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Background. Pauci-immune renal vasculitis with focal glomerular necrosis and crescent formation is usually associated with anti-neutrophil cytoplasmic antibodies (ANCAs). However, ANCA’s are absent in up to 10% of cases, which constitutes a rarely studied variant of renal vasculitis. Methods. This retrospective multicentre cohort study analyzed the presenting features, renal histology and outcome in 20 patients with pauci-immune crescentic necrotizing renal vasculitis in whom indirect immunofluorescence did not detect ANCA. Results. Renal histology revealed a high percentage of active glomerular lesions (50%), mainly cellular crescents, 28% of them with glomerular necrosis. Chronic tissue damage with glomerulosclerosis (21%) and diffuse interstitial fibrosis (40%) was already present at diagnosis, more prominent than in historical PR3-positive patients. Infiltrates of polymorphonuclear neutrophils in glomerular capillary loops were observed in 40% of all biopsies, mainly in necrotic lesions. The subsets of interstitially infiltrating leukocytes similar to ANCA-associated disease. Microscopic polyangiitis was diagnosed in 17 patients, Wegener’s granulomatosis in two and renal-limited vasculitis in one. The patients median disease extent index (DEI) of 5 (range 4–11) reflected a systemic vasculitis. ANCA-negative vasculitis was not associated with infection or malignancy. Renal outcome was correlated to DEI (P ¼ 0.032) and serum creatinine at diagnosis (P ¼ 0.04). The mortality rate was high (35%) and closely related to age above 65 years at diagnosis (P ¼ 0.014). Conclusions. The histological findings and prognosis in ANCA-negative renal vasculitis are comparable with those of ANCA-positive disease. Our data underline the importance of the exact diagnosis in an active vasculitic disease process even in the absence of ANCAs.

Background Adefovir (ADV), an orally administered nucleotide analogue active against hepadnaviruses, retroviruses and herpes viruses was shown to be effective in HIV-infected patients, but the prevalence of nephrotoxicity with doses of 60-120 mg/day was considered unacceptable. Recently, lower doses of ADV were shown to be effective for the treatment of HIV-1 patients with chronic lamivudine (LAM)-resistant hepatitis B. Methods In a cohort of 35 patients infected with both HIV-1 and LAM-resistant hepatitis B virus, we investigated the renal tolerance of a once-daily dose of ADV 10 mg over 52 weeks. Their mean baseline creatinine clearance was within the normal range (105 +/- 3 ml/min/1.73 m(2)). No patient had significant changes in renal function or electrolyte balance secondary to ADV treatment. Results Transient increases in serum creatinine, which resolved by the end of the study were noted in two patients and three developed proteinuria, which was felt to be unrelated to ADV treatment. The cohort's mean serum phosphate level, 2.45 +/- 0.09 mg/dl at baseline, did not change significantly under treatment (2.66 +/- 0.12 mg/dl at week 52, P = NS). Conclusions Our study shows that ADV dosed at 10 mg/day for the treatment of LAM-resistant chronic hepatitis B in patients co-infected with HIV is not associated with renal tubular dysfunction or a significant change in renal function.

Morphological examination of 2 renal biopsy specimens obtained from a 69-year-old woman with a nephrotic syndrome, high blood pressure, and a reduced glomerular filtration rate revealed, in ultrastructural study, a type of a glomerulonephritis with fibrillar deposits in a subendothelial position which were unusual in their immunoglobulin components (mainly IgM). The fibrillar components were of irregular size, 13 to 18 nm in diameter and presented a very particular "barbed wire" morphological aspect, not hitherto described. Diffraction studies and image analysis, revealed spiraled fibrils with regular alternating elements that we suggest may correspond to IgM molecules. The clinical (isolated renal symptoms) and laboratory (traces of 3 monoclonal components in the serum and 2 normal bone marrow biopsy specimens) data provided no evidence of hematopoietic malignancy, viral hepatitis or cryoglobulinemia.

