Biomedical subjects
M Jadoul
Publications and source records attributed to M Jadoul.
Prevalence of histological beta2-microglobulin amyloidosis in CAPD patients compared with hemodialysis patients.
BACKGROUND: The prevalence of beta2-microglobulin amyloidosis (Abeta2m) in patients on continuous ambulatory peritoneal dialysis (CAPD) is unknown. METHODS: We prospectively obtained a median of 2 (range 1 to 4) joint samples from 26 CAPD patients aged 44 to 93 (median 73) years at post-mortem evaluation after 4.5 to 126 (median 27) months solely on CAPD (N = 19) or primarily on CAPD (that is, < or = 10% and < or = 1 year of renal replacement therapy time on other modalities; N = 7). The diagnosis of Abeta2m rested on Congo red staining (typical birefringence) and positive immunostaining of amyloid deposits by a monoclonal anti-beta2m antibody. RESULTS: Abeta2m was diagnosed in 8 of 26 patients (31%). Prevalence ranged from 20% (2 of 10 patients) within < or = 24 months CAPD to 30% (3 of 10 patients) after 24 to 48 months and 50% (3 of 6 patients) after 49 to 126 months (P = 0.11). The prevalence of Abeta2m was similar in patients without or with one or more peritonitis episodes. No significant difference in prevalence (P = 0.118) was found between CAPD patients (8+/26; 31%) and hemodialysis patients (13+/26; 50%) carefully matched for time on dialysis and age at the onset of dialysis. CONCLUSIONS: The prevalence of histological Abeta2m reaches 31% after a median duration of 27 months of CAPD. This prevalence is not significantly different from that observed in a group of HD patients matched for age and dialysis duration.
Dialysis-related amyloidosis: importance of biocompatibility and age.
The histological prevalence of dialysis-related amyloidosis (DRA) is much greater than suspected on clinical grounds: one-third of patients are affected after less than 4 years on haemodialysis (HD) and over 90% after more than 7 years HD. Risk factors include the time on dialysis, the type of HD membrane, and the age of the patient at onset of dialysis. The protective effect of high-flux membranes such as AN69 probably results mainly from the greater clearance of beta2-microglobulin. Other potential but more controversial explanations include a protective influence on residual renal function, a lower stimulation of beta2-microglobulin synthesis or release, or a beneficial influence on advanced glycosylation end (AGE) products. The higher risk of DRA in older patients has recently been suggested to result from an age-related AGE-modification of osteoarticular collagen. The best prevention and treatment of DRA is successful renal transplantation. In patients unsuitable for transplantation, high flux membranes such as AN69 should be used from the start of dialysis. Palliative treatment includes analgesics, low dose prednisone in severe cases, and surgical treatment of complications.
Universal precautions prevent hepatitis C virus transmission: a 54 month follow-up of the Belgian Multicenter Study. The Universitaires Cliniques St-Luc (UCL) Collaborative Group.
The isolation of anti-hepatitis C virus (HCV) in hemodialyzed (HD) patients has been repeatedly advocated to prevent nosocomial HCV transmission. We evaluated the incidence of seroconversion for HCV in Belgian HD patients, and demonstrate the complete prevention of HCV transmission by adherence to the universal precautions advocated by the Centers for Disease Control (Atlanta, GA, USA). All (N = 963) HD patients from 15 units, none of which isolates anti-HCV positive patients, were tested by a second or third generation enzyme-linked immunosorbent assay (with confirmation by a second- or third-generation recombinant immunoblot assay or the polymerase chain reaction) every 18 months from May 1991 to November 1995. Follow-up was available in 488 patients (drop-outs resulting from death or transplantation mainly). The yearly incidence of seroconversion for HCV over the initial 18 months was 1.41%, with evidence suggestive of nosocomial HCV transmission. Universal precautions were therefore reinforced. The incidence of seroconversion subsequently fell to 0.56% and 0%, respectively (P = 0.014), despite the facts that the average transfusion load and the proportion of patients with dialyzer reuse or with monitors disinfected after each session did not change significantly. We conclude that the strict enforcement of universal precautions fully prevents HCV transmission to HD patients. The isolation of anti-HCV positive patients is not warranted.
