Granulomatous Tubulointerstitial Nephritis Research Articles

Atteintes rénales de la sarcoïdose

Sarcoidosis is a chronic multisystemic inflammatory disorder of unknown etiology, characterized by the presence of non-necrotizing epithelioid and giant cell granulomas. Various renal manifestations have been reported in patients with sarcoidosis. Disorders of bone and mineral metabolism related to the overexpression of 25-hydroxyvitamin-D1α-hydroxylase by alveolar and granuloma macrophages are frequently associated with sarcoidosis. Hypercalcemia and hypercalciuria are a major cause of renal injury predisposing to pre renal azotemia, acute tubular necrosis, nephrolithiasis and nephrocalcinosis. Therapeutic management of hypercalcemia includes preventive measures (limited sunlight exposure, limited vitamin D and calcium intakes, and adequate hydration) and specific treatment in cases of severe hypercalcemia (corticosteroid therapy, chloroquine or ketoconazole). Granulomatous tubulointerstitial nephritis is the most common renal lesion associated with sarcoidosis leading to end stage renal disease in some patients. In these cases, interstitial fibrosis seems to appear early in the course of sarcoidosis and is a major prognostic factor requiring rapid corticosteroid therapy to reduce the risk of severe renal impairment. Membranous nephropathy seems to be the most frequent glomerular disease that may occur in association with sarcoidosis. Among kidney allograft recipients, the risk of recurrence of granulomatous tubulointerstitial nephritis is high and may have a negative impact on the graft survival.

Granulomatous tubulointerstitial nephritis in a renal allograft: three cases report and review of literature

Granulomatous interstitial nephritis (GIN) is a rare histologic diagnosis in renal allografts. We report three cases with GIN. Case 1: a 37-yr-old woman received a kidney from her mother. On follow-up 15 months later, serum creatinine was increased and a graft biopsy showed epithelioid granuloma in the center of massive mononuclear cell infiltration. She had presented with refractory urinary tract infection treated with antibiotics before biopsy. The case was presumed to be GIN associated with UTI or hypersensitivity to medication. Case 2: a 47-yr-old woman received a second graft from a non-heart-beating donor. A protocol graft biopsy was performed six months after transplantation and showed several granulomatous nodules. She was followed closely without therapy. Case 3: a 27-yr-old woman received an ABO-incompatible kidney from her father. A protocol graft biopsy was performed three months after transplantation and showed granulomatous reaction with severe mononuclear cell infiltration. She received steroid pulse therapy. The two latter patients had no obvious factor contributing to GIN. Therefore, they were presumed to have idiopathic GIN. Infection is considered to be the main causative factor of GIN in renal allografts. This paper describes rare cases of GIN that had no infectious episode in the renal allografts.

Successful treatment of progressive renal injury due to granulomatous tubulointerstitial nephritis with uveitis

Acute tubulointerstitial nephritis and bilateral uveitis (TINU) syndrome is a rare disease usually occurring in young women. We report the exceptional case of a 48-year-old man with TINU syndrome who had a 10-month history of interstitial nephritis before the onset of uveitis. Findings from the renal biopsy specimen indicated tubular atrophy, dense infiltration of lymphocytes, granulomatous infiltration with multinucleated giant cells, and disruption of the vessel wall. The patient was initially diagnosed to have chronic kidney disease; interstitial nephritis could not be diagnosed until blurred vision occurred. However, he was successfully treated with steroid pulse and oral maintenance therapy. Steroid therapy may be effective to treat TINU syndrome irrespective of the onset of the disease.

Presentation, diagnosis, and treatment outcome of tuberculous-mediated tubulointerstitial nephritis

