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.     

Serial renal biopsies in three girls with tubulointerstitial nephritis and uveitis syndrome

Tubulointerstitial nephritis and uveitis (TINU) syndrome is considered to have a good prognosis even without any immunosuppressive therapy, although there is no histological evidence to support this. The objective of this study was to evaluate, retrospectively, serial renal biopsy findings in three girls with TINU syndrome who were treated with prednisolone. At presentation, all patients had significantly elevated urinary β₂-microglobulin levels (7583–19,313 μg/l) and high serum creatinine levels (0.93–1.3 mg/dl). The elevated β₂-MG and creatinine levels persisted for 1 month, and renal biopsies were performed to establish a definitive diagnosis. The initial biopsy specimens of all patients revealed marked interstitial enlargement consisting of infiltration of lymphocytes; there was also notable tubulitis and infiltration of eosinophils. All patients received prednisolone therapy following the diagnosis. A second renal biopsy was performed 9 months after the first biopsy for two of three patients, and 2 years later for the third patient. The biopsy specimens taken at 9 months still showed histological changes of acute inflammation; in contrast, that taken at 2 years showed a lower degree of acute inflammation, but scar formation was observed in some regions. Based on these results, we conclude that selected TINU syndrome patients require some immunosuppressive therapy.     

Tubulointerstitial nephritis and uveitis in monozygotic twin boys

We describe monozygotic male twins who developed tubulointerstitial nephritis and uveitis (TINU) almost 2 years apart. They presented with non-specific symptoms and were noted to have glycosuria and renal impairment. Both children have uveitis. One had biopsy-proven interstitial nephritis and the other had biochemical evidence of transient tubular dysfunction. While the renal parameters improved, they are still under treatment for uveitis. The occurrence of TINU in identical twins at an interval of just under 2 years supports a strong genetic element in the aetiology of this syndrome. We believe this is the first report of male twins with TINU.     

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.     

Predominant tubulointerstitial nephritis in a patient with systemic lupus nephritis

In most cases of systemic lupus erythematosus (SLE), glomerular lesions are the main renal complication. Although tubulointerstitial lesions are often associated with severe glomerular lesions, predominant or isolated tubulointerstitial injury in the presence of minimal glomerular abnormalities with SLE, so-called predominant tubulointerstitial lupus nephritis, is rare. Only ten cases are reported in the English literature. Herein, we describe the case of a 64-year-old man with SLE who presented with acute renal deterioration attributable to acute tubulointerstitial nephritis. Renal biopsy showed diffuse infiltration of inflammatory mononuclear cells in the interstitium and tubulitis without significant glomerular lesions. Immunofluorescence study revealed positive staining for IgG, C3, and C1q along the renal tubular basement membrane (TBM). Electron microscopy also showed electron-dense deposits in the TBM. Other causes of tubulointerstitial injury, such as drug use and infection, were ruled out. Taking these findings together with the presence of antitubular basement membrane antibody, predominant tubulointerstitial lupus nephritis was diagnosed. Treatment with oral corticosteroids for 6 weeks improved renal function. Even after tapering of the corticosteroid, renal function and serological markers of SLE activity have remained stable in this patient for more than 12 months.     

Repeat renal biopsy in children with severe idiopathic tubulointerstitial nephritis

Idiopathic (primary) tubulointerstitial nephritis (TIN) of childhood is relatively rare. Four children, two with concomitant uveitis, aged 8–14 years, with idiopathic TIN who underwent repeat renal biopsy were retrospectively evaluated. At presentation, all had a significant elevation of the urinary ₂-microglobulin/creatinine ratio (2MG ratio), ranging from 10,100 to 44,550, with increased histological indices of tubulointerstitial scores (TI scores) in excess of 6 points. Three of the children received prednisolone (PSL) therapy following diagnosis, while the remaining child received the therapy 30 months after the first renal biopsy. In the children that received prompt PSL therapy, a rapid decrease in urinary 2MG ratio was observed and the TI scores obtained at a mean interval of 16 months after the first biopsy decreased to less than 5, while preserving renal function. In the remaining child that received delayed PSL therapy, persistent elevations of urinary 2MG ratio and TI scores were observed. He subsequently progressed to chronic renal insufficiency. These clinical findings suggest that persistent elevations of urinary 2MG ratio and TI scores are indicators of progression of renal failure in TIN. For successful treatment, early therapeutic intervention should be deployed in selected patients with severe idiopathic TIN.     