Cyclosporine (CsA), a widely used immunosuppressive drug, is an effective treatment of sight-threatening posterior idiopathic uveitis. CsA's main side effect is nephrotoxicity. The aim of this single-center prospective cohort study (conducted in a tertiary care teaching hospital in Paris, France) was to assess the long-term renal tolerance of a low-dose CsA treatment in patients with previously healthy kidneys on clinical, biologic, and pathologic criteria. Forty-one patients treated with 4.3 +/- 1.6 mg/kg body wt per day CsA for 44.9 +/- 3.6 mo were included. Mean follow-up was 55.4 +/- 0.2 mo. BP, CsA trough level, and renal function were prospectively monitored together with blood urea, creatinine clearance, GFR, and effective renal plasma flow. Eleven patients underwent serial kidney biopsies before and after 2 yr of a 4 +/- 0.9 mg/kg daily CsA treatment. Sustained low-dose CsA treatment induced a significant increase in plasma creatinine (P < 0.0001), a significant decrease in creatinine clearance (P < 0.0001), and isotopic GFR (P < 0.0001) over time. The highest dose induced more severe alterations in any of the renal parameters than the lowest dose. Prevalence of hypertension was particularly high. Histopathologic data showed significant interstitial fibrosis (P < 0.003) and tubular atrophy (P < 0.003) after 2 yr. Low-dose long-term CsA treatment induces significant renal impairment and a high incidence of hypertension. Our study suggests that lowering daily dosage may prevent CsA-induced nephrotoxicity if a daily dose of < or =3 mg/kg is used. Whether once established it is reversible is still prospective, although the occurrence of interstitial fibrosis in the kidney would argue against reversibility.

Resume Introduction. – Des vascularites associees a la presence d’anticorps anticytoplasme des polynucleaires (ANCA) ont ete decrites au cours de maladies de Basedow traitees par les antithyroidiens de synthese (ATS), essentiellement par le propylthiouracile (PTU). Exegese. – Nous rapportons le cas d’un patient traite par benzylthiouracile (Basdene®) pour hyperthyroidie basedowienne. Le traitement fut complique d’une insuffisance renale aigue due a une glomerulonephrite extracapillaire a pANCA. A l’arret du benzylthiouracile et sous corticoides, l’insuffisance renale, le syndrome inflammatoire ainsi que le titre des pANCA ont regresse. Conclusion. – La connaissance de vascularites a pANCA secondaires aux autres antithyroidiens de synthese, essentiellement le propylthiouracile, qui ont des similitudes chimiques avec le benzylthiouracile est en faveur d’une relation causale. A notre connaissance, c’est la premiere fois que le benzylthiouracile est implique dans ce type de manifestation.

Background Erythropoietin (Epo) is a growth factor whose synthesis mainly takes place in the kidney. Epo has been shown to support the growth not only of erythroid progenitor cells but also of certain other cell types. We attempted to establish whether Epo enhances the recovery from acute renal failure induced by cisplatin. Methods Sprague-Dawley rats were randomized into three groups. In the cisplatin group, animals received one intraperitoneal injection of cisplatin (6 mg/kg) and a daily injection of placebo for 9 days. In the cisplatin+Epo group, animals received intrapertoneal cisplatin and a daily injection of Epo (100 IU/kg) for 9 days. In the control group, animals received both placebo preparations alone. Para-aminohippuric acid and inulin clearances were determined after 4 and 9 days to evaluate renal blood flow and glomerular filtration rate. In addition, light microscopy and immunohistochemistry examinations were performed, and in situ proliferating cell nuclear antigen (PCNA) staining was done to estimate the degree of renal tubular cell regenerative activity. The potential role of epithelial growth factor (EGF) was evaluated by semi-quantitative assessment of EGF immunostaining. Results Renal blood flow and glomerular filtration rate decreased significantly in cisplatin and cisplatin+Epo groups versus control group at day 4. However, at day 9, they both were significantly greater in cisplatin+Epo-treated animals than in rats that had received cisplatin alone. Tubular cell regeneration was significantly enhanced at day 4 in cisplatin+Epo group, compared with cisplatin and control groups respectively. EGF immunostaining was not significantly different between the three groups. Conclusion Epo significantly enhanced the rate of recovery from acute renal failure induced by cisplatin. PCNA staining indicated that Epo might act directly via stimulation of tubular cell regeneration.

The purpose of this study was to evaluate the potential reversibility of kidney lesions in an experimental model of acute renal failure using ultra-small particles of iron oxide (USPIO)-enhanced magnetic resonance (MR) imaging. This study was conducted in 21 uninephrectomized rats using a model of iodinated contrast media-induced renal failure. Thirteen rats received selective intraarterial renal administration of diatrizoate (370 mg/ml) and were compared with two control groups, including six animals injected with saline and two noninjected animals. MR imaging was performed 28 hours, 8 days, and 22 days after the procedure. Each MR session included axial and coronal T1- and coronal T2-weighted images before and after intravenous administration of 60 μmol Fe/kg of USPIO. The rats were sacrificed immediately after the last MR session for pathologic evaluation. MR images were qualitatively and quantitatively interpreted with respect to pathologic data, and differences were statistically studied. At day 22, histology showed 4 severely diseased kidneys with focal areas of necrosis, 5 mildly diseased kidneys with tubular vacuolization, and 12 normal kidneys. On quantitative data, a high correlation between the percentage of negative enhancement and histologic data was observed (P < 0.05). Qualitative interpretation showed a sensitivity and specificity of USPIO-enhanced T2-weighted MR images of 88% and 91%, respectively. Follow-up enhancement curves showed a constant increase of intrarenal USPIO negative enhancement in normal kidneys between day 1 and day 22, whereas all severely involved kidneys displayed higher USPIO negative enhancement at day 1 without significant changes over time until day 22. USPIO may be useful for in vivo follow-up of the reversibility of experimentally induced iodinated contrast media renal impairment in animals. J. Magn. Reson. Imaging 2000;12:278–288. © 2000 Wiley-Liss, Inc.

