A case of acute tubulo-interstitial nephritis and uveitis syndrome

We report herein the case of a 14-year-old female who has acute tubulo-interstitial nephritis (AIN) associated with bilateral diffuse uveitis. She was admitted for the evaluation of "proteinuria", following general fatigue and weight loss about 2 weeks ago. Her laboratory data showed mild anemia, hyper gamma-globulinemia, mild proteinuria, and the reduced glomerular filtration rate with the increased urinary excretion of beta 2-microglobulin. The histological examination obtained by renal biopsy showed mild edema and diffuse infiltration of mononuclear cells in interstitium without any glomerular or vascular abnormalities, which were compatible with AIN. As for the etiology of AIN, clinical investigations could not reveal any specific causes, such as bacterial and viral infections, drugs and systemic diseases. About 4 months after the onset of nephritis, she also became to suffer from bilateral diffuse uveitis. Therefore, the diagnosis of the acute tubulo-interstitial nephritis and uveitis syndrome (TINU syndrome) (Vanhaesebrouck et al., 1985) could be confirmed. In her clinical course, it was noteworthy that uveitis relapsed frequently in spite of systemic administration of prednisolone, and it took two years until uveitis cured, whereas the AIN subsided spontaneously prior to the specific treatment. In this case, characteristic findings of granulomatous uveitis was closely similar to those of sarcoidosis, which has been rarely reported in TINU syndrome. In this respect, the involvement of immune processes, especially cell-mediated, was suggested as the possible pathogenesis in this case.     

Acute renal failure due to idiopathic tubulo-intestinal nephritis and uveitis: "TINU syndrome". Case report and review of the literature

Acute renal failure due to idiopathic tubulo-interstitial nephritis associated with bilateral uveitis (TINU syndrome) is a rare clinical event, contracted mainly by girls or women. Here we report the clinical follow-up regarding a 22-year-old woman with acute renal failure (creat. clearance 13.5 ml/min) due to idiopathic tubulo-interstitial nephritis documented by renal biopsy, after bilateral uveitis which healed with local prednisone. The clinical history and the clinical follow-up of our patient were typical of the TINU syndrome. We were able to exclude all diseases causing acute tubulo-interstitial nephritis such as systemic infection, hypersensitivity to drugs, Behcet's disease, Sjogren syndrome, sarcoidosis, systemic lupus or vasculitides. The patient recovered after systemic prednisone.     

Delayed onset of uveitis in TINU syndrome

We report here the clinical features and outcomes of two patients who presented idiopathic tubulo-interstitial nephritis and uveitis syndrome (TINU syndrome) with ocular disease following the onset of nephropathy. The initial symptoms were renal impairment with asthenia, anorexia and weight loss. An increase in urinary beta2-microglobulin was noticed at the initial checkup in both patients. Renal biopsies showed interstitial cellular infiltration without granulomas or tubular atrophy. No glomerular and vascular alterations were seen and immunofluorescent staining was uniformly negative. Systemic steroid therapy was given and renal function returned to normal within three months. Anterior uveitis occurred in both patients eight months later and responded well to local steroid therapy. Renal involvement in TINU syndrome mostly has a favorable outcome. Despite the possibility of spontaneous regression, systemic steroids may be beneficial in reducing the development of interstitial fibrosis.     

A case of acute tubulointerstitial nephritis and uveitis syndrome with a dramatic response to corticosteroid therapy

A 23-year-old female with acute renal failure associated with acute tubulointerstitial nephritis and uveitis is reported. Renal tubular acidosis and inflammatory reactions consisting of markedly increased erythrocyte sedimentation rate and high serum immunoglobulin levels were seen on admission. Light microscopy revealed infiltration of mononuclear cells in the interstitium. Immunofluorescence of renal tissues was negative in staining for immunoglobulins, fibrinogen, and complement components. Bone marrow specimens did not show any granulomatous lesions. The etiology of this tubulointerstitial nephritis and uveitis syndrome was not clear. Immunological evaluation showed a slight decrease of the OKT4/OKT8 ratio in the peripheral blood. OKT8- and OKM1-positive cells had infiltrated diffusely into the renal interstitium. Acute tubulointerstitial nephritis and uveitis responded dramatically to steroid therapy. It was suggested that immunological factors might correlate with the onset and/or development of this syndrome. It is indicated that high-dose steroid therapy might be useful for patients with acute interstitial nephritis and uveitis.     

