The clinical spectrum of tubulointerstitial nephritis

acute interstitial nephritis analgesic-induced tubulointerstitial nephritis acetosalicylic acid chronic renal failure computer tomography chronic tubulointerstitial nephritis end-stage renal disease glomerular filtration rate granulomatous interstitial nephropathy human immunodeficiency virus interleukin nonsteroidal anti-inflammatory drugs odds ratio platelet-derived growth factor red blood cells relative risk systemic lupus erythrematosus transforming growth factor-Β tubulointerstitial nephritis white blood cells Tubules and interstitium make up approximately 80% of the renal volume, and occupy the compartment referred to as the tubulointerstitium. The interstitium space takes up 13% of rat and up to 17% of dog and rabbit kidneys, including 7 to 9% of renal cortex, 3 to 5% of outer medulla and 30 to 40% of inner medulla and papillary tip1.Wolgast M.A. Larson M. Nygren K. Functional characteristics of renal interstitium.Am J Physiol. 1981; 241 (Renal Fluid Electrolyte Physiol 10): F105-F111PubMed Google Scholar,2.Lemley K.V. Kriz W. Anatomy of the renal interstitium.Kidney Int. 1991; 39: 370-381Abstract Full Text PDF PubMed Scopus (187) Google Scholar. It is made up of both cellular and matrix components. There are two main cell types. (a) Type I interstitial cells are fibroblast-like cells capable of producing and degrading extracellular matrix. The lipid-rich interstitial cells in the inner medulla, a possible source of prostaglandins, are also considered to be a form of type I interstitial cells. (b) Type II interstitial cells, found in all renal zones, include monocyte derived macrophages with capacity for phagocytosis and dendritic antigen-presenting cells found primarily in the cortex. The matrix is made up of a fibrillar net of interstitial and basement membrane collagens and associated proteoglycans, glycoproteins, and interstitial fluid. The interstitial compartment not only provides structural support for the individual nephrons, but also serves as a conduit for solute transport2.Lemley K.V. Kriz W. Anatomy of the renal interstitium.Kidney Int. 1991; 39: 370-381Abstract Full Text PDF PubMed Scopus (187) Google Scholar. It is also the site of production of several hormones and cytokines such as erythropoietin and prostaglandins. Renal diseases can broadly be classified as glomerular, vascular, tubulointerstitial or obstructive in origin. Diseases of tubulointerstitial compartment may be the result of primary injury to this compartment or secondary to injury to other compartments. Several studies in patients with a variety of renal diseases have shown that changes in the tubulointerstitial compartment are a better predictor of the severity of renal dysfunction and long-term outcome than changes in other compartments3.Striker G.E. Schainuck L.I. Cutler R.E. Benditt E.P. Structural-functional correlations in renal diseases. Part 1: A method for assaying and classifying histophatholgic changes in renal disease.Hum Pathol. 1970; 1: 615-630Abstract Full Text PDF PubMed Scopus (126) Google Scholar, 4.Mujais S. Battle D.C. Functional correlates of tubulo-interstitial damage.Semin Nephrol. 1988; 8: 94-99PubMed Google Scholar, 5.Eknoyan G. Mc Donald M.A. Appel D. Truong L.D. Chronic tubulo-interstitial nephritis: Correlation between structural and functional findings.Kidney Int. 1990; 38: 736-743Abstract Full Text PDF PubMed Scopus (38) Google Scholar, 6.Bohle A. Mackensen-Haen S. Gise H. The consequences of tubulointerstitial changes for renal function in glomerulopathies,.in: Amerio A. Cortelli P. Massry S.E. Tubulo-Interstitial Nephropathies. Kluwer Academic Press, Boston, Dordrecht, London1991: 29-40Crossref Google Scholar, 7.Nath K.A. Tubulointerstitial changes as a major determinant in the progression of renal damage.Am J Kidney Dis. 1992; 20: 1-17Abstract Full Text PDF PubMed Scopus (806) Google Scholar. Recent advances in our understanding of the process of injury and repair in general, and tubulointerstitial compartment in particular, have helped elucidate some of the important pathogenic events leading to tubulointerstitial nephritis (TIN). These advances have been summarized in several excellent reviews8.Wilson C.B. Nephritogenic tubulointerstitial antigens.Kidney Int. 1991; 39: 501-517Abstract Full Text PDF PubMed Scopus (16) Google Scholar, 9.Nielson E.G. Pathogenesis and therapy of interstitial nephritis (clinical conference).Kidney Int. 1989; 35: 1257-1270Abstract Full Text PDF PubMed Scopus (179) Google Scholar, 10.Jones C.L. Eddy A.A. Tubulointerstitial nephritis.Pediatr Nephrol. 