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.     

Repeat renal biopsy in tubulointerstitial nephritis and uveitis syndrome: report of a case

A Japanese girl aged 12 years who presented with a month history of uveitis developed a significant elevation of urinary beta 2 microglobulin (beta 2MG) up to 13,933 micrograms/l. A percutaneous renal biopsy revealed a dense CD4-positive T-cell infiltration with focal tubulitis in the interstitium. The tubulointerstitial score (TI score) described by Foster et al. was 7 points. She was diagnosed as having tubulointerstitial nephritis and uveitis syndrome (TINU). Due to the severe interstitial infiltration, a 6-month course of prednisolone at the dose of 30 mg per alternate day was started. The levels of urinary beta 2MG dramatically decreased following treatment and the renal function remained normal. The second renal biopsy performed 6 months later revealed mild persistent CD4-positive T-cell infiltration associated with 19% periglomerular thickening, with the TI score of 4 points. These clinical observations suggest that the interstitial cell infiltration persists for a relatively long time in a proportion of patients with TINU. Since persistent interstitial infiltration has been known to be harmful to the kidney, we therefore speculate that prompt administration of corticosteroids might be beneficial to these patients. Although the renal outcome of TINU has been reported to be favorable to date, patients with severe interstitial infiltration should be followed under close observation. Study of similar patients is needed to clarify our understanding of effective therapy for TINU.     

Pseudotumor cerebri following cyclosporine A treatment in a boy with tubulointerstitial nephritis associated with uveitis

An 11-year-old boy with recurrent nephritis due to tubulointerstitial nephritis associated with uveitis (TINU syndrome) was treated with cyclosporin A (CSA) to induce sustained remission. CSA was introduced as a steroid-sparing drug because of extreme obesity (body mass index 32 kg/m²). Although the boy did not complain of any clinical symptoms, eye inspection after 7 months revealed bilateral disk edema with retinal bleeding and the patient developed cerebrospinal hypertension. Pseudotumor cerebri was diagnosed by measuring the intracranial pressure (31 cmH₂O) and normal computer tomography and brain magnetic resonance imaging. Cessation of CSA therapy and treatment with mycophenolate mofetil led to resolution within 12 weeks.Supported by Forschungsunterstützungskreis Kindernephrologie e.V. Essen     

Tubulointerstitial nephritis and uveitis: association with suppressed cellular immunity

It is suggested that tubulointerstitial nephritis and uveitis(TINU) is a cell-mediated immune disease with a favourable responseto treatment with steroids. However, long-term follow-up hasnot been described and data on immunological studies are limited.The aim of this study was to evaluate the clinical featuresin patients with TINU who have had a long follow-up period,and in parallel to assess their cellular immunity and HLA typing.Four women with TINU were followed for 5.7±3.6 years.On remission they were studied for T-cell-mediated immunityby skin tests, T-cell subpopulations, and lymphokine secretionin vitro. The lymphokines included interleukin-2, -interferon,tumour necrosis factor, and colony-stimulating factor. The invitro response to AS101, a previously described immunomodulator,was evaluated. HLA-typing was also performed. The nephritis,which occurred once, was resolved in all patients and did notrecur. In contrast, numerous relapses of uveitis occurred despitetopical or systemic steroid treatment. The patients' T-cellsubpopulations did not differ from controls, but they revealedanergy to skin tests and a very low secretion rate of lymphokines.AS101 corrected the suppressed secretion in vitro. A high frequencyof HLA-DR6 antigen was found in the TINU patients. TINU is probably a systemic disease with a chronic relapsingcourse of the uveitis but with complete clinical recovery ofthe nephritis. Both in vivo and in vitro T-cell functions aresuppressed during remission.     

