate that in 14% of the cases the symptoms persist for more than 3 months55 Liakopoulos V, Ioannidis I, Zengos N, Karabatsas CH, Karasavvidou F, Salmas M, et al. Tubulointerstitial nephritis and uveitis (TINU) syndrome in a 52-year-old female: a case report and review of the literature. Ren Fail 2006;28:355-9. DOI: http://dx.doi.org/10.1080/08860220600577775
http://dx.doi.org/10.1080/08860220600577...
,99 Han JM, Lee YJ, Woo SJ. A case of tubulointerstitial nephritis and uveitis syndrome in an elderly patient. Korean J Ophthalmol 2012;26:398-401. DOI: http://dx.doi.org/10.3341/kjo.2012.26.5.398
http://dx.doi.org/10.3341/kjo.2012.26.5....
and uveitis recurrence occurs in about 50% of patients.77 Weinstein O, Tovbin D, Rogachev B, Basok A, Vorobiov M, Kratz A, et al. Clinical manifestations of adult tubulointerstitial nephritis and uveitis (TINU) syndrome. Int Ophthalmol 2010;30:621-8. DOI:http://dx.doi.org/10.1007/s10792-010-9369-9
http://dx.doi.org/10.10077 /s10792-010-9...
,2626 Levinson RD, Park MS, Rikkers SM, Reed EF, Smith JR, Martin TM, et al. Strong associations between specific HLA-DQ and HLA-DR alleles and the tubulointerstitial nephritis and uveitis syndrome. Invest Ophthalmol Vis Sci 2003;44:653-7. PMID: 12556395 DOI: http://dx.doi.org/10.1167/iovs.02-0376
http://dx.doi.org/10.1167/iovs.02-0376...
In a series of 33 cases, the median value for disease persistence was 7 months, ranging from 1 to 147 months.2727 Mackensen F, Billing H. Tubulointerstitial nephritis and uveitis syndrome. Curr Opin Ophthalmol 2009;20:525-31. DOI: http://dx.doi.org/10.1097/ICU.0b013e3283318f9a
http://dx.doi.org/10.1097/ICU.0b013e3283...

Although this patient of ours manifested the TINU syndrome at 60 years of age, she developed a favorable renal function outcome, presenting azotemic values within the normal range even after 52 months of follow-up. Due to the increase of intraocular pressure with use of topical corticosteroids, we decided to use cyclosporine eye drops, making continuous use without possibilities of discontinuing it, as it always resulted in uveitis recurrence.

Conclusion

This tubulointerstitial nephritis and uveitis case makes us suggest that this rare syndrome should be considered in the differential diagnosis of unexplained tubulointerstitial nephritis, especially in the presence of ocular disorders, even in older patients. There is evidence suggesting that TINU is underdiagnosed, especially in young patients who have mild and asymptomatic kidney disease. It is necessary to disclose this information among nephrologists, internists and ophthalmologists, because their interaction is paramount in the treatment of patients with the TINU syndrome.

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    » http://dx.doi.org/10.1097/ICU.0b013e3283318f9a

Publication Dates

  • Publication in this collection
    Jan-Mar 2016

History

  • Received
    16 June 2015
  • Accepted
    28 Sept 2015
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