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LOUISIANA STATE UNIVERSITY HEALTH SCIENCES CENTER VETERANS AFFAIRS MEDICAL CENTER NEW ORLEANS, LOUISIANA |
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SLE 8. References. |
LES 8. Referencias. |
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SLE 8. References |
LES 8. Referencias. |
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Classification /
Clasificación: Addequate biopsy /
Biopsia
adecuada: Renal biopsy / Biopsia
renal: Prognosis (activity
and chronicity) / Pronóstico (actividad y
cronicidad): Extraglomerular SLE /
LES
Extraglomerular: Abstracts of recent publications / Resumenes de publicaciones recientes. J. STEWART CAMERON: DISEASE OF THE MONTH. Lupus Nephritis. J Am Soc Nephrol 10:413-424, 1999. http://www.jasn.org/cgi/content/full/10/2/413?ijkey=MLxZo6EMIwQV. DOMINIQUE NOCHY*, ERIC DAUGAS*, DOMINIQUE DROZ, HELENE BEAUFILS, JEAN-PIERRE GRÜNFELD, JEAN-CHARLES PIETTE, JEAN BARIETY* and GARY HILL*: The Intrarenal Vascular Lesions Associated with Primary Antiphospholipid Syndrome. J Am Soc Nephrol 10:507-518, 1999. Correspondence to Dr. Dominique Nochy, Service d'Anatomie Pathologique, 96 Rue Didot, Hôpital Broussais, 75014 Paris, France. Phone: + 33 1 43 95 92 10; Fax: + 33 1 43 95 92 12; E-mail: edaugas@infobiogen.fr Abstract. Even 10 yr after the identification of the antiphospholipid syndrome (APS), renal involvement in the course of APS is still relatively unrecognized, and is probably underestimated. The association of anticardiolipin antibodies and/or lupus anticoagulant with the development of a vaso-occlusive process involving numerous organs is now confirmed. In a multicenter study, 16 cases of "primary" APS (PAPS) were found and followed for 5 yr or more, all with renal biopsy. In all 16 cases of PAPS, there was a vascular nephropathy characterized by small vessel vaso-occlusive lesions associated with fibrous intimal hyperplasia of interlobular arteries (12 patients), recanalizing thrombi in arteries and arterioles (six patients), and focal cortical atrophy (10 patients). In combination, these led to progressive destruction of the kidney, accelerated by acute glomerular and arteriolar microangiopathy in five patients. Focal cortical atrophy is a distinctive lesion, present in 10 biopsies, and likely represents the histologic and functional renal analogue to the multiple cerebral infarcts detected on imaging studies. The clinical hallmark of this vascular nephropathy in PAPS is systemic hypertension, only variably associated with renal insufficiency, proteinuria, or hematuria. The ensemble of histologic renal lesions defined in this study should aid in the separation of the lesions found in cases of secondary APS, especially systemic lupus erythematosus, into those lesions related to APS and those related to the underlying disease. Douglas A. Charney, MD, George Nassar, MD, Luan Truong, MD and Tibor Nadasdy, MD: "Pauci-Immune" Proliferative and Necrotizing Glomerulonephritis With Thrombotic Microangiopathy in Patients With Systemic Lupus Erythematosus and Lupus-Like Syndrome. American Journal of Kidney Diseases, Vol 35, No 6 (June), 2000: pp 1193-1206. From the Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD; and the Deparments of Medicine and Pathology, Baylor College of Medicine, Houston, TX. In the glomerulonephritides of systemic lupus erythematosus (SLE), the number of subendothelial deposits, when present, generally corresponds to the degree of light microscopic glomerular hypercellularity; only very rarely are no or few such deposits present in cases of focal (WHO class III) or diffuse (WHO class IV) proliferative lupus nephritis. We have recently encountered five cases of active diffuse proliferative glomerlonephritis with no subendothelial and few or no mesangial deposits and thrombotic microangiopathy (TMA) in four patients with SLE and one patient with lupus-like syndrome. Three of the five patients were tested for circulating lupus anticoagulants or anticardiolipin antibodies, and two were positive. All five patients tested negatively for antineutrophil cytoplasmic antibodies (ANCA). Three patients responded to steroid and cyclophosphamide treatment, although one of them died of acute bacterial bronchopneumonia. One patient was lost to follow-up. We conclude that "pauci-immune" proliferative lupus nephritis is rare and should be treated as proliferative lupus nephritis with a proportionate number of subendothelial deposits. The negative ANCA suggests that these cases do not represent incidental ANCA-associated pauci-immune necrotizing and crescentic glomerulonephritis in patients with SLE. Of particular interest is that, in patients with SLE, if associated with TMA, an active proliferative necrotizing glomerulonephritis may be present even in the absence