Tubulointerstitial nephritis and uveitis syndrome associated with hyperthyroidism

We report a 17-year-old male patient with tubulointerstitial nephritis and uveitis (TINU) associated with hyperthyroidism. He presented with a 2-month history of fatigue, loss of appetite, low-grade fever, and a 12-kg weight loss when he was admitted to our hospital. He had iritis, which was complicated by fibrin in the anterior chamber, diagnosed by slit-lamp examination. On laboratory examinations, deteriorated renal function (blood urea nitrogen level was 25.9 mg/dl and creatinine level was 2.82 mg/dl) and elevated urinary levels of N-acetyl-β-D-glucosaminidase (33.1 U/l) and β2-microglobulin (78 600 μg/l) were observed. Serum thyroid-stimulating hormone (TSH) was undetectable, at less than 0.01 μIU/ml, and free triiodothyronine and free thyroxine were elevated, up to 5.23 pg/ml and 2.85 ng/dl, respectively. The titers of antithyroglobulin and antithyroid microsomal and TSH-receptor antibodies were not elevated. Abdominal and thyroidal ultrasonography showed evident bilateral enlargement of the kidneys and diffuse enlargement of the thyroid gland. Iodine-123 scintigraphy showed low uptake in the thyroid gland. The biopsied renal specimen showed mild edema and severe diffuse infiltration of mononuclear cells and few eosinophils in the interstitium, without any glomerular or vascular abnormalities. Based on the clinical features and pathological findings, a diagnosis of TINU syndrome with associated hyperthyroidism was made. Treatment was started with 30 mg/day of prednisolone. The iritis disappeared, and the patient's clinical status improved remarkably. This case suggests the possibility of thyroid dysfunction in some patients with TINU syndrome, and we believe thyroid function should be measured in all TINU patients. Moreover, histopathological diagnosis of the thyroid glands before treatment is necessary for TINU patients with thyroid dysfunction.     

Outcomes of small renal mass needle core biopsy, nondiagnostic percutaneous biopsy, and the role of repeat biopsy

Background

Percutaneous needle core biopsy has become established in the management of small renal masses ≤4 cm (SRMs). Recent series have reported success rates of ≥80%. Nondiagnostic results continue to be problematic.

Objective

To determine the results of SRM biopsy and the outcomes of nondiagnostic biopsy and repeat biopsy.

Design, setting, and participants

Patients undergoing renal tumor biopsy (RTB) for suspected renal cell carcinoma (RCC) were included in a prospectively maintained database.

Measurements

The database was analyzed retrospectively to determine the pathology and outcomes of SRM biopsy. Outcomes of patients with nondiagnostic biopsy were determined. Patients undergoing repeat biopsy were identified and their outcomes analyzed.

Results and limitations

Three hundred forty-five biopsies were performed (mean diameter: 2.5 cm). Biopsy was diagnostic in 278 cases (80.6%) and nondiagnostic in 67 cases (19.4%). Among diagnostic biopsies, 221 (79.4%) were malignant, 94.1% of which were RCC. Histologic subtyping and grading of RCC was possible in 88.0% and 63.5% of cases, respectively. Repeat biopsy was performed in 12 of the 67 nondiagnostic cases, and a diagnosis was possible in 10 (83.3%). Eight lesions were malignant and two were oncocytic neoplasms. Pathology was available for 15 masses after initial nondiagnostic biopsy; 11 (73%) were malignant. Larger tumor size and a solid nature on imaging predicted a successful biopsy on multivariate analysis. Grade 1 complications were experienced in 10.1% of cases, with no major bleeding and no seeding of the biopsy tract. There was one grade 3a complication (0.3%).This is a retrospective study and some data are unavailable on factors that may affect biopsy success rates. Repeat biopsy was not standard practice prior to this analysis.

Conclusions

RTB can be performed safely and accurately in the investigation of renal masses ≤4 cm. A nondiagnostic biopsy should not be considered a surrogate for the absence of malignancy. Repeat biopsy can be performed with similar accuracy, providing a diagnosis for most patients.     

重复肾活检检测Ⅳ型狼疮肾炎的病理转型特点

目的探讨弥漫增殖型狼疮肾炎（Ⅳ型）的病理转型特点及影响因素。方法经肾活检确诊的Ⅳ型狼疮肾炎32例，平均间隔686天后行重复肾活检，观察其病理转型特点与临床表现的关系。结果病理转型为Ⅱ型者12例、Ⅲ型者3例、Ⅳ型者13例、Ⅴ型者2例、Ⅵ型者1例。临床病理分析显示病理转型为Ⅲ型及Ⅳ型者舒张压、24h尿蛋白定量、血清BUN与SCr明显升高。单因素分析显示男性、首次肾活检收缩压与舒张压均升高、尿红细胞数较多、肾脏血管病变的发生比率高、重复肾活检间隔时间长、未应用免疫抑制剂的患者多转型为Ⅲ型和Ⅳ型；多因素分析显示重复肾活检间隔时间、未用免疫抑制剂治疗与肾脏血管病变的差异具有统计学意义。结论Ⅳ型狼疮肾炎可有各种病理转型。恰当地治疗可以缓解病情，有助于改善病理类型与远期预后。     

Incidental detection of renomedullary interstitial cell tumour in a renal biopsy specimen.

