Predictive power of the second renal biopsy in lupus nephritis: significance of macrophages.

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.

A new morphologic index for the evaluation of renal biopsies in lupus nephritis.

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.

[Renal complications in HIV-1 infection]. / Complicaciones renales de la infección por VIH-1.

Renal involvement in AIDS may be specific or unspecific. Unspecific lesions, the most common, are usually an acute tubular necrosis produced by hemodynamic, infectious or electrolytic alterations that lead to an acute renal failure or drug nephrotoxicity. Specific lesions are segmental and focal hyalinosis, immune complex glomerulonephritis and thrombotic microangiopathy. Focal and segmental hyalinosis is observed almost exclusively in black people and produces a rapidly progressive renal failure. Lesions are a consequence of HIV stimulation of TGF beta in mesangial cells. Immune complex glomerulonephritis, formed by HIV antigens and anti HIV antibodies, is observed in white and black people. The glomerular lesion in this condition is less severe than in the former. Thrombotic microangiopathy could be a consequence of a pathogenic effect of the virus over glomerular capillaries and arterioles. It is clinically expressed as a hemolytic uremic syndrome. This paper reports briefly the renal pathological study of 46 patients infected with HIV-1, seen at the Nephrology Service of the Bichat Hospital in Paris.

Observations on renal replacement services in Russia, Belarus and Lithuania.

This report describes the current financial, technical and medical status of nephrology, dialysis and renal transplant services in these countries with the hope of helping our colleagues there to upgrade their standards of care. The general impression is that physicians as well as administrators in these countries are eager to improve conditions of patient care despite a disastrous economical climate. Our view is that we can help by providing literature, textbooks, journals, travel funds, by offering visiting fellowships to individual physicians, and by forming partnerships between nephrology centres.

Two-dimensional time-of-flight magnetic resonance angiography of renal arteries without maximum intensity projection: a prospective comparison with angiography in 21 patients screened for renovascular hypertension.

PURPOSE: We compared magnetic resonance angiography (MRA) with conventional angiography to establish its value as a screening test in the workup for renal hypertension. METHODS: Twenty-one patients underwent MRA and angiography within a three-day interval. Fifteen patients were suspected of having renovascular hypertension on the basis of clinical findings; the remaining six had multivessel atherosclerosis with renal insufficiency. MRA was performed on a 1 Tesla magnet in three planes: axial, coronal and perpendicular to the axis of each renal artery, by means of several contiguous or overlapping individual slice acquisitions. The two examinations were read by the same two independent observers, before and after an interval of 3 months. RESULTS: Conventional angiography showed 48 renal arteries. All main and three of six accessory renal arteries were correctly identified by MRA, as well as 11 of 14 significant stenoses or thromboses. Overreading of stenoses by MRA was observed in 4 cases. There were two false negatives for the two readers. The sensitivity and specificity of MRA for the detection of stenoses of the main renal arteries were found to be 70 and 78% respectively, for the first reading and 85 and 86% for the second reading. CONCLUSION: MRA is considered a useful noninvasive method to determine the need for conventional angiography in patients in whom renal artery stenosis is suspected.

Functional evaluation of normal and ischemic kidney by means of gadolinium-DOTA enhanced TurboFLASH MR imaging: a preliminary comparison with 99Tc-MAG3 dynamic scintigraphy.

