Kidney manifestations of sarcoidosis.

Renal involvement is a clinically relevant organ manifestation of sarcoidosis, leading to increased morbidity and complications. Although the exact incidence remains unknown, renal disease is likely to occur in up to one third of all sarcoidosis patients. Every patient with newly diagnosed sarcoidosis should receive a renal work-up and screening for disrupted calcium metabolism. Amid various forms of glomerulonephritis, granulomatous interstitial nephritis is the most common one, but it rarely leads to renal impairment. Histologically, granulomas can be absent. Nephrocalcinosis and nephrolithiasis are frequent forms when hypercalcaemia or hypercalciuria occur. Drugs used for treatment of systemic sarcoidosis can also cause renal damage. Due to its high heterogeneity, renal sarcoidosis can be difficult to treat. Glucocorticoids and various immunosuppressive treatments have been proven to be effective based on case series, but clinical trials are lacking. A treatment guideline for renal sarcoidosis is urgently needed. In this review article, we present an overview of the different forms of renal sarcoidosis and the diagnostic steps to confirm renal involvement; in addition, we provide insights on the management and available treatments. A better understanding regarding the pathogenesis of sarcoidosis is the key for the development of more specific, targeted therapies.

A Rare Presentation of Sarcoidosis in a Young Male With Acute Renal Failure: A Case Report and Literature Review.

Sarcoidosis presents in a variety of ways, but historically, renal involvement has been considered rare with an incidence of 0.7% and is seldom the presenting feature of the illness. Concomitant involvement of kidney and bone marrow is extremely rare. Atypical forms of presentation, such as in this case, may pose a true diagnostic challenge. A 20-year-old African-American male presented to the emergency department with vague symptoms including fatigue, malaise, anorexia, right-sided lower back pain, and nausea. Acute kidney injury was clearly evident, creatinine was 19.78 mg/dL (normal range 0.60-1.20 mg/dL), and BUN was 124.0 mg/dL (normal range 5.0-25.0 mg/dL). Laboratory results were also remarkable for leukopenia, microcytic anemia, hyperkalemia, anion gap metabolic acidosis, and non-PTH dependent hypercalcemia. Interestingly, urinalysis was equivocal and both chest x-ray (CXR) and abdominopelvic computed tomography (CT) scan were unrevealing. The patient was admitted to the hospital and required renal replacement therapy to stabilize his clinical condition while planning for a renal biopsy that was later performed. While awaiting pathological results, pancytopenia developed, and a bone marrow biopsy was then obtained. On further investigation, angiotensin-converting enzyme (ACE) turned out to be significantly elevated suggesting sarcoidosis. Renal biopsy showed moderate acute tubular injury, tubulitis, extensive interstitial edema, and infiltration by numerous non-caseating granulomas, which confirmed the diagnosis of sarcoidosis. Bone marrow histopathology revealed hypocellularity but no granulomatous infiltration. The patient remained largely asymptomatic throughout his hospital stay, with no signs or symptoms suggesting the involvement of other organs. High-dose corticosteroids were started and continued outpatient after discharge while still on hemodialysis. Pancytopenia resolved while on glucocorticoids and improvement in renal function was such that after roughly two months of steroids, renal replacement therapy was no longer necessary. Overall, kidney injury severe enough to require hemodialysis associated with pancytopenia in a previously healthy 20-year-old constitutes a rather rare sarcoidosis presentation. This highlights the importance of considering sarcoidosis as a possible cause of kidney and bone marrow dysfunction and emphasizes the need for timely biopsy to facilitate accurate diagnosis and early initiation of appropriate therapy to avoid delayed or inadequate care, especially considering that even severe damage is potentially reversible when identified early and treated promptly.

Clozapine-Induced Granulomatous Interstitial Nephritis: A Case Report.

Granulomatous interstitial nephritis is a rare form of tubulointerstitial nephritis and has been uncommonly observed with clozapine usage. Additionally, the progression of the disease to manifest as renal failure requiring dialysis is also uncommon. We describe a case of a 56-year-old female who presented with syncope and was diagnosed with granulomatous interstitial nephritis on biopsy. While hemodialysis may play a role in the management of the disease, steroids provide a definitive treatment. Large-scale studies are needed to evaluate the role of clozapine in causing interstitial nephritis and the characteristics of these features to establish a therapeutic goal.

Biopsy-proven granulomatous interstitial nephritis associated with vancomycin in an adult patient: a case report.