Accumulation of carbonyls accelerates the formation of pentosidine, an advanced glycation end product: carbonyl stress in uremia.
Advanced glycation end product (AGE) formation is related to hyperglycemia in diabetes but not in uremia, because plasma AGE levels do not differ between diabetic and nondiabetic hemodialysis patients. The mechanism of this phenomenon remains elusive. Previously, it was suggested that elevation of AGE levels in uremia might result from the accumulation of unknown AGE precursors. The present study evaluates the in vitro generation of pentosidine, a well identified AGE structure. Plasma samples from healthy subjects and nondiabetic hemodialysis patients were incubated under air for several weeks. Pentosidine levels were determined at intervals by HPLC assay. Pentosidine rose to a much larger extent in uremic than in control plasma. Pentosidine yield, i.e., the change in pentosidine level between 0 and 4 wk divided by 28 d, averaged 0.172 nmol/ml per d in uremic versus 0.072 nmol/ml per d in control plasma (P < 0.01). The difference in pentosidine yield between uremic and control plasma was maintained in samples ultrafiltrated through a filter with a 5000-Da cutoff value and fortified with human serum albumin (0.099 versus 0.064 nmol/ml per d; P < 0.05). Pentosidine yield was higher in pre- than in postdialysis plasma samples (0.223 versus 0.153 nmol/ml per d; P < 0.05). These results suggest that a large fraction of the pentosidine precursors accumulated in uremic plasma have a lower than 5000 Da molecular weight. Addition of aminoguanidine and OPB-9195, which inhibit the Maillard reaction, lowered pentosidine yield in both uremic and control plasma. When ultrafiltrated plasma was exposed to 2,4-dinitrophenylhydrazine, the yield of hydrazones, formed by interaction with carbonyl groups, was markedly higher in uremic than in control plasma. These observations strongly suggest that the pentosidine precursors accumulated in uremic plasma are carbonyl compounds. These precursors are unrelated to glucose or ascorbic acid, whose concentration is either normal or lowered in uremic plasma. They are also unrelated to 3-deoxyglucosone, a glucose-derived dicarbonyl compound whose level is raised in uremic plasma: Its addition to normal plasma fails to increase pentosidine yield. This study reports an elevated level of reactive carbonyl compounds ("carbonyl stress") in uremic plasma. Most have a lower than 5000 Da molecular weight and are thus partly removed by hemodialysis. Their effect on pentosidine generation can be inhibited by aminoguanidine or OPB-9195. Carbonyl stress might contribute to AGE modification of proteins and thus to clinically relevant complications of uremia.
Beta-2 microglobulin in renal disease.
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Molecular analysis of GB virus C isolates in Belgian hemodialysis patients.
GB virus C (GBV-C) has been detected in Belgian hemodialysis patients. To study their genomic diversity and phylogenetic relationship, a 592 nucleotide fragment extending from the 5' non-coding region to part of the E1 gene of the GBV-C genome was amplified and sequenced from 12 Belgian hemodialysis patients in two different centers. Together with strains from different geographical origins, these sequences were analyzed phylogenetically using three different methods. A consistent tree topology was obtained with all methods. Three GBV-C genotypes were observed with two subtypes in type 2 and a questionable subtyping in type 1. Except for one isolate falling into type 1 cluster which mainly consists of African strains, all the other Belgian strains clustered within the type 2a branch. Two GBV-C isolates in two patients from the same hemodialysis center clustered together closely, suggesting a nosocomial transmission. In view of their long branch length, it seems unlikely that the other Belgian strains evolved recently from a common ancestor. Our results indicate that the major type circulating among Belgian hemodialysis patients seems to be 2a, which is usual for Europe and North America, but that the African type 1 also exists to a minor extent. Although patient to patient transmission of GBV-C in Belgian hemodialysis centers did occur, it may not account for the majority of infections.
