[Experience about more than 2000 renal transplantations at the university of Brussels]. / A propos de 2000 greffes rénales a l'U.L.B.: le parcours d'un patient transplanté rénal en 2007.

Since 1965, more than 2000 renal transplantations (including more than 100 living-donor transplantations) have been performed at the University of Brussels. An end-stage renal disease patient candidate to renal transplantation will be therefore followed from his enrolment on the waiting list to the long-term post-transplant period. Improvement in the outcome of renal transplantation is achieved due to better knowledge in many fields of medicine, such as immunology, infectious disease, metabolic diseases (hyperlipemia, diabetes mellitus), pharmacology, use of immunosuppressive regimen, a more adequate cardiovascular prevention and treatment. If the best results were achieved with kidneys from living donors, the graft survival rate at the University of Brussels was nearly 80% for the last period (2000-2006). Unfortunately, renal transplantation cannot cure certain comorbid conditions and even may promote them: infectious diseases, neoplasia, metabolic disorders (e.a diabetes mellitus, hyperlipemia). Many efforts have to be done to develop less toxic and more immune selective therapeutic strategies. Living donation and extension of the pool of cadaveric donors will reduce the length of time spent on the waiting list and will significantly impact on mortality and morbidity after kidney transplantation.

High-pressure injection injuries to the hand.

High-pressure injection injury hides the true extent of the lesions behind an apparent small and harmless puncture of the finger or the hand. Through clinical description, we wish to point out the need for prompt treatment to avoid mutilating and function-threatening complications. We wish to outline the role of the emergency physician who must be aware of the incidence of high-pressure injection injury and become accustomed to early referral to a surgeon, experienced in extensive surgical exploration, removal of foreign bodies, and rehabilitation. The open-wound technique gives the best results. We also point out that failure to refer may become an increasing focus of negligence claims.

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.

[Herbal remedies and nephrotoxicity]. / Phytotherapie et nephrotoxicite.

Numerous substances from vegetal origin used as herbal remedies can be nephrotoxic. This article summarizes several circumstances of development of acute or chronic renal failure in which the responsible agent has been identified after a thorough toxicologic study. The Chinese herbs nephropathy is extensively described, detailing not only the epidemiological and histological aspects but also the extrarenal and neoplastic complications recently reported.

Proximal tubular injury in Chinese herbs nephropathy: monitoring by neutral endopeptidase enzymuria.

Neutral endopeptidase (NEP) is a 94 kDa ectoenzyme of the proximal tubule brush border, physiologically released into the urine with apical membrane fragments. As proximal tubular atrophy was a histological hallmark of Chinese herbs nephropathy (CHN), this study firstly determined renal excretion of NEP in healthy control subjects (N = 31), in patients with CHN (N = 26) and in women having consumed Chinese herbs and whose renal function was normal but running the risk of developing CHN (N = 27). Another patient group consisted of female patients with glomerular diseases (N = 12). At the same time, measurements of urinary microproteins (Clara cell protein, retinol binding protein, beta 2-microglobulin and alpha 1-microglobulin) were performed, as indicators of tubular dysfunction. Cell damage was estimated by the excretion of N-acetyl-beta-D-glucosaminidase (NAG). In the control group, the physiological NEP enzymuria was 43.1 micrograms/24 hr (geometric mean). In CHN patients, levels of urinary NEP were significantly decreased in those with moderate renal failure (26.7 micrograms/24 hr; N = 21; P < 0.05) and almost abolished in end-stage renal failure patients (4.35 micrograms/24 hr; N = 5; P < 0.05). In patients at risk as well as in patients with glomerular diseases, urinary NEP levels were not statistically different from those observed in control subjects (40.68 micrograms/24 hr and 48.5 micrograms/24 hr, respectively). Several degrees of tubular dysfunction and injury were noted in patients groups, as attested by increased urinary microproteins and NAG excretions. Considering the data from control and CHN patients, NEP enzymuria positively correlated with individual creatinine clearance values (r = 0.76; P = 0.0001) and negatively correlated with urinary microproteins levels (r = -0.55; P = 0.00001). Finally, NEP was regularly quantitated in the urine of 6 CHN patients for a period ranging from six months to two years and in 19 patients at risk during two years, respectively. In the first group, renal function progressively deteriorated in 3 patients, leading them to renal replacement therapy after 38 to 115 weeks. Stable parameters were observed in the remaining 3 patients. A direct correlation between creatinine clearance and NEP excretion was found longitudinally in each case. In the second group, no significant change of urinary NEP levels was observed (45.9 micrograms/24 hr), in parallel with stable renal function. Taken together, these results indicate that, in CHN patients, NEP enzymuria provides a rapid and noninvasive determination of the degree of structural impairment affecting the proximal tubular population and further reflecting the severity of the renal disease. The interest of this urinary marker in monitoring the progression of other tubulointerstitial diseases remains to be assessed.