Impaired potassium and magnesium homeostasis in acute tubulo-interstitial nephritis

Although acute tubulo-interstitial nephritis is increasingly recognized as a cause of acute renal failure, little is known about renal tubular function in this disease. We report on two patients with acute tubulo-interstitial nephritis who demonstrated abnormalities in proximal and distal tubular function. The first patient developed hyperkalemia presumably from a potassium secretory defect in the distal nephron. The second patient developed an incomplete Fanconi's syndrome with glycosuria and aminoaciduria and two heretofore unreported complications of acute interstitial nephritis: hypokalemia and hypomagnesemia secondary to urinary losses of these cations. Careful monitoring of renal tubular function is indicated in patients with acute tubulo-interstitial nephritis.     

Tubulointerstitial nephritis and uveitis in association with Epstein-Barr virus infection

 The case of a 13.5-year-old girl with acute tubulointerstitial nephritis and uveitis (TINU syndrome) is presented. The etiology of this rare syndrome, which in most cases involves female adolescents and usually regresses spontaneously, is still unknown. An infection-triggered pathological immune reaction has been considered to play a role in the pathogenesis of this disorder. Here we report for the first time the association of TINU syndrome and Epstein-Barr virus infection. Received: 4 May 1998 / Revised: 20 August 1998 / Accepted: 26 August 1998     

IgA nephropathy and Henoch-Sch?nlein purpura nephritis with anterior uveitis

Two patients with IgA nephropathy and a patient with Henoch-Sch?nlein purpura nephritis each associated with anterior uveitis are described. As anterior uveitis accompanying IgA nephropathy improved, renal manifestations were relieved. The patient with Henoch-Sch?nlein purpura nephritis suffered from not only anterior uveitis but also keratitis. It is suggested that immune mechanisms which induce IgA nephropathy may play a role in the development of anterior uveitis and keratitis.     

Non-steroidal anti-inflammatory drugs-associated acute interstitial nephritis with granular tubular basement membrane deposits

Acute tubulo-interstitial nephritis (ATIN) is an important cause of acute renal failure resulting from a variety of insults, including immune complex-mediated tubulo-interstitial injury, but drugs such as non-steroidal anti-inflammatory drugs (NSAIDs) are a far more frequent cause. Overall, as an entity, ATIN remains under-diagnosed, as symptoms resolve spontaneously if the medication is stopped. We report on a 14-year-old boy who developed acute renal failure 2 weeks after aortic valve surgery. He was put on aspirin following surgery and took ibuprofen for fever for nearly a week prior to presentation. He then presented to the emergency department feeling quite ill and was found to have a blood urea nitrogen (BUN) concentration of of 147 mg/dl, creatinine of 15.3 mg/dl and serum potassium of 8.7 mEq/l. Dialysis was immediately initiated. A kidney biopsy showed inflammatory infiltrate consistent with ATIN. However, in the tubular basement membrane (TBM), very intense granular deposits of polyclonal IgG and C3 were noted. He needed dialysis for 2 weeks and was treated successfully with steroids for 6 months. His renal recovery and disappearance of proteinuria took a year. In conclusion, this is a first report of NSAIDs-associated ATIN, showing deposits of granular immune complex present only in the TBM and not in the glomeruli.     

Tubulointerstitial nephritis and uveitis: an immunological disorder?