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.

Three acquired immune deficiency syndrome patients given foscarnet to treat cytomegalovirus retinitis developed renal failure with crystal deposits within the renal glomeruli. We identified these crystals as a mixture of sodium salt, calcium salt, and a mixed salt containing both sodium and calcium ions. This composition has not been previously reported. Foscarnet can complex available ionized calcium and secondarily precipitate in glomeruli. The percentage of complexing depends on calcium concentration in serum and the poor calcium salt solubility.

We herein report on the first two primary sequences (BOU and RAC) of monoclonal light chains of the lambda type responsible for nonamyloid lambda light chain deposition disease. Both patients were affected with severe forms of myeloma complicated with renal failure. The pathological presentation typically featured Congo red-negative deposits along tubular basement membranes but differed somewhat from the typical "Randall-type" kappa light chain deposition disease: they lacked the prominent glomerulosclerosis pattern often featuring nonamyloid kappa deposits and were associated with cylinders or myeloma casts. Both protein sequences were deduced from those of the corresponding complementary DNAs in the bone marrow plasma cells. For each chain, products of three independent amplifications by polymerase chain reaction were sequenced and found to be identical. BOU and RAC lambda mRNAs had a normal overall structure consisting of Vlambda2 segments rearranged to Jlambda2Clambda2 but displayed a number of unusual features within their primary sequences. These substitutions are likely responsible for changes in light chain conformation that promote their aggregation and deposition along renal tubule basement membranes.

To compare the histologic effects on rat tubular cells of two nonionic contrast media with equivalent osmolalities and viscosities.Histologic, functional (creatinine clearance), and biochemical (proteinuria and enzymuria) profiles of iohexol and iobitridol (both at 350 mg I/mL) were compared in the uninephrectomized rat. A control group (n = 14) received compared isotonic saline solution. Test substances (3 mL) were injected into the kidney at a rate of 1 mL/minute while transitory ischemia was induced by clamping the aorta above the renal artery.In terms of their (moderate) effects on creatinine clearance, proteinuria, and urinary N-acetyl-beta-D-glucosaminidase activity, no statistically significant difference was detected between the two low-osmolar contrast agents either 24 or 48 hours after injection. However, blinded histologic analysis of the kidneys showed significantly greater epithelial cell vacuolization in the proximal convoluted tubules of the outer cortex with iohexol (14 of 14 rats versus 3 of 14 rats for iobitridol; P.001). The same degree of vacuolization in the inner cortex was observed for all three substances. Iobitridol also induced fewer congestive lesions in the glomerular capillaries than iohexol (4 of 14 versus 10 of 14, respectively; P.05) and saline (5 of 6; P.05). It is difficult to explain the lesser degree of cytoplasmic vacuolization using standard physicochemical parameters.Although iobitridol and iohexol showed similar functional and biochemical profiles when selectively injected into the single remaining kidney of rats, iobitridol induced significantly less tubular vacuolization and capillary congestion than iohexol.

