Granulomatous Tubulointerstitial Nephritis Research Articles

Granulomatous interstitial nephritis with CTLA-4 haploinsufficiency: a case report

BackgroundCytotoxic T lymphocyte antigen-4 (CTLA-4) is an essential inhibitory regulator of immune activation. CTLA-4 haploinsufficiency is known to be associated with dysregulation of FOXP3+ regulatory T cells, hyperactivation of effector T cells, and lymphocytic infiltration of multiple organs. However, there have only been a few reports of renal involvement with CTLA-4. Herein, we present a case of acute granulomatous tubulointerstitial nephritis (TIN) in a patient with CTLA-4 haploinsufficiency.Case presentationA 44-year-old man presented with a 3-week history of fever and malaise, and subsequently developed acute kidney injury (AKI) a few days after treatment with levofloxacin (LVFX). A kidney biopsy and immunohistochemical staining revealed granulomatous TIN with dominantly infiltrating CD4+ T cells. General symptoms and renal impairment showed improvement after discontinuation of LVFX and initiation of oral steroids. However, they worsened following steroid tapering. Further, a colon biopsy analysis showed similar findings to the renal tissue analysis. We suspected that granulomatous TIN was possibly associated with CTLA-4 haploinsufficiency. Therefore, the patient was transferred to another hospital for further treatment of CTLA-4 haploinsufficiency using immunosuppressive agents.ConclusionsThere have been few reports regarding renal involvement of CTLA-4 haploinsufficiency. In the present case, granulomatous TIN could have arisen due to instability of immune regulatory functions, such as CTLA-4 haploinsufficiency, and treatment with LVFX could have triggered immunologic activation and severe inflammation as well as renal dysfunction.

Crohn’s Disease Identified as Granulomatous Tubulointerstitial Nephritis

Crohn’s disease is usually diagnosed according to intestinal symptoms, but extra-intestinal manifestations are important in approximately one-third of cases. Although several extra-intestinal symptoms associated with various organs have been reported, renal involvement is uncommon in patients with Crohn’s disease. Tubulointerstitial nephritis in a patient with Crohn’s disease is usually caused by infection, sarcoidosis, or medications. However, primary tubulointerstitial nephritis caused by Crohn’s disease alone is extremely rare. A 19-year-old male patient was referred to our hospital because of an increase in serum creatinine level. He underwent a kidney biopsy with renal insufficiency. Renal histological findings revealed granulomatous tubulointerstitial nephritis. Thereafter, a colonoscopy was performed with suspicion of Crohn’s disease. Ultimately, he was diagnosed with granulomatous tubulointerstitial nephritis based on Crohn’s disease. The patient had improved gastrointestinal symptoms after the last treatment. This case report presents a rare case of primary tubulointerstitial nephritis caused by Crohn’s disease.

P053 Interstitial Nephritis from IBD: Complicated Conclusions.

