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Pediatric Nephrology (Berlin, Germany) Apr 2017Tubulointerstitial nephritis (TIN) is a frequent cause of acute kidney injury (AKI) that can lead to chronic kidney disease (CKD). TIN is associated with an... (Review)
Review
Tubulointerstitial nephritis (TIN) is a frequent cause of acute kidney injury (AKI) that can lead to chronic kidney disease (CKD). TIN is associated with an immune-mediated infiltration of the kidney interstitium by inflammatory cells, which may progress to fibrosis. Patients often present with nonspecific symptoms, which can lead to delayed diagnosis and treatment of the disease. Etiology can be drug-induced, infectious, idiopathic, genetic, or related to a systemic inflammatory condition such as tubulointerstitial nephritis and uveitis (TINU) syndrome, inflammatory bowel disease, or immunoglobulin G4 (IgG4)-associated immune complex multiorgan autoimmune disease (MAD). It is imperative to have a high clinical suspicion for TIN in order to remove potential offending agents and treat any associated systemic diseases. Treatment is ultimately dependent on underlying etiology. While there are no randomized controlled clinical trials to assess treatment choice and efficacy in TIN, corticosteroids have been a mainstay of therapy, and recent studies have suggested a possible role for mycophenolate mofetil. Urinary biomarkers such as alpha1- and beta2-microglobulin may help diagnose and monitor disease activity in TIN. Screening for TIN should be implemented in children with inflammatory bowel disease, uveitis, or IgG4-associated MAD.
Topics: Child; Humans; Kidney Function Tests; Nephritis, Interstitial; Prognosis
PubMed: 27155873
DOI: 10.1007/s00467-016-3394-5 -
Clinical Journal of the American... Dec 2017
Review
Topics: Acute Disease; Adult; Aged; Anti-Bacterial Agents; Ceftriaxone; Deprescriptions; Female; Glucocorticoids; Humans; Male; Methylprednisolone; Nephritis, Interstitial; Prednisone; Trimethoprim, Sulfamethoxazole Drug Combination
PubMed: 28893923
DOI: 10.2215/CJN.07630717 -
Kidney International Jun 2010Acute interstitial nephritis (AIN) represents a frequent cause of acute kidney injury, accounting for 15-27% of renal biopsies performed because of this condition. By... (Review)
Review
Acute interstitial nephritis (AIN) represents a frequent cause of acute kidney injury, accounting for 15-27% of renal biopsies performed because of this condition. By and large, drug-induced AIN is currently the commonest etiology of AIN, with antimicrobials and nonsteroidal anti-inflammatory drugs being the most frequent offending agents. Pathogenesis is based on an immunologic reaction against endogenous nephritogenic antigens or exogenous antigens processed by tubular cells, with cell-mediated immunity having a major pathogenic role. The characteristic interstitial infiltrates, mostly composed of lymphocytes, macrophages, eosinophils, and plasma cells, experience a rapid transformation into areas of interstitial fibrosis. A significant proportion of AIN has nowadays an oligosymptomatic presentation, although the presence of specific extrarenal symptoms such as fever, skin rash, arthralgias, and peripheral eosinophilia has an important role to orientate clinical diagnosis. Identification and removal of the offending drug are the mainstay of the treatment, but recent studies strongly suggest that early steroid administration (within 7 days after diagnosis) improves the recovery of renal function, decreasing the risk of chronic renal impairment. Delayed steroid treatment, when interstitial fibrosis has taken place, would have a less pronounced or nule therapeutic benefit.
Topics: Acute Disease; Animals; Disease Progression; Humans; Kidney Tubules; Nephritis, Interstitial; Predictive Value of Tests; Recovery of Function; Risk Factors; Steroids; Time Factors; Treatment Outcome
PubMed: 20336051
DOI: 10.1038/ki.2010.89 -
Nephron 2023Acute interstitial nephritis (AIN) is one of the chief causes of acute kidney injury (AKI). AIN might be produced by drugs, infections, autoimmune diseases, or can be... (Review)
Review
BACKGROUND
Acute interstitial nephritis (AIN) is one of the chief causes of acute kidney injury (AKI). AIN might be produced by drugs, infections, autoimmune diseases, or can be idiopathic. Among these etiologies, drug-induced AIN (DI-AIN) is the dominant one in many countries. Even when DI-AIN is suspected, identification of the putative drug is challenging.