Insidious Mycobacterium tuberculosis infection causing tubulointerstitial nephritis is a rare disorder. Here we report on a single-center case series of patients with tubulointerstitial nephritis due to tuberculosis, addressing clinicopathologic features and treatment outcome. Twenty-five adult patients with clinical evidence of tuberculosis and significant renal disease were assessed, 17 of whom had a kidney biopsy and were subsequently diagnosed with chronic granulomatous tubulointerstitial nephritis as the primary lesion. All patients were given standard antitubercular treatment, with some receiving corticosteroids, and showed a good response in clinical symptoms and inflammatory markers. Nine of the 25 patients, however, started renal replacement therapy within 6 months of presentation. Of the remaining 16, renal function improved for up to a year after presentation but subsequently declined through a median follow-up of 36 months. This case series supports that chronic tubulointerstitial nephritis is the most frequent kidney biopsy finding in patients with renal involvement from tuberculosis. Thus, a kidney biopsy should be considered in the clinical evaluation of kidney dysfunction with tuberculosis since tubulointerstitial nephritis presents late with advanced disease. A low threshold of suspicion in high-risk populations might lead to earlier diagnosis and treatment, preserving renal function and delaying initiation of renal replacement therapy.

Chronic Interstitial Nephritis in An HIV Type-1-Infected Patient Receiving Ritonavir-Boosted Atazanavir

Here, we report a case of chronic granulomatous tubulo-interstitial nephritis related to atazanavir crystals in a HIV type-1-infected patient. Renal function in this patient was partially recovered after atazanavir withdrawal and steroid therapy. Many reports have described atazanavir-associated urolithiasis, but this is the first case that describes chronic granulomatous nephropathy.

A Case of Phospholipase A 2 Receptor–Positive Membranous Nephropathy Preceding Sarcoid-Associated Granulomatous Tubulointerstitial Nephritis

We report the case of a 29-year-old man with membranous nephropathy that was associated with a sarcoidosic granulomatous tubulointerstitial nephritis, but was without an apparent calcium metabolism disorder. Corticosteroid treatment was associated with remission of nephrotic syndrome. We discuss the relationship between membranous nephropathy and sarcoidosis based on the close appearance of the 2 diseases and the detection of phospholipase A₂ receptor in glomerular immune deposits.

Sarkoidose

We report the case of a 13-year-old boy who presented with impaired exercise tolerance, loss of weight and fever. Laboratory data indicated systemic inflammation and renal failure suggestive of tubular dysfunction. A kidney biopsy showed epithelioid granulomatous tubulointerstitial nephritis. The boy developed granulomatous uveitis during follow-up. TINU syndrome (tubulointerstitial nephritis and uveitis) was diagnosed and sarcoidosis was considered to be the most probable cause. Treatment was started with prednisone and methotrexate and renal function completely recovered, whereas after 2 years of treatment the uveitis is still mildly active. Sarcoidosis is a rare disease of childhood; nevertheless it must be considered in the differential diagnosis of granulomatous uveitis and tubulointerstitial nephritis.

Cystic fibrosis with sarcoidosis—genetics vs immunology: a paradigm shift?

Introduction The authors describe coexistence of sarcoid and cystic fibrosis (CF), previously reported in only four childhood cases. Sarcoidosis has a UK annual incidence of 2–4 per 100 000 while CF is seen in 1/2000 live births. Rarity of both conditions makes coexistence by chance unlikely. Methods A 12-year-old girl, with pseudomonas positive CF (diagnosed age 7 months with positive sweat test and delta F508/1507 genotype), presented with a 2 year history of intermittent skin rash, joint pains, fever and conjunctivitis. Examination revealed petechial rash, hepatosplenomegaly and small joint arthritis. Results Investigations showed acute renal impairment (creatinine 200 μmol/l, eGFR 31, albumin/creatinine ratio 22.5 mg/mmol), elevated angiotensin converting enzyme levels (120 μ/l), hypercalcaemia (corrected- 4.57 mmol/l) and positive cANCA (non-PR3/MPO). Renal biopsy demonstrated granulomatous tubulo-interstitial nephritis. Conjunctival biopsy showed non-necrotising epitheloid granuloma. Skin biopsy revealed vasculitis and angiography demonstrated small vessel renal vasculitis. Chest x-ray was consistent with CF (normal CT chest, stable lung function). Treatment was given for sarcoid vasculitis using intravenous methylprednisolone, oral prednisolone and azathioprine. Persistent symptoms 7 months later led to substitution of azathioprine with mycophenolate mofetil and regular IVIG. Disease is currently well controlled. Frequent pseudomonas chest infections are problematic. Conclusion Increased incidence of CFTR mutations has been observed in twenty-six unrelated adults with sarcoidosis. Similarly, familial clustering with recurrence risk 1:100 among first-degree relatives and presence of HLA B8 and DR3 types has raised questions about common genetic aetiology. However, genotype analysis of families with two or more siblings with sarcoidosis failed to find evidence to support CFTR gene mutations. Sarcoid granulomas resemble those associated with mycobacteria, fungi or hypersensitivity. Aetiology remains obscure, but evidence favours chronic immunological response to unidentified environmental factors with possible genetic susceptibility. Both sarcoidosis and CF show defective T cell mediated immune functions and enhanced B cell activation. Children with CF develop frequent chest infections and progressive lung damage. Chronic immune stimulation with persistent antigenaemia and hyperimmunoglobulinaemia could generate large immune complexes resistant to phagocytosis, stimulating granuloma formation. CF may predispose to sarcoidosis through foreign material in the lung or by an altered immunological reaction.