A 14-year-old boy with tubulointerstitial nephritis and uveitis (TINU syndrome) is described. Nephropathy improved without systemic cortisone treatment, whereas uveitis relapsed and was treated with topical steroids. Blood cell immunological analysis and serum analysis revealed signs of cytotoxic T-cell, macrophage and granulocyte activation, which declined as the clinical symptoms improved. This may be interpreted as an indication of their significance as markers in the pathogenesis of this syndrome or as part of a microbial-triggered immune response.     

Tubulointerstitial nephritis and uveitis syndrome (TINU) with Fanconi's syndrome

We report a 57-year-old woman with concurrent tubulointerstitial nephritis and uveitis syndrome (TINU) and Fanconi's syndrome. She presented with sudden onset of bilateral ocular pain, blurred vision, acute renal failure, glucosuria and proteinuria. Slit lamp examination revealed acute bilateral anterior uveitis. Tubulointerstitial nephritis was confirmed by kidney biopsy. Laboratory examination revealed normoglycemic glucosuria, proteinuria, normal anion-gap metabolic acidosis, phosphaturia, urinary uric acid wasting and kaliuresis leading to hypokalemia. Her vision and renal function improved gradually after systemic steroid therapy. There have been rare reports of TINU syndrome which had features of Fanconi's syndrome. The prevalence of TINU syndrome may be underestimated, and its association with Fanconi's syndrome requires further investigation.     

Acute interstitial nephritis with bone marrow granulomas and uveitis

A case of interstitial nephritis with bone marrow granulomas and uveitis was presented. A 53-year-old woman was found to be uremic in the course of rheumatoid arthritis. The renal biopsy revealed acute interstitial nephritis with eosinophilic infiltration. She also had bone marrow granulomas and uveitis. These findings were compatible with those of the syndrome described by Dobrin et al. The etiology and the pathogenesis of this syndrome remain unknown. However, the elevation of the erythrocyte sedimentation rate, raised levels of serum immunoglobulins, presence of circulating immune complexes and decreased T-cell population observed in this patient suggest the involvement of immunological disorders.     

Mechanisms of immune-deposit formation and the mediation of immune renal injury

The passive trapping of preformed immune complexes is responsible for some forms of glomerulonephritis that are associated with mesangial or subendothelial deposits. The biochemical characteristics of circulating antigens play important roles in determining the biologic activity of immune complexes in these cases. Examples of circulating immune complex diseases include the classic acute and chronic serum sickness models in rabbits, and human lupus nephritis. Immune deposits also form “in situ”. In situ immune deposit formation may occur at subepithelial, subendothelial, and mesangial sites. In situ immune-complex formation has been most frequently studied in the Heymann nephritis models of membranous nephropathy with subepithelial immune deposits. While the autoantigenic target in Heymann nephritis has been identified as megalin, the pathogenic antigenic target in human membranous nephropathy had been unknown until the recent identification of neutral endopeptidase as one target. It is likely that there is no universal antigen in human membranous nephropathy. Immune complexes can damage glomerular structures by attracting circulating inflammatory cells or activating resident glomerular cells to release vasoactive substances, cytokines, and activators of coagulation. However, the principal mediator of immune complex-mediated glomerular injury is the complement system, especially C5b-9 membrane attack complex formation. C5b-9 inserts in sublytic quantities into the membranes of glomerular cells, where it produces cell activation, converting normal cells into resident inflammatory effector cells that cause injury. Excessive activation of the complement system is normally prevented by a series of circulating and cell-bound complement regulatory proteins. Genetic deficiencies or mutations of these proteins can lead to the spontaneous development of glomerular disease. The identification of specific antigens in human disease may lead to the development of fundamental therapies. Particularly promising future therapeutic approaches include selective immunosuppression and interference in complement activation and C5b-9-mediated cell injury.     