Splenic lymphoma presenting as necrotizing glomerulonephritis.
The authors report a case of necrotizing glomerulonephritis, with granular immune deposits, leading to the etiologic diagnosis of splenic non-Hodgkin's Lymphoma (NHL). The serum creatinine, initially markedly elevated, decreased under steroids and chlorambucil. Unfortunately, the patient died from septic complications. The importance of a careful search for a (localized) NHL in case of necrotizing glomerulonephritis with granular immune deposits is emphasized.
Clearance of pentosidine, an advanced glycation end product, by different modalities of renal replacement therapy.
We recently demonstrated that pentosidine, an advanced glycation end product, accumulates markedly as albumin-linked form (Palb) and in free-form (Pfree) in the plasma of patients with end-stage renal failure. The present study was undertaken to examine the clearance of Palb and Pfree by different modalities of renal replacement therapy, that is, hemodialysis (HD), continuous ambulatory peritoneal dialysis (CAPD), and renal transplantation. HD cleared Pfree (9.4 +/- 4.3 nmol/kg/HD) but not Palb, by diffusion but not by membrane adsorption, whereas CAPD cleared both Palb (4.03 +/- 2.01 nmol/kg/day) and Pfree (2.43 +/- 1.24 nmol/kg/day). Plasma total pentosidine levels were significantly (P < 0.05) lower in CAPD (0.97 +/- 0.41 nmol/ml) than in HD (1.19 +/- 0.41 nmol/ml), as the result of a lower serum albumin level in the former patients. Indeed, Palb expressed per mg albumin was virtually identical in HD and CAPD. By contrast, Pfree was significantly lower in CAPD than in HD. Palb levels were significantly correlated with plasma Pfree levels in both HD and CAPD patients, but not in the CAPD dialysate. Pentosidine transport across the peritoneum occurs mainly by diffusion, both as Palb and Pfree. Interestingly, peritoneal Palb clearance (0.17 +/- 0.07 ml/min) significantly (P < 0.00001) exceeded albumin clearance (0.11 +/- 0.05 ml/min). Palb levels being significantly higher (P < 0.0005) in the peritoneal fluid (36.28 +/- 18.55 pmol/mg) than in the serum (27.12 +/- 11.71 pmol/mg), thus raises the possibility of a facilitated diffusion of Palb or an active transport mechanism for protein-linked pentosidine into the peritoneal cavity. After renal transplantation, plasma Pfree fell rapidly, remained barely detectable after one month, and returned to normal at six months. By contrast, Palb fell more slowly and remained significantly above normal at six months, but returned eventually to normal levels. These findings demonstrate that: (1) both HD and CAPD remove Pfree; (2) the peritoneal clearance of Palb, might contribute to the lower level of plasma pentosidine in CAPD than in HD patients; and (3) renal transplantation is the best therapeutic modality to normalize both Palb and Pfree levels.
Histological prevalence of beta 2-microglobulin amyloidosis in hemodialysis: a prospective post-mortem study.