of significant glomerular immune complex deposition. Nossent H, Berden J, Swaak T: Renal immunofluorescence and the prediction of renal outcome in patients with proliferative lupus nephritis. Lupus 2000 Sep;9(7):504-510. Department of Rheumatology, University Hospital Tromso, Norway. The risk for endstage renal failure in patients with proliferative lupus nephritis (PLN) depends largely on the severity and reversibility of the inflammatory process as determined by light microscopy (LM). As the intrarenal formation of immune complexes is thought to initiate this inflammation, we studied whether renal immunofluorescence microscopy (IFM) provides clinical or prognostic information in addition to LM findings. Clinical data at the time of renal biopsy and during a mean follow-up of 46 months were extracted from the records of 69 SLE patients with proliferative LN (WHO class III/IV). Biopsy specimens were analyzed by LM for AI and CI, while IFM was performed on cryostat sections with the use of antisera against IgG, 1gM, IgA, C3, C1q and fibrin. IFM findings were recorded in terms of the localization (glomerular, tubular or vascular) and intensity of fluorescence (score from zero to three). IFM findings were then related to clinical and LM findings and its prognostic value studied by survival analysis. Glomerular immune deposits were present in 99% of patients, tubular deposits in 38% and vascular deposits in 17%. A 'full-house' pattern (all three Ig classes) was found in 67% of biopsies and C3 and C1q deposits in 93% and 74% respectively. Median scores for AI and CI were 6 (1-18) and 3 (0-10); aside from a negative correlation between IgA deposits and CI, we found no other correlation between the amount or type of immune deposits and AI or CI. IgM deposits were associated with high serumlevels of anti-dsDNA, while IgG deposits correlated with high ESR and serumcreatinin levels. IFM scores were not related to steroiddose at the time of biopsy and neither type of glomerular, tubular or overall renal immunedeposits had prognostic value for renal survival. Renal immunofluorescence does not reflect light microscopy findings in patients with PLN and does not contribute prognostic information in patients with PLN. Lupus (2000) 9, 504-510. Hvala A, Kobenter T, Ferluga D. Fingerprint and other organised deposits in lupus nephritis. Wien Klin Wochenschr 2000 Aug 25;112(15-16):711-5. Institute of Pathology, Faculty of Medicine, University of Ljubljana, Slovenia. A prominent feature of lupus glomerulonephritis is extracellular, predominantly homogenous electron dense deposits. Fingerprint-like deposits have been reported in 6 to 10% of cases. On electron microscopy, we studied the frequency and characteristics of organised deposits in 227 kidney tissue samples obtained by biopsy in 185 patients with systemic lupus erythematosus (SLE). Fingerprint forms of deposits were demonstrated in 34 biopsies of 32 patients (17.3%). In the control group of 626 kidney biopsies of patients with primary renal and systemic diseases other than SLE, no fingerprint deposits were found. In 227 kidney biopsy samples, fingerprint deposits were found to be associated with mesangial (8.8%), mesangial-subendothelial (3.8%), subepithelial (28.6%), mesangial-subepithelial (11.1%) and mesangial-transmembranous (19.4%) glomerular deposit distribution patterns. They were demonstrated more often at different locations along the peripheral capillary glomerular basal membrane (77.4%) than within the mesangial matrix (43.7%). In extraglomerular locations, fingerprint deposits were present in the interstitium in 8.8%, along the tubular in 23.5% and peritubular capillary basal membrane in 20.5%, in the wall of the arterioles in 64.7% and in the juxtaglomerular apparatus in 18.2% of biopsies. Organised fingerprint deposits consisted of semicircular dark and light lines, each with a diameter of about 10 to 15 nm. Unilaterally, spiky processes at a periodicity of 10 to 15 nm were seen. Among 14 of 185 SLE patients with cryoglobulinemia, fingerprint deposits were demonstrated in only 2 patients. We conclude that fingerprint deposits are characteristic, diagnostically relevant for SLE and represent morphologically a homogeneous group of organised deposits unrelated to cryoglobulins. In 3 SLE patients, 20 to 100 nm tubules and in 2 SLE patients, 10 and 18 nm Congo red negative fibrils were found. By their morphology and their structural characteristics, the tubules and fibrils resemble the tubules in primary immunotactoid glomerulopathy and fibrils in primary fibrillary glomerulonephritis. Jeruc J, Jurcic V, Vizjak A, Hvala A, Babic N, Kveder R, Praprotnik S, Ferluga D. Tubulo-interstitial involvement in lupus nephritis with emphasis on pathogenesis. Wien Klin Wochenschr 2000 Aug 25;112(15-16):702-6. Institute