The nephrotoxic potentials of a high-osmolar contrast medium, diatrizoate, and of a low-osmolar contrast medium, ioxaglate, were compared during early degenerative gentamicin-induced nephropathy in the rat. Male rats (13-22/group) were uninephrectomized. Six days later, the aorta was clamped above the renal artery, and either diatrizoate or ioxaglate was administered (1 ml/min for 3 min) via an aortic puncture into the remaining kidney. Some of the rats received chronic treatment with gentamicin (50 mg/kg/day i.m., 4 days), starting 2 days before and ending 1 day after contrast medium administration. Two control groups, only one of which received gentamicin, were subjected to a 3-min renal ischemia. The creatinine clearance (CrCl) per 100 g body weight was determined before and 24 and 48 h after contrast medium injection. A second study (6 rats/group) evaluated urinary N-acetyl-beta-D-glucosaminidase (NAG) excretion and the histologic appearance of the kidneys (blinded analysis) in the same experimental groups. Gentamicin induced a significant decrease in CrCl at baseline (0.35 +/- 0.19 vs. 0.41 +/- 0.19 ml/min; p0.01) and an increase in urinary NAG (128 +/- 92 vs. 39 +/- 57 mumol/h/mmol creatinine; p0.01). Taking into account these differences at baseline, univariate repeated-measures analysis showed that on day 1 diatrizoate caused a more marked decrease in CrCl than ioxaglate (p0.05), whether or not gentamicin was also administered. On day 2, the depressant effect of diatrizoate associated with gentamicin persisted (CrCl vs. day 0 = -0.19 +/- 0.10 ml/min), while that of diatrizoate alone returned to baseline (-0.05 +/- 0.24 ml/min).(ABSTRACT TRUNCATED AT 250 WORDS)

Two cases of hemolytic and uremic syndrome in heart transplant recipients are reported. Among solid organ transplantations, this complication mainly occurred in renal transplantation and only 1 case was reported in heart transplantation in the literature. Cyclosporine was the only etiologic factor found. The renal outcome was severe with end-stage renal failure and no recovery of the renal function despite stopping cyclosporine, corticoids and plasma exchange.

The objectives of this study were first to develop a reproducible and reversible model of acute renal failure following contrast medium infusion in the rat; second to use that method to compare the nephrotoxicity of low- and high-osmolar contrast agents. Contrast media or saline were perfused in the aorta while a clamp was applied on the aorta just above the renal artery. Three minutes of renal ischemia with or without infusion of isotonic saline induced no change in serum creatinine and a slight and transient decrease in creatinine clearance at 24 h. Urinary N-acetyl glucosaminidase (NAG) excretion was not modified in this control group. All 17 kidneys which were examined were normal. 2,100 mosm/kg hypertonic saline induced a significant increase in serum creatinine and a significant decrease in creatinine clearance (from 1.8 +/- 0.1 to 0.8 +/- 0.1 and 1.0 +/- 0.2 ml/min at 24 and 48 h, respectively). Urinary NAG excretion increased from 23 +/- 18 to 48 +/- 20 and 8 +/- 4 mumol h-1/mmol creatinine at 24 and 48 h, respectively (p less than 0.05). Histologic analysis of 5 kidneys revealed acute tubular necrosis (n = 3) and no histologic abnormalities (n = 2). Diatrizoate induced an acute and reversible renal failure. Creatinine clearance decreased from 1.6 +/- 0.1 to 0.4 +/- 0.1 and 0.8 +/- 0.1 ml/min at 24 and 48 h, respectively (p less than 0.01). Urinary NAG excretion increased also significantly from 43 +/- 9 to 352 +/- 79 and 64 +/- 23 mumol h-1/mmol creatinine at 24 and 48 h, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

We retrospectively reviewed the clinicopathological features of a series of 68 renal AA amyloidosis observations collected between 1990 and 2005. The amyloidogenic disease was a chronic infection (40.8%), a chronic inflammation (38%), a tumor (9.9%), a hereditary disease (9.9%), or was undetermined in 1.4% of cases. Nephrotic syndrome and renal insufficiency were noted in 63.1% and 75% of patients, respectively. The distribution pattern of glomerular amyloid deposits was mesangial segmental (14.7%), mesangial nodular (26.5%), mesangiocapillary (32.3%), and hilar (26.5%). Glomerular form was observed in 80.9% of cases and vascular form in 19.1%. AA amyloidosis-related inflammation was noted in 30 patients (44.1%) and appeared as a multinucleated giant cell reaction (27.9%) or a glomerular inflammatory infiltrate (25%), including glomerular crescents (17.6%). At the end of follow-up, 26 patients (38.2%) showed end-stage renal disease. The clinical presentation of glomerular and vascular forms was distinct with a clear predominance of proteinuria in glomerular form. Inflammatory reaction was preferentially observed in biopsies with a codeposition of immunoglobulin chains and/or complement factors in AA amyloid deposits. The distribution pattern of glomerular amyloid deposits and glomerular inflammatory reaction were independent factors influencing proteinuria level. Tubular atrophy, abundance, and distribution pattern of glomerular amyloid deposits at the time of biopsy were independent predictors of renal outcome. In conclusion, the glomerular involvement appeared as the determining histological factor for clinical manifestations and outcome of renal AA amyloidosis. AA amyloidosis-related inflammation could partly result from an immune response directed against AA fibrils and could induce amyloid resolution and crescents.