The functional value of TurboFLASH MR imaging in the assessment of dynamic contrast enhancement and renal perfusion anomalies was evaluated in seven patients, who also underwent renal scintigraphy in baseline conditions. The basal renograms obtained from MAG-3 scintigraphy (mercapto acetyl triglycine, MAG3-S) and from Gd-DOTA-enhanced turboFLASH MRI were compared. After hydration, the protocol used consisted in breath-hold coronal turboFLASH acquisitions after IV bolus of Gd-DOTA (4 s every 20 s during 10 min) for MRI, and IV bolus of 370 MBq of 99mTc-MAG3 followed by 60 frames of 1 s and then 120 frames of 10 s for MAG3-S. Relative renal functions were computed for both methods by calculation of the integral of the uptake phase between the first and the second minute. Renograms exhibited 10 normal and 4 ischemic kidneys. There was a close correlation between the contrast enhancement of MRI and isotopic uptake in normal and ischemic kidneys. Global renograms of MRI correlated with MAG3-S (r = .82, p < .001) with similar curve shape and time to peak. Relative renal function of the right and left kidney were closely correlated in all patients (r = .98, p < .001), although there was a tendency for MR to overestimate MAG3-S evaluation in kidneys with severe basal dysfunction. Enhanced turboFLASH provides noninvasive assessment of renal perfusion in patients with renovascular disease. Accurate renograms are obtained with dynamic-enhanced MRI, but the relative renal function seems to be overestimated in low values of ischemic kidneys, and needs further comparative evaluation.

[Fibrillary glomerulopathies]. / Glomérulopathies fibrillaires.

Fibrillary glomerulonephritis is characterized by the presence, mainly in the mesangium, of fibrils demonstrated by electron microscopy of the renal parenchyma. There are several varieties of this disease, depending on the size and, above all, the composition of these fibrils. Thus, fibrillary glomerulonephritis in which the fibrils are made of the normal glomerular basement membrane components can be distinguished from a more frequent variety in which the fibrils are composed of circulating proteins deposited in glomeruli. For a long time, amyloid glomerular nephropathy has been the sole representative of the latter variety, but we now know that, beside renal amyloidosis, there is a non-amyloid fibrillary glomerulonephritis the fibrils of which are made of monoclonal or non-monoclonal immunoglobulins. If it were confirmed that the principal member of this variety, described as immunotactoid glomerulopathy, is frequently associated with monoclonal gammapathy, it would represent, together with amyloidosis and light chain deposition, another variety of glomerular lesions which may occur in monoclonal gammapathy.

Renal disease associated with HIV infection: a multicentric study of 60 patients from Paris hospitals.

Sixty HIV-infected patients presenting renal symptoms who underwent percutaneous renal biopsies were analysed. According to the CDC classification, 44 patients were staged in group IV, five in group III, and 11 in group II. Patients were divided in two groups according to their ethnic origin (29 black patients and 31 white patients). Risk factors such as homosexuality, multiple transfusions or intravenous drug abuse (IVDA) were identified in all white patients except two, but in only nine (31%) of the black patients. Three main patterns of renal disease were observed: focal and segmental glomerulosclerosis (FSGS) was found predominantly in black patients (23 black patients versus 3 Caucasians, P < 0.001) and was associated with the nephrotic syndrome; immune-complex-type glomerulonephritis (ICGN) was frequent in black and white patients (21% and 52% respectively) including four cases of IgA nephritis all seen in white patients; and 10 cases of lupus-like nephritis (4 black and 6 white patients). The frequent hypergammaglobulinaemia in those patients suggests a pathogenic role of polyclonal B cell activation in ICGN. Interstitial nephritis was present in 48 and 52% of the black and white patients respectively and did not seem related to drug toxicity or superimposed infectious disease. In addition to interstitial nephritis, the coexistence of multivisceral lymphocytic infiltration involving accessory salivary glands, liver and/or lung, found in six patients possibly suggests a virus-induced immune disorder.

[Pheochromocytoma, first manifestation of Von Hippel-Lindau disease: a possibility to be considered]. / Phéochromocytome, première manifestation de la maladie de von Hippel-Lindau: une éventualité à connaître.