of Pathology, Faculty of Medicine, Ljubljana, Slovenia. Glomerular lesions in lupus nephritis have been extensively studied in recent decades, but much less attention has been paid to the tubulo-interstitial compartment. The aim of this study was to contribute to the understanding of the pathogenesis of tubulo-interstitial lesions in lupus nephritis by analysing their incidence, character, and their associations. One hundred and ninety kidney biopsies of 190 patients fulfilling American Rheumatology Association (ARA) criteria of systemic lupus erythematosus (SLE) were examined by traditional light, immunofluorescence and electron microscopy. Interstitial inflammatory infiltration and tubulo-interstitial immune deposits concurred in 72 cases (37.9%). Their frequency was the highest in WHO class IV lupus glomerulonephritis. By multivariate analysis, the intensity of interstitial inflammatory infiltration correlated best with the percentage of renal corpuscules with extracapillary crescents and the extent of interstitial fibrosis. On immunohistochemical assessment, the inflammatory infiltrate was found to be composed of CD45RO positive T lymphocytes (191.3/mm2), CD68 positive macrophages (101.7/mm2) and CD45RA positive B lymphocytes (17.2/mm2). For all cell types the median value was higher in cases with extracapillary crescents, and did not correlate with presence and intensity of tubulo-interstitial immune deposits. Infiltration showed the tendency of periglomerular distribution, especially around glomeruli showing extracapillary proliferation and destruction of the capsular basal membrane. Rare S100 positive cells were only found in the interstitium. Tubulo-interstitial lesions estimated semiquantitatively correlated with the degree of proteinuria. Our findings suggest that tubulo-interstitial deposits do not play a major role in the pathogenesis of tubulo-interstitial lesions. The formation of interstitial cell infiltrates appears to be greatly influenced by the development of extracapillary crescents, perhaps by direct transmission of the severe inflammatory process to the adjacent interstitium. The composition of the infiltrate, including antigen presenting cells may signalize an additional involvement of cell-mediated immune mechanisms acting against so far hypothetical tubular epithelial neoantigens. Schwartz MM. The Holy Grail: pathological indices in lupus nephritis. Kidney Int. 2000 Sep;58(3):1354-5. No abstract available. Kidney International 58 (3), 1354-1355 Interpretation of renal biopsies from patients with systemic lupus erythematosus (SLE) is complicated by the marked variability of the pathology. The nature and the distribution of the glomerular lesions vary among patients, among the glomeruli within a biopsy, and even within individual glomeruli. SLE is a chronic disease, and the glomeruli often show both acute inflammation and scarring. In addition, SLE tubulointerstitial and vascular pathology may accompany the glomerular lesions. Despite the many pathological permutations, the very first renal biopsy study in patients with SLE demonstrated that outcome was a function of the extent of glomerular inflammation [1]. Confirmation of this seminal observation and the contributions of many nephrologists and renal pathologists culminated in the World Health Organization (WHO) Classification of SLE Glomerulonephritis in 1982 [2]. The WHO classification is easily learned, readily performed and reproducible, and it has become the standard method by which the pathologist communicates the extent and severity of glomerular pathology to the nephrologist. Because the prognosis is related to the WHO Class of glomerular disease [3], the renal biopsy serves as a guide for the clinician concerned with therapy for the SLE patient with renal involvement [4]. Despite its success in defining the classes of glomerular disease that require therapy, the WHO Classification does not identify which patients with segmental glomerulonephritis, diffuse glomerulonephritis, and mixed membranous and proliferative lesions will develop progressive renal disease. Admittedly, the simplicity of the WHO Classification ignores the individual histological components of the acute inflammatory lesion, does not quantitate the extent of glomerular inflammation and scarring, does not separately categorize lesions which are more characteristic of a protracted clinical course, and does not include tubulointerstitial and vascular pathology. It has been suggested that a more inclusive and quantitative pathological analysis might improve the prognostic power of the renal biopsy. Conrad Pirani, the renal pathologist for many of the early, influential clinicopathological studies of lupus nephritis, and his clinician colleagues [1, 5] developed a semiquantitative method for analyzing renal biopsies