Granulomatous tubulointerstitial nephritis in early renal allograft: a case report

Abstract: Here we report a case of granulomatous tubulointerstitial nephritis occurring seven d after kidney transplantation. The development of macroscopic hematuria, acute prostatitis, a mild elevation of serum creatinine, and high‐grade fever together with a urine culture positive for adenovirus antigen suggested adenovirus infection. Episode biopsy seven d after kidney transplantation showed granulomatous tubulointerstitial nephritis evidenced by predominantly CD68‐positive cell infiltration and epithelioid cells at focal tubulointerstitial spaces with severe tubulitis, such as destruction of the tubular basement membrane. After intervention consisting of a reduction of the immunosuppressive therapy and administration of intravenous immunoglobulin (IVIG) and ganciclovir, renal function returned to normal, with a rapid recovery of the pathological as well as clinical features within a month. In renal allografts, adenovirus infection should be considered during the early phase following transplantation, even within seven d, especially when granulomatous tubulointerstitial nephritis is present.

Giant Cell Tubulitis with Tubular Basement Membrane Immune Deposits

This paper presents two elderly patients who had normal baseline renal function and had stenotic valvular lesions secondary to rheumatic fever and underwent aortic valve replacements with mechanical valves. Both patients developed acute renal failure after cardiac valve replacement procedures. The renal biopsies revealed acute granulomatous tubulointerstitial nephritis. The unique histologic features were tubular basement membrane (TBM) immune complex deposition detected by both immunofluorescence and electron microscopy and prominent multinucleated giant cells surrounding intact TBM. The temporal relationship to the surgical procedure and the subsequent recovery of the patients' renal functions upon therapy suggested that the renal failure may have been due to an allergic drug reaction from the perioperative exposure to unknown agents, such as prophylactic antibiotics and furosemide. The literature on TBM immune complex deposition was reviewed, and the pathophysiologic mechanisms that may account for the similarities between the clinicopathologic features of these two cases were examined. These two cases expand the histopathologic spectrum of previously described cases of putative drug-induced acute tubulointerstitial nephritis.

Sarcoid tubulo-interstitial nephritis: Long-term outcome and response to corticosteroid therapy

Sarcoidosis is a chronic relapsing multi-systemic disorder characterized by the development of non-caseating granulomas. Granulomatous tubulo-interstitial nephritis is an uncommon manifestation of this condition. We identified 39 patients with sarcoidosis and renal disease from a single center of whom 17 patients had biopsy-proven tubulo-interstitial nephritis. They were analyzed with respect to demographic and clinical features, including response to corticosteroids and length of follow-up. They all presented with significant renal impairment. At presentation the mean+/-s.d. estimated glomerular filtration rate (eGFR) was 26.8+/-14 ml/min by modification of diet in renal disease (MDRD) equation 7. With treatment there was a significant improvement in renal function with eGFR 49.6+/-5.2 ml/min (P<0.01) at 1 year, and 47.9+/-6.8 ml/min (P<0.05) at the last review. The median follow-up was 84 months (range 6-284 months). Patients with chronic kidney disease (CKD) 3, the mean eGFR was 38.30+/-2.4 ml/min at presentation and 60.2+/-7.4 ml/min at 1 year (P=0.02) and in CKD 4 it improved from 19+/-2 to 38+/-6.6 ml/min at 1 year (P<0.05). After the 1st year, the change in eGFR was +0.8 ml/min/year for CKD 3 and -2 ml/min/year for CKD 4 (P<0.05). Three patients ceased their therapy either due to complications or poor compliance and experienced a worsening of renal function which was then reversed on re-commencing corticosteroids. Corticosteroids are effective in advanced tubulo-interstitial nephritis due to sarcoidosis. Long-term treatment is necessary to preserve renal function and to delay the onset of end-stage renal disease.