BACKGROUND: Kidney injury in IBD is challenging. Tubulointerstitial nephritis (TIN) is linked to aminosalicylates, but also described in drug-naïve patients, suggesting that TIN may be a direct manifestation of IBD. We describe three cases of TIN in IBD to illustrate the challenges in determining the etiology of the injury. Case #1: 58-year-old male with a horseshoe kidney deformity, uncontrolled hypertension, GERD and small bowel stricturing Crohn's disease (CD), previously on mercaptopurine and allopurinol, subsequently transitioned to adalimumab, maintaining clinical and radiologic remission. Two years later, he developed acute kidney injury in setting of high fevers and sweats, with negative infectious evaluation. Medications included adalimumab, PPI, valacyclovir and torsemide. Renal biopsy revealed TIN with dense, zonal and focal granulomatous features suggestive of drug-induced hypersensitivity, chronic infection, sarcoidosis or an extra-intestinal manifestation of CD. Case #2: 45-year-old female with SLE, nephrolithiasis, GERD, hypertension and ulcerative colitis (UC), initially on mesalamine, then vedolizumab, with clinical and endoscopic remission. Her SCr increased at the time of her UC diagnosis, and worsened over 6 months while on mesalamine, vedolizumab, PPI and losartan. Renal biopsy demonstrated acute and chronic TIN with eosinophils raising concern for an allergic/drug-induced injury. Nephrology concluded that her TIN was secondary to either UC or one of her medications. Case #3: 33-year-old male with UC transitioned to vedolizumab, having failed budesonide and mesalamine. He had latent TB and received 9 months of isoniazid. While on mesalamine, vedolizumab and PPI, he developed fever, chills and night sweats, with an acute rise in SCr, prompting discontinuation of meds. Three months later, still in remission and with improved SCr, he restarted vedolizumab. A year later he developed low-grade fever with elevated SCr, prompting discontinuation. Renal biopsy revealed acute and chronic TIN with severe interstitial fibrosis, tubular atrophy and focal global glomerulosclerosis. He started prednisone and remained off other IBD therapy for 6 months, but repeat colonoscopy revealed mild colitis. He restarted mesalamine, but again developed elevated SCr 2 months later. Repeat renal biopsy revealed TIN with less interstitial fibrosis and focal global glomerulosclerosis, and nephrology suggested his interstitial nephritis was likely secondary to UC over his medications. He started azathioprine with significant improvement in SCr and clinical remission of UC. In all three cases, neither nephrology consultation nor renal biopsy helped distinguish the etiology of renal injury, defaulting to either the IBD meds or an extra-intestinal manifestation of IBD, and not accounting for the acute inflammatory symptoms in two of the cases. While literature review reveals several cases that allege kidney injury as an extra-intestinal target of IBD serious doubts remain. TIN secondary to aminosalicylates is well-documented, but there are few reports of adalimumab-induced granulomatous TIN and only one report of vedolizumab-induced TIN. Each of our patients had well-controlled IBD and multiple confounding variables that could impact kidney function or cause TIN, including hypertension and multiple potential culprit medications, illustrating the dilemma of determining the etiology of renal injury in IBD patients.

Granulomatous Tubulointerstitial Nephritis in a Kidney Transplant Recipient: Case Report and Review of the Literature

Granulomatous tubulointerstitial nephritis (GTIN) is a rare pathologic finding on kidney biopsy. GTIN can be associated with drugs, infection, systemic granulomatous disease, and tubulointerstitial nephritis with uveitis syndrome. We present a case of GTIN in a kidney transplant recipient (KTR) and a literature review of published cases of GTIN in KTRs. A 65-year-old man with a history of pulmonary and ocular tuberculosis (TB), who had undergone deceased donor kidney transplant 8 years prior, was admitted for acute kidney injury, hypercalcemia, and uveitis. His medications included rifabutin, isoniazid, and tacrolimus. Serum laboratory tests revealed creatinine of 2.65 mg/dL (baseline 1.1-1.5 mg/dL) and corrected calcium of 13.2 mg/dL. Hypercalcemia workup showed parathyroid hormone 7 pg/mL, 1,25(OH) vitamin D 54 pg/mL, parathyroid hormone-related peptide <2.0 pmol/L, and angiotensin-converting enzyme 47 U/L. Kidney biopsy showed GTIN with noncaseating granulomas. Universal polymerase chain reaction testing for acid-fast bacilli, fungus, and bacteria was negative. He was treated with prednisone, and his kidney function returned to baseline, and his hypercalcemia resolved. GTIN is a rare entity seen in less than 1% of transplanted kidney biopsies. The exactly etiology of this GTIN case remains unknown. TB could not be entirely ruled out, because the patient was receiving active anti-TB therapy. Our literature review showed infection to be the leading cause of GTIN in KTRs and that GTIN with concomitant uveitis remains exceedingly rare. Steroids may be useful in certain cases.