because "it compels the pathologist to examine in detail each individual histologic feature," and they developed a scoring system and lists of "active" (potentially reversible acute inflammation) and "inactive" (irreversible scars) lesions [5]. In subsequent analyses, indices of renal pathology were created from the semiquantitative scores, and the activity (AI) and chronicity (CI) indices developed by Austin et al are the most widely accepted and influential [6, 7]. However, histological indices have been criticized because the AI does not predict outcome, and study of the CI yields mixed results, with some investigators finding them prognostically useful while others find that they do not predict outcomes [reviewed in 8]. Although they are unable to define a score that has the sensitivity and specificity to reliably identify patients who will subsequently develop progressive renal disease [3], the AI and CI may find application as pathological summaries [6, 7]. In the current issue of Kidney International, Hill et al attempt to improve upon the information revealed by a renal biopsy of SLE nephritis by utilizing a more detailed histological analysis [9]. Their model comprises the sum of four indices: the glomerular activity index, modified from the AI of Austin et al [6, 7] adds the presence of glomerular monocytes while eliminating interstitial inflammation; the tubulointerstitial activity index includes histological signs of tubular injury and interstitial inflammation but excludes tubular atrophy; the chronic lesions index, modified from the CI of Austin et al [6, 7], includes both glomerular sclerosis and tubular atrophy; and the immunofluorescence index is based on semiquantitation of immunofluorescence staining. In developing the index the authors demonstrated correlations among the morphological features, the component indices, and the clinical parameters that imply that the assignment of the histological elements to the component indices is valid and that the indices reflect the underlying pathogenetic mechanism. In addition, significant correlations were observed between the biopsy index and the clinical parameters at the time of the initial biopsy and at the protocol biopsy performed six months later, and these correlations were higher than for the predecessor indices. The study also sought to optimize correlations between the biopsy index and study outcomes at the time of the initial biopsy and in biopsies following treatment. Although weak correlations were observed between the biopsy index and the study outcomes at the time of the first biopsy, at the protocol biopsy performed after treatment, correlations between the biopsy index and the final serum creatinine, end-stage renal disease, and doubling of the serum creatinine were statistically significant and much stronger than before. Despite the apparent improvement, the correlations between the biopsy index and outcome and the predecessor indices and outcome were not significantly different. It is apparent that the WHO Classification does not utilize all available information in the renal biopsy, but the present study demonstrates that a detailed pathological analysis, using all available morphological data, does not improve upon either the diagnostic or prognostic value of the histological (WHO) classification at the time of the initial biopsy. The improved correlation of the biopsy index with the study outcomes seen at the time of the second biopsy merits further comment: The biopsy index and, importantly, its component indices that reflect active glomerular inflammation and immune complex deposition, correlate with doubling of the serum creatinine, final renal function and end-stage renal disease. This focus on active, potentially reversible pathology that persists after therapy and not on signs of irreversible nephron loss and scarring suggests that the biopsy index may have a role in evaluating the response to treatment. However, there is a caveat: the reported correlations were for a group of patients, and the present study does not demonstrate that the biopsy index can or should be applied to individual patients for the purpose of predicting the outcome. In any case, the limitation in caring for patients with lupus nephritis is not only identification of those with the worse prognosis. In fact, all 18 patients in this study who doubled their serum creatinine despite "induction therapy" had diffuse lupus glomerulonephritis (WHO Class IV), and given the natural history of untreated lupus glomerulonephritis [4], those with comparable glomerular pathology who did not progress should be considered therapeutic remissions. Current treatment of lupus glomerulonephritis, that narrowly focuses on anti-inflammatory drugs and immunosuppressive agents, is a more pressing problem for the clinician