Background: The association of thrombotic events and/or pregnancy complications with circulating antiphospholipid antibodies defines antiphospholipid syndrome (APS). In previous reports, renal involvement in APS consisted mainly of thrombotic vascular complications involving large vessels or intrarenal small-sized vessels (APS nephropathy). We report 9 cases of glomerulonephritis associated with APS. These cases are characterized by predominant pathological features distinct from vascular APS nephropathy. Methods: We reviewed consecutive renal biopsies examined in 2 French university hospitals between 1980 and 2002 and identified renal biopsies performed in patients with primary APS. Results: We identified 29 biopsies performed in patients with APS. Twenty biopsies showed characteristic features of APS nephropathy. In 9 cases, predominant pathological features distinct from vascular APS nephropathy were noted: membranous nephropathy (3 cases), minimal change disease/focal segmental glomerulosclerosis (3 cases), mesangial C3 nephropathy (2 cases), and pauci-immune crescentic glomerulonephritis (1 case). In 7 cases, the presentation of renal symptoms was subacute or chronic. Two patients experienced episodes of acute renal failure. At referral, median creatinine clearance was 50 mL/min (0.83 mL/s) (range, 18 to 117 mL/min [0.30 to 1.95 mL/s]). Proteinuria was noted in all cases (range, 1.5 to 15 g/d), with nephrotic syndrome in 4 cases. Lupus anticoagulant was present in all cases, and anticardiolipin antibodies, in 8 cases. Anti-DNA antibodies repeatedly were negative in all cases. Treatment consisted of antihypertensive therapy (6 cases), anticoagulant drugs (5 cases), steroids (4 cases), and antiplatelet drugs (3 cases). At last follow-up, renal function remained stable in 7 patients. Of 2 patients presenting with acute renal failure, 1 patient recovered normal renal function, whereas the other patient progressed to end-stage renal failure. Conclusion: The cases reported here represent a new aspect of the expanding spectrum of renal diseases encountered in association with APS.

Background & Aims: In Crohn's disease, cases of interstitial nephritis with renal failure have been reported in connection with the use of mesalamine. Methods: We observed 4 patients with severe interstitial nephritis proven by examination of kidney biopsy specimens. Renal failure was discovered before or simultaneously with the diagnosis of Crohn's disease, and patients were not treated with mesalamine. Impairment of renal function progressed to end-stage renal failure in 3 of the 4 patients. Results: Our results show that the kidney can be an extraintestinal target of Crohn's disease. Conclusions: Several unanswered questions remain concerning the frequency of interstitial nephritis in patients with Crohn's disease, as well as the exact role of mesalamine in the development of chronic interstitial nephritis. GASTROENTEROLOGY 2002;123:1436-1440

Background: Idiopathic collapsing glomerulopathy (ICG) and HIV-associated nephropathy (HIV-AN) are characterized by severe nephrotic syndrome, collapse and sclerosis of the glomerular tuft with prominent podocyte alterations and extensive tubulointerstitial lesions. We previously showed phenotypic changes in podocytes from patients with diffuse mesangial sclerosis, a severe glomerulopathy sharing several morphological features with collapsing glomerulopathy. The aim of this study was to analyze the podocyte phenotype in ICG and HIV-AN. Methods: Using immunohistochemical techniques, we studied the podocyte expression of the transcription factor WT1 and its target PAX2, GLEPP1, synaptopodin and vimentin as markers of podocyte maturity and of proliferating cell nuclear antigen (PCNA) as a marker of proliferation. Apoptosis was analyzed by the TUNEL method. Results from renal biopsies of ICG and HIV-AN were compared with those obtained from normal kidney, minimal change nephrotic syndrome (MCNS), focal and segmental glomerulosclerosis (FSGS) and membranous glomerulonephritis (MGN). Results: Abnormal distribution of WT1 and PAX2 and extensive loss of podocyte markers were observed in ICG and HIV-AN; this dysregulation was associated with podocyte proliferation without detectable apoptosis. In contrast, no podocyte changes were detected in MCNS or MGN. In FSGS, phenotypic changes, without proliferation, were restricted to podocytes surrounding focal and segmental glomerular lesions. Increased PCNA expression and apoptosis were observed in ICG and HIV-AN tubular cells. Conclusion: Dysregulation of podocyte phenotype and proliferation are present in both ICG and HIV-AN. This suggests that, whatever their etiology, both types of collapsing glomerulopathy share a common pathogenic pathway. Upregulation of cell proliferation and apoptosis observed in tubular epithelial cells is probably involved in the occurrence of severe tubulointerstitial lesions in collapsing glomerulonephritis.

