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� ABSTRACTAcute tubulo-interstitial nephritis with concomitant

uveitis is a rare condition. While its aetiology isunknown, cellular immunological mechanisms havebeen implicated in its pathogenesis.

The authors describe a case report of a forty-nineyear-old patient who presented with ocular symp-toms that preceded a constitutional syndrome andacute renal failure (serum creatinine 6.6 mg/dl). Therenal pathology study showed acute tubulointersti-tial nephritis with an inflammatory infiltrate, with pre-dominant lymphocytes. The immunofluorescence wasnegative. Administration of corticosteroids led to aclinical and biochemical improvement.

We stress the importance of diagnosing this clin-ical entity, the role of kidney biopsy, and the suc-cess of steroid treatment when started early.

Key-Words:Tubulointerstitial nephritis; uveitis.

� INTRODUCTION

Acute interstitial nephritis (AIN) is an acute dis-ease characterised by the presence of inflammatoryinfiltrates within the interstitium which can causeacute renal failure. There is evidence that it is animmunologically-induced hypersensitivity reaction toan antigen that is classically a drug or an infectiousagent. Less often it may be secondary to immunereactions to a renal antigen.

The association of idiopathic AIN with anterioruveitis (TINU syndrome) has been reported as a dis-tinct clinical entity. It is a rare condition and wasfirst described in 1975 by Dobrin1. This syndromeis found most commonly in pubertal girls and youngwomen but it also appears in young males and inadults.

Approximately 140 cases have now been report-ed. The majority have been documented in ophthal-mology and paediatric nephrology literature in casereports and small descriptive series.

Initial symptoms are generally of a systemic naturewith fever myalgia and asthenia but ocular pain andvisual impairment may also be present at presenta-tion. Acute renal failure, which may range from mildto severe, develops as the disease progresses.

Renal biopsy shows interstitial inflammatory infil-trate with mononuclear cells, such as lymphocytes,plasma cells, and histiocytes. Eosinophils and non--caseating granulomas are rarely seen. There are noimmune deposits. Granuloma may be present in bonemarrow, lymph-nodes kidney and liver1,2.

The pathogenesis of this disorder is not wellunderstood. Delayed-type hypersensitivity andsuppressed cell-mediated immunity with a predom-inance of T-lymphocytes seems to be implicatedwith proliferation and activation of T-lymphocytesby IL-23,4.

We report the case of a forty-nine year-old malepatient who presented with acute renal failure due

Tubulo-interstitial nephritis and uveitis syndrome

Ana Tomás Mateus, Aura Ramos, Pedro Ponce

Department of Nephrology. Hospital Garcia de Orta, Almada, Portugal

Port J Nephrol Hypert 2007; 21(1): 49-52

Received for publication: 24/11/2006

Accepted in revised form: 19/12/2006

CASE REPORT

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50 Port J Nephrol Hypert 2007; 21(1): 49-52

to idiopathic tubulo-interstitial nephritis document-ed by renal biopsy and uveitis. We excluded all dis-eases causing acute tubulo-interstitial nephritis suchas Behçet’s disease, Sjögren’s syndrome, hypersen-sitivity to drugs, systemic drugs or vasculitis andsystemic infection. The patient recovered after cor-ticotherapy.

� CASE REPORT

A forty-nine year-old male patient came to our hos-pital with fatigue, anorexia and fever of two weeksduration. He had been losing weight since the pre-vious month. Since then he had complained of severepain in the right eye, with no precipitating factors,accompanied by photophobia, weeping and impairedvision. He had no evidence of recent infection, artic-ular pain or skin rash.

He had been treated for hypertension with lisino-pril since the age of 30 with reasonable results; dys-lipidemia had recently been diagnosed and he wastaking a statin. He denied taking other drugs or beingexposed to toxic substances.

Examination revealed normal body temperature(36.5°C) and blood pressure (120/60 mmHg) and nor-mal cardio-pulmonar findings. There was a moder-ate malleolar oedema. There were no skin changesor enlarged lymph-nodes. He was not oliguric.

The main baseline laboratory findings wereanaemia (Hb 9.6 g/dl), a rapid sedimentation rate,decreased renal function, creatinine 6.6mg/dl, urea180 mg/dl, and urinalysis positive for proteinuria withno blood or casts. Blood electrolytes were normal.There was moderate hypoalbuminemia (3.8mg/dl).Liver tests and iron metabolism were normal. Urineculture was negative.

Further laboratorial investigation included immuno-logical and virological study. He had normal comple-ment levels. ANA, anti-DNA, ANCA and RA test werenegative. Levels of immunoglobulins were respective-ly IgG 1700mg/dl, IgA 335mg/dl and IgM 270 mg/dl.Quantitative proteinuria was 4.2g per day.

Serologic tests were negative for HBV, HCV, CMV,Epstein Barr virus, HIV and toxoplasmosis.

Renal echography showed kidneys normal in sizeand morphology. Ophthamological examinationshowed anterior uveitis of the right eye.

The renal biopsy showed inflammatory intersti-tial infiltrate with lymphocytes and eosinophils.Tubulitis was present with scarce infiltrating lym-phocytes. Glomeruli were normal and there were novascular changes. There were no immune deposits.The diagnosis of acute interstitial nephritis wasmade (Fig. 1, 2).

Ana Tomás Mateus, Aura Ramos, Pedro Ponce

Figure 1

Renal biopsy with an acute interstitial infiltrate

Figure 2

Presence of interstitial eosinophils

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Port J Nephrol Hypert 2007; 21(1): 49-52 51

The patient was treated with pulse methylpred-nisolone 1g i.v q.i.d. for three consecutive days fol-lowed by oral prednisolone 1 mg per Kg per day fortwo months. Then the dose was tapered off to amaintenance dose of 10 mg q.i.d. There was rapidamelioration of ocular pain and of visual acuity whichrecovered completely. Peripheral oedema disappearedand renal function and urinary changes showed pro-gressive recovery. At the end of the second monthof therapy there was no anaemia, serum creatininewas 1.8 mg/dl and there was only trace proteinuria.Therapy was maintained unchanged for one year. Atthat time serum creatinine was 1.3mg/dl and therewere no urinary changes. Only anti-hypertensive ther-apy was maintained.

At 36 months follow-up renal function remains sta-ble (serum creatinine 1.2 mg/dl) and ocular symptomsdid not relapse.

� DISCUSSION

TINU syndrome is a distinct clinical entity whichis characterised by the association of idiopathicacute interstitial nephritis with anterior uveitis. Forits diagnosis infection and drug allergy must beexcluded.

The patient described above had symptoms ofuveitis associated with systemic changes followed byacute renal failure one month afterwards. Drug expo-sure and infection were excluded by patient historyand laboratory tests. While uveitis may be associat-ed with Sjögren, Behçet or Reiter syndromes as wellas with sarcoidosis, there were no clinical or labo-ratory findings here suggesting the presence of anyof these diseases.

Renal biopsy showed acute tubulointerstitialnephritis with an inflammatory infiltrate, with predom-inant lymphocytes. The immunofluorescence was neg-ative. These findings associated with the diagnosisof anterior uveitis are typical of TINU syndrome. Theonset of uveitis most commonly follows the onsetof interstitial nephritis but may also precede inter-stitial nephritis or occur concurrently.

The finding of transient nephrotic range protein-uria is not commonly seen and may be related to

glomerular changes which were not evident at thelight microscopy level.

The patient responded well to corticotherapy withrecovery of systemic, renal and ocular changes. Sim-ilar results have been reported in other TINU syn-drome patients5-7. Patients who have been report-ed to recover spontaneously were most often in thepaediatric age range8,9. On the other hand somepatients did not recover completely3 and some wereeven on dialysis for some time4.

The therapy for TINU syndrome is not well estab-lished in general and neither the dose and durationof corticotherapy or the use of other immunosupres-sor drugs5 are well established in particular. In thecases reported so far therapy has been establishedbased on clinical grounds. In this particular patientrenal function was severely impaired and he hadsevere systemic and ocular symptoms. High dosesof corticosteroids were given and a rapid responsewas observed. However renal function remained mod-erately impaired after two months and for this rea-son low dose steroids were maintained for one year.Similar results have been described in literature10.

Conclusion: Urine analysis and evaluation of renalfunction are recommended in patients with uveitisat presentation and during long term follow-up. Thediagnosis of TINU syndrome is based on renal biop-sy. Early treatment can prevent chronic renal disease.

Conflict of interest statement. None declared.

References

11 Dobrin RS, Vernier RL, Fish AL. Acute eosinophilic interstitial nephritis and renal failu-re with bone marrow-lymph node granulomas and anterior uveitis. A new syndrome.Am J Med 1975;59:325-333

22 Navarro JF, Gallego E, Gil J, Perera A, Garcia J. Idiopathic acute interstitial nephritis anduveitis associated with deafness. Nephrol Dial Transplant 1997;12:781-784

33 Rodriguez Pérez JC, Cruz Alamo M, Pérez-Aciego P. Clinical and immune aspects of idio-pathic tubulo-interstitial nephritis and uveitis syndrome. Am J Nephrol 1995;15:386--391

44 Gafter U, Kalechman Y, Zevin D, et al. Tubulo-interstitial nephritis and uveitis: associa-tion with supressed cellular inmunity. Nephrol Dial Transplant 19938:821

55 Hirano K, Tomino Y, Mikami H, Ota K, Aikawa Y, Shirato I, Koide H. A case of acutetubulointerstitial nephritis and uveitis syndrome with a dramatic response to corticos-teroid therapy. Am J Nephrol 1989;9:499-503

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66 Cacoub P, Deray G, Le Hoang P, Baumelou A, Beaufils H, de Groc F, Rousselie F, Jouan-neau C, Jacobs Idiopathic acute interstitial nephritis associated with anterior uveitisin adults. Clin nephrol 1989;31:307-310

77 Takemura. T, Okada. M, Hino. S, et al. Course and outcome of tubulointerstitial neph-ritis and uveitis syndrome. Am J kidney Dis 1999;34:1016

88 Morey A, Larcón A, Casco JM, Bestard X: Remisión espontánea de un síndrome de nefro-patía tubulointersticial aguda asociado a uveitis. Nefrologia 1995;14:120

99 Vanhaesebrouck P, Carton D, De-Bel C, Praet M, Proesmans W: Acute tubulo-intersti-tial nephritis and uveitis syndrome (TINU syndrome). Nephron 1985;40:418-422

1100 Mandeville Jt, Levison RD, Holland GN. The tubulointerstitial nephritis and uveitis syndro-me. Surv ophthalmol 2001;46:195-208

1111 Van Leusen, R, Assmann, KJ. Acute tubulo-interstitial nephritis with uveitis and favou-rable outcome after five months of continuous ambulatory peritoneal dialysis (CAPD).Neth J Med 1988;33:133

1122 Sánchez J, González Y, Castillo MJ, Roche JC: Uveitis posterior asociada a nefritis tubu-lointersticial aguda con respuesta favorable a ciclosporina. Implicaciones patogénicas.Med Clin (Barc) 1995;104:44

Correspondence to:Dr Ana Tomás MateusDepartment of NephrologyHospital Garcia de OrtaAv. Torrado da Silva1801-951 Almada, Portugale-mail: anaamateus@yahoo.com

Ana Tomás Mateus, Aura Ramos, Pedro Ponce

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