whose patient with lupus nephritis has a suboptimal response to therapy. As new approaches are developed, morphologic methods, such as the index proposed by Hill et al [9] that focus on reversible pathology and specific pathogenic mechanisms, may be helpful in evaluating therapeutic efficacy. One must concur with the authors that "the greatest value of the new biopsy index will lie in the systematic evaluation of entire series of patients" and not in the identification of individuals at risk of adverse outcomes. REFERENCES Muehrcke RC, Kark RM, Pirani CL, Pollak VE: Lupus nephritis: A clinical and pathologic study based on renal biopsies. Medicine 36:1&endash;146, 19572. CHURG J, SOBIN LH: Lupus nephritis, in Renal Disease, Classification and Atlas of Glomerular Diseases, New York, Igaku-Shoin, 1982, pp 127&endash;1493. Schwartz MM: The pathological classification of lupus nephritis (Ch. 5), in Lupus Nephritis, edited by Lewis EJ, Schwartz MM, Korbet SM, New York, Oxford University Press, 1999, pp 126&endash;1584. Lewis EJ: The natural history and treatment of lupus nephritis (Chapt. 7), in Lupus Nephritis, edited by Lewis EJ, Schwartz MM, Korbet SM, New York, Oxford University Press, 1999, pp 185&endash;2185. Pollak VE, Pirani CL, Schwartz FD: The natural history of the renal manifestations of systemic lupus erythematosus. J Lab Clin Med 63:537&endash;550, 19646. Austin Ha III, Muenz LR, Joyce KM, Antonovych TA, Kullick ME, Klippel JH, Decker JL, Balow JE: Prognostic factors in lupus nephritis. Contribution of renal histologic data. Am J Med 75:382&endash;391, 1983 Austin Ha III, Muenz LR, Joyce KM, Antonovych TA, Balow JE: Diffuse proliferative lupus nephritis: Identification of specific pathologic features affecting renal outcome. Kidney Int 23:689&endash;695, 19848. Esdaile JM, Levinton C, Federgreen W, Hayslett JP, Kashgarian M: The clinical and renal biopsy predictors of long-term outcome in lupus nephritis: A study of 87 patients and review of the literature. Q J Med 269:779&endash;833, 19899. Hill GS, Delahousse M, Nochy D, Tomkiewicz E, Rémy P, Mignon F, Méry J-P: A new morphologic index for the evaluation of renal biopsies in lupus nephritis. Kidney Int 58:1160&endash;1173, 2000 Hill GS, Delahousse M, Nochy D, Tomkiewicz E, Remy P, Mignon F, Mery JP. :A new morphologic index for the evaluation of renal biopsies in lupus nephritis. Kidney Int. 2000 Sep;58(3):1160-73. Background. Various morphologic indices for the evaluation of renal biopsies in lupus nephritis have been developed, of which the most successful have been the NIH Activity Index (AI) and Chronicity Index (CI). We wished to develop a biopsy index from standard light and immunofluorescence (IF) material that would correlate yet more closely with clinical and outcome parameters than the current indices, and be applicable to both treated and untreated cases. Methods. A cohort of 71 patients with lupus nephritis who had initial renal biopsies (Bx1) with systematic second biopsies (Bx2) at six months after induction therapy was studied, with a large number of light microscopic and IF variables evaluated. These were examined statistically to choose the combinations of variables with the highest overall correlations with clinical and outcome parameters. Results. The adopted biopsy index comprised four elements: Glomerular Activity Index (GAI), a modification of the standard AI with the addition of glomerular monocytes and elimination of interstitial inflammation; Tubulointerstitial Activity Index (TIAI), evaluating several tubular epithelial and inflammatory components, including interstitial inflammation, but excluding tubular atrophy; Chronic Lesions Index, a modification of the standard CI, with the addition of glomerular scars; IF Index (IFI), a semiquantitative index of IF staining for six standard antisera for glomerular capillary, mesangial, tubulointerstitial, and vascular elements. The Biopsy Index showed a statistically higher correlation with clinical and outcome parameters than the NIH AI (P = 0.0170), the NIH CI (P = 0.0009), or their combination (P = 0.0444). At Bx1, comparisons between correlation coefficients for the appropriate AI or CI value and for the Biopsy Index, were: anti-DNA antibodies (0.30 vs. 045), serum creatinine (SCr; 0.33 vs. 0.48), proteinuria (0.22 vs. 0.36), hemoglobin (-0.21 vs. -0.45), and final renal function (0.22 vs. 0.40). Spearman rank correlations showed similar superiority for outcome parameters: doubling of SCr (0.1810 vs. 0.3018) and end-stage renal disease (0.0529 vs. 0.1925). The same improvement of correlations was seen at Bx2 for most parameters, particularly doubling of SCr (0.2716 vs. 0.4753). Conclusions. The Biopsy Index and/or its components show better correlations with clinical and outcome parameters than the standard AI and CI and