Renal complications of disseminated histoplasmosis include chronic recurrent abcesses of the interstitium and urogenital tract. To our knowledge, glomerulonephritis has never been reported in histoplasmosis. We describe a case of proven histoplasmosis presenting with oral granulomatous ulceration and segmental glomerulonephritis that mimicked Wegener's granulomatosis (WG). All symptoms and renal parameters remitted under itraconazole treatment alone. In conclusion, glomerulonephritis may complicate the course of chronic disseminated histoplasmosis. Since it can masquerade as WG, systematic tissue staining for intracellular microorganisms should be done when WG is suspected.

In the course of the antiphospholipid syndrome (APS), the existence of vaso-occlusive lesions capable of affecting numerous organs is now well established. The renal involvement attributable to primary APS, APS nephropathy (APSN), corresponds to vaso-occlusive lesions of the intrarenal vessels, associating side-by-side, acute thromboses with chronic arterial and arteriolar lesions, leading to zones of cortical ischemic atrophy. A retrospective study of 114 lupus patients undergoing renal biopsy was undertaken to determine the following: (1) if APSN can be found in the course of systemic lupus erythematosus (SLE); (2) if certain clinical and biologic factors can permit the prediction of the presence of APSN; and (3) if APSN is a superadded renal morbidity factor in lupus patients. This study shows the following: (1) APSN occurs in SLE (32% of patients with renal biopsies) in addition to, and independently of, lupus nephritis; (2) APSN is statistically associated with lupus anticoagulant but not with anticardiolipin antibodies; (3) APSN is associated with extrarenal APS, mainly arterial thromboses and obstetrical fetal loss, but not with the venous thromboses of APS; (4) APSN is an independent risk factor, over and above lupus nephritis, that contributes to an elevated prevalence of hypertension, elevated serum creatinine, and increased interstitial fibrosis. Thus, it seems likely that, because of its associations with hypertension, elevated serum creatinine, and increased interstitial fibrosis, APSN may worsen the prognosis in these patients. APSN may also have therapeutic significance in that its recognition should permit a better balance between immunosuppressor and antithrombotic and/or vasoprotective therapy. Finally, this study suggests that APSN should be considered as an element to be included in the classification criteria of APS.

Renal hyperplasia and hypertrophy are early events after nephron reduction which precede progressive destruction of the remnant kidney. Restriction of dietary sodium content was shown to reduce renal lesions following nephron reduction. AP-1 is a transcription factor, resulting from heterodimerization of fos and jun proteins, which mediates the effects of mitogenic growth factors. To elucidate the role of AP-1 in growth processes involved in renal deterioration, we evaluated whether restriction of dietary sodium content (0.25 vs. 0.50% sodium w/w) affected AP-1-DNA binding and hyperplasia in the remnant kidney after nephron reduction (70% nephrectomy). Cell proliferation, evaluated by PCNA immunostaining, increased progressively from day 7 to day 60 in glomeruli, proximal and distal tubules and loops of Henle of nephrectomized (Nx) rats compared to control sham-operated (C) animals. AP-1-DNA binding activity increased 7 and 14 days after surgery, but it was reduced below C values at day 60. c-fos and c-jun expression were also reduced in Nx rats at day 60. Sodium restriction significantly reduced the number of PCNA-stained cells in glomeruli and tubules at days 14 and 60, but not at day 7, whereas it decreased AP-1 activation at all times of the study. This effect was associated to a marked reduction of renal lesions in Nx rats. In conclusion, we showed that, after nephron reduction, the beneficial effect of sodium restriction was associated with a reduction of hyperplasia and AP-1 activation, but that the latter did not parallel delayed cell proliferation rate in remaining nephrons. Thus, we propose that different transduction pathways are involved in cell proliferation after nephron reduction, according to the time of evolution of renal lesions.

The objective of this study was to evaluate the renal tolerance of a new magnetic resonance contrast agent, AMI 25. This agent has an affinity for the reticuloendothelial system and is used for the detection of focal liver lesions. A combination of renal ischemia and intra-arterial iodinated contrast agent infusion (diatrizoate) leads to a reproducible and reversible model of acute renal failure in the rat. Using this model, AMI 25 was perfused directly into the aorta at the dose of 1 ml/kg--ten times the dose used in humans. AMI 25 induced no change in serum creatinine (45 +/- 7, 40 +/- 6, 40 +/- 9 mumol/L before infusion and at 24 and 48 hours, respectively), in creatinine clearance (2.1 +/- 0.6, 2.1 +/- 0.6, 2.1 +/- 0.6 mL/mn), or in urinary N-acetyl glucosaminidase (NAG) excretion (72 +/- 16, 98 +/- 12, 58 +/- 9.8 mumol hour-1/mmol creatinine). Blinded histologic analysis of 11 kidneys perfused with AMI 25 revealed no abnormalities, whereas diatrizoate induced acute tubular necrosis in four of the seven kidneys examined. In our animal model, AMI 25 has no nephrotoxicity, even at ten times the expected clinical dose for humans.