Case A 51-year-old woman with asymptomatic proteinuria and haematuriawas admitted for a renal biopsy. Upon admission, her blood pressurewas 118/68 mmHg. Urinalysis revealed proteinuria 1+, blood 2+,but glucose-negative. A microscopic examination showed 0–1white and 20–30 red blood     

Experience of renal biopsy in children with nephrotic syndrome

Percutaneous renal biopsy (PRB) is useful in childhood renal diseases. This study was done to determine the indications for renal biopsy in nephrotic children, to correlate the indications with histology and to document the complications of PRB. This study included 250 nephrotic children younger than 18 years old who had renal biopsy from January 1988 to December 2002. Ultrasonographic guidance was used in the latter part of the study. Coagulation profile and renal function assessment and blood group testing were done prior to biopsy. Children were monitored clinically during and after the procedure. All children had local anesthesia and 202 children also had short-acting general anesthesia. All biopsies were done on the left kidneys. The specimens were studied under light and immunofluorescent microscopy. All had a post-biopsy ultrasonography at 24 h. Biopsy was diagnostic in 95.2% of children, with a failure rate of 4.8%. The most common indication for biopsy was steroid-resistant nephrotic syndrome (65.2%), and minimal change disease (52.1%) was the most common histology, irrespective of the indications for renal biopsy. Mild (16.0%) and gross (16.8%) hematuria and subcapsular hematoma (6.0%) were the common complications. Fifty-five percent of the children had no complications. Only two children (0.8%) had biopsy site infection.     

Acute interstitial nephritis and uveitis syndrome: activated immune cell infiltration in the kidney

Infiltrating cells were analysed in renal biopsy tissue obtained from a 15-year-old girl with acute interstitial nephritis and uveitis using monoclonal antibodies specific for mononuclear cell surface markers. The interstitial infiltrates consisted mainly of T cells and monocytes/macrophages. A considerable proportion of the infiltrating cells were identified by a monoclonal antibody against the interleukin-2 receptor, indicating that a majority of those immune cells are activated. This observation documents the participation of cell-mediated immune injury in interstitial nephritis associated with uveitis.     

Acute plasmacytic interstitial nephritis in a child with Down syndrome

 A 7.5-year-old boy with Down syndrome presented in acute renal failure (ARF) needing dialysis. When 1.5 years old he had a neuroblastoma, was treated for 1 year with chemotherapy and radiotherapy, and off chemotherapy had since been in remission. Renal biopsy revealed an interstitial inflammation, principally of plasma cells with some lymphocytes and eosinophils. Immunofluorescence showed no deposition of immunoglobulins or complement (C3). The plasma cells were a mixture of kappa and lambda light chain-producing cells. The patient spontaneously improved a week after admission. Initial ultrasonography showed enlarged kidneys with loss of corticomedullary differentiation. We are unaware of a report of ARF in a child, resulting primarily from a polyclonal plasmacytic interstitial nephritis. The etiology remains unclear. Received: 31 March 1988 / Revised: 19 August 1998 / Accepted: 30 September 1998     

Tubulointerstitial immune complex nephritis in a patient with systemic lupus erythematosus: role of peritubular capillaritis with immune complex deposits in the pathogenesis of the tubulointerstitial nephritis

Class IV-G (A/C) diffuse lupus nephritis and tubulointerstitial (TI) nephritis in a 31-year old woman was studied by light, immunofluorescence (IF), and electron microscopy (EM), to determine the pathogenesis of the TI lesions. The light microscopic findings showed peritubular capillaritis in the interstitium, with ruptures in the capillary structure, lysis of the surrounding tubular basement membrane (TBM), extravasated red blood cells (RBCs), the infiltration of neutrophils and mononuclear cells, and edema. The IF study revealed IgG, IgA, IgM, C1q, C3, and C4 depositions along the TBM, on the capillary walls, and in the interstitium proper. The EM study disclosed the deposition of immune complexes in the TBM, the capillary wall, and the interstitium proper. Based on these findings, the TI nephritis in this patient was considered to be due to peritubular capillaritis secondary to the immune complex depositions in the capillary wall of the interstitium.