Tubulointerstitial nephritis and uveitis (TINU) syndrome in a 52-year-old female: a case report and review of the literature

Tubulointerstitial nephritis and uveitis (TINU) syndrome is a rare entity first described in 1975, affecting mainly young women and adolescents. We present a case of a 52-year-old female patient (one of the oldest in the literature) who complained of fever, anorexia, nausea, and vomiting. After she was admitted to our hospital, laboratory tests revealed tubular proteinuria, elevated erythrocyte sedimentation rate (ESR), anemia, and renal insufficiency (serum creatinine 4.2 mg/dL) with metabolic acidosis. Ophthalmologic examination revealed anterior uveitis (iritis) and renal biopsy showed acute tubulointerstitial nephritis. The diagnosis of TINU syndrome was established and the patient was treated with oral corticosteroids. All symptoms and ophthalmologic abnormalities disappeared after 6 weeks of treatment. Renal function also recovered completely and remained stable at follow-up. TINU syndrome should be considered in the differential diagnosis of unexplained tubulointerstitial nephritis, especially in the presence of ocular findings. Corticosteroid therapy is still controversial, but it helps in the quick resolution of renal and mainly eye abnormalities.     

Adult onset tubulointerstitial nephritis and uveitis syndrome

A Turkish woman aged 44 years who presented with a 1 month history of abdominal pain, fatigue and weight loss of 10 kg was diagnosed as having acute tubulointerstitial nephritis. Opthalmological evaluation revealed unilateral uveitis and contralateral chorioretinal scarring. X-ray films of the pelvis revealed unilateral sacroileitis. An elevated erythrocyte sedimentation rate, C-reactive protein, tubular proteinuria and renal glucosuria returned to normal 2 weeks after treatment was started. It is important to be aware of tubulointerstitial nephritis and uveitis syndrome in order to achieve a quick diagnosis in patients with renal impairment and tubular dysfunction with minor symptoms so that appropriate management can be started early.     

A case of tubulointerstitial nephritis and uveitis syndrome with severe immunologic dysregulation

Idiopathic tubulointerstitial nephritis and uveitis (TINU) syndrome is an uncommon condition, characterized by acute tubulointerstitial nephritis (TIN) with a favorable course and uveitis with a chronic relapsing course. The pathogenesis remains unclear, but a lymphocyte-mediated immune mechanism has been suggested. A 9-year-old boy was evaluated for fatigue and 2 kg of weight loss. Renal glucosuria, elevated urine ₂-microglobulin (MG), progressive renal dysfunction, polyclonal hypergammaglobulinemia, various autoantibodies and abnormal lymphocyte phenotypes were found. A renal biopsy revealed acute TIN. After 2 months of treatment with prednisolone, renal function and polyclonal hypergammaglobulinemia were normalized. While tapering prednisolone, anterior uveitis developed, which was improved with topical steroid. But abnormal lymphocyte phenotypes and autoantibodies persisted on low-dose prednisolone. Uveitis became aggravated, and urine ₂-MG increased again. The second renal biopsy (7 months later) was normal except for minimal focal interstitial fibrosis. Uveitis was not responsive to systemic steroids, but improved with additional cyclosporin. Abnormal lymphocyte phenotypes improved, and most autoantibodies disappeared. We report a rare case of idiopathic TINU syndrome with severe immunologic dysregulation, which correlated with the clinicopathological and biochemical parameters. The information about lymphocyte phenotypes and autoantibodies may provide more insight into the pathophysiology and the clinical course of uveitis in this rare disorder.     

Acute tubulointerstitial nephritis with uveitis syndrome presenting as multiple tubular dysfunction including Fanconi's syndrome

We describe an 11-year-old male patient with acute tubulointerstitial nephritis with uveitis (TINU) syndrome. He presented with easy fatigability, pallor, nocturia and weight loss. laboratory examination disclosed anaemia, polyclonal hypergammaglobulinaemia, low molecular weight proteinuria, glycosuria, aminoaciduria, proximal and distal renal tubular acidosis, a urine concentration defect and decreased creatinine clearance. The multiple renal tubular dysfunction and slight glomerular dysfunction subsided spontaneously. Bilateral anterior uveitis was manifested 7 months after the onset of the disease. This is the first reported case of TINU syndrome with multiple proximal and distal tubular dysfunction including a complete type of Fanconi's syndrome.     