1992; 6: 572-586Crossref PubMed Scopus (40) Google Scholar, 11.Dodd S. The pathogenesis of tubulointerstitial disease and mechanisms of fibrosis.Curr Topic Pathol. 1995; 88: 51-67Crossref PubMed Scopus (11) Google Scholar, 12.Eddy A.A. Experimental insights into the tubulointerstitial disease accompanying primary glomerular lesions.J Am Soc Nephrol. 1994; 5: 1273-1287Crossref PubMed Google Scholar and will only be discussed briefly here. This review focuses primarily on clinical aspect of the diseases where the tubulointerstitial compartment is the primary target of the pathogenic process rather than being secondarily involved by damage to the glomerular, vascular compartment or collecting system. The term acute interstitial nephritis was first used a century ago in 1898 by Councilman in describing a group of patients with systemic bacterial infection, primarily scarlet fever and diphtheria. This term was applied to acute inflammation of the kidney characterized by cellular and fluid exudation in the interstitial tissue that was not dependent on the presence of bacteria13.Councilman W.J. Acute interstitial nephritis.J Exp Med. 1898; 3: 303-420Crossref Scopus (97) Google Scholar. For many decades, the term chronic pyelonephritis was used to describe renal diseases associated with chronic injury to interstitum, despite the lack of evidence for the presence of active infection in a majority of the patients. Beginning in early 1950s, the work of Spuhler and Zollinger in Switzerland on the role of analgesics14.Zollinger H. Spuhler O. Die nicht-eitrige chronische interstitielle Nephritis.Scheizerische Zeitschrift fuer Allgemeine Pathologie. 1950; 13: 807-811PubMed Google Scholar,15.Spuhler O. Zollinger H.U. Die chronisch-interstitielle nephritis.Zeitschrift fuer Med. 1953; Scholar, and and in on the role of in the of chronic tubulointerstitial nephritis Chronic nephritis in Med. Scholar, evidence that the chronic was not in origin. It is that a group of diseases that are to a variety of and pathogenic the between glomerular, vascular and tubulointerstitial a between the clinical of the diseases in the clinical of both on and the severity of renal this are in patients than patients with glomerular These a lack of and the presence of and white blood cell rather than and red blood cell the presence of a in and and the presence of other such as renal nephropathy and to These with progression of renal is important of renal failure and end-stage renal disease The of primary by and of M. nephropathy in the clinical and Int. 13: Full Text PDF PubMed Scopus Google Scholar, of of J Med. PubMed Google Scholar, W. G. M. The in the the of of nephropathy and Nephrol. Scholar, W. A. K. M. and the of end-stage renal J Nephrol. 1989; PubMed Scopus Google Scholar, and chronic renal J Med. 1989; PubMed Scopus Google Scholar, Renal and of J Kidney Dis. Google Scholar. renal the are to patients with clinical and of than patients with glomerular the of is on clinical and rather than renal the of was for acute and for chronic H.U. Renal in Google Scholar. a of with patients for a of in this G. M. H. Nephrol. Google Scholar. and of patients to a a to with a of and of than M. nephropathy in the clinical and Int. 13: Full Text PDF PubMed Scopus Google Scholar. The of and a a in was also the of for of the The was analgesic-induced considered as in and in of patients with Chronic renal failure and end-stage renal disease in of associated Med. 1981; PubMed Scopus Google Scholar. both studies the of was primarily on and on renal The of patients in M.A. M. of chronic renal failure in 1: PubMed Scopus Google Scholar, in W. A. K. M. and the of end-stage renal J Nephrol. 