Atypical post-infectious glomerulonephritis with c-ANCA positivity followed by endocarditis.

Post-infectious glomerulonephritis (PIGN), an uncommon variety of glomerulonephritis (GN), is characterized by emergence of nephritic syndrome within a few weeks following an infectious event. PIGN typically presents as a mild condition and tends to resolve by the time of diagnosis for GN. Aggregatibacter actinomycetemcomitans belongs to the HACEK group of bacteria, which constitutes less than 3% of bacteria responsible for community-acquired infective endocarditis. We present a case of 29-year-old man suspected of lymphoma with B-symptoms along with severe splenomegaly and nephromegaly. Shortly after, he developed an episode of nephritic syndrome accompanied by acute kidney injury (AKI) and high titers of cytoplasmic ANCA (c-ANCA)-positivity. Kidney biopsy revealed PIGN with tubulointerstitial nephritis. Despite treatment with antibiotics and corticosteroid, he visited the emergency room due to worsening dyspnea and multi-organ failure. An echocardiogram showed a bicuspid aortic valve with vegetation unseen on previous echocardiogram. He underwent aortic valve replacement immediately without adverse events. Four months after valve replacement, his renal function and cardiac performance have remained stable. We report a case of PIGN with AKI and high titers of c-ANCA appearing later as an infective endocarditis due to Aggregatibacter actinomycetemcomitans. With careful clinical observation and appropriate and timely management, satisfactory outcomes for patient health are possible.

Inflammation drives renal scarring in experimental pyelonephritis.

Acquired renal scarring occurs in a subset of patients following febrile urinary tract infections and is associated with hypertension, proteinuria, and chronic kidney disease. Limited knowledge of histopathology, immune cell recruitment, and gene expression changes during pyelonephritis restricts the development of therapies to limit renal scarring. Here, we address this knowledge gap using immunocompetent mice with vesicoureteral reflux. Transurethral inoculation of uropathogenic Escherichia coli in C3H/HeOuJ mice leads to renal mucosal injury, tubulointerstitial nephritis, and cortical fibrosis. The extent of fibrosis correlates most significantly with inflammation at 7 and 28 days postinfection. The recruitment of neutrophils and inflammatory macrophages to infected kidneys is proportional to renal bacterial burden. Transcriptome analysis reveals molecular signatures associated with renal ischemia-reperfusion injury, immune cell chemotaxis, and leukocyte activation. This murine model recapitulates the cardinal histopathological features observed in humans with acquired renal scarring following pyelonephritis. The integration of histopathology, quantification of cellular immune influx, and unbiased transcriptional profiling begins to define potential mechanisms of tissue injury during pyelonephritis in the context of an intact immune response. The clear relationship between inflammatory cell recruitment and fibrosis supports the hypothesis that acquired renal scarring arises as a consequence of excessive host inflammation and suggests that immunomodulatory therapies should be investigated to reduce renal scarring in patients with pyelonephritis.

Fungal infection presenting as giant cell tubulointerstitial nephritis in kidney allograft.

Giant cell tubulointerstitial nephritis in the kidney allograft caused by infection is rare, and donor-transmitted infection in transplanted kidneys is also rare. In this case report, we describe an unusual histological manifestation of Candida albicans in the graft biopsy of a 53-year-old male kidney transplant recipient with decreased renal function 12 days post transplant. Several giant cells were present in the tubulointerstitial inflammation, as well as yeasts, with no evidence of rejection, and the histological diagnosis was confirmed by urine culture. Donor urine culture was positive for C. albicans, suggestive of a possible donor-transmitted infection. Prompt antifungal treatment eradicated the infection, and averted systemic spread. To our knowledge, there are no previous reports of Candida infection with giant cell tubulointerstitial nephritis in human renal allograft.

Unusual manifestations of acute Q fever: autoimmune hemolytic anemia and tubulointerstitial nephritis.

Q fever is a worldwide zoonotic infection that caused by Coxiella burnetii, a strict intracellular bacterium. It may be manifested by some of the autoimmune events and is classified into acute and chronic forms. The most frequent clinical manifestation of acute form is a self-limited febrile illness which is associated with severe headache, muscle ache, arthralgia and cough. Meningoencephalitis, thyroiditis, pericarditis, myocarditis, mesenteric lymphadenopathy, hemolytic anemia, and nephritis are rare manifestations. Here we present a case of acute Q fever together with Coombs' positive autoimmune hemolytic anemia (AIHA) and tubulointerstitial nephritis treated with chlarithromycin, steroids and hemodialysis. Clinicians should be aware of such rare manifestations of the disease.