SUMMARY
DI-AIN is an increasingly common cause of AKI. Diagnosis continues to pose a challenge for physicians due to nonspecific clinical symptoms, and the fact that it can be triggered by a wide variety of medications. Furthermore, the gold standard for the diagnosis is kidney biopsy. All these aspects render the diagnosis more difficult. The withdrawal of the causative drug of DI-AIN is the centerpiece of the treatment, and if early restoration of original kidney function is not obtained, several studies support the treatment with steroids especially when they are started quickly.
KEY MESSAGES
Almost all drugs have the potential to produce drug-induced acute interstitial nephritis (DI-AIN); however, antibiotics, nonsteroidal anti-inflammatory agents, and proton pump inhibitors account for the majority of the reported cases. DI-AIN is produced by an idiosyncratic delayed type IV hypersensitivity reaction, but the precise pathophysiological mechanism remains to be elucidated. DI-AIN symptoms are nonspecific, and most of the patients will present mild symptoms including malaise, nausea, and vomiting. The classical triad, associating fever, rash, and eosinophilia, is seldom present. Nonoliguric acute kidney injury is the main renal manifestation of DI-AIN. Tubular nonnephrotic range proteinuria is usually present. Diagnosis of DI-AIN relies on maintaining a high index of suspicion in those patients at greater risk, but kidney biopsy is required to confirm diagnosis. Histologically, AIN is characterized by the presence of an extensive interstitial infiltrate, mainly composed of lymphocytes and monocytes, but eosinophils, plasma cells, histiocytes, and polymorphonuclear cells can also be found. The withdrawal of the presumed causative drug of DI-AIN is the mainstay of the treatment. When there is no evidence of kidney function recovery after an interval of 5-7 days since interrupting the treatment with the suspected drug, several studies support the treatment with steroids, especially when they are promptly started. Early corticosteroids would decrease the inflammatory infiltrates of the kidney interstitium, thus preventing the risk of subsequent fibrosis.
Topics: Humans; Nephritis, Interstitial; Kidney; Acute Kidney Injury; Steroids; Acute Disease
PubMed: 35830831
DOI: 10.1159/000525561 -
Experimental and Clinical... Jun 2023Abnormalities of the renal interstitium were noted early while identifying chronic kidney disease in 1827; however, interest in glomerular and vascular lesions was then...
Abnormalities of the renal interstitium were noted early while identifying chronic kidney disease in 1827; however, interest in glomerular and vascular lesions was then distracted from their further study. As a complication of scarlet fever, interstitial lesions attracted attention in 1859 and came to be defined as acute interstitial nephritis in 1898. The chronic form of interstitial nephritis was traditionally attributed to pyelonephritis until the advent of kidney biopsy in the 1950s, when interstitial lesions were recognized as an independent primary cause of chronic kidney disease from studies of analgesic nephropathy and vesico-ureteral reflux. The term tubulointerstitial nephritis was introduced in 1963 and promoted to denote the role of the tubules in the pathogenesis and the clinical presentation of interstitial nephritis as tubular dysfunction. Studies since then have established that fibrotic tubulointerstitial nephritis lesions correlate best with the severity and progression of kidney diseases independent of their etiology.
Topics: Humans; Nephritis, Interstitial; History, 19th Century; History, 20th Century
PubMed: 37496342
DOI: 10.6002/ect.IAHNCongress.10 -
European Journal of Human Genetics :... Apr 2009Nephronophthisis (NPHP) is an autosomal recessive kidney disorder characterized by chronic tubulointerstitial nephritis and leading to end-stage renal failure. NPHP as a...