The histological prevalence of beta-2 microglobulin amyloidosis (A beta 2m) was evaluated in a prospective study of joint samples obtained at autopsy in 54 patients on hemodialysis (HD) for 2 to 163 (median 47) months, aged 20 to 80 (median 63) years at HD onset. Carpal tunnel syndrome surgery or radiological signs of A beta 2m were present in 2 and 4% of them, respectively. A control group of 34 patients without end-stage renal disease, autopsied during the same period was used as a reference. The 153 sampled joints (1 to 8, median 2 per patient) were sternoclavicular joints (N = 77), shoulders (N = 35), knees (N = 28), others (N = 13). A beta 2m was diagnosed (positive Congo red with typical birefringence and positive immunostaining of deposits for beta 2m) in 26 of 54 (48%) patients. Prevalence reached respectively 21%, 33%, 50%, 90% and 100% within two years, after 2 to 4 years, 4 to 7 years, 7 to 13 years and more than 13 years HD. The calculated sensitivity of the various joints for A beta 2m detection is significantly higher (P < 0.03) for sternoclavicular joints (97%) and knees (91%) than for shoulders (57%). Multivariate stepwise logistic regression with discriminant analysis identified both HD duration (P = 0.0008) and age at HD onset (P = 0.0093) but not diabetic nephropathy (P = 0.23) or gender (P = 0.25) as independent risk factors for A beta 2m. The probability of joint A beta 2m was quantitated as a function of age and HD duration. In conclusion, A beta 2m may be observed in the large joints early after HD onset. Overall prevalence reaches 48% of the patients on HD for a median of 47 months. It is much higher than that reported on the basis of clinical or radiological evidence. The sternoclavicular and knee joints are more frequently (P < 0.03) involved than the shoulder. The easily accessible sternoclavicular joint therefore appears to be the best site for the early detection of A beta 2m. Both HD duration and age at HD onset, but not diabetic nephropathy, are independent risk factors for A beta 2m.
Allogeneic bone marrow transplantation for AL amyloidosis.
AL amyloidosis is an infiltrative disorder characterized by the extracellular deposition of insoluble fibrillar immunoglobulin light chains whose production results from a plasma cell dyscrasia. Treatment with melphalan has resulted in an improvement in a few patients. Recently, intensive chemotherapy followed by autologous or syngeneic stem cell support has been shown to offer potential benefit. Allogeneic stem cell support after intensive therapy would retain the benefits of autologous transplantation, with the additional advantages of a tumor-free graft and of a possible graft-versus-tumor effect. We report a patient with AL amyloidosis and significant proteinuria. She improved after an allogeneic bone marrow transplantation.
Chinese herbs nephropathy presentation, natural history and fate after transplantation.
BACKGROUND: Chinese herbs nephropathy is a new type of subacute interstitial nephropathy reported in women who had followed a slimming regimen including Chinese herbs. METHODS: We report the clinical presentation and follow-up of 15 cases and compare them with a control group of 15 women with interstitial nephropathies of other origins, matched for age, sex, and initial serum creatinine (mean 3 mg/dl). RESULTS: At presentation the Chinese herbs nephropathy group differed from the control group by a lower proteinuria (P = 0.009), a more severe anaemia (P = 0.002), and a higher prevalence of aortic insufficiency (42% vs 0%, P < 0.05). It was further characterized by mild hypertension in 80%, glycosuria and leukocyturia in 40% and asymmetric kidneys in 54% of the cases. During follow-up, deterioration of renal function was faster in the Chinese herbs nephropathy than in the control group (P < 0.05). It was influenced by the duration of Chinese herbs treatment (P = 0.037) and the delay between the end of Chinese herbs ingestion and diagnosis of the disease (P = 0.013). In three cases, renal failure developed 3 years after Chinese herbs ingestion. Complications included severe aortic regurgitation requiring surgery (n = 1), urothelial carcinoma (n = 2), bilateral ureterohydronephrosis due to periureteral fibrosis (n = 1). Five patients with Chinese herbs nephropathy were successfully transplanted, without evidence of recurrence of the disease. CONCLUSIONS: Chinese herbs nephropathy is characterized by a lower proteinuria, more severe anaemia, and a faster progression to renal failure than other interstitial nephropathies. The duration of Chinese herbs treatment and interval between withdrawal of Chinese herbs and diagnosis are correlated with the rate of progression. Severe, unusual extrarenal complications may affect Chinese herbs nephropathy patients.
Does dialysis-related amyloidosis regress after transplantation?
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ANCA-positive rapidly progressive glomerulonephritis: there may be more to the diagnosis than you think!
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Hepatitis G virus infection in haemodialysed patients: epidemiology and clinical relevance.