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.

Prevention of OKT3 nephrotoxicity after kidney transplantation.

In our experience the use of OKT3 as prophylaxis in renal transplantation has been associated with an increased incidence of both delayed graft function and thromboses of graft vessels. OKT3 nephrotoxicity might have been favored by restriction of perioperative fluid infusion to prevent pulmonary edema and by the use of very high dose (30 mg/kg) of methylprednisolone (mPDS) before the first OKT3 injection to reduce the release of cytokines. This led us to modify our perioperative management in three ways: (1) hydration status was optimalized; (2) the calcium-channel blocker diltiazem, considered beneficial for recovery of graft function, was administered on the day of transplantation; and (3) the dose of mPDS given before the first OKT3 injection was fixed at 8 mg/kg. Comparison of two consecutive series of patients (group 1, control patients, N = 172; group 2, managed as described above, N = 173) showed that: (1) the incidence of delayed graft function fell from 52% in group 1 to 22% in group 2 (P < 0.0001): (2) the incidence of pulmonary edema was not significantly increased in group 2 (3.5% vs. 1.7% in group 1, P = 0.5); and (3) the frequency of intragraft thrombosis fell from 7.6% in group 1 to 1.2% in group 2 (P = 0.0034). Multivariate analysis showed that the volemia/diltiazem program and avoidance of high mPDS dose were the most important factors responsible for the reduced occurrence of delayed graft function and graft vessels thrombosis, respectively. We conclude that a combined strategy of appropriate dosage of steroids before the first OKT3 injection, administration of a calcium-channel blocker and optimalization of volemia is safe and efficiently prevents against OKT3 nephrotoxic effects.

Effects of N-acetylcysteine in endotoxic shock.

PURPOSE: The release of oxygen-free radicals has been implicated in both peripheral vascular and myocardial alterations of septic shock. N-Acetylcysteine (N-AC), a substrate for the production of glutathione, has potent antioxidant effects. As a nitrosothiol, it may also improve capillary blood flow. We studied the effects of N-AC in a dog model of endotoxic shock. METHODS: Ten pentobarbital-anesthetized, mechanically ventilated dogs were randomly assigned to receive either N-AC (150 mg/kg loading dose in 1 hour, followed by 20 mg/kg.h maintenance dose) or D5W. After the loading dose, each dog received 3 mg/kg Escherichia coli endotoxin intravenously. After 30 minutes, saline infusion was started to restore and maintain baseline filling pressures. RESULTS: The loading dose of N-AC increased DO2 significantly (from 661 +/- 54 to 914 +/- 190 mL/min, P < .05), but VO2 remained stable. After the administration of endotoxin, fluid challenge restored cardiac output to baseline, in both groups. Hemoglobin and, thus, DO2 were slightly lower in the N-AC-treated dogs, but VO2 was similar in both groups. At the end of the study, O2ER was significantly higher in the N-AC-treated dogs than in the control dogs. Blood lactate levels fell more rapidly in the N-AC dogs than in the control dogs. Blood lactate levels returned to normal in the N-AC dogs but not in the control dogs. Tumor necrosis factor (TNF) also decreased significantly in the N-AC dogs but remained elevated in the control dogs. CONCLUSION: These data indicate that N-AC administration in endotoxic shock is well tolerated, may increase oxygen availability to the tissues, and is associated with an attenuation of TNF release.