other similar indices. Ward MM. Outcomes of renal transplantation among patients with end-stage renal disease caused by lupus nephritis. Kidney Int. 2000 May;57(5):2136-43. Palo Alto Health Care System, Palo Alto, CA 94304, USA. mward@leland.stanford.edu BACKGROUND: Although the outcomes of renal transplantation among patients with end-stage renal disease (ESRD) caused by lupus nephritis have generally been found to be comparable to those of patients with other causes of ESRD, some studies indicate that cadaveric graft failure is more common among these patients. However, most previous studies examined small numbers of patients and did not adjust for important confounding factors. METHODS: Graft failure and patient mortality after the first cadaveric renal transplantation were compared between 772 adults with ESRD caused by lupus nephritis and 32,644 adults with ESRD caused by other causes who received a transplant between 1987 and 1994 and were included in the United States Renal Data System. The median follow-up times were 4.9 and 5.0 years in the two groups, respectively. Multivariate Cox regression models were used to adjust the risks of graft failure and mortality for group differences in recipient and donor characteristics. Similar comparisons were performed between 390 adults with ESRD caused by lupus nephritis and 10,512 adults with ESRD caused by other causes after first living-related renal transplantation. RESULTS: In an unadjusted analysis, the risk of graft failure after first cadaveric transplant was slightly but significantly greater among patients with ESRD caused by lupus nephritis than among those with ESRD caused by other causes [hazard ratio (HR), 1.13; 95% CI, 1.01 to 1. 26, P = 0.04]. However, after adjustment for potential confounding factors, the risk of graft failure was not increased in patients with ESRD caused by lupus nephritis (HR, 1.08; 95% CI, 0.94 to 1.23, P = 0.28). Mortality after the first cadaveric transplantation did not differ between groups. The adjusted risks of graft failure (HR, 1.06; 95% CI, 0.84 to 1.32, P = 0.62) and patient mortality (HR = 0. 69; 95% CI, 0.45 to 1.05, P = 0.09) after the first living-related renal transplant were also not significantly higher among patients with ESRD caused by lupus nephritis. CONCLUSIONS: Graft and patient survival after first cadaveric and first living-related renal transplants are similar in patients with ESRD caused by lupus nephritis and patients with ESRD from other causes. Abraham MA, Korula A, Jayakrishnan K, John GT, Thomas PP, Jacob CK. Prognostic factors in diffuse proliferative lupus nephritis. J Assoc Physicians India. 1999 Sep;47(9):862-5. Christian Medical College and Hospital, Vellore, India. BACKGROUND: Patients with diffuse proliferative lupus nephritis (DPLN) can have variable clinical course. Identification of the predictors of outcome would help to improve the management. We have studied the prognostic significance of clinical, laboratory and histological parameters in patients with DPLN. METHODS: Twenty nine patients diagnosed to be having DPLN seen between 1987 and 1991 were followed up for over 57 months. Parameters assessed for prognostic significance included serum creatinine, urine protein at the time of biopsy, blood pressure, type of immunosuppression, composite scores and individual components of activity index (AI) and chronicity index (CI). Kaplan-Meier survival curves were plotted and the results were compared using log rank test. Fishers' exact test was used to study the risk factors. RESULTS: End stage renal failure developed in 7/29 (24.1%) patients; 7/19 (36.8%) who had hypertension and 7/16 (43.8%) who had nephrotic proteinuria developed renal failure, while none who had normal blood pressure or nonnephrotic proteinuria, developed renal failure (p < 0.01). Three patients had high activity index (> 12) and all three developed renal failure. Other parameters such as age, gender, serum creatinine, type of immunosuppression, CI and individual components of AI failed to predict the outcome (p > 0.05). CONCLUSION: Hypertension, nephrotic proteinuria and high AI were predictive of progression to end stage renal failure in patients with diffuse proliferative lupus nephritis. Stoll ML, Gavalchin J. Systemic lupus erythematosus-messages from experimental models. mRheumatology (Oxford). 