Drug-induced TINU syndrome and genetic characterization

Tubulointerstitial nephritis and uveitis (TINU) syndrome is due to a disregulation of cell-mediated immunity and genetical predisposition due a particular molecular characterization. We report the case of a 50-year-old woman who was admitted for acute renal failure. She had recently taken flurbiprofen for 10 d for recurrent bronchitis. A renal biopsy revealed acute tubulointerstitial nephritis. Prednisone was started and prognosis was favorable. Three months later the patient developed transitory blurred vision. The diagnosis was bilateral uveitis and she received topic and systemic corticosteroid therapy, with resolution of ocular symptoms. Recurrent episodes of uveitis experienced during the next 12 months were treated with same therapy. Genomic haplotype in our patients was HLA A*0278/2631,-B*1517/3802,- Cw*0701/1202, -DRB1*0101/1359 (DRB3* 52), -DQA1*0102/0102, DQB1*0603/0603. TINU syndrome is characterized by tubulointerstitial nephritis that tends to be selflimiting, whereas uveitis tends to relapse. HLA-DQA1*01 and -DQB1*06 haplotypes are strongly associated with TINU syndrome. This is the first report of TINU syndrome induced by flubiprofen intake. Our case emphasizes the importance of the association between drug exposure and strong susceptibility to TINU syndrome giving the molecular characterization.     

人类免疫缺陷病毒感染伴肾病患者的临床病理分析

目的对行肾组织活检的人类免疫缺陷病毒(HIV)感染合并肾病患者进行病理分析。方法纳入2011年1月至2018年12月四川大学华西医院肾内科接受肾组织活检的HIV合并肾病患者,分析其病理特征、干预措施和预后等。结果共纳入9例患者,其中肾病综合征患者6例,急性肾功能损伤患者1例,慢性肾炎综合征患者2例。组织学诊断:肾小球微小病变患者3例,膜性肾病患者1例,塌陷型局灶节段性肾小球肾炎(FSGS)伴膜性肾病患者1例,FSGS非特异型(NOS)患者1例,急性间质性肾炎患者1例,Ig A肾病患者1例,糖尿病肾病患者1例。5例患者在肾组织活检时首诊HIV感染(其中塌陷型FSGS伴膜性肾病、糖尿病肾病、急性间质性肾炎各1例,2例为肾小球微小病变),其余4例在HIV感染确诊后的不同时期(均行抗逆转录病毒治疗)发病。并发症:糖尿病1例,梅毒感染1例,甲状腺功能减退2例,乙型肝炎病毒感染3例。随访情况:3例患者失访,6例患者随访期间未发生严重感染,其中2例仍有大量蛋白尿,其余4例患者血尿消失,肾功能恢复正常水平,复查尿蛋白定量显著减少至可疑阳性或24 h定量<300 mg/d。结论HIV感染者出现肾脏损伤的临床表现多样,可出现不同程度蛋白尿和(或)血尿,伴或不伴肾功能不全,病理类型不仅限于人类免疫缺陷病毒相关性肾病(HIVAN),可出现糖尿病肾病、肾小球轻微病变、膜性肾病、非塌陷型FSGS、急性间质性肾炎、Ig A肾病。肾组织活检有助于明确诊断。抗逆转录病毒治疗有效情况下,依据患者的病理诊断,有针对性地给予糖皮质激素及细胞毒药物,并加强随访,有助于改善患者预后。肾病患者应加强HIV筛查。     

A syndrome of acute interstitial nephritis and anterior uveitis

A syndrome of acute interstitial nephritis (AIN) and anterior uveitis is described in two children and the literature is reviewed. These disorders appear to improve, in uncontrolled studies, with systemic and topical ophthalmic corticosteroid treatment. Although the renal and ocular prognoses appear good, it is important to recotnize that patients with AIN are at risk for uveitis and if present, consultation with an ophthalmologist is recommended.