Michel Depierreux

Rapidly progressive interstitial renal fibrosis in young women: association with slimming regimen including Chinese herbs

Two similar cases of rapidly progressive fibrosing interstitial nephritis in young women who followed the same slimming regimen prompted us to conduct an epidemiological survey of the nephrology centres of Brussels and to further investigate the exact nature of this slimming treatment. Seven other women under the age of 50 in terminal or preterminal renal failure were admitted for dialysis in 1991 and 1992. They had all followed a slimming regimen in the same medical clinic. Renal biopsy samples in eight of the nine cases showed extensive interstitial fibrosis without glomerular lesions. Two of the patients were seen for the first time in terminal renal failure and were started immediately on dialysis. For the seven other women, the nephropathy was characterised by a rapid deterioration in renal function, with initial serum creatinine doubling within about 3 months. The clinic had specialised in slimming treatments for the previous 15 years without any problems. In May, 1990, therapy was changed, with the introduction of two Chinese herbs (Stephania tetrandra and Magnolia officinalis). In June, 1992, three of twenty-five randomly selected women who had followed the same regimen during at least 3 months from 1990 had impaired renal function. Chemical analysis of some brands of these Chinese herbs did not show nephrotoxic contaminants of fungal or plant origin (ochratoxin or aristolochic acid) or adulteration by diuretics or antiinflammatory drugs. However, the medicinal preparation of the capsules taken by patients had different alkaloid profiles from those expected in Chinese plants. The striking relation between a specific type of fibrosing interstitial nephritis in young women and a slimming treatment involving Chinese herbs adds support to the arguments against uncontrolled therapy with herbal preparations.

Urothelial carcinoma associated with the use of a Chinese herb (Aristolochia Fangchi)

BACKGROUND Chinese-herb nephropathy is a progressive form of renal fibrosis that develops in some patients who take weight-reducing pills containing Chinese herbs. Because of a manufacturing error, one of the herbs in these pills (Stephania tetrandra) was inadvertently replaced by Aristolochia fangchi, which is nephrotoxic and carcinogenic. METHODS The diagnosis of a neoplastic lesion in the native urinary tract of a renal-transplant recipient who had Chinese-herb nephropathy prompted us to propose regular cystoscopic examinations and the prophylactic removal of the native kidneys and ureters in all our patients with end-stage Chinese-herb nephropathy who were being treated with either transplantation or dialysis. Surgical specimens were examined histologically and analyzed for the presence of DNA adducts formed by aristolochic acid. All prescriptions written for Chinese-herb weight-reducing compounds during the period of exposure (1990 to 1992) in these patients were obtained, and the cumulative doses were calculated. RESULTS Among 39 patients who agreed to undergo prophylactic surgery, there were 18 cases of urothelial carcinoma (prevalence, 46 percent; 95 percent confidence interval, 29 to 62 percent): 17 cases of carcinoma of the ureter, renal pelvis, or both and 1 papillary bladder tumor. Nineteen of the remaining patients had mild-to-moderate urothelial dysplasia, and two had normal urothelium. All tissue samples analyzed contained aristolochic acid-related DNA adducts. The cumulative dose of aristolochia was a significant risk factor for urothelial carcinoma, with total doses of more than 200 g associated with a higher risk of urothelial carcinoma. CONCLUSIONS The prevalence of urothelial carcinoma among patients with end-stage Chinese-herb nephropathy (caused by aristolochia species) is a high.

Pathologic Aspects of a Newly Described Nephropathy Related to the Prolonged Use of Chinese Herbs

A new cause of chronic interstitial fibrosis of the kidney, recently identified in Belgium, was found to be related to a slimming regimen that included Chinese herbs. Thirty-three biopsy-proven cases of this nephropathy are discussed, with special reference to the pathologic aspects. Extensive interstitial fibrosis with atrophy and loss of the tubules was the major lesion; it was predominantly located in the superficial cortex. The glomeruli were relatively spared. They nevertheless showed a mild collapse of the capillaries and wrinkling of the basement membrane. Thickening of Bowmans capsule was the rule. Interlobular and afferent arterioles showed thickening of their walls due to swelling of the endothelial cells. These aspects suggest that the primary lesions could be located in the vessel walls, leading to ischemia and interstitial fibrosis. On the other hand, they are characteristic enough to allow the pathologist to suspect the diagnosis even in the absence of an anamnesis of ingestion of Chinese herbs.

Computerized Analysis of Smooth Muscle Fibers in Potent and Impotent Patients

Reduction or dysfunction of the intracavernous smooth muscle fibers can provoke impotence. Computerized digital image analysis of corpus cavernosum biopsies was performed in potent and impotent patients to quantify the percentage of smooth muscle fibers. In 5 normal patients the smooth muscle area represented 40 to 52% of the specimen, in 20 patients with cavernous dysfunction it was 10 to 36% and in 10 patients with arterial disease it was 13 to 25%. This method appears to be important to understand better certain mechanisms of impotence and to approach the potential treatment.