2000 Jan;39(1):18-27. Review. Contributions to the development of SLE in humans include multiple genetic factors such as intrinsic immunological abnormalities, MHC genes, sex hormones, and environmental factors such as infectious agents, among others, with a complex network involved in its regulation. Although no single murine model for the disease encompasses all of these factors, we are fortunate that each of these models possesses many of the features of human SLE, enabling investigators to address specifically the relevance of contributory agents and identify specific immunoregulatory defects that may predispose to the disease. In addition, the use of murine models facilitates the development and testing of immunotherapies that may specifically downregulate the pathogenic immune processes without the use of immunosuppressive agents. Ito MR, Terasaki S, Kondo E, Shiwaku H, Fukuoka Y, Nose M: Department of Pathology, Tohoku University School of Medicine, Sendai, Japan. Clin Exp Immunol 2000 Feb;119(2):340-5. MRL/Mp-lpr/lpr (MRL/lpr) mice develop glomerular lesions with regular variations in their histopathological manifestations, similar to those in lupus nephritis. These lesions are mainly either cell-proliferative or wire loop-like and are associated with glomerular deposits of immunoglobulins, most frequently IgG and IgM. We previously established a nephritogenic IgG3-producing hybridoma clone, B1, from an MRL/lpr mouse, which induces only a 'wire loop-like' type of glomerular lesion when injected into SCID mice. Injection of SCID mice with an anti-trinitrophenyl IgM antibody-producing hybridoma clone, Sp6, following injection of the B1 clone, however, resulted in the development of a 'cell-proliferative' type of glomerular lesion, associated with an accumulation of both antibodies in glomeruli. This accumulation occurred even though Sp6 IgM antibodies did not react with B1 IgG3 antibodies and vice versa. A mutant clone of Sp6, T/13microE/3.1, which produces antibodies deficient in C1q binding, produced a similar effect as that of the Sp6 clone, i.e. 'cell-proliferative' lesions. Again the B1 antibodies did not react with T/13microE/3. 1-IgM antibodies and vice versa. We therefore conclude that bystander IgM antibodies contribute to the remodelling of glomerular lesions in situ, following glomerular injury by the nephritogenic antibodies. Hurtado A, Asato C, Escudero E, Stromquist CS, Urcia J, Hurtado ME, de La Cruz S, Wener MH, Zavala R, Johnson RJ. Clinicopathologic correlations in lupus nephritis in Lima, Peru. Nephron. 1999;83(4):323-30. Division of Nephrology, Hospital Loayza, Cayetano Heredia University, Lima, Peru. BACKGROUND: We assessed whether immunohistologic markers for glomerular or tubulointerstitial injury might provide better correlations with ongoing renal function and disease activity as compared with the WHO classification or the NIH activity and chronicity indices in lupus nephritis. METHODS: Thirty-three patients with clinically defined systemic lupus underwent renal biopsy over a 1-year period at Hospital Loayza in Lima, Peru. Biopsy specimens were evaluated for macrophages, proliferating cells, alpha-actin expression, and type IV collagen deposition in both glomeruli and the tubulointerstitium and the results compared with the current WHO and NIH classifications in relation to the clinical presentation. RESULTS: Patients with WHO class IV lupus nephritis were more likely to have lower serum complements, greater proteinuria and hematuria, and worse renal function. An elevated NIH activity index correlated with microhematuria, proteinuria, and impaired renal function, whereas an elevated chronicity index correlated with renal function, hypertension, and microhematuria, but not with proteinuria. The presence of glomerular macrophages correlated with both glomerular alpha-actin expression and type IV collagen deposition, but did not correlate with renal function or proteinuria. In contrast, interstitial macrophages correlated not only with interstitial collagen deposition and myofibroblast accumulation, but also correlated with both renal function and the presence of nephrotic syndrome. CONCLUSIONS: Both the WHO classification and the NIH activity/chronicity indices correlate with clinical manifestations of lupus nephritis. While glomerular macrophage accumulation correlates with mesangial cell activation (alpha-actin expression) and collagen deposition, and interstitial macrophage accumulation correlates with interstitial fibroblast activation and collagen deposition, only interstitial macrophages correlate with renal function. Of particular interest will be future studies to determine whether these markers correlate with the prognosis. Copyright Copyright 1999 S. Karger AG, Basel Lim CS, Chin HJ, Jung YC, Kim YS, Ahn C, Han JS, Kim S, Lee JS. Prognostic factors of diffuse proliferative lupus nephritis. Clin Nephrol 1999 Sep;52(3):139-47. Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University, Korea. BACKGROUND: Diffuse proliferative lupus nephritis (DPLN) is the most severe form in lupus nephritis. PATIENTS AND METHODS: We retrospectively analyzed 90 DPLN patients who were confirmed by kidney biopsy and treated at least for 12 months to compare the effectiveness of treatment modalities and to investigate the prognostic factors of DPLN. The patients were categorized to intravenous cyclophosphamide pulse (CY) group and oral corticosteroid (with/without cytotoxic drug, PO) group. RESULTS: When the CY group (69 patients) and PO group (21 patients) were compared, there were no differences between two groups in sex, age, histologic chronicity index (CI, 4.55 vs 3.76; CY vs PO, respectively), mortality rate (4.3% vs 0%), remission rate of nephritis (at 3-year 59. 1 % vs 75.5%), renal survival rate (at 5-year 88.0% vs 91.7%) and complications of treatment, but significant differences in the frequency of nephrotic syndrome (66.7% vs 33.3%) and initial azotemia (30.4% vs 0%). histologic activity index (7.14 vs 4.33) and relapse rate (2.9% vs 42.9%). When the remission group (49 patients) and non-remission group (41 patients) were compared, CI, initial renal insufficiency, male sex and the duration of nephritis were the prognostic factors for remission in univariate analysis, and male sex (OR 10.99) and CI (OR 9.89) in multivariate analysis. When the remission group (35 patients) and non-remission (34 patients) group were compared in the CY group, CI was the prognostic factor in univariate analysis, and CI (OR 8.63) and male sex (OR 5.54) in multivariate analysis. The initial renal insufficiency (OR 12.74) and male sex (OR 7.99) were the prognostic factors for renal survival. The renal survival rate was 100% in remission-induced patients. CONCLUSION: We conclude that CI, male sex, initial renal insufficiency were the prognostic factors of DPLN, and treatment with oral corticosteroid could induce remission in patients who had mild histologic and clinical features. Therefore it would be necessary to evaluate the prognostic factors before the selection of treatment modality. |
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Hill GS, Delahousse M, Nochy D, Remy P, Mignon F, Mery JP, Bariety J. Predictive power of the second renal biopsy in lupus nephritis: significance of macrophages. Kidney Int 2001 Jan;59(1):304-16 Hopitaux Broussais, St. Louis, Henri Mondor, and Bichat, Paris, France. BACKGROUND: A new Biopsy Index containing the Glomerular Activity (GAI), Tubulointerstitial Activity (TIAI), Chronic Lesion (CLI), and Immunofluorescence (IFI) indices was developed, showing better correlations with clinical and outcome parameters than the National Institutes of Health Activity and Chronicity Indices (AI and CI) in lupus nephritis. This report examines the ability of these indices and individual morphologic variables to predict doubling of serum creatinine (SCr; CRX2). METHODS: Renal biopsies from 71 patients with lupus nephritis with an initial biopsy (Bx1) and systematic control biopsy (Bx2) after six months of therapy were studied. Kaplan-Meier survival curves were developed for each index and morphologic variable at each biopsy. A subset of 30 biopsies was stained with the macrophage marker PGM1. RESULTS: At Bx1, only the TIAI and the quantity of C3 and vascular staining on IF were predictive of CRX2. At Bx2, particularly predictive of CRX2 were the GAI, IFI, Biopsy Index, and BxInfl, a composite variable comprised of all of the inflammatory variables. Among individual variables, glomerular and tubular macrophages correlated the best with clinical and outcome parameters. Crescents and karyorrhexis/fibrinoid necrosis also correlated with outcome. Neither the NIH CI or our CLI, nor the TIAI correlated with outcome. In 30 biopsies stained with PGM1, PGM1+ cells correlated well with glomerular and tubular macrophages identified on routine stains and showed even better correlations with SCr, proteinuria, and progression to renal insufficiency than the latter. A diffuse membranoproliferative (MPGN) pattern was seen in seven patients at Bx1. In four of the seven patients, MPGN disappeared with therapy, and all finished with normal renal function. However, among the three patients in whom MPGN persisted and eight patients in whom MPGN, focal or diffuse, appeared under therapy, six reached end-stage renal disease, and a seventh died with marked renal insufficiency. CONCLUSIONS: The biopsy index and its components correlate modestly with CRX2 at Bx1, but strongly at Bx2, particularly IFI, BxInfl, and glomerular and tubular macrophages. Stains for macrophage markers form a valuable adjunct in interpretation of renal biopsies in systemic lupus erythematosus (SLE). MPGN features do not have an ominous significance at Bx1, but their persistence or appearance under therapy are associated with poor outcome. |
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Dube GK, Markowitz GS, Radhakrishnan J, Appel GB, D'Agati VD. Minimal change disease in systemic lupus erythematosus. Clin Nephrol. 57:120-126, 2002. |
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