Acute encephalopathy and tubulointerstitial nephritis associated with Yersinia pseudotuberculosis.

We report the case of a 28-month-old boy with encephalopathy and acute tubulointerstitial nephritis possibly associated with Yersinia pseudotuberculosis (Yp) infection. He was transferred to our center because of impairment of renal function and altered consciousness. He had fever for 5 days after recurrent vomiting and diarrhea. Computed tomography scan was normal, but electroencephalogram (EEG) analyses showed generalized slow wave patterns. Continuous hemodialysis was undergone and then his renal function was improved, but altered consciousness persisted. Single photon emission computed tomography (SPECT) revealed abnormally low signals at entire field, which suggested that he was suffered from encephalopathy. Phenobarbital administration and post-encephalopathy rehabilitation were started, and he recovered in fully premorbid state with normal EEG and SPECT findings on the 33rd hospital day. Various bacterial cultures were negative, but both Yp antibody and Yp-derived mitogen (YPM) antibody, the antibody of a specific Yp exotoxin, had an extremely high titer. This is the first report of encephalopathy potentially caused by Yp, indicated by the presence of a high Yp and YPM antibody titer.

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.

Tuberculosis and tubulointerstitial nephritis: an intriguing puzzle.

Classical renal tuberculosis is a well-known cause of urinary tract scarring and calcification, and sometimes renal dysfunction. In the past two decades there have been reports, particularly from the United Kingdom among immigrants from the Indian subcontinent, of a more insidiously progressive form of renal disease. Ultrasound shows small smooth kidneys, and histology reveals tubulointerstitial nephritis including granulomas but not acid-fast bacilli. Evidence is mounting that the underlying cause may be tuberculosis, but the mechanism remains obscure.

Granulomatous interstitial nephritis associated with disseminated histoplasmosis in an immunocompetent patient.

We present a case of a 64-year-old man with a prolonged history of fatigue, weight loss, fever, and kidney failure. Kidney biopsy showed severe granulomatous interstitial nephritis with numerous giant cells. Silver stains identified fungal micro-organisms consistent with Histoplasma species. Despite antifungal treatment, the patient died of overwhelming infection a few weeks later. This report emphasizes the importance of diagnosing histoplasmosis early. A high degree of suspicion is required to make the diagnosis of histoplasmosis in a case of granulomatous interstitial nephritis.

[Chronic renal failure: unexpected late sequela of pulmonary tuberculosis after 30 years]. / Kronik Böbrek Yetmezligi: Pulmoner Tüberkülozun 30 Yil Sonra Gelen Beklenmeyen Geç Sekeli.

Tuberculosis-related chronic granulomatous tubulointerstitial nephritis (GTN) and chronic renal dysfunction as a consequence of GTN is a rarely seen clinical condition, with a few case reports in the literature. In this report, a case with end stage renal failure as an unexpected late extrapulmonary sequela of tuberculosis has been presented. A 60 years old female patient was admitted to hospital with the complaints of fever, malaise and nausea. Her history revealed that she had pulmonary tuberculosis 30 years ago and received antituberculosis therapy for nine months. The laboratory results on admission were as follows: blood urea nitrogen 90 mg/dl, serum creatinine 9 mg/dl, sodium 116 mEq/L, potassium 6.6 mEq/L, albumine 2.9 g/dl, hemoglobin, 8.4 g/dl, white blood cell count 10.800/mm3, C-reactive protein 187 mg/L and erythrocyte sedimentation rate 110 mm/hour. Urinalysis showed 8.1 g/L protein, 10-12 leukocytes, 1-2 erythrocytes, while 24-hours urinalysis yielded proteinuria with 8 ml/minutes creatinine clearance value. Urine and blood cultures of the patient revealed neither bacteria or mycobacteria. PPD skin test was negative. Acid-resistant bacilli (ARB) were not detected in sequential urine samples obtained on three consecutive days. Since sputum samples could not be obtained, diagnostic procedures for sputum were not performed. Abdomen ultrasonography yielded bilateral edema and grade II echogenity in kidneys. Computed tomography of the chest showed bilateral pulmonary nodules, chronic sequela lesions, pleural scarring and calcifications, as well as minimal interstitial infiltrate. Transthoracic lung biopsy showed chronic inflammation and fibrosis, while amyloid was negative. Renal biopsy showed GTN with central caseified necrosis and granulomas, multinuclear giant cells, tubular atrophy and interstitial fibrosis. Amyloid was negative and ARB were not detected in renal biopsy sample. Definitive diagnosis was achieved by the demonstration of Mycobacterium tuberculosis nucleic acid in kidney biopsy by polymerase chain reaction (PCR). Antituberculosis therapy was not initiated since there were no signs of active tuberculosis. The patient became clinically stable following dialysis and was discharged, however, she has been undergoing hemodialysis three times a week. The aim of this case presentation was to emphasize that renal tuberculosis should be considered in the differential diagnosis of patients with end stage renal failure, especially in countries like Turkey where tuberculosis incidence is high.