Tubulointerstitial nephritis and uveitis syndrome in an adolescent female: a case report

BackgroundTubulointerstitial nephritis with uveitis syndrome is a rare disease affecting mainly children and young women. Tubulointerstitial nephritis with uveitis is a diagnosis of exclusion, requiring a high degree of clinical suspicion. Studies report recent infections or certain drugs as precipitating factors of a lymphocytic oculorenal immune response. The prognosis is usually favorable with topical and systemic corticosteroid therapy.Case presentationWe report a literature review and the case of a 14-year-old white girl, who presented to the ophthalmology department with features of one-sided uveitis. Upon transfer of patient to nephrological care, diagnostic work-up revealed renal involvement. Renal biopsy showed a mixed-cell and granulomatous tubulointerstitial nephritis with some noncaseating granulomas, leading to a diagnosis of tubulointerstitial nephritis with uveitis syndrome. With topical ocular and systemic corticosteroid therapy, the patients’ condition improved over several weeks.ConclusionsOur case highlights the importance of early recognition and treatment of this syndrome, where cross-specialty care typically leads to a favorable outcome.

Granulomatous interstitial nephritis in a patient with SARS-CoV-2 infection

BackgroundAcute kidney injury (AKI) associated with severe coronavirus disease 19 (COVID-19) is common and is a significant predictor of morbidity and mortality, especially when dialysis is required. Case reports and autopsy series have revealed that most patients with COVID-19 – associated acute kidney injury have evidence of acute tubular injury and necrosis - not unexpected in critically ill patients. Others have been found to have collapsing glomerulopathy, thrombotic microangiopathy and diverse underlying kidney diseases. A primary kidney pathology related to COVID-19 has not yet emerged. Thus far direct infection of the kidney, or its impact on clinical disease remains controversial. The management of AKI is currently supportive.Case PresentationThe patient presented here was positive for SARS-CoV-2, had severe acute respiratory distress syndrome and multi-organ failure. Within days of admission to the intensive care unit he developed oliguric acute kidney failure requiring dialysis. Acute kidney injury developed in the setting of hemodynamic instability, sepsis and a maculopapular rash. Over the ensuing days the patient also developed transfusion-requiring severe hemolysis which was Coombs negative. Schistocytes were present on the peripheral smear. Given the broad differential diagnoses for acute kidney injury, a kidney biopsy was performed and revealed granulomatous tubulo-interstitial nephritis with some acute tubular injury. Based on the biopsy findings, a decision was taken to adjust medications and initiate corticosteroids for presumed medication-induced interstitial nephritis, hemolysis and maculo-papular rash. The kidney function and hemolysis improved over the subsequent days and the patient was discharged to a rehabilitation facility, no-longer required dialysis.ConclusionsAcute kidney injury in patients with severe COVID-19 may have multiple causes. We present the first case of granulomatous interstitial nephritis in a patient with COVID-19. Drug-reactions may be more frequent than currently recognized in COVID-19 and are potentially reversible. The kidney biopsy findings in this case led to a change in therapy, which was associated with subsequent patient improvement. Kidney biopsy may therefore have significant value in pulling together a clinical diagnosis, and may impact outcome if a treatable cause is identified.

Characteristics of renal sarcoidosis and tubulointerstitial nephritis and uveitis syndrome in Slovenia: An analysis of the national renal biopsy registry and patient datasets in the last decade.

Sarcoidosis is characterized by granulomatous inflammation in multiple organs. Renal involvement is rare, and granulomatous tubulointerstitial nephritis (TIN) is the predominant histologic feature. TIN is also a hallmark of tubulointerstitial nephritis and uveitis (TINU) syndrome. Diagnoses of both sarcoidosis and TINU syndrome are usually made by exclusion and by combining clinical and histological findings, and often remain misdiagnosed. The aim of this retrospective study was to determine the characteristics of renal sarcoidosis and TINU syndrome in Slovenia in the last decade (2010-2020). A thorough search of the national database of renal biopsies from January 2010 to December 2020 was performed. Inclusion criteria were TIN and a clinical history of either sarcoidosis or TINU syndrome. To compare the characteristics of our cohort with others, we also reviewed the global literature reported since 2010. 13 patients (9 female, 4 male) were included in our study. Indications for kidney biopsy were acute kidney injury (n=8), acute exacerbation of chronic kidney disease (n=4), and proteinuria (n=1). Seven patients had clinical and histological evidence of sarcoidosis, and 6 patients were classified as having TINU syndrome. All patients were treated with corticosteroids. Of the 13 patients, 11 had improved kidney function 6 months after treatment, and proteinuria decreased in 9 patients. One patient was on dialysis at the time of diagnosis and remained so thereafter. Renal sarcoidosis and TINU syndrome are rare but important causes of kidney injury, with a favorable long-term prognosis if properly diagnosed and treated in a timely manner.

A renal biopsy-based clinicopathological study of primary tubulointerstitial nephritis in children

Background: Inflammation of the tubular and interstitial compartment without involving the glomeruli and vessels is called as primary tubulointerstitial nephritis (TIN), which may be due to varied etiologies. This is relatively uncommon in children as compared to primary glomerular disorders. Infections and drugs are the most common causes of primary TIN worldwide. Objectives: The objectives of the study were to assess primary TIN in pediatric patients using findings from renal biopsies at a tertiary care center of Western India. Materials and Methods: All biopsy-proven cases of primary TIN in pediatric patients over a period of 10 years were included in the study. All cases with glomerular or vascular diseases, or where data were inadequate were excluded from the study. The cases were reviewed in detail for epidemiological data, clinical presentation, etiology, and histomorphological features. Depending on their clinical and morphological features, the cases were categorized into acute, chronic, and granulomatous TIN. Results: A total of 30 cases of primary TIN were assessed with a mean age of 12.4 years and range of 6–18 years. Pedal edema and facial puffiness were the most common symptoms followed by oliguria. The common causes of TIN were drugs, namely antibiotics and non-steroidal anti-inflammatory drugs and infections. Acute TIN was more common than chronic TIN. Conclusion: Primary TIN is an uncommon renal disease in pediatric patients with varied presentations and etiologies. However, early diagnosis by renal biopsy, detailed history, and withdrawal of the offending agent along with prompt treatment helps in recovery and avoids chronic renal damage.

Increase of 1,25 dihydroxyvitamin D in sarcoidosis patients with renal dysfunction

In sarcoidosis, renal involvement includes hypercalcemia-related nephrocalcinosis and granulomatous tubulointerstitial nephritis. Hypercalcemia is thought to be due to increased production of 1,25 dihydroxyvitamin D (1-25D), but 1-25D levels have not been evaluated in sarcoidosis patients with renal dysfunction. We enrolled 9 sarcoidosis patients who underwent renal biopsy, and compared the serum 1-25D concentration and eGFR with those in 428 non-sarcoidosis patients who had renal dysfunction (stage 2 or higher CKD with an estimated glomerular filtration rate < 90). Serum calcium and 1-25D levels were significantly higher in the sarcoidosis patients than in the non-sarcoidosis patients (p < 0.01 and p = 0.01, respectively). There was a positive correlation between 1-25D and eGFR in the patients without sarcoidosis (r = 0.693; p < 0.01). As the renal function of sarcoidosis patients was improved by steroid therapy, the serum 1-25D and adjusted serum calcium levels decreased to near the median values in non-sarcoidosis patients. On renal biopsy, CD68 staining was positive for tissue macrophages in all 8 patients who had tubulointerstitial nephritis (with or without typical granulomas), while Von Kossa staining showed calcification of tubules near or inside granulomas in 6 of these 8 patients. While tissue macrophages promote development of tubulointerstitial nephritis and 1-25D overproduction in renal sarcoidosis, hypercalcemia secondary to elevation of 1-25D may be related to renal calcification and granuloma formation.

Disseminated adenovirus infection in a 10-year-old renal allograft recipient.

Disseminated adenovirus infection can result in high mortality and morbidity in immunocompromised patients. Here, we report the case of a 10-year-old renal allograft recipient who presented with hematuria and dysuria. Adenovirus was isolated from his urine. His urinary symptoms decreased after intravenous hydration and reduction of immunosuppressants. However, 2 weeks later he presented with general weakness and laboratory tests indicated renal failure necessitating emergency hemodialysis. Adenovirus was detected in his sputum; therefore, intravenous ganciclovir and immunoglobulin therapy were initiated. Renal biopsy revealed diffuse necrotizing granulomatous tubulointerstitial nephritis compatible with renal involvement of the viral infection. Adenovirus was detected in his serum. Despite cidofovir administration for 2 weeks, adenovirus was also detected in the cerebrospinal fluid, resulting in generalized tonic-clonic seizure. The patient died 7 weeks after the onset of urinary symptoms. Adenovirus should be considered in screening tests for post-renal transplantation patients who present with hemorrhagic cystitis.

Granulomatous inflammation in BK polyomavirus-associated nephropathy.

Evolving BK polyomavirus-associated nephropathy (BKPyVAN) is characterized by tubulointerstitial inflammation that closely resembles acute T-cell-mediated allograft rejection if tubulitis is significant. The cellular composition of the inflammation varies during the course of BKPyVAN, and clusters of plasma cells may herald resolution of the infection. Less commonly, BKPyVAN can present with a predominance of histiocytes and granuloma formation. Granulomatous interstitial nephritis is uncommon in biopsies of either native or transplant kidneys. In both settings, this distinctive type of inflammatory response requires a systematic approach with careful clinicopathological assessment to determine its etiology. We present three patients with granulomatous BKPyVAN in the first year post-transplantation. These allograft biopsies at 4, 6, and 12months post-transplant exemplify spontaneously resolving BKPyVAN, resolving infection after immunosuppression reduction, and early BKPyVAN, respectively. In immunosuppressed patients, BKPyVAN should be added to the relatively broad differential diagnosis of granulomatous tubulointerstitial nephritis.

Clinical characteristics of biopsy-proven renal sarcoidosis in Japan.

Background: Although some articles have described renal sarcoidosis, the incidence among biopsy cases remains unclear. Here, we defined the incidence of renal sarcoidosis among renal biopsy cases and analyzed the clinical course. Methods: We performed an epidemiological study examining renal biopsy cases treated at 5 centers between January 2000 and September 2015 and identified 16 cases (7 men, 9 women; mean (±SD) age, 59.4±18.6 years) out of a total of 14191 renal biopsy cases. Renal involvement of sarcoidosis was defined as granulomatous tubulointerstitial nephritis, tubulointerstitial nephritis without granulomatous lesions, and renal calcinosis. Fifteen of the cases were treated with steroid therapy. One case initially received steroid pulse therapy. The outcome was evaluated based on the estimated glomerular filtration rate (eGFR), CKD stage, and the change in eGFR (ΔeGFR) after treatment. A favorable response was defined as ΔeGFR ≥25%. Results: The incidence of renal sarcoidosis was 0.11%. The mean eGFR was 28.2±16.1 mL/min/1.73 m2. At the last observation, the mean eGFR was 43.7±19.7 mL/min/1.73 m2. Although a favorable response to steroid therapy was found in the majority of cases (10/15, 67%), 12 of the 15 cases (80%) had residual renal dysfunction at the last observation and 8 cases (53%) had moderate to severe renal dysfunction. Conclusion: Renal sarcoidosis is extremely rare among renal biopsy cases. Among cases with an unfavorable response to steroid therapy, pathogenetic mechanisms other than sarcoidosis and severe nephron damage were observed. (Sarcoidosis Vasc Diffuse Lung Dis 2018; 35: 252-260).