Acute kidney injury (AKI) caused by vancomycin mainly manifests as acute interstitial nephritis or acute tubular necrosis. Here, the rare case of a 71-year-old female patient with no history of kidney disease, who was diagnosed with granulomatous interstitial nephritis associated with vancomycin, is reported. The patient had been treated with vancomycin for over a month for an abscess in her right thigh. She presented to the emergency department with a history of fever, scattered rash, oliguria and elevated serum creatinine for >10 days. After hospitalization, the vancomycin trough concentration was confirmed to be >50 µg/ml. The patient received furosemide and continuous renal replacement therapy for AKI, teicoplanin and piperacillin/tazobactam for pulmonary infection, and urapidil, sodium nitroprusside and nifedipine for elevated blood pressure. Percutaneous ultrasound-guided kidney biopsy was performed. Light microscopy revealed granuloma formation, and diffuse infiltration of lymphocytes, monocytes, eosinophils, and some multinucleated giant cells. Finally, the patient was diagnosed with vancomycin-induced granulomatous interstitial nephritis and was treated with high-flux haemodialysis and 16 mg oral methylprednisolone, daily, for 3 weeks, which contributed to a significant recovery of renal function. This case suggests the need for regular vancomycin concentration testing during treatment. When AKI due to vancomycin occurs, a renal biopsy may be performed to help diagnose and treat the condition.

Clinicopathological Characteristics and Outcomes of Renal Sarcoidosis: A Series Study of 18 Patients from a Single Center.

INTRODUCTION: Sarcoidosis is characterized by noncaseating granulomatous inflammation in multiple organs. Renal involvement is rare, and granulomatous interstitial nephritis (GIN) is the predominant histological feature. Renal sarcoidosis (RS) is usually diagnosed by exclusion, combining clinical and histological findings, and often remains misdiagnosed. This retrospective study aimed to describe the characteristics and prognosis of patients with RS in China. METHODS: Eighteen patients with RS from a single center were enrolled, of whom 15 had biopsy-proven tubulointerstitial nephritis. Their clinicopathological features and renal outcomes were analyzed to understand this rare disease better. RESULTS: Eighteen patients (14 male/4 female) were included in our study. The median estimated glomerular filtration rate (eGFR) was 30.36 (11.57, 60.14) mL/min/1.73 m2. In 15 patients undergoing a renal biopsy, GIN was the most common pathological phenotype (66.67%). Seventeen patients had follow-up records, with a median follow-up of 24.07 (8.82, 60.90) months. One month after treatment, median eGFR increased significantly from 30.36 (11.57, 60.14) mL/min/1.73 m2 to 58.53 (39.35, 80.65) mL/min/1.73 m2, and proteinuria decreased from 1.10 (0.69, 1.58) g/24 h to 0.68 (0.52, 1.05) g/24 h. No patients relapsed or developed end-stage renal disease. CONCLUSION: RS is a rare but important cause of tubulointerstitial injury, with a favorable long-term prognosis if properly diagnosed and treated promptly.

Renal sarcoidosis.

Sarcoidosis is a systemic inflammatory disease of unknown etiology. The pathogenesis rests on an aberrant T cell response to unidentified antigens in individuals predisposed by genetic and environmental factors. Increased expression of polarized macrophages and disequilibrium between effector and regulator T cells contribute to the formation of noncaseating granulomas, that are frequently found in affected organs. The main kidney abnormalities in sarcoidosis are granulomatous interstitial nephritis (GIN) and hypercalcemia-related disorders. The clinical diagnosis is difficult. The outcome is variable, ranging from spontaneous remission to end-stage kidney disease (ESKD). Early diagnosis and prompt treatment with corticosteroids can improve the prognosis. Hypercalcemia may be responsible for acute kidney injury (AKI) caused by vasoconstriction of afferent arterioles. Complications of persistent hypercalcemia include nephrocalcinosis and renal stones. In patients with ESKD, dialysis and transplantation can offer results comparable to those observed in patients with other causes of kidney failure. Based on a review of the literature, we present an overview of the etiopathogenesis, the renal manifestations of sarcoidosis and their complications, management and prognosis.

Interferon-gamma Release Assay-positive Granulomatous Interstitial Nephritis in a Patient with a History of Diffuse Large B Cell Lymphoma.

Tuberculosis is a common etiology of granulomatous interstitial nephritis (GIN). However, the absence of evidence of lung involvement and lack of mycobacterial isolation in cultures make the etiological diagnosis and treatment decision challenging. We herein report a 46-year-old man with severe renal failure, a persistent fever, and a history of lymphoma. A renal biopsy exhibited GIN. Despite no evidence of tuberculosis except for a positive interferon-gamma release assay (IGRA), the patient was successfully treated with anti-tuberculosis drugs. Our case suggests that anti-tuberculosis therapy should be considered for patients with IGRA-positive GIN after excluding other etiologies.

