Search

The need for immunization in solid organ transplant recipient can arise from three factors: immune deficit owing to underlying disease, rejection of the organ graft, and immunosuppressive therapy given after transplantation. As a general rule, primary immunizations should be given as early as possible before transplantation because the immune response to vaccines is decreased in patients with end-stage organ disease. There are three categories of vaccines: Live vaccines--oral polio, vaccinia, bacillus Calmette-Guerin, live oral typhoïd, and intranasal influenza vaccines--are contraindicated in solid organ transplant recipients. The use of varicella vaccine remains controversial. The use of rubella vaccine is recommended in young women of childbearing age. Of the killed vaccines or genetically engineered vaccines, the following are recommended: pneumococcal vaccine, influenza vaccine, hepatitis A vaccine, hepatitis B vaccine, diphtheria, and tetanus vaccine. Vaccination of household contacts and health care workers in transplant centers is recommended. However, live vaccine (with the exception of varicella vaccine) should be avoided in these contacts.

Three main bone disorders may occur after organ transplantation: epiphyseal impactions, avascular bone necrosis, and osteoporosis. Their main clinical characteristics, causes, diagnostic approaches, and therapies are discussed in this review.

Background: Patients starting peritoneal dialysis (PD) show a significant variability in small solute transport across the peritoneal membrane (PM). The latter parameter determines dialysis prescription and survival. Clinical factors probably influence solute transport across the PM, but the putative role of genetic variants is unknown., Methods: We have investigated the influence of functional polymorphisms of VEGF, ENOS, and IL-6, together with clinical and biological factors, on baseline peritoneal equilibration test (PET) parameters in a homogeneous population of 152 unrelated Caucasian PD patients from Belgium and the North of France., Results: The distribution of the 21 alleles (7 polymorphisms) and linkage disequilibrium parameters were similar in PD patients and healthy subjects. Univariate and multivariate analyses identified comorbidity, serum albumin, and the -174G/C polymorphism of IL-6 as independent predictors of small solute transport. The -174G/C polymorphism of IL-6 was associated with significantly higher IL-6 mRNA levels in the PM and higher plasma and dialysate IL-6 concentrations, suggesting a dominant effect of the C allele. Patients harboring the CC and GC genotypes (N= 92) were characterized by significantly higher permeability parameters and inflammatory markers than patients harboring the GG genotype (N= 60). In contrast with IL-6, VEGF and ENOS polymorphisms had no influence on baseline peritoneal permeability., Conclusion: These data (1) show that, together with clinical parameters, the functionally relevant -174G/C polymorphism of IL-6 contributes to the interpatient variability in small solute transport rate at the start of PD; and (2) substantiate the critical role played by IL-6 in the PM.

Adult polycystic liver disease (APLD) is a rare disorder of the liver parenchyma, the treatment of which is still controversial. Conservative surgery may have a significant morbidity and is often ineffective in the long run. Liver replacement may be indicated in case of incapacitating hepatomegaly. Patients (one male, five females) undergoing liver transplantation for symptomatic APLD is presented in this study. The particular nature of this series is the fact that successful transplantation was performed in all cases with preservation of the recipient's inferior vena cava and without use of veno-venous bypass despite massive hepatomegaly and previous extensive liver surgery (in three cases). There was minimal morbidity and no mortality. All patients have excellent quality of life with a median follow-up of 41 months (range: 12-58) as testified by a median Karnofsky score of 90% (range: 80-100%).

The antiplasmodial activity of crude extracts of 19 species of Strychnos (Loganiaceae) was assessed in vitro against a chloroquine-susceptible strain of Plasmodium falciparum. For each species, ethyl acetate (EtOAc) extracts were analysed and, for the most active species, methanolic (MeOH) extracts were also tested. Among them, Strychnos variabilis De Wild. seemed to be very promising (inhibitory concentration 50% (IC50) < 5 microg/ml) whereas two other species, Strychnos gossweileri Exell and Strychnos mellodora S. Moore, could be interesting (IC50 < 15 microg/ml) in further antimalarial studies.