Effects of steroids on the progression of renal failure in chronic interstitial renal fibrosis: A pilot study in Chinese herbs nephropathy

Chinese herbs nephropathy is characterized by an extensive interstitial fibrosis and by a rapid evolution to end-stage renal failure. We thus decided to try steroid therapy (prednisolone 1 mg/kg for 1 month, tapered off 0.1 mg/kg every 2 weeks) in cases with moderate renal failure and evidence of deterioration in renal function. Our steroid group (SG) consisted of 12 female patients with biopsy-proven renal fibrosis who were followed for at least 12 months after the initiation of steroids. Plasma creatinine level (Pcreat) ranged from 1.8 to 3.9 mg/dL (mean +/- SEM, 2.8 +/- 0.2 mg/dL) when steroids were initiated at t = 0. Renal failure was in progression since Pcreat was 2.1 +/- 0.1 mg/dL (P = 0.022) 3 months before t = 0. Our control group (CG; N = 23) was selected retrospectively from among the 81 patients in the Belgian Register of Chinese Herbs Nephropathy. Compared with the CG, renal function was better preserved in the SG (Pcreat; mean +/- SEM): SG v CG, 2.9 +/- 0.3 mg/dL v 5.3 +/- 0.5 mg/dL at 6 months (P = 0.0024) and 4.0 +/- 0.7 mg/dL v 7.1 +/- 0.5 mg/dL at 1 year (P = 0.001). The slope of the reciprocal serum creatinine concentration was similar in both groups before t = 0 (-0.0463 mg/dL/mo in the SG v -0.0438 mg/dL/mo in the CG; P = 0.83), but it became less steep after initiation of steroid therapy (between 0 and 6 months, -0.000742 mg/dL/mo in the SG v -0.0284 mg/dL/mo in the CG; P < 0.001). Finally, only two of the 12 patients in the SG required dialysis at 1 year compared with 16 of the 23 patients in the CG (P = 0.0045). We conclude that steroid therapy slows the progression of renal failure in a disease characterized by an interstitial fibrosis that progresses quickly despite the fact that the insulting agent has been withdrawn. This supports the hypothesis that renal interstitial fibrosis may be an immune-mediated process.

Failure of two subsequent renal grafts by anti-GBM glomerulonephritis in Alport's syndrome: case report and review of the literature

Abstract. We describe a patient with Alports syndrome who developed severe crescentic glomerulonephritis after each of two successive transplantations, leading to accelerated graft failure on both occasions. This complication occurred in the 7th postoperative month for the first transplant and in the immediate postoperative period for the second. Immunopathological studies of the second transplant demonstrated that the glomerular lesions were mediated by antiglornerular basement membrane (GBM) antibodies displaying the same pattern of reactivity as the MCA‐P1 monoclonal antibody directed against the Goodpasture antigen. This observation indicates that the anti‐GBM immunization induced by renal transplantation in some patients with Alports syndrome may be responsible for recurrent graft failure.

Neurotensin high affinity binding sites and endopeptidase 24.11 are present respectively in the meningothelial and in the fibroblastic components of human meningiomas

The presence of neurotensin receptors and endopeptidase 24.11 (E-24.11) in 16 human meningioma specimens, obtained at surgery, was assessed by measuring the binding of 125I-[tyrosyl3]neurotensin(1-13) (125I-NT) and the inhibitor 3H-N(2RS)-3-hydroxyaminocarbonyl-2-benzyl-1-oxopropyl)glycine (3H-HACBO-Gly), for the receptor and enzyme, respectively. E-24.11 activity was also measured. Autoradiography, on the 16 meningiomas, showed that specific 125I-NT labeling (nonspecific labeling was assessed in the presence of excess NT) was exclusively located in the meningothelial regions. In contrast, specific 3H-HACBO-Gly labeling (nonspecific labeling was assessed in the presence of an excess of the E-24.11 inhibitor thiorphan) was exclusively found in fibroblastic regions. No specific labeling of either ligand was found on collagen or blood vessels. In vitro binding assays were performed on membranes of 10 of the 16 meningiomas. In the 4 meningiomas rich in meningothelial cells, 125I-NT specifically bound to one population of sites with Bmax ranging from 57 to 405 fmol/mg protein and Kd around 0.3 nM. These sites share common properties with the brain NT receptor, since the carboxy terminal acetyl NT(8-13) fragment bound to the same sites but with a higher affinity. The carboxy terminal analogue of NT, neuromedin N, also bound to the same sites with a 10-fold lower affinity and the sites were bradykinin and levocabastine insensitive. In the 4 meningiomas rich in fibroblastic cells, 3H-HACBO-Gly specifically bound to one population of sites with Bmax ranging from 251 to 739 fmol/mg protein and Kd around 2.8 nM.(ABSTRACT TRUNCATED AT 250 WORDS)

Neuropeptide Y, somatostatin, and cholecystokinin neurone preservation in anaplastic astrocytomas.

SummaryUsing immunohistochemistry, well-preserved neuronal cell bodies and fibres containing neuropeptide Y, somatostatin, and cholecystokinin immunoreactivity have been identified in all seven supratentorial anaplastic astrocytomas studied. These neurones have been shown not only on the edge but also in the depth of the neoplastic tissue. These neuropeptides were not present in 18 other intracranial tumours (3 astrocytomas, 1 subependymoma, 8 glioblastoma multiformes, 1 meningioma, and 5 metastases). In all 25 intracranial tumours studied, no immunoreactivity was found for vasoactive intestinal polypeptide, substance P, methionine-enkephalin, leucine-enkephalin, synenkephalin, neurophysin I-II, and corticotropin releasing factor.

Nephrotic syndrome and renal failure as an unusual presentation of solid tumour.

Glomerular diseases may occur as primary manifestation of cancer, especially in patients older than 60 years. Among glomerulopathies, membranous nephropathy is preferentially associated with respiratory and gastrointestinal tract adenocarcinomas, whereas minimal change disease is most often seen in haematological malignancies. Though breast cancer is one of the most frequent malignancies in women, paraneoplastic glomerular disease is rarely observed. We describe the case of a 79-year-old female patient who presented with nephrotic syndrome and renal failure. Breast cancer was found. Pathological studies of kidney and breast biopsy revealed a minimal change disease and an infiltrating ductal carcinoma, respectively.