Challenges in the Diagnosis and Management of Nephrotic Syndrome in a Child With Multisystemic Tuberculosis.

We report the case of a child who had tuberculosis associated with nephrotic syndrome. In this case, it was difficult to identify if the renal involvement was due to renal infection with mycobacterium tuberculosis, the consequence of nephrotoxicity of anti-bacillary drugs, or due to new onset of nephrosis. Management was complex as the use of high-dose steroids can disseminate the infection.

Renal replacement therapy in sarcoidosis.

Sarcoidosis is a systemic inflammatory disease of unknown etiology. Kidney involvement in sarcoidosis may be present in up 25-30% of cases. An early diagnosis and prompt treatment with corticosteroids can improve the prognosis but rarely renal sarcoidosis can lead to kidney failure needing renal replacement therapy (RRT). Acute kidney injury (AKI) in sarcoidosis may be caused by granulomatous interstitial nephritis (GIN) or hypercalcemia. These disorders are usually clinically silent and may lead end stage renal disease (ESKD) if not diagnosed or detected too late. In patients with ESKD, dialysis and renal transplantation can offer results comparable to those observed in patients with other causes of kidney failure. Based on a review of literature, we present an overview of RRT in patients with AKI or chronic kidney disease (CKD) caused by sarcoidosis.

Granulomatous interstitial nephritis secondary to the use of the anti-TNF adalimumab / Nefritis intersticial granulomatosa secundario al uso del anti TNF adalimumab

Abstract We present the case of a 56-year-old patient with progressive kidney function deterioration whose kidney biopsy reported granulomatous interstitial nephritis. The medical chart was reviewed, and it was noted that the deterioration coincided with the initiation of the medication adalimumab. It was discontinued and steroid plus cytostatic treatment was begun, with improvement. (Acta Med Colomb 2021; 46. DOI:https://doi.org/10.36104/amc.2021.2050).

Resumen Se presenta el caso de una paciente de 56 años, quien presenta deterioro progresivo en la función renal, y en quien la biopsia renal reportó nefritis intersticial granulomatosa. Se revisó historia clínica, y se detectó que el deterioro coincidía con el inicio del medicamento adalimumab. Se suspendió, inicio terapia de esteroide más citostático con mejoría. (Acta Med Colomb 2021; 46. DOI:https://doi.org/10.36104/amc.2021.2050).

A Case of Adalimumab-Induced Granulomatous Interstitial Nephritis.

Adalimumab is a monoclonal antibody targeting tumour necrosis factor-alpha (TNF-alpha) and is used for the treatment of numerous autoimmune conditions. There is a paucity of evidence linking adalimumab with granulomatous interstitial nephritis (GIN). We describe a renal biopsy-proven case of GIN secondary to adalimumab therapy. A 52-year-old gentleman with a background of psoriatic arthropathy was referred to the nephrology department by his general practitioner with a progressive decline in renal function over 18 months after initiating adalimumab. A renal biopsy confirmed tubulointerstitial nephritis with focal aggregates of histiocytes, organized as granulomata. Screening for other GIN causing aetiology, including tuberculosis (TB) and sarcoidosis, was negative. Adalimumab was withheld, leading to a slow improvement in renal function over a course of six months. It is essential to monitor renal function when administrating anti-TNF alpha agents as they can rarely paradoxically cause autoimmune reactions such as GIN seen in our case.

Different renal manifestations associated with very early onset pediatric inflammatory bowel disease: case report and review of literature.

BACKGROUND: Inflammatory bowel diseases are characterized by chronic inflammation of the gastrointestinal tract. In particular, Crohn disease and ulcerative colitis represent the two most common types of clinical manifestations. Extraintestinal manifestations of inflammatory bowel diseases represent a common complications, probably reflecting the systemic inflammation. Renal involvement is reported in 4-23% of cases. However, available data are limited to few case series and retrospective analysis, therefore the real impact of renal involvement is not well defined. CASE PRESENTATION: We report the case of a 10-years old male affected by very early onset unclassified-Inflammatory bowel diseases since he was 1-year old, presenting with a flare of inflammatory bowel diseases associated with acute kidney injury due to granulomatous interstitial nephritis. Of interest, at 7-year-old, he was treated for IgA nephropathy. To our knowledge, no previous reports have described a relapse of renal manifestation in inflammatory bowel diseases, characterized by two different clinical and histological phenotypes. CONCLUSIONS: The link between the onset of kidney injuries with flares of intestinal inflammation suggest that nephritis maybe considered an extra-intestinal manifestation correlated with active inflammatory bowel disease. However, if granulomatous interstitial nephritis represents a cell-mediated hypersensitivity reaction than a true extraintestinal manifestation of inflammatory bowel diseases is still not clarified. We suggest as these renal manifestations here described may be interpreted as extraintestinal disorder and also considered as systemic signal of under treatment of the intestinal disease.