1989; PubMed Scopus Google Scholar, and in of of J Med. PubMed Google Scholar to in Chronic renal failure and end-stage renal disease in of associated Med. 1981; PubMed Scopus Google Scholar. in a on in of for for and for K.A. in the of of end-stage renal J Med. PubMed Scopus Google Scholar. a renal of patients with renal failure and was the and was in of K. Renal in patients with renal and kidney J Med. 1989; Google Scholar. The of only all patients on Renal and of J Kidney Dis. Google Scholar. obstructive disease and associated with is also the than the This may be to several including lack of the in the of patients with and other systemic diseases on and and of tubulointerstitial Part of the is in the role of in the of There is of The is the a pathogenic and possible to diseases H. Renal and of Tubulointerstitial Scholar. a of a into primary and secondary of or of the disease is of diseases where the pathogenic process in the tubulointerstitial only secondarily other compartments. diseases where the primary pathogenic process in vascular, glomerular or collecting by damage to the tubulointerstitial This is by all and not diseases that than compartment such as systemic systemic lupus or human immunodeficiency virus associated of tubulointerstitial in a of tubulointerstitial nephritis in a the can only in a to a variety of the of can the of the the long-term and in some patients the pathogenesis of the The of the of is dependent on the presence or of a in the diseases where the is the characteristics of the cellular of the in the of with The structural changes of injury include changes injury to in growth including and and the of in the changes include and the of the changes and the presence of renal or other in can tubulointerstitial disease in such a as to the variety of and pathogenic mechanisms that or acute or active of interstitial nephritis the interstitium is and is a cellular that may cells or including of the may be to the of chronic interstitial and is the that may be by only of to a of events where to and the of This process both to the and the of function in chronic interstitial in chronic renal Topic Pathol. 1995; 88: PubMed Scopus Google Scholar. The mechanisms by can renal tubulointerstitial injury can be or by the of systemic or mechanisms are and such as is in and are as in the acute interstitial nephritis associated with nonsteroidal The of the injury may be to some by to the such as renal or that can renal such as the in of can the renal to such as with in and in human disease evidence for mechanisms of tubulointerstitial and have been E.G. Pathogenesis and therapy of interstitial nephritis (clinical conference).Kidney Int. 1989; 35: 1257-1270Abstract Full Text PDF PubMed Scopus (179) Google The in progression of renal Med. Google Scholar. These mechanisms are in some to glomerular disease membrane or other are to the of the and to cell or and by or interstitial dendritic cells to the in cell of and interstitial cells in of a variety of cytokines and growth such as platelet-derived growth factor and transforming growth factor-Β can to and in the tubulointerstitial C.L. Eddy A.A. Tubulointerstitial nephritis.Pediatr Nephrol. 1992; 6: 572-586Crossref PubMed Scopus (40) Google Scholar, 12.Eddy A.A. Experimental insights into the tubulointerstitial disease accompanying primary glomerular lesions.J Am Soc Nephrol. 1994; 5: 1273-1287Crossref PubMed Google Scholar, K.A. the interstitium by platelet-derived growth for renal J Pathol. Google Scholar. of be considered in with renal failure drugs and are major of primary a of drugs the drugs as as and be patients with systemic and systemic the renal be considered in the of a systemic The clinical of the of the disease and severity of renal are between the clinical of glomerular and tubulointerstitial several may between two with to have systemic and and a rate of G. Mc Donald M.A. Appel D. Truong L.D. Chronic tubulo-interstitial nephritis: Correlation between structural and functional findings.Kidney Int. 1990; 38: 736-743Abstract Full Text PDF PubMed Scopus (38) Google A of J Med. Google Scholar. The may be by clinical of the such as or such as and A of J Med. Google Scholar. may evidence for the presence of with and presence of are than and are G. Mc Donald M.A. Appel D. Truong L.D. Chronic tubulo-interstitial nephritis: Correlation between structural and functional findings.Kidney Int. 1990; 38: 736-743Abstract Full Text PDF PubMed Scopus (38) Google Scholar. to active with and rather than and a is and be by the clinical and This may include and studies renal The role of renal in