Nephronophthisis (NPHP) is an autosomal recessive kidney disorder characterized by chronic tubulointerstitial nephritis and leading to end-stage renal failure. NPHP as a renal entity is often part of a multisystem disorder and has been associated with many syndromes including Joubert syndrome (and related disorders) and Senior-Loken syndrome. Recent molecular genetic advances have allowed identification of several genes underlying NPHP. Most of these genes express their protein products, named nephrocystins, in primary cilial/basal body structures. Some nephrocystins are part of adherens junction and focal adhesion kinase protein complexes. This shared localization suggests that common pathogenic mechanisms within the kidney underlie this disease. Functional studies implicate nephrocystins in planar cell polarity pathways, which may be crucial for renal development and maintenance of tubular architecture.
Topics: Adaptor Proteins, Signal Transducing; Cytoskeletal Proteins; Humans; Kidney Failure, Chronic; Membrane Proteins; Models, Genetic; Mutation; Nephritis, Interstitial
PubMed: 19066617
DOI: 10.1038/ejhg.2008.238 -
The Journal of Clinical Investigation Jul 2023BackgroundAcute tubulointerstitial nephritis (AIN) is one of the few causes of acute kidney injury with diagnosis-specific treatment options. However, due to the need to...
BackgroundAcute tubulointerstitial nephritis (AIN) is one of the few causes of acute kidney injury with diagnosis-specific treatment options. However, due to the need to obtain a kidney biopsy for histological confirmation, AIN diagnosis can be delayed, missed, or incorrectly assumed. Here, we identify and validate urinary CXCL9, an IFN-γ-induced chemokine involved in lymphocyte chemotaxis, as a diagnostic biomarker for AIN.MethodsIn a prospectively enrolled cohort with pathologist-adjudicated histological diagnoses, termed the discovery cohort, we tested the association of 180 immune proteins measured by an aptamer-based assay with AIN and validated the top protein, CXCL9, using sandwich immunoassay. We externally validated these findings in 2 cohorts with biopsy-confirmed diagnoses, termed the validation cohorts, and examined mRNA expression differences in kidney tissue from patients with AIN and individuals in the control group.ResultsIn aptamer-based assay, urinary CXCL9 was 7.6-fold higher in patients with AIN than in individuals in the control group (P = 1.23 × 10-5). Urinary CXCL9 measured by sandwich immunoassay was associated with AIN in the discovery cohort (n = 204; 15% AIN) independently of currently available clinical tests for AIN (adjusted odds ratio for highest versus lowest quartile: 6.0 [1.8-20]). Similar findings were noted in external validation cohorts, where CXCL9 had an AUC of 0.94 (0.86-1.00) for AIN diagnosis. CXCL9 mRNA expression was 3.9-fold higher in kidney tissue from patients with AIN (n = 19) compared with individuals in the control group (n = 52; P = 5.8 × 10-6).ConclusionWe identified CXCL9 as a diagnostic biomarker for AIN using aptamer-based urine proteomics, confirmed this association using sandwich immunoassays in discovery and external validation cohorts, and observed higher expression of this protein in kidney biopsies from patients with AIN.FundingThis study was supported by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) awards K23DK117065 (DGM), K08DK113281 (KM), R01DK128087 (DGM), R01DK126815 (DGM and LGC), R01DK126477 (KNC), UH3DK114866 (CRP, DGM, and FPW), R01DK130839 (MES), and P30DK079310 (the Yale O'Brien Center). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Topics: Humans; Nephritis, Interstitial; Kidney; Biomarkers; RNA, Messenger; Chemokine CXCL9
PubMed: 37395276
DOI: 10.1172/JCI168950 -
Journal of Nephrology Aug 2016IgG4-related disease (IgG4-RD) is a recently recognized disorder, often with multiple organ involvement, characterized by dense tissue infiltration of IgG4-positive... (Review)
Review
IgG4-related disease (IgG4-RD) is a recently recognized disorder, often with multiple organ involvement, characterized by dense tissue infiltration of IgG4-positive plasma cells, storiform fibrosis, obliterative phlebitis and frequently elevated serum IgG4 concentration. The kidney can be involved either directly or indirectly. The most frequent direct renal manifestations of IgG4-RD are IgG4-related tubulointerstitial nephritis (TIN) and membranous glomerulonephropathy. Retroperitoneal fibrosis (RPF) is another condition that is frequently IgG4-related and that can indirectly affect the kidney causing ureteral obstruction and hydronephrosis. Contrast-enhanced computerized tomography, magnetic resonance imaging and (18)F-fluorodeoxyglucose positron emission tomography/computed tomography show different imaging findings and are useful tools for monitoring therapeutic response. Steroid treatment is the first line of therapy, but relapsing or refractory forms of the disease are frequently observed and require more aggressive therapeutic approaches. At our centre, we treated three cases of aggressive IgG4-related TIN and two cases of IgG4-related RPF with an intensified, immune suppressive protocol, obtaining good results without severe adverse effects.
