Favorable outcome of IgA nephropathy on antituberculous treatment.

We report the case of an association of IgA nephropathy and tuberculosis with superimposed vasculitis lesions on the renal biopsy. Three previous cases of the same association are discussed. The nephropathy had a favorable course in all of these cases on antituberculous treatment only. Tuberculosis is another infection related to IgA nephropathy.

[ANCA associated glomerulonephritis related to benzylthiouracil]. / Glomérulonéphrite associée aux ANCA secondaire au benzylthiouracile.

INTRODUCTION: Vasculitis associated with antineutrophil cytoplasmic antibodies (ANCA) have been reported in patients suffering from Graves' disease treated with anti-thyroid drugs and especially propylthiouracil (PTU). EXEGESIS: We report a case of Graves' disease treated with benzylthiouracil (Basdène). This therapy was complicated by acute renal insufficiency due to crescentic glomerulonephritis associated with pANCA. After benzylthiouracil withdrawal and under corticosteroids, renal insufficiency, biological inflammation and pANCA levels decreased. CONCLUSION: Similar vasculitis associated with pANCA secondary to anti-thyroid drugs, especially propylthiouracil, were described. This suggests a causal relation between drug and vasculitis. To our best knowledge, it is the first case of vasculitis secondary to benzylthiouracil.

[Low cost telepathology]. / Télépathologie à moindre coût.

Low cost, high-quality consumer-type digital cameras are now available on the market to be used for taking macrophotographs and microphotographs by simply fixing the camera over the eyepiece of a conventional light microscope using an adaptator. The quality of the images obtained is as good as obtained with more expensive materials using Tri CCD cameras. Using the JPEG format for compression, the image file size is approximately 180 Ko. We present a low cost approach we have tested for one year in our pathology department.

Retinopathy, hematuria, and diabetic nephropathy.

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.

Amyloid goiter as the initial manifestation of systemic amyloidosis due to familial mediterranean fever with homozygous MEFV mutation.

We describe a case of amyloid goiter revealing a systemic amyloidosis secondary to familial Mediterranean fever (FMF) with homozygous MEFV mutation, and we review the literature. A 45-year-old euthyroid Sephardic man, known to suffer from FMF, developed a goiter with cold nodule, after which a subtotal thyroidectomy was performed. Histologic evaluation revealed diffuse AA amyloid deposition without any associated thyroid neoplasia. At that time, no other organ was found to be affected by amyloidosis. Colchicine and levothyroxine were prescribed. Eight years later, the patient presented with a rapidly growing neck enlargement. He reported that he had discontinued colchicine therapy 2 years earlier. The serum thyrotropin (TSH) and calcitonin levels were normal. Renal, digestive, and salivary gland biopsies confirmed the presence of systemic AA amyloidosis. Despite the reintroduction of colchicine, the onset of compressive symptoms led to the completion of the total thyroidectomy. The histopathology again demonstrated amyloid deposition, and excluded a malignant neoplasm. Nine cases of amyloid goiter associated with FMF have been reported in the literature; none of them had an amyloid goiter as the first manifestation of systemic amyloidosis. To our knowledge, this is the first case of FMF in which an amyloid goiter preceded the development of secondary systemic amyloidosis. The cessation of colchicine therapy may have played a role in local relapse and the secondary spread of amyloid deposits.

Pregnancy in past or present lupus nephritis: a study of 32 pregnancies from a single centre.

OBJECTIVE: To study maternal and fetal outcome in women with past or present histologically proven systemic lupus erythematosus (SLE) nephritis. METHOD: Retrospective study of 32 pregnancies in 22 women with past or present histologically proven SLE nephritis in a single French centre. RESULTS: Pregnancy (25 planned and 7 not planned) occurred in a mean (SD) of 8 (5) years after SLE diagnosis and 6 (4) years after renal disease onset. Seven occurred in women with antiphospholipid syndrome. At pregnancy onset, all but one woman had creatininaemia below 100 micromol/l, five had proteinuria >0.5 g/day, none had hypertension. Twelve pregnancies occurred in women previously treated with immunosuppressant drugs. Treatment comprised prednisone (n=31), hydroxychloroquine (n=11), aspirin (n=22), heparin (n=12), and azathioprine in one patient with steroid resistant nephrotic syndrome disclosing SLE. No therapeutic abortion was done. During pregnancy or the postpartum period, or both, proteinuria >0.5 g/day occurred in 10 women (five related to pre-eclampsia, four to renal flare, one to stable nephrotic syndrome). One flare consisted of mild arthralgias. Pregnancy outcome comprised one feto-maternal death in SLE disclosed by pregnancy, five embryonic losses, two fetal deaths, and 18 premature (one neonatal death) and six full term births. No criterion appeared to influence fetal survival significantly. At long term, one patient died during an SLE flare, three women had renal relapses. At the last visit, all had creatininaemia below 100 micromol/l except one woman with creatinine level 115 micromol/l, nine had proteinuria >0.5 g/day, and one was treated for hypertension. CONCLUSION: Pregnancy need not be discouraged in women with a history of SLE nephritis with normal or mildly impaired renal function. Deterioration of renal function rarely occurs. However, these pregnancies are at high risk of pre-eclampsia and prematurity.