Records of 102 patients with biopsy-proven HIV-associated nephropathy (HIVAN) admitted to 18 hospitals in the Paris area from 1984 through 1996 were retrospectively reviewed. Demographics and clinical and laboratory features of the cohort were determined, and prognostic factors of renal and patient survival were analyzed. Renal and patient survival curves were estimated with the actuarial method. Prognostic factors were assessed by uni- and multidimensional analyses based on Cox regression models. Values were expressed as median with interquartile. The total population (median age 34) included 97% blacks and 71.5% males. Median patient follow-up was 165 d (range, 43 to 493). At the time of renal biopsy, median values of serum creatinine, proteinuria, and CD4+ cell count were 496 micromol/L, 6.5 g/24 h, and 48.5 cells/mm3, respectively. Fifteen patients were given steroids after the onset of HIVAN. Overall patient survival at 0.5, 1, and 3 yr was 73 +/- 5, 55 +/- 6, and 38 +/- 7%, respectively. The proportion of patients free of dialysis at 0.5, 1, and 3 yr was 73 +/- 5, 60 +/- 7, and 18 +/- 10%, respectively. Predictors of poor patient prognosis were a low CD4+ cell count (relative risk [RR; per 50 cells/mm3 decrease] 1.35; confidence interval [CI], 1.13 to 1.6) and antiretroviral therapy before the onset of HIVAN (RR 1.9; CI, 1.05 to 3.6). Main independent factors associated with better renal outcome were: steroid therapy (RR 0.29; CI, 0.1 to 0.9); low proteinuria level (RR [per 50% decrease] 0.7; CI, 0.5 to 0.98); low serum creatinine (RR [per 1.1 mg/dl decrease] 0.78; CI, 0.7 to 0.87); and hemoglobin level (RR [per g/dl increase] 0.76; CI, 0.58 to 1.00). HIVAN is not a rare nephropathy in Paris and its suburbs. Renal prognosis and patient survival are better than what was reported previously. Steroids may delay the downward course of HIVAN. It is not certain that in the new era of HIV therapy, the possible renal benefits of corticosteroids outweigh their potential risks. The only reliable predictor of patient survival is the intensity of immunodeficiency.

The purpose of this study was to determine the diagnostic value of ultrasmall particles of iron oxide (USPIO)-enhanced MR imaging at different concentrations to evaluate experimental nephropathy. This study was conducted in 23 uninephrectomized rats using a model of iodinated contrast media-induced renal failure. Eleven rats received selective intra-arterial renal administration of diatrizoate (370 mg I/ml) and were compared to two control groups, including five animals injected with isotonic saline and seven noninjected animals. MR imaging was performed 28 hours after the procedure, including T1- and T2-weighted images before and after intravenous administration of successively 5 mumol Fe/kg and 60 mumol/kg of USPIO. Results were interpreted qualitatively and quantitatively with respect to pathologic data, and differences were studied statistically. The maximal signal intensity decrease was noted in normal kidneys in cortex (-65 +/- 4%) and medulla (-84 +/- 5%) on T2-weighted images after injection of 60 mumol/kg of USPIO. At this dose, diseased kidneys displayed less signal intensity decrease than normal kidneys on T2-weighted images (p = .05). Moreover, qualitative analysis showed that the highest sensitivity and specificity to diagnose kidney involvement were obtained with T2-weighted MR images (75% and 91%, respectively) when 60 mumol/kg of USPIO were used (p < .01). USPIO should be useful for in vivo evaluation of the severity of experimentally induced iodinated contrast media renal impairment in animals.

A 56-year-old man with Sjogren's syndrome was found to have acute renal failure. Immunopathologic analysis of renal biopsy specimens showed polyclonal lymphocytic interstitial infiltration. DNA analysis of the T-cell receptor and the heavy chain immunoglobulin genes showed a polyclonal pattern of gene rearrangements. Renal failure caused by this pseudolymphoma regressed dramatically with steroid therapy. This is the first reported case of proven renal pseudolymphoma that regressed with steroid therapy.