Acute granulomatous interstitial nephritis and acute rejection in a kidney transplant recipient after zoledronic acid therapy – a case report and review of the literature

Acute granulomatous interstitial nephritis (AGIN) in native kidneys is most commonly linked to drugs. In allografts, it is a rare complication, and it occurs mostly with infections. Our case report presents AGIN with simultaneous acute cellular rejections and acute tubular necrosis in a kidney transplant patient 2weeks after intravenous application of zoledronic acid. A kidney biopsy showed signs of destructive AGIN with acute cellular rejection. After treatment with methylprednisolone pulses and immunosuppressive therapy modification, rebiopsy confirmed complete regression of AGIN with less intense persistent acute cellular rejection and acute tubular necrosis. Kidney function improved after glucocorticoid and intravenous immunoglobulin G therapy. To our knowledge, this is the first case of AGIN related to bisphosphonate zoledronate in a kidney transplant patient with consequent acute cellular rejection. In using intravenous zoledronate infusion in a kidney transplant recipient, we should be aware that it could potentially induce acute granulomatous tubulointerstitial nephritis and acute rejection. .

Quiz: Acute Kidney Injury in a Patient on a TNF-α Blocking Agent

Quiz: Acute Kidney Injury in a Patient on a TNF-α Blocking Agent

Etiological diagnosis of granulomatous tubulointerstitial nephritis in the tropics.

BackgroundGranulomatous tubulointerstitial nephritis (GIN) is common due to infections, drugs or sarcoidosis. However, the cause is often difficult to establish and the studies are limited. We studied the etiology of GIN and compared the clinical and histological features and outcome in different etiologies at a tertiary care center in North India.MethodsRenaö biopsies from GIN cases diagnosed from January 2004 to April 2014 were retrieved. Stain for acid fast bacilli was performed in all biopsies. Etiological diagnosis was based on clinical features, extra-renal manifestations, radiology, history of drug intake and demonstration of infective agent. Tissue PCR for tubercular DNA was performed in seven biopsies.ResultsSeventeen GIN patients [mean age 35 ± 15 years; males 11] were identified. Tuberculosis was the commonest etiology followed by idiopathic, sarcoidosis and fungal. Both tuberculosis and sarcoidosis patients presented with subnephrotic proteinuria and raised serum creatinine. Acid fast bacilli were demonstrated in 1/9 and necrosis was demonstrated in 3/9 granulomas in tuberculosis. Tissue PCR for tubercular DNA was positive in six TB patients and negative in one sarcoidosis patient. Patients responded well to appropriate therapy.ConclusionEtiological diagnosis of GIN is essential for timely and appropriate therapy. Tuberculosis is the commonest etiology (53%) in the tropics. Necrosis in granuloma, demonstration of acid fast bacilli, blood interferon gamma release assay and urine culture is not sensitive for the diagnosis of tuberculosis in GIN. Our findings suggest that tissue PCR for tuberculosis performed in an appropriate clinical setting is useful in the diagnostic evaluation of GIN.

From Polyuria to Renal Mass: An Unexpected Link

From Polyuria to Renal Mass: An Unexpected Link

Lamotrigine-Induced Tubulointerstitial Nephritis and Uveitis-Atypical Cogan Syndrome

To report a case of lamotrigine-induced tubulointerstitial nephritis and uveitis (TINU)-atypical Cogan syndrome. Case report. A 16-year-old boy with traumatic brain injury and seizures presented to the emergency department with facial swelling, rash, and back pain several days after increasing lamotrigine dose secondary to a breakthrough seizure. Creatinine, urine β2 microglobulin, and eosinophils were elevated. Antinuclear antibodies, antineutrophil cytoplasmic antibodies, angiotensin-converting enzyme, and complement were normal. Renal biopsy showed acute granulomatous tubulointerstitial nephritis. Lamotrigine was discontinued, intravenous steroids were initiated, and the patient was discharged on Ativan and prednisone. Subsequently, he was diagnosed with bilateral anterior uveitis (vision 20/30 bilaterally) and started on prednisolone and cyclopentolate. Two months later, he developed a branch retinal artery occlusion in the right eye (vision 20/70) and bilateral ocular hypertension for which timolol-brimonidine and dorzolamide were added. Neuroimaging and hypercoagulability workup was unremarkable. Vision and intraocular pressure improved, while uveitis remained recalcitrant. Several months later, the patient developed central serous retinopathy in the right eye (vision 20/30). Prednisone was stopped but restarted due to methotrexate intolerance. A month later, he reported dizziness and was diagnosed with severe bilateral sensorineural hearing loss. Brain magnetic resonance imaging showed foci of perivascular, subcortical, and cochlear enhancement. Transtympanic Decadron injections and infliximab infusions were initiated. At the final visit, vision remained at 20/30 with trace anterior chamber reaction bilaterally while on timolol-brimonidine, dorzolamide, and prednisolone. An idiosyncratic drug reaction should be considered in the differential diagnosis of TINU-atypical Cogan syndrome.