Von Hippel-Lindau (VHL) disorder is an autosomal dominant disease characterized by the almost constant development of hemangioblastomas in the central nervous system (cerebellum, spinal cord and retina). In addition, various types of tumors including renal cell carcinomas, pancreatic cysts and pheochromocytomas are frequently observed in VHL gene carriers. Linkage of the VHL locus to the RAF-1 oncogene on the short arm of chromosome 3 (3p25-26) has been recently reported. Pheochromocytoma is of particular interest because of the risk of inaugural malignant hypertensive crisis but especially because of a great degree of interfamily variability (from 0 to 92% of affected members in previously reported large kindreds). We have studied a French series of 25 pheochromocytoma (11 males, 14 females) in VHL affected patients. Twenty pheochromocytoma (80%) occurred in a familial context, whereas 5 (20%) were consistent with "apparent sporadic cases". The mean age at pheochromocytoma diagnosis was 27 years (5-55 years). Bilateral tumours have been documented in 13 cases (52%). The prevalence of pheochromocytoma revealing VHL was 14 out 25 (56%). In these cases, VHL diagnosis was considered up to 25 years later. In 6 cases (2 deceased) pheochromocytoma was the only manifestation of VHL. Thus, search for VHL must be systematic in the presence of pheochromocytoma, in the interest of the patients themselves and of potential at-risk family members (prevention of hypertensive crisis linked to latent tumours). Basic check-up (neurological and somatic examination, ophthalmoscopy, familial inquiry) may be completed with cerebral CT scan or MRI and abdominal ultrasonography followed, if positive or doubtful, by abdominal MRI or selective angiography.

Thrombosis in systemic lupus erythematosus: a French collaborative study.

A retrospective study was undertaken of 120 children with systemic lupus erythematosus (SLE) seen in Paris and its immediate suburbs who fulfilled at least four of the American College of Rheumatology diagnostic criteria for SLE, and in whom the disease was diagnosed before the age of 16 and between January 1975 and December 1987. Eleven of these children (eight girls and three boys) all more than 10 years of age (mean follow up 8.1 years; range 3-13) had thrombotic episodes (9%). Thrombosis was one of the presenting signs in seven patients; in five it was associated with typical symptoms of SLE, and in the other two the thrombotic episode was isolated and diagnosis of SLE was delayed one and three years. Of a total of 16 thrombotic episodes (six of which were recurrent), 14 involved the leg veins, and in four there was associated pulmonary embolism. There were two episodes that affected cerebral arteries. The American College of Rheumatology diagnostic criteria for SLE as well as the incidence of lupus anticoagulant, positive direct Coombs test, and vasculitis in this group of patients was compared with the incidence in patients with SLE but no thrombosis. Only lupus anticoagulant was significantly associated with thrombotic episodes: eight of 11 (73%) of patients with SLE and thrombotic (arterial or venous) episodes had lupus anticoagulant compared with only 10 of 74 patients (14%) with no history of thrombotic events in the same age group.

Induction of tumour necrosis factor-alpha during haemodialysis. Influence of the membrane type.

Some of the secondary clinical effects induced by long-term haemodialysis in patients with end-stage renal failure have been related to an increased production of interleukin-1 (IL-1). We investigated the role of another cytokine which shares a number of biological properties with IL-1, tumour necrosis factor-alpha (TNF-alpha). In long-term haemodialysed patients, we found at the beginning of the dialysis increased plasma TNF-alpha levels and enhanced monocyte capacity to produce TNF-alpha spontaneously ex vivo. Non-haemodialysed uraemic patients also presented increased plasma TNF-alpha levels. During dialysis with cellulose acetate (CA) or polysulphone (PS) membranes, plasma TNF-alpha levels and the spontaneous and lipopolysaccharide-induced production of TNF-alpha by monocytes remained at predialysis levels. In contrast, when cuprophane membranes were used, there was a significant increase in plasma TNF-alpha levels and in both spontaneous (10-fold) and lipopolysaccharide-induced (seven-fold) ex vivo TNF-alpha production by monocytes. These results suggest that monocytes are stimulated during haemodialysis with the poorly biocompatible cuprophane membrane.