the of not been the renal is to glomerular patients with possible or granulomatous interstitial nephritis and interstitial nephritis associated with cell is in many such as or nephropathy the are the of patients of be by the clinical and of as as by the The and our that the of disease is This associated with infection, drugs and and review of the of have to that are and a type of injury to the tubulointerstitium. These diseases are analgesic-induced granulomatous interstitial nephritis of and interstitial to the of several other such as associated interstitial nephritis to and the interstitial nephritis are not in this are the used in the These primarily in the of the as or for of include such as such as such as and Spuhler and Zollinger in the early to that of patients in Switzerland with interstitial renal disease analgesics14.Zollinger H. Spuhler O. Die nicht-eitrige chronische interstitielle Nephritis.Scheizerische Zeitschrift fuer Allgemeine Pathologie. 1950; 13: 807-811PubMed Google Scholar,15.Spuhler O. Zollinger H.U. Die chronisch-interstitielle nephritis.Zeitschrift fuer Med. 1953; Scholar. the of as factor was not and other several other a between the of and of renal This is by both and this review will the to The of analgesic-induced tubulointerstitial nephritis in in to in to in and to in M. W. S. D. of Renal disease of the Scholar. The of in patients in of of J Med. PubMed Google Scholar, in Chronic renal failure and end-stage renal disease in of associated Med. 1981; PubMed Scopus Google Scholar to in A of J Med. Google D. of nephropathy in Nephrol. Google Scholar and in for of renal J Google Scholar. to and of the is a in all with a ratio as as M. W. S. D. of Scholar. is a of both clinical as as support this with a in the of papillary and For the of papillary is only in the to in and K.A. the interstitium by platelet-derived growth for renal J Pathol. Google Scholar. The in the of and papillary is by the rate of the type in a Renal disease of the Scholar. This is by the of of in many in early of of the of and the of A in and 1995; Google Scholar. O. renal failure in of Google Scholar, A. The of of the of on the of papillary 5: Google Scholar, chronic interstitial nephritis and in PubMed Scopus Google Scholar, of nephropathy in Google Scholar, and M. The of of on the of kidney and and renal Nephrol. 1989; Google Scholar a in the of in but not where The only was by and with evidence of and and in and work of of Renal and J Med. PubMed Scopus (97) Google Scholar. that a of renal of and but not was than of the with renal other for and of renal function and was The of and was in than and The relative risk for was for renal and disease and for disease the for of not of of Renal and J Med. PubMed Scopus (97) Google Scholar. the and a decades, studies have been the between and renal disease and renal of studies in a These are not The of or and the of is by The papillary renal and of of J Med. PubMed Google Scholar, a and chronic renal J Med. 1989; PubMed Scopus Google Scholar, of kidney failure associated with the of and nonsteroidal J Med. 1994; PubMed Scopus Google Scholar, drugs and risk of chronic renal failure Med. 1991; PubMed Scopus Google Scholar, W. A. K. M. and the of end-stage renal J Nephrol. 1989; PubMed Scopus Google Scholar, and both as as patients with renal failure papillary M. The of of on the of kidney and and renal Nephrol. 1989; Google Scholar. and the role of and found that renal failure was the with drugs and risk of chronic renal failure Med. 1991; PubMed Scopus Google Scholar. This the rather than structural of a between studies is in understanding the role of not only in the of but of renal in a of patients with and patients with papillary with a risk ratio of for between and papillary M. The of of on the of kidney and and renal Nephrol. 1989; Google Scholar. The for not not be of patients in and of of J Med. PubMed Google Scholar. This not between and or a W. A. K. M. and the of end-stage renal J Nephrol. 1989; PubMed Scopus Google Scholar found a between and with a of to for of and for the majority or the that was in with the of of is for this group or the group with associated The by where the of was than a of for of and for and chronic renal J Med. 1989; PubMed Scopus Google Scholar. This was for but for other renal diseases including nephropathy as as was in M. The of of on the of kidney and and renal Nephrol. 