Between November 1983 and December 1991, we undertook a systematic study of kidney in deceased AIDS patients using light and immunofluorescence microscopy. Among the 116 examined kidneys (from 106 men and 10 women), nine (7.75%) showed diffuse mesangial IgA deposits. By light microscopy, glomerular lesions were absent or moderate (mesangial hypertrophy or some mesangial deposits). Urinary abnormalities were mild in all cases. Our study shows that the association between IgA nephropathy and HIV infection is not rare, and a review of the literature disclosed 18 reported cases. Some reported immunopathogenic data support the possibility of a link between HIV infection and IgA nephropathy.

The long-term renal effects of cisplatin have been very poorly studied. Therefore we investigated the chronic renal effects of various doses of cisplatin in three groups of male Sprague-Dawley rats. Group I received two injections of 5 mg/kg body weight (bw) at 4-week intervals, group II four injections of 2.5 mg/kg bw at 4-weeks intervals, and group III one injection of 5 mg/kg bw and four injections of 2.5 mg/kg bw at 4-weeks intervals. Controls received an equivalent amount of isotonic saline. Each group was evaluated 1, 3, or 6 months after the last injection of cisplatin. One, 3 and 6 months after the last injection, cisplatin induced a marked decrease in glomerular filtration rate (GFR) evaluated as clearance of [99mTc]DTPA and creatinine clearance in all treated rats. Urinary NAG excretion remained unaltered. At 3 months post-cisplatin treatment GFR was significantly less (P < 0.05) in group III (0.18 +/- 0.02 ml/min/100 g bw) when compared with group I (0.23 +/- 0.02 ml/min/100 g bw) or II (0.23 +/- 0.04 ml/min/100 g bw). In group I GFR was similar 1 month (0.24 +/- 0.02), 3 months (0.23 +/- 0.02) and 6 months (0.23 +/- 0.03 ml/min/100 g bw) after cisplatin treatment. Cisplatin induced atrophy and dilatation of tubules with mononuclear cell infiltration associated with cyst formation. The glomerular and tubulointerstitial lesions were significantly enhanced in group III when compared with groups I and II. This study indicates that repeated administration of cisplatin may induce a chronic tubulointerstitial nephropathy associated with a marked decrease in GFR, which is stable over time. The incidence and severity of chronic cisplatin toxicity is dose-related and is not modified by dividing the dose.

We have retrospectively analyzed the incidence of diabetic nephropathy in 21 diabetic patients who underwent renal biopsy between 1985 and 1995 for microscopic hematuria and/or proteinuria >2.5 g/day without retinopathy. Diabetic nephropathy was observed in 13 of 21 patients (62%). 50% of our patients with diabetic nephropathy had hematuria, the incidence being higher in type I as compared with type II diabetic patients (30 vs. 20%). Diabetic nephropathy without retinopathy but with hematuria was noted in 5 of 13 patients, and diabetic nephropathy without retinopathy and hematuria was also noted in 5 of 13 patients. We suggest from our retrospective analysis that renal-retinal diabetic syndrome really exists.

To the Editor: We retrospectively studied the seasonal variations in microscopic polyarteritis (MPA) as established by renal biopsy and perinuclear antineutrophil cytoplasmic antibody (pANCA). Patients diagnosed between December 1985 and December 2001 were studied. The prevalence of MPA was estimated and patients were classified according to the American College of Rheumatology 1990 vasculitis criteria and the Chapel Hill Consensus definitions. The seasonal distribution was tested versus a uniform distribution using a goodness-of-fit chi-squared test1 (P < 0.05 considered significant). Sixty-one cases of MPA were collected. The overall annual incidence of MPA among the renal biopsy register was 1.52% (95% CI: 1.16–1.95; 36 men, 25 women; age, mean 64.1, median 65.5, 25th percentile 59.25, 75th percentile 70.25, range, 35–76). All patients had necrotizing glomerulonephritis on renal biopsy with evidence of small vessel vasculitis.

We report on 5 patients with antiphospholipid syndrome secondary to systemic lupus erythematosus, that developed malignant systemic hypertension and renal insufficiency due to unilateral renal artery lesion such as stenosis (n = 3) or thrombosis (n = 2), in absence of overt diffuse lupus nephritis.

We retrospectively analyzed the records of 5 patients with antiphospholipid syndrome, primary (n = 1) or secondary to systemic lupus erythematotus (n = 4), who developped a malignant systemic hypertension with renal insufficiency and biopsy-proven intra-renal vascular lesions, in the absence of lupus nephritis.