Objectives: Peritonitis due to peritoneal dialysis (PD) is best treated empirically while waiting for the results of the dialysate culture. Thus, antibiotic therapy must cover both gram-positive and gram-negative micro-organisms. First, over a period of 9 years in a multicenter study we evaluated the efficiency of a vancomycin and ciprofloxacin combination given as the first-line treatment protocol for PD peritonitis. Second, we evaluated whether a systemic route of administration of the antibiotics could be an interesting alternative to the usual cumbersome intraperitoneal drug administration., Methods: Vancomycin 15 mg/kg body weight, intravenous, and oral ciprofloxacin 250 mg two times per day (500 mg twice per day if residual creatinine clearance was above 3 mL/minute) were prescribed at diagnosis of peritonitis. Vancomycin injections were repeated (when blood trough level was expected to be below 12 microg/mL) in cases of gram-positive organisms for a total duration of 3 weeks. Ciprofloxacin was given for a total of 3 weeks in cases of gram-negative and a total of 10 days for susceptible gram-positive infections., Results: A total of 129 episodes of peritonitis occurred; 28 of them were not included in the study because of protocol violation (n = 15) or fungal (n = 7) or fecal (n = 6) peritonitis, leaving 101 peritonitis episodes for analysis. 52 (51.5%) gram-positive and 28 (27.7%) gram-negative organisms were grown; 38 gram-positive organisms were coagulase-negative staphylococci. No organism was identified in 8 peritonitis episodes, whereas 13 peritonitis episodes were caused by more than 1 organism. 35% of the coagulase-negative staphylococci were resistant to first-generation cephalosporin and methicillin, whereas all were susceptible to vancomycin. For gram-negative bacilli, the susceptibility rate was 96% and 95% for ciprofloxacin and ceftazidime respectively. The overall treatment success rate was 77.2% (78 of the 101 peritonitis episodes): 61.4% at first intention and 15.8% after optimization of the antibiotic therapy (second intention). The protocol failed in 22.8% of the peritonitis episodes. Hospitalization was required in 52% of the peritonitis episodes; average hospitalization was 11 (range 1-45) days., Conclusion: Systemic vancomycin and ciprofloxacin administration is a simple and efficient first-line protocol antibiotic therapy for PD peritonitis. In our opinion, vancomycin should still be used for gram-positive infections because of its high susceptibility rate compared with first-generation cephalosporins, providing a close monitoring of the local epidemiology. Oral ciprofloxacin provides satisfactory results in gram-negative infections, comparable to those obtained with intraperitoneal ceftazidime or aminoglycosides.

Isostrychnopentamine (ISP) is an asymmetric indolomonoterpenic alkaloid isolated from the leaves of Strychnos usambarensis. The in vitro antiplasmodial activities against five Plasmodium falciparum cell lines were evaluated: ISP possessed an in vitro IC (50) near 0.1 microM against all P. falciparum cell lines tested (chloroquine-resistant and chloroquine-sensitive lines) and showed antiplasmodial selectivity compared to cytotoxicity on human cell lines. The stage-dependent susceptibility to a short exposure of ISP was then investigated. The ring stage was shown to be the most sensitive one, but all stages were affected by ISP treatment. By means of fluorescence microscopy, it was shown that ISP was not accumulated inside the food vacuole of the parasite. Finally, the in vivo antimalarial activities against the P. berghei NK173 and P. vinckei petteri murine strains were determined. The ED (50) in vivo was about 30 mg/kg/day by the intraperitoneal route (after 4 days treatment).

Tagitinin C, an antiplasmodial compound, identified as one major compound of the subtropical medicinal plant, Tithonia diversifolia, was determined by FT-IR spectroscopy method. The crude ether extracts from aerial parts of the plant were evaporated to dryness and re-dissolved in tetrachloroethylene (C(2)Cl(4)) before analysis. The magnitude of the absorbance of the very specific CO stretching vibration (nu(CO)) at 1664.8cm(-1) was exploited in order to quantify tagitinin C. The determination coefficient (r(2)) of the calibration scale was 0.9994, the detection limit was lower than 3mugml(-1) and the quantification limit was lower than 10mugml(-1). Recovery values from 100.5 to 101.7% were found for spiked concentration levels from 19.91 to 89.95mugml(-1). The main characteristics of the curves obtained from the calibration standards and from the standard addition technique were not statistically different (Student t-test) suggesting that matrix effects were negