Case Report
Syndrome of Tubulointerstitial Nephritis and Uveitis S Ramakrishnan, R Dilip Abstract We report a case of acute tubulointerstitial nephritis and uveitis syndrome (TINU syndrome) in an elderly Indian woman. TINU is one of the rare causes of acute tubulo interstitial nephritis and is likely to be missed as there is often temporal gap between the appearance of the renal and ocular manifestations. ©
A
INTRODUCTION
cute Interstitial Nephritis (AIN) is not an uncommon cause of acute renal failure. Drugs and infections are the most common etiological agents. Idiopathic AIN is a rare entity and has been reported in association with uveitis especially in young females. They seem to share an immunological basis. It is important to be aware of this association as it has tendency to respond to immunosuppression and the diagnosis is likely to be missed in view of the temporal gap in the manifestations. In this case report we are presenting its occurrence in an elderly woman.
CASE REPORT 61 year old Indian woman presented in March 2007 for evaluation of elevated serum creatinine. She had history of ischemic heart disease since 10 years and was on diet control for DM since 1 year. While undergoing evaluation for head ache in January 2007, she was found to have 1+ proteinuria, bland urine sediment and serum creatinine 2.4mg/dl. Serum protein electrophoresis was normal and VDRL was non reactive. She was normotensive and otherwise asymptomatic then. There was no prior regular or OTC medicine intake nor was there any preceding or associated fever or other symptoms suggestive of active infection. There was no history of anorexia or weight loss. Evaluation in March 2007 revealed normal blood pressure and no diabetic retinopathy. Laboratory investigations showed the following results: proteinuria (1.1 gram/24 hrs), 6-8 wbcs in urine, normocytic hypochromic anemia (Hemoglobin 9.9gm/dl), elevated ESR (75mm/hour), renal failure (Serum creatinine-2.4mg/dl) and normal serum albumin (Serum Total Protein 7.9gm/dl, albumin 5gm/dl, globulin 2.9gm/dl), serum cholesterol (195 mg/dl) and normal blood sugar (101 mg/dl). Serology for Hepatitis NU Trust, Bangalore, Department of Nephrology, Padmanabhanagar, Bangalore - 560070, Karnataka, India. Received : 31.7.2008; Revised : 20.10.2008; Re-revised : 22.2.2008; Accepted : 7.1.2009 © JAPI • VOL. 57 • FEBRUARY 2009
B, Hepatitis C and HIV were negative. Chest x ray was unremarkable except for mild increase in cardiothoracic ratio. USG abdomen revealed normal sized kidneys. She underwent renal biopsy in April 2007 which, under light microscope, revealed 4 normal glomeruli and diffuse interstitial edema and inflammation; tubules and vessels were unremarkable; Immunofluorescence was negative. ANA was negative. A diagnosis of idiopathic acute interstitial nephritis was made in the absence of preceding drug intake and definite clinical features for infection or connective tissue disease and oral Prednisolone (1mg/kg/day) was started in April 2007 (as there was unresolved, persistent renal failure over 2months duration). Subsequently there was steady decline in serum creatinine. When serum creatinine reached 1.3mg/ dl, Prednisolone was tapered over 6 weeks and stopped in June 2007. In November 2007 she had painful red eye on the left side. Anterior nongranulomatous uveitis was diagnosed
Fig. 1: Renal Biopsy - Light Microscopy showing significant interstitial inflammation (white arrows) Haematoxylin & Eosin stain (High power).
www.japi.org
177
and she was restarted on steroid eye drops. That time, she revealed that she had a similar episode in February 2007 and ophthalmology consult records showed that she had been treated for anterior nongranulomatous uveitis in the left eye with steroid eye drops. During her last visit a month back, serum creatinine was 1.2mg/dl, urine protein was nil and she continued to have episodes of uveitis both eyes.
DISCUSSION TINU is a distinct entity comprising of tubulo interstitial nephritis and uveitis in the absence of systemic illness associated with either condition and is very much likely to be under diagnosed in view of asynchronous development of these two features. Tubulo interstitial nephritis and uveitis (TINU) syndrome was first described in 1975 by Dobrin in two teen aged girls.1 In a review of three series of 128 patients with acute tubulo interstitial nephritis, it was observed that 6 (4.7%) had TINU.2 Though originally observed in children and young adults, it can occur even in elderly, as in our patient.3 Females are affected more often than males. There is often a time interval, usually two to seven months between the diagnosis of uveitis and that of acute interstitial nephritis, making the diagnosis of TINU difficult. In 35% of patients with TINU, ocular findings precede or develop concurrently with acute interstitial nephritis. In 65% of patients, ocular symptoms follow acute interstitial nephritis by a median time of 1 month, but can occur up to 14 months later.4 They generally suffer from weight loss and anemia, and have a raised ESR. Our patient had uveitis preceding the presentation of renal failure and we did not think of this possibility until she had the second episode of uveitis when she recollected the first episode. In the absence of clinical features to suggest infections like cytomegalovirus, herpes zoster, Epstein Barr virus and Toxoplasmosis and in view of therapeutic response to steroids alone, we did not proceed to evaluate for these infections. Uveitis is typically bilateral acute and non granulomatous involving the anterior segment; Mandeville et al. had described in their review of TINU from the world’s published medical literature the occurrence of anterior uveitis in 97 out of 122 cases (80%) and posterior uveitis in the remaining 25 (20%); granulomatous uveitis was observed in only 2 of these 122 cases.4 The uveitis tends to be recurrent, and relapses typically occur at discontinuation of treatment. Renal disease in patients with TINU is usually self-limited and, in most patients, can be expected to spontaneously resolve. There can be significant proximal tubular and distal tubular dysfunction resulting in defects of acidification and concentration. At least 50% of cases are idiopathic based on the absence of risk factors for acute interstitial nephritis. Associations that have been reported include: drugs (antibiotics, non-steroidal anti-inflammatory drugs), infections (cytomegalovirus, herpes zoster, Epstein–Barr virus, toxoplasmosis), and systemic diseases (hyperthyroidism, 178
hypoparathyroidism, rheumatoid arthritis, Juvenile Rheumatoid Arthritis, Spondyloarthropathy, Behcet’s syndrome, Reiter’s syndrome, sarcoidosis).4 The main differential diagnosis is sarcoidosis. Although uveitis associated with sarcoidosis is typically granulomatous, uveitis associated with TINU is mostly non-granulomatous and frequently relapsing despite treatment with local or systemic steroids. Sarcoidosis rarely causes acute interstitial nephritis and frequently affects the lungs, whereas lung involvement has not been reported with TINU. Sjögren’s syndrome is not a differential diagnosis because patients with Sjögren’s syndrome do not develop uveitis despite having sore eyes (sicca). The pathogenesis of TINU-syndrome is not clear though immunological cause is very much likely in view of numerous CD4+ and CD8+ cells in the interstitium of renal biopsies, hypergammaglobulinemia and favorable response to steroids in some instances. Abnormalities of both humoral and cellular immunity have been reported, including antineutrophil cytoplasmic antibodies (ANCA),5 immune complexes in the aqueous and serum, elevated serum IgG1 and suppressed T-cell function in vivo and in vitro during remission.6 Various HLA associations have also been described. Patients with progressive renal insufficiency are typically treated with prednisone at a dose of 1 mg/kg per day (typically between 40 to 60 mg/day) for three to six months (duration of therapy depending upon the response). Most patients recover normal renal function. This regimen is similar to (but more prolonged) therapy in acute interstitial nephritis. However, relapses are more likely to occur in TINU syndrome because of the potential immunological basis of the disease and the lack of a possible culprit agent. Topical and systemic steroids have been used for uveitis with success. However, recurrences and relapses of uveitis are common; infrequently, steroid-sparing immunosuppressive agents, such as Cyclosporin, methotrexate and mycophenolate mofetil are needed. To summarize, it is better to enquire specifically for episodes of uveitis in any patient presenting with unexplained acute interstitial nephritis.
REFERENCES 1.
Dobrin RS, Vernier RL, Fish AL. Acute eosinophilic interstitial nephritis and retinal failure with bone marrow-lymph node granulomas and anterior uveitis. A new syndrome. Am J Med 1975;59:325-33.
2.
Richard J Baker, Charles D Pusey The changing profile of acute tubulointerstitial nephritis. Nephrol Dial Transplant 2004;19:8-11.
3.
Salu P, Stempels N, Vanden Houte K, Verbeelen D Acute tubulointerstitial nephritis and uveitis syndrome in the elderly. Br J Opthalmol 1990;74(1):53-55.
4.
Mandeville JTH, Levinson RD, Holland GN. The tubulointerstitial nephritis and uveitis syndrome. Surv Opthalmol 2001;46:195-208.
5.
Simon AH, Alves-Filho G, Ribeiro-Alves MA. Acute tubulointerstitial nephritis and uveitis with immune antineutrophil cytoplasmic antibody. Am J Kidney Dis 1996;28:124-27.
6.
Gafter U, Kalechman Y, Zevin D, Korzets A, Livni E, Klein T, Sredni B, Levi J. Tubulointerstitial nephritis and Uveitis: Association with suppressed
www.japi.org
© JAPI • VOL. 57 • FEBRUARY 2009
cellular immunity. Nephrol Dial Transplant 1993;8:821-26.
DOCTOR 2007 Medical Software CONVENIENT, IDEAL, MOST ECONOMICAL MEDICAL SOFTWARE JUST FOR YOU Clinical : Case sheets, speciality sheets, Inpatient, ICU, Lab, PDR, Auto Casesummary, Certificates, letters, USS, X-ray, Pathology, Endoscopy, Echo, Proc. reports, very little typing needed. Prescription Autodose, Allergy, diseasecontraindication, interaction alert, Fonts option (Hindi, Tamil etc) Overdose treatment, Ther. level, dose in organ failures Store Recall at a single click. ADMINISTRATIVE : Appointment schedular; OP Card, Pt. List, Statisics, Finance billing; salary, room, manpower management; Drugstore, Inventory. Secure, NETWORK ready. Auto backup Store/Link photos, X-ray, ECG, Videos; Change Header/Footer; Diet advisor-autocalory calculator EDUCATIVE : Disease guidelines Medical graphs; Patient education videos and printouts. Reliable. Saves Life, Time and Money. Hospital pack, and excl. medicine, surgery, OBG, clinic packs available. Address : MEDISOFT, Achutha Warrier Lane, Cochin-682035. http://www.medisoftindia.com E-mail :
[email protected] Ph 09847294414 © IPR.All Rights Reserved
Two Yoga books by Eminent Physician and Yoga Expert
Dr. Prakash C. Malshe, M.D.
1.“Yoga Book For Doctors” (Price Rs. 120) (See book review in JAPI Jan 2007)
Some pranayamas produce hypoxia which can bring about beneficial effects in the form of raised erythropoietin levels and in ischaemic myocardium, VEGF leading to generation of coronary collaterals. Many more revolutionary concepts on different yogic practices!
2.“Drink Air, Stay Fit” (Price Rs. 50)
Presenting Yogic Treatment for Amoebic and Helicobacter Infections !! Human stomach contains air in the fundus. H. pylori is anaerobic organism.That is the reason why it does not live in the fundus of the stomach. One can manouver the air bubble in the fundus to the pyloric region by yogic postures and get rid of helicobacter infection!!
Both the books available for preview on Google book search To get the books by VPP (Postage charges extra) write to Director, Antar Prakash Centre for Yoga SF 19.20 Surya Complex, Ranipur Mode Haridwar (Uttarakhand) 249 407 INDIA Tel +919412073252 e-mail
© JAPI • VOL. 57 • FEBRUARY 2009
www.japi.org
179