Nitrofurantoin-Associated Acute Granulomatous Interstitial Nephritis.

We report the case of a 71-year-old female who was incidentally found to have nonoliguric acute kidney injury on a routine workup for new-onset visual hallucination. Further history revealed inadvertent usage of nitrofurantoin for 3 months for an anticipated urological procedure. Renal biopsy demonstrated acute granulomatous interstitial nephritis. The renal function significantly improved following discontinuation of nitrofurantoin and corticosteroid administration. We highlight a rare association of nitrofurantoin with acute granulomatous interstitial nephritis through this case report.

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

BACKGROUND: Acute 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 PRESENTATION: The 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. CONCLUSIONS: Acute 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.

Granulomatous interstitial nephritis in the setting of disseminated Mycobacterium simiae: a rare presentation of immune reconstitution inflammatory syndrome.

Disseminated Mycobacterium simiae is a rare opportunistic infection reported most commonly in advanced human immunodeficiency virus (HIV) infection. Treatment can be further complicated by the occurrence of severe immune reconstitution inflammatory syndrome (IRIS). We present the first case of disseminated multi-drug-resistant M. simiae in the setting of advanced HIV, complicated by IRIS in the form of granulomatous interstitial nephritis causing acute renal failure. This case highlights the importance of recognizing rare complications of IRIS, as delays in therapy can be life threatening.

Prosthetic valve endocarditis from Mycobacterium chimaera infection causing granulomatous interstitial nephritis.

Mycobacterium chimaera is a rare infection associated with cardiopulmonary bypass. We describe a case of granulomatous interstitial nephritis caused by M. chimaera in a patient with prosthetic aortic valve endocarditis. A 63-year-old female with a mechanical aortic valve replacement developed fatigue, 20 lbs. weight loss, anemia, and an elevated creatinine. Fat pad aspirate at an outside hospital was suspicious for amyloidosis which prompted hematology referral at our institution. Bone marrow biopsy revealed a single granuloma, negative for amyloid or acid fast bacillus (AFB). She was admitted to our hospital for worsening kidney function refractory to intravenous fluid challenge. Transesophageal echocardiogram showed aortic root abscess and valve vegetation with negative blood cultures at seven days. Renal biopsy showed granulomatous interstitial nephritis and negative AFB stain. Prednisone 40 mg was started and renal function partially improved. Blood cultures obtained before biopsy subsequently grew M. chimaera. Three-drug antimicrobial therapy was initiated and prednisone discontinued. One month later, creatinine improved and follow up echocardiogram showed no lesion. Our case highlights this rare infection inducing granulomatous interstitial nephritis despite lack of positive AFB or gram stains on renal biopsy.

Granulomatous Interstitial Nephritis - A Series of Six Cases.

Granulomatous interstitial nephritis is an uncommon variant accounting for about 6% of all tubulointerstitial nephritis. The etiology can be drugs such as antibiotics and nonsteroidal anti-inflammatory drugs and infections such as tuberculosis, sarcoidosis, and fungal infections. Renal biopsy remains the gold standard for establishing the diagnosis. Here, we present a series of six cases of granulomatous interstitial nephritis, of which two cases were associated with lupus nephritis and another two cases with crescentic glomerulonephritis. Focal segmental glomerulosclerosis and mesangiosclerosis with chronic tubulointerstitial nephritis were detected in the rest of the cases. Most of the patients presented with features of nephrotic syndrome. Urine analysis showed albuminuria in all cases. In renal biopsy, interstitial epithelioid cell granuloma was a constant feature along with which there were foci of necrosis and moderate fibrosis in few cases. But none of our cases had any relevant history of prolonged drug intake. Tuberculosis and fungal infections were also ruled out. Thereby in this case series, we subgroup all the cases into two category four cases associated with granulomatous nephritis and two cases with idiopathic granulomatous nephritis.