Erythropoietin enhances recovery after cisplatin-induced acute renal failure in the rat.

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.

Hemolytic and uremic syndrome after heart transplantation.

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.

Reversibility of experimental acute renal failure in rats: assessment with USPIO-enhanced MR imaging.

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 micromol 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.

Transjugular versus percutaneous renal biopsy for the diagnosis of parenchymal disease: comparison of sampling effectiveness and complications.

PURPOSE: To compare the effectiveness and safety of transjugular renal biopsy with those of percutaneous renal biopsy for diagnosis of renal parenchymal disease. MATERIALS AND METHODS: Results and complications of 400 consecutive transjugular renal biopsies performed between 1993 and 1998 with a modified Colapinto transjugular hepatic biopsy system were compared retrospectively with those of 400 percutaneous renal biopsies performed during the same period. Transjugular renal biopsy was associated with 14 cardiac and 35 hepatic biopsies. Number of glomeruli per tissue core, adequacy of tissue core for histopathologic diagnosis, and rate and severity of complications were analyzed. RESULTS: Renal tissue was obtained with percutaneous renal biopsy in 382 (95.5%) of 400 patients and with transjugular renal biopsy in 383 (95.8%) of 400 patients. The mean numbers of intact glomeruli per tissue core with optical microscopy were 11.2 +/- 7.7 (SD) and 9.8 +/- 7.6 for percutaneous renal biopsy and transjugular renal biopsy, respectively. With immunofluorescent microscopy, the mean numbers were 6.4 +/- 5.3 and 4.6 +/- 4.6 for percutaneous renal biopsy and transjugular renal biopsy, respectively. Tissue cores were adequate for histopathologic diagnosis in 98.2% with both techniques. Major complications occurred with transjugular renal biopsy in four patients and with percutaneous renal biopsy in three patients. CONCLUSION: Use of transjugular renal biopsy provides diagnostic yield and safety similar to those of percutaneous renal biopsy and allows multiorgan biopsy during the same procedure. It can be recommended in patients with percutaneous renal biopsy contraindication or failure.

Sodium restriction decreases AP-1 activation after nephron reduction in the rat: role in the progression of renal lesions.

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.

Retroperitoneal fibrosis and membranous nephropathy.

We report on a patient with a past history of Pott's abscess who suffered both from a retroperitoneal fibrosis and a membranous glomerulonephritis. Five cases of retroperitoneal fibrosis and immune complex glomerulonephritis are already reported in the literature. These associations might result from a particular systemic immune response to an unknown antigen. Consequently, we consider the role of tuberculosis in our case.

Renal involvement in systemic lupus erythematosus. A study of 180 patients from a single center.

Charts of 180 patients (147 women, 33 men) with systemic lupus erythematosus (SLE) complicated by renal involvement were retrospectively analyzed from a series of 436 patients. Mean age at renal disease onset was 27 years. Thirty-six percent of the patients had renal involvement after diagnosis of lupus, for 30.7% of that group it was more than 5 years later. Renal involvement occurred more frequently in young male patients of non-French non-white origin. Patients with renal involvement suffered more commonly from malar rash, psychosis, myocarditis, pericarditis, lymphadenopathy, and hypertension. Anemia, low serum complement, and raised anti-dsDNA antibodies were more frequent. According to the 1982 World Health Organization classification, histologic examination of initial renal biopsy specimen in 158 patients showed normal kidney in 1.5% of cases, mesangial in 22%, focal proliferative in 22%, diffuse proliferative in 27%, membranous in 20%, chronic sclerosing glomerulonephritis in 1%, and other forms of nephritis in 6.5%. Distribution of initial glomerulonephritis patterns was similar whether renal involvement occurred before or after the diagnosis of lupus. Transformation from 1 histologic pattern to another was observed in more than half of the analyzable patients (those who underwent at least 2 renal biopsies). Nephritis evolved toward end-stage renal disease in 14 patients despite the combined use of steroids and cyclophosphamide in 12. Initial elevated serum creatinine levels, initial hypertension, non-French non-white origin, and proliferative lesions on the initial renal biopsy were indicators of poor renal outcome. Twenty-four patients died after a mean follow-up of 109 months from SLE diagnosis. Among our 436 patients, the 10-year survival rate was not significantly affected by the presence or absence of renal involvement at diagnosis (89% and 92%, respectively).

The intrarenal vascular lesions associated with primary antiphospholipid syndrome.

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.

HIV-associated nephropathy: outcome and prognosis factors. Groupe d' Etudes Néphrologiques d'Ile de France.

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.

[Reversible nephrotic syndrome in Crohn's disease complicated with renal amyloidosis]. / Syndrome néphrotique réversible au cours d'une maladie de Crohn compliquée d'amylose rénale.

A 24-year-old woman suffered from ano-rectal Crohn's disease and nephrotic syndrome due to glomerular amyloidosis AA. She received azathioprine and colchicine for two years. Both Crohn's disease and nephrotic syndrome resolved. However amyloid renal lesions were still present. This course is exceptional, and leads to a discussion of the treatment of amyloidosis associated with Crohn's disease.