1989; Google M. for in Google Scholar, W. A. K. M. and the of end-stage renal J Nephrol. 1989; PubMed Scopus Google Scholar, and and chronic renal J Med. 1989; PubMed Scopus Google Scholar both and than The of by patients in with papillary was the in all patients was by only of and of of of J Med. PubMed Google Scholar. the two in the of and in the group was This the that the between the in the of in The the of with papillary and renal It is possible that in with to the is and primarily as renal failure in patients with or renal The in this group of patients is not and is to be interstitial the of in and that some are to the of or other are The studies by drugs and risk of chronic renal failure Med. 1991; PubMed Scopus Google Scholar, of kidney failure associated with the of and nonsteroidal J Med. 1994; PubMed Scopus Google Scholar and M. D. renal disease and A J 1990; PubMed Scopus Google Scholar, the with drugs the role of other including and and that for to of in the of kidney failure associated with the of and nonsteroidal J Med. 1994; PubMed Scopus Google Scholar. The ratio for up to to to for than The for the a of than was of nephropathy in Google Scholar. The in are by the that the are to of as lack of renal in patients. These to important the role of used the drugs in the and patients with renal is considered to be the main the role of other be The in nephropathy is of the G.E. of the renal for the of and Google Zollinger H.U. of and of 20: Scholar. A of is in the inner medulla and can be in Donald nephropathy in of chronic with or in renal and in of and 1990; PubMed Scopus Google Scholar. This will to papillary by interstitial the is interstitial that is with cells, are is also is also as a secondary but the are not and of the renal a of the inner medulla, is to the changes of interstitial and to this M. The of PubMed Scopus Google Scholar. are in or Donald nephropathy in of chronic with or in renal and in of and 1990; PubMed Scopus Google Scholar, nephropathy in of chronic with or 1991; PubMed Scopus (16) Google Scholar, Experimental renal papillary Int. 13: Full Text PDF PubMed Scopus Google Scholar. the presence of changes with clinical evidence of papillary are with the of analgesic-induced The pathogenesis of nephropathy is and to the and have all been as For been that may to of and of cells in the with repair by The of the to a a of may by the of the of and are in the Experimental renal papillary Int. 13: Full Text PDF PubMed Scopus Google Scholar, M. Renal of and mechanisms in the nephropathy of Google Scholar, renal of and Exp Google Scholar. may be by to form that can or all of the or interstitial cellular of by and in rabbit 1981; PubMed Scopus Google Scholar. and production by of Renal blood is dependent on systemic as as production of This is for renal medulla, of and is to The injury is to both as as of drugs in papillary and S. in analgesic-induced papillary J Kidney Dis. Full Text PDF PubMed Scopus Google Scholar. a of to in than The major of this is and renal is to or in chronic blood and J 1988; PubMed Scopus Google Scholar. include and in and These are than in patients with glomerular of renal dysfunction in with 1992; Google Scholar. The clinical of the associated on the of and are in is a of or It is that approximately of patients with P. renal Diseases of the and Scholar. a term the clinical and of renal damage including papillary and in a The be in individual with renal in the presence of of to the renal a of papillary or or papillary A of is to and be by on for of renal dysfunction in with 1992; Google Scholar. of the and associated with as not have and to be in a of studies have evidence that by computer tomography and than other clinical and in the of to P. M. W. D. of nephropathy in patients with end-stage renal of the 1992; Google D. K. W. A. H. H. H. D. D. O. M. M. D. of for in patients with end-stage renal of 1995; Google Scholar. These changes in renal renal and papillary a in a of patients with with and to patients with renal A. W. D. M. A. P. D. M. of for nephropathy in patients with to renal Int. 1995; Full Text PDF PubMed Scopus Google Scholar. patients with renal the papillary the The of and