Posttransplant Tubulointerstitial Nephritis: Clinicopathological Correlation

As a cause of graft dysfunction, tubulointerstitial nephritis (TIN) seems to be the third most common pathology after rejection and cyclosporine nephrotoxicity. Among 540 needle biopsies obtained from 280 renal transplant patients between 1996 and 1999, acute TIN was detected in 23 patients (8%). The cause of acute TIN was secondary to bacterial infection in 17 patients and secondary to cytomegalovirus (CMV) infection in three patients. The remaining three cases showed granulomatous pyelonephritis due to Mycobacterium tuberculosis ( n = 2) and Candida albicans ( n = 1). During follow-up, 13 of 23 patients (56.5%) showed at least one acute rejection episode. The average number of urinary tract infection (UTI) episodes in the 23 patients was 1.4 ± 07. We observed that the number of UTI episodes showed a significant association with the development of chronic allograft nephropathy ( P = .03) and graft loss ( P < .01). Twelve patients (52.2%) lost their grafts during 5 years posttransplantation. Only 6 of 17 patients with bacterial TIN lost their graft at a mean time of 52.5 ± 14 months. But all patients with CMV TIN or granulomatous TIN lost their grafts at a mean time of 31 ± 3.1 months and 39 ± 3 months, respectively ( P < .05). In conclusion, these results support the pathological role of tubulointerstitial nephritis as a pathway of graft rejection or renal allograft deterioration among recipients after transplantation.

Acute granulomatous tubulointerstitial nephritis caused by intravesical BCG

Acute granulomatous tubulointerstitial nephritis caused by intravesical BCG

Granulomatous tubulointerstitial nephritis in the renal allograft

Granulomatous tubulointerstitial nephritis has rarely been described in renal allografts. Of 1,574 renal allograft tissue specimens obtained from 514 patients in the period 1993 to 1998, we report three cases (0.6%) with interstitial nephritis containing multiple noncaseating granulomas. Biopsy specimen 1 was obtained from a 44-year-old woman with a 6-day history of systemic Candida albicans infection and showed multiple granulomas containing budding yeasts. Biopsy specimen 2 was from a 33-year-old man who presented with miliary spread of Mycobacterium tuberculosis 12 days before the allograft biopsy. Biopsy specimen 3 was from a 23-year-old woman who presented with Escherichia coli urinary infection and bacteremia that was treated with antibiotics for 10 days before the biopsy. Granulomatous inflammation in reponse to infectious agents or drugs in immunosuppressed kidney transplant recipients can rarely give rise to allograft interstitial nephritis that is distinct from acute rejection. To our knowledge, there are no prior reports of granulomatous tubulointerstitial nephritis associated with C albicans and E coli infection or antibiotic therapy in human renal allografts.

Steroid-Responsive Renal Insufficiency due to Idiopathic Granulomatous Tubulointerstitial Nephritis

A 26-year-old male was admitted to our hospital having suffered from subfever, sterile pyuria and renal insufficiency for 1 year. There had been no apparent hematuria/proteinuria, and evidence of infection, allergy or intoxication was not demonstrated. Open renal biopsy revealed severe tubulointerstitial changes with granuloma accompanied by neither caseous necrosis nor giant cells. Infiltrating cells mostly consisted of CD4 and CD8 T cells, and some proximal tubular cells presented MHC class II antigen. Following the negative culture of biopsied specimen for acid-fast bacilli, diagnosis of idiopathic granulomatous tubulointerstitial nephritis was made, and steroid therapy was started. Two months later, pyuria disappeared and renal function improved significantly, proving the effectiveness of steroid on idiopathic granulomatous tubulointerstitial nephritis.