Renal manifestations in children co-infected with HIV and disseminated tuberculosis.

Many children in Cape Town are co-infected with human immunodeficiency virus (HIV) and tuberculosis (TB). Granulomatous TB interstitial nephritis is a recognized entity. Our objective was to establish if TB plays a role in renal disease in HIV-infected children. We identified children co-infected with TB and HIV from our database and reviewed their biopsies and clinical notes. Since 2002, 12 renal biopsies or postmortem examinations were performed on HIV-infected children at our institution. The clinical scenario and renal biopsies in four cases (median age 73 months, range 24-108 months) were consistent with TB involvement. The mean CD4 count and percentage of these four patients were 508 cells/microl and 23%, respectively. All four patients presented with culture-proven disseminated TB (not yet on treatment) and had nephrotic range proteinuria and hypoalbuminemia. Three of these patients had renal impairment. The prominent features of the renal biopsies were a severe interstitial inflammatory infiltrate and mild to moderate mesangial proliferation. An interstitial granuloma was seen in one patient. With treatment for the TB, the proteinuria resolved and renal function improved in all four patients. Based on these results, we conclude that TB contributes to proteinuric renal disease in HIV-infected children and that the renal disease improves following TB treatment.

Tubulointerstitial nephritis and uveitis (TINU) syndrome and recent Streptococcus infection in a 9-year-old girl.

A 9-year-old girl presented to hospital with a 6-week history of non-specific constitutional symptoms and weight loss. She initially underwent extensive medical investigation without diagnosis being achieved. Although raised inflammatory markers and impaired renal function were noted during her initial admission to hospital, it was her subsequent presentation 2 weeks later with sudden-onset bilateral anterior uveitis that prompted a renal biopsy that indicated acute tubulointerstitial nephritis. A diagnosis of tubulointerstitial nephritis and uveitis (TINU) syndrome was made and systemic glucocorticoid treatment initiated to prevent visual loss and preserve renal function. She has subsequently been reviewed in multidisciplinary outpatient clinics and treated with a tapering regimen of immunosuppressive therapy. Her treatment has been complicated by the side effects of glucocorticoids and by persistent relapses in ocular disease and abnormalities on urinalysis. Recent clinical investigations indicate that her uveitis is controlled and that renal function remains well preserved.

Dysbiosis of intestinal microbiota mediates tubulointerstitial injury in diabetic nephropathy via the disruption of cholesterol homeostasis.

Background: Our previous study demonstrated that the disruption of cholesterol homeostasis promotes tubulointerstitial injury in diabetic nephropathy (DN). This study aimed to further investigate the effects of gut microbiota dysbiosis on this process and explored its potential mechanism. Methods: Diabetic rats treated with broad-spectrum oral antibiotics or faecal microbiota transplantation (FMT) from the healthy donor group and human kidney 2 (HK-2) cells stimulated with sodium acetate were used to observe the effects of gut microbiota on cholesterol homeostasis. The gut microbiota distribution was measured by 16S rDNA sequencing with faeces. Serum acetate level was examined by gas chromatographic analysis. Protein expression of G protein coupled receptor 43 (GPR43) and molecules involved in cholesterol homeostasis were assessed by immunohistochemical staining, immunofluorescence staining, and Western Blotting. Results: Depletion of gut microbiota significantly attenuated albuminuria and tubulointerstitial injury. Interestingly, serum acetate levels were also markedly decreased in antibiotics-treated diabetic rats and positively correlated with the cholesterol contents in kidneys. An in vitro study demonstrated that acetate significantly increased cholesterol accumulation in HK-2 cells, which was caused by increased expression of proteins mainly modulating cholesterol synthesis and uptake. As expected, FMT effectively decreased serum acetate levels and alleviated tubulointerstitial injury in diabetic rats through overriding the disruption of cholesterol homeostasis. Furthermore, GPR43 siRNA treatment blocked acetate-mediated cholesterol homeostasis dysregulation in HK-2 cells through decreasing the expression of proteins governed cholesterol synthesis and uptake. Conclusion: Our studies for the first time demonstrated that the acetate produced from gut microbiota mediated the dysregulation of cholesterol homeostasis through the activation of GPR43, thereby contributing to the tubulointerstitial injury of DN, suggesting that gut microbiota reprogramming might be a new strategy for DN prevention and therapy.