a renal or papillary a and of patients with renal failure papillary was and of papillary with a renal or not or A. W. D. M. A. P. D. M. of for nephropathy in patients with to renal Int. 1995; Full Text PDF PubMed Scopus Google Scholar. clinical is important to that the of this other is dependent on the of the disease in the This be only in patients with a risk for and not as a The of renal failure is to the is early in the of renal is or in renal many patients to the despite to the and K. P. of renal in of 1991; Full Text PDF PubMed Scopus Google Scholar. The of interstitial damage patients not the of These patients have other renal diseases and the of the of renal of kidney failure associated with the of and nonsteroidal J Med. 1994; PubMed Scopus Google Scholar, drugs and risk of chronic renal failure Med. 1991; PubMed Scopus Google Scholar, M. D. renal disease and A J 1990; PubMed Scopus Google Scholar. This group the majority of patients in with to to of patients. that a of be in all patients with renal of drugs is in as as with renal term of drugs be as result in or the of the renal G. A. S. G.E. Kidney and the and to the of the Kidney of the Kidney J Kidney Dis. Full Text PDF PubMed Scopus Google The renal of nonsteroidal anti-inflammatory and J Kidney Dis. Full Text PDF PubMed Scopus Google Scholar. is a systemic disease of characterized by the presence of in The clinical is by and Renal is to of renal by by in interstitial nephritis in other diseases including interstitial and D. K. W. A. H. H. H. D. D. O. M. M. D. of for in patients with end-stage renal of 1995; Google Scholar, P. interstitial Nephrol. 13: Google Scholar, interstitial Pathol. 1995; Full Text PDF PubMed Scopus Google Scholar, M. nephritis in J Kidney Dis. 1995; Full Text PDF PubMed Scopus Google Scholar. The are can renal include interstitial and is in patients with and or inflammation to a and of a of macrophages and primarily in the of the are capable of to the and can into or cells. are primarily cells with a of cells a on the of The in of macrophages and both as as the These events are by of cytokines including interleukin and factor for injury is a of this and of capable of tissue by This process of into by cytokines including and The and to matrix in G. M. and and Scholar. The of renal in is A of 7 and is in two to of a with including and review of evidence in of as found in Med. PubMed Scopus Google W. M. A review of including J Pathol. Google Scholar. Renal is and patients and found with a clinical renal that was primarily patients renal some in the of the the patients renal H. Renal in 1970; PubMed Scopus Google Scholar. These are by a of patients by of renal Renal in patients in Renal and in J Scholar. as renal failure to and that of in all but renal failure S. S. D. G. of Scholar. is many patients have including renal and in a capable of to active The in of the and as The of is to be to and The kidney in and Scholar. a group of in 3 with with and with and Renal and in J Scholar. The is in that is not by the It also to It to by M.A. of of by macrophages patients with Med. PubMed Scopus Google Scholar. nephropathy be considered in with renal failure and renal or These patients have and of with The to this a The presence of on renal not to this in P. interstitial Nephrol. 13: Google interstitial Pathol. 1995; Full Text PDF PubMed Scopus Google Scholar. patients with nephropathy be considered in the presence of renal or renal can be with Renal and in J Scholar. with in renal this on the and severity of inflammation and is There are the or of the the anti-inflammatory of to for by by of and of disease The also to but a may the is the to this is than the to and can be as as of D. of on in PubMed Scopus Google Scholar. by the of is therapy for the G. A. D. M. The of on and in J Med. PubMed Scopus Google Scholar. of been used in a not It was in the of active as as and K. of with J Kidney Dis. 1991; Full Text PDF PubMed Scopus Google Scholar. The of of the is dependent on the of of the disease and may be in a of patients. been a of human for The major of are into and and and many in and renal Acute in of is primarily to and in and damage as Acute J Med. Scholar. The blood in is and the is The the presence of that with therapy chronic tubulointerstitial nephritis may