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 Bowman's 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.

Mediastinitis caused by Aspergillus fumigatus with ruptured aortic pseudoaneurysm in a heart transplant recipient: case study.

The case of a heart transplant recipient with a ruptured aortic pseudoaneurysm caused by an Aspergillus fumigatus mediastinitis is reported. Contamination of surgical fields occurring by air seeding during surgery appears to be the most probable source of infection. Subtle infectious signs of the wound and subacute course are remarkable features of this case.

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.

Influence of the endothelium on the responses to endogenous agonists in human internal mammary and gastroepiploic arteries.

The higher patency rate of internal mammary artery grafts compared to venous grafts has been ascribed to its endothelial function, namely a greater capacity to release endothelium-derived relaxing factor and to inhibit serotonin-induced contractions. Gastroepiploic and mammary arteries were obtained intraoperatively from 27 patients and suspended in organ chambers to record isometric tension. The relaxations to acetylcholine were similar in both vessels. The contractions to serotonin, normalized as a per cent of KCl (90 mM)-induced contractions, were 46 +/- 15% for the internal mammary artery and 18 +/- 5% for the gastroepiploic artery. Endothelium removal equally potentiated the responses to serotonin: the maximal responses (% of KCl) increased to 63 +/- 18% and 41 +/- 6%, respectively. The contractions to endothelin were also higher in the internal mammary artery: 166 +/- 19% vs 102 +/- 6% of KCl (p < 0.05), but were not affected by endothelium removal. However, the capacity to contract, expressed in tension developed, was higher in the gastroepiploic artery: the KCl (90 mM)-induced contraction was 2.6 +/- 0.3 g in the internal mammary vs 7.9 +/- 0.9 g in the gastroepiploic artery (p < 0.001). Histologically, similar wall thickness and paucity of atherosclerotic lesions were observed, but the medium was mainly elastic in the internal mammary and muscular in the gastroepiploic artery. Thus, despite a similar endothelial function and greater responsiveness of the mammary artery to endogenous vasoconstrictors when compared to a receptor-independent vasoconstrictor, the higher contractile capacity of the gastroepiploic artery might be a disadvantage in terms of graft function and patency.

Tumour-like presentation of pulmonary sarcoidosis.

We report a case of pulmonary sarcoidosis, which initially presented as a left apical infiltrate. The later course mimicked a pulmonary neoplasm, with left upper lobe atelectasis secondary to bronchial stenosis, resulting from both endobronchial sarcoidosis and extrinsic compression by enlarged lymph nodes. Extrinsic pressure from sarcoid nodes on the left main pulmonary artery and recurrent laryngeal nerve, also caused a reduction in pulmonary parenchymal perfusion and left vocal cord paresis.

Venous thromboangiitis associated with regional enteritis.

Thromboembolic complications occurring in patients with Crohn's disease are increasingly reported and are associated with a high mortality. The mechanism by which the thrombogenic process occurs is unclear. As recent findings suggest that Crohn's disease is a chronic vasculitis with multifocal gastrointestinal infarctions secondary to an imbalance of the cellular hemostatic pathway, extradigestive thrombotic complications might be mediated by the same vascular immune reaction. We report an unusual case of recurrent venous thrombosis associated with regional enteritis, the main point of interest being two-fold: first, this case provides a morphological evidence for an angiitic process as the cause of extradigestive thrombosis; second, the gastrointestinal disease remained subclinical for more than four years although the patient developed major venous thrombotic complications.

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.