BACKGROUND: The prevalence, incidence, risk factors, and clinical impact of infection by the recently discovered hepatitis G virus (HGV) in haemodialysed (HD) patients, are poorly defined. METHODS: All 119 HD patients from two Belgian units selected for their different hepatitis C virus (HCV) prevalences (A: 19.2%, B: 3.4%) were tested for the presence of HGV-RNA, using the reverse transcriptase polymerase chain reaction (RT-PCR) and primers from the 5'-NC and NS 5a genome regions. The results of anti-HCV antibodies and alamine aminotransferase levels (ALT) at the time of RT-PCR, number of transfusions from the onset of HD, and time on HD were retrieved from the medical charts. Forty patients were retested by RT-PCR 3-64 months later. RESULTS: HGV-RNA was detected with both sets of primers in 11/78 patients (14.1%) from centre A and 8/41 patients (19.5%) from centre B, for an average prevalence of 16%. One patient was indeterminate (positive with one set of primers). The presence of HGV-RNA correlated neither with time on HD (P = 0.18), nor with the number of transfusions on HD (P = 0.14). It was associated with the presence of anti-HCV antibodies in centre A (P < 0.01) but not B (P > 0.5). Twenty-seven initially negative (-) patients (A: n = 18; B: n = 9) were retested: two became positive (+) both in the absence of transfusions for years, giving a yearly incidence of 1.7%. The 13 initially HGV-RNA (+) patients remained so over time (33 patient-years). The presence of HGV-RNA alone does not increase significantly the ALT level, in contrast to the strong influence of HCV. CONCLUSION: The prevalence and yearly incidence of HGV infection are 16% and 1.7%, respectively, in our HD patients. Neither the number of transfusions on HD nor the time on HD are significant risk factors. Although mixed HCV/HGV infections indicate common risks, the prevalence of HCV in a particular setting does not predict prevalence of HGV. As new infections are detected in the absence of blood transfusions, HGV may be another marker of nosocomial viral transmission. Once acquired, the infection persists for many years in HD patients.
Sonographic findings in patients with dialysis-related amyloidosis.
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Hepatitis C virus genotypes in hemodialyzed patients: a multicentric study.
The few studies concerning HCV genotypes in hemodialyzed patients concerned small groups of patients, issued from single units. Using the RFLP typing method in the 5' non-coding region (5' NCR), we performed the genotyping of HCV strains of 80 patients issued from 14 Belgian dialysis units. Forty-seven of the 80 patients were also tested by Inno-Lipa II (Innogenetics, Gent, Belgium). Sixty-four of 80 patients (80%) were infected with subtype 1b, 2 (2.5%) with subtype 1a, 6 (7.5%) with subtype 2a and 1 (1%) with subtype 2b; 6 patients (7.5%) showed a type 4 and 2 patients (2.5%) a type 5 infection, respectively. Only 1 patient (1%) showed a mixed infection (1a and 1b). In the 47 patients tested by both methods, we observed a very good agreement (98%) between RFLP and Inno-Lipa II's results. Our multicentric study detected HCV genotypes 4 or 5 in 8/80 (10%) of hemodialyzed patients in Belgium. The substantial prevalence of these genotypes could not be fully explained by a nosocomial spread of HCV infection: indeed, four patients belonged to dialysis units located in different cities, and two appeared infected with distinct subtypes in a same unit. Thus, the discovery of a "rare" HCV genotype in several hemodialyzed patients does not always point to nosocomial HCV transmission.
[Prevention of hepatitis C virus transmission in hemodialysis].
The strategy to prevent hepatitis C virus (HCV) transmission to hemodialysed patients includes the screening of blood donors, the use of erythropoietin and the actual, strict application of Universal Precautions. In particular, articles should not be shared between patients, gloves changed and handwashing performed systematically after caring for a patient. The isolation of anti HCV (+) hemodialysed patients is not warranted. The prevention of HCV transmission to staff members relies mainly on the prevention of accidental needlestick injuries.