Granulomatous Interstitial Nephritis as the Presenting Manifestation of Crohn’s Disease: A Case Report and Review of Literature

Introduction: Extraintestinal manifestations are reported in 6-47% of patients with IBD and may be diagnosed before, concurrently. or after the diagnosis of IBD. We hereby report an unusual presentation of granulomatous interstitial nephritis preceding the GI manifestations of Crohn’s disease. Case Report: A 17-year-old male with history of obesity and attention deficit hyperactivity disorder on dextroamphetamine presented with new onset of acute kidney injury with creatinine (Cr) level of 4.5 mg/dL. After an extensive negative blood work, renal biopsy was performed, which revealed marked chronic granulomatous tubulointerstitial nephritis. Further work-up for granulomatous disease (chest CT) was negative. Prednisone was initiated for presumed autoimmune process and the serum Cr improved to 2-3 mg/dL. Six months later, the patient developed chronic watery, non-bloody diarrhea. Colonoscopy with terminal ileal biopsy showed active enteritis with granulomatous inflammation consistent with Crohn’s disease. Azathioprine and prednisone were initiated with modest response. Infliximab was then started and his diarrhea resolved. His renal function was restored back to baseline. Unfortunately, he was lost to follow-up and did not receive infliximab. His serum Cr worsened to 9.2 mg/dL. Infliximab was promptly reinstituted and his Cr again improved to his baseline. However, his renal function gradually deteriorated and he eventually needed renal transplant after 5 years from the initial diagnosis. Discussion: To our knowledge, this is the first case of Crohn’s with renal involvement preceding GI symptom. Table 1 summarizes a total of 9 previously reported patients with granulomatous tubulointerstitial nephritis related to Crohn’s disease. All the cases progressed to chronic kidney disease; 2 with end stage renal disease. Eight cases initially presented with GI manifestations; 1 with both diarrhea and renal failure. In conclusion, granulomatous interstitial nephritis associated with Crohn’s disease usually portends a poor prognosis. It is important for clinicians to promptly recognize it as a possible extraintestinal manifestation of Crohn’s disease, as this condition often demands early aggressive treatment with immunomodulators.Table 1

Corticosteroids in tubulointerstitial nephritis

Sir, In a recent article published in Pediatric Nephrology, Timo Jahnukainen et al. [1] concluded that prednisone speeds up recovery from symptoms of tubulointerstitial nephritis (TIN) in children but that the renal prognosis of glucocorticoidtreated patients did not differ from that of patients without glucocorticoid treatment at 6–12 months after diagnosis. This may raise the question of the necessity of glucocorticoid treatment in some patients. The authors did not mention in their paper that there is an important exception: sarcoidosis. Granulomatous TIN is a renal lesion associated with sarcoidosis that leads to end stage renal disease in some patients [2]. In these cases, interstitial fibrosis seems to appear early in the course of sarcoidosis and is a major prognostic factor. Treatment consists of rapid corticosteroid therapy to reduce the risk of severe renal impairment. Thus, the conclusions of these authors are not valid. Renal sarcoidosis in childhood is rare, but in an earlier study we reported 11 cases [3], with some patients reaching end stage renal failure, thereby confirming the necessity of a rapid corticosteroid treatment and the need for the treating physican to be aware of sarcoidosis in cases of TIN in children.

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.