Topics: Glomerulonephritis, Membranous; Humans; Immunoglobulin G; Kidney; Nephritis, Interstitial; Retroperitoneal Fibrosis
PubMed: 26972314
DOI: 10.1007/s40620-016-0279-4 -
Renal Failure Dec 2021IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. It is considered that the pathogenesis of IgAN involves the 'multiple hit theory' and the... (Review)
Review
IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. It is considered that the pathogenesis of IgAN involves the 'multiple hit theory' and the immune-inflammatory mechanism; however, these theories have certain limitations. The gold standard for diagnosing IgAN is still renal biopsy. Although renal biopsy is accurate, it is traumatic and is associated with some risks and limitations, so there is a need for non-invasive diagnostic methods. According to recent studies, microRNAs (miRNAs) play important roles in the occurrence and development of IgAN; thus, they provide the possibility of the noninvasive diagnosis of IgAN and also have some value in predicting prognosis. This review summarizes the current research status of miRNAs in the occurrence, development, diagnosis, and prognosis of IgAN. We also highlight some interesting and challenging points that require further study.
Topics: Biomarkers; Glomerulonephritis, IGA; Humans; MicroRNAs; Nephritis, Interstitial; Prognosis; Severity of Illness Index
PubMed: 34547971
DOI: 10.1080/0886022X.2021.1977320 -
Iranian Journal of Kidney Diseases Jan 2015Drug-induced acute interstitial nephritis (DAIN) is a common cause of acute kidney injury and often presents as an unexplained rise in serum creatinine level. Kidney... (Review)
Review
Drug-induced acute interstitial nephritis (DAIN) is a common cause of acute kidney injury and often presents as an unexplained rise in serum creatinine level. Kidney biopsy is therefore frequently required to make a definitive diagnosis. The hallmark pathologic features of DAIN are interstitial edema, interstitial inflammation, and tubulitis with a predominance of CD4+ T lymphocytes and mononuclear cells, with variable numbers of eosinophils. This is a result of a type B idiosyncratic non-immunoglobulin-E-mediated immune reaction marked by cell-mediated immune injury to the renal tubulointerstitium. The drug becomes immunogenic via various mechanisms such as haptenization, antigen mimicry, and neo-antigen formation. Renal interstitial dendritic cells, and renal tubular epithelial cells play an important role in further propagating this immunologic injury. Acute DAIN can progress within days to weeks to a chronic form triggered by fibroblast activation and manifested as interstitial fibrosis and tubular atrophy. The mainstay of treatment of DAIN is discontinuation of the offending drug. Incomplete renal recovery is seen in one-third of the patients and depends on the duration of injury prior to diagnosis. Use of steroids for treatment of DAIN makes biological sense, but lack of randomized controlled trials and conflicting data from retrospective studies makes the approach unclear. Positive effects include faster recovery of kidney function, more complete recovery with less chronic kidney disease, and reduced need for chronic dialysis. Therefore, it seems reasonable to employ corticosteroids in patients that do not rapidly improve 3 to 5 days following discontinuation of the offending agent.
Topics: Acute Kidney Injury; Adrenal Cortex Hormones; Animals; Biopsy; Humans; Immunosuppressive Agents; Kidney; Nephritis, Interstitial; Predictive Value of Tests; Recovery of Function; Renal Dialysis; Risk Factors; Time Factors; Treatment Outcome
PubMed: 25599729
DOI: No ID Found