Cryptococcal granulomatous interstitial nephritis and dissemination in a patient with untreated lupus nephritis.

Infection is a significant cause of mortality and morbidity in systemic lupus erythematosus (SLE). There are many reports of cryptococcal infection in patients with SLE, on immunosuppression. However, untreated lupus with cryptococcal infection and dissemination is rare. CD4 lymphopaenia is not reported in such patients. We describe a patient with untreated SLE to be having cryptococcal granulomatous interstitial nephritis and dissemination with CD4 lymphopaenia.

Mycobacterium avium-intracellulare-associated acute interstitial nephritis: a rare cause of renal allograft dysfunction.

Nontuberculous mycobacterium (NTM) infections are unusual in the renal transplant population. We present a case of disseminated Mycobacterium avium-intracellulare in a renal transplant recipient who was negative for human immunodeficiency virus infection. Our patient developed renal allograft dysfunction in the setting of disseminated disease and reduced immunosuppression. Transplant biopsy showed acute interstitial nephritis with granulomas and acid-fast bacilli. Acute renal failure resolved completely with further reductions in immunosuppression and anti-mycobacterial therapy. Our patient demonstrates the challenges in diagnosis and treatment of this rare infectious complication.

Overlapping presentation of fungal tubulointerstitial nephritis in an immunosuppressed pediatric patient.

With the expanding use of immunosuppressive therapies and broad-spectrum antibiotics, Candida species has become an increasingly important cause of infections, particularly in the presence of anti-tumor necrosis factor-alpha therapy. We report the case of a 17-year-old female with ulcerative colitis who developed oliguric renal failure following immunosuppressive and nephrotoxic therapy. Although urine cultures and urinary tract imaging were negative in the face of fungemia, renal biopsy was the key to establishing the diagnosis of fungal tubulo-interstitial nephritis as the primary reversible cause of the renal failure.

Expression of major histocompatibility complex class II antigens in porcine leptospiral nephritis.

Class II major histocompatibility complex (MHCII) is required for the presentation of antigens to CD4 helper T cells. During nephritis, not only primary antigen presenting cells such as histiocytes and lymphocytes, but also cytokine-stimulated tubular epithelial cells express MHCII. Leptospirosis in fattening pigs is characterized by several degrees of nephritis, from absence of lesions to severe multifocal tubulo-interstitial inflammation. Renal tissue from 20 8-month-old pigs with spontaneous nephritis and 6 control pigs without renal lesions were investigated for leptospirosis by indirect immunohistochemistry (IHC) and polymerase chain reaction (PCR). IHC for MHCII also was performed on renal samples. Serum samples were tested for different serovars of Leptospira interrogans. Control pigs were free of interstitial nephritis and negative for leptospirosis by all tests. In pigs with nephritis, serology was positive for serovar Pomona in 19/20 pigs. In 16 of these 19 pigs, leptospiral renal infection was confirmed by PCR and/or indirect IHC. Nephritic lesions were classified histologically into perivascular lymphocytic (4 pigs), lymphofollicular (6 pigs), lymphohistiocytic (8 pigs), and neutrophilic (2 pigs) pattern. MHCII expression by histiocytes and lymphocytes was observed in all lesions. Prominent MHCII expression in regenerating tubular epithelium was observed in lymphofollicular and lymphohistiocytic nephritis. No tubular colocalization between leptospiral and MHCII antigen was observed. Results suggest that during leptospiral nephritis, MHCII contributes to the intensity of the inflammatory response. Furthermore de novo MHCII expression in regenerating tubules may play a role in the defence mechanism against leptospiral tubular colonization.

Tuberculosis as a microbiologically proven etiology of membranous nephropathy and interstitial nephritis.

Secondary causes of membranous glomerulonephritis (GN) include systemic lupus erythematosus, other autoimmune diseases, neoplasms, and infections such as hepatitis B and C viruses, syphilis, and parasites. The association of tuberculosis (TB) with membranous GN is rare. We report the first case of microbiologically proven tubercular interstitial nephritis and membranous nephropathy (MN) occurring concurrently in the same patient. The patient improved with the use of antitubercular therapy alone. TB should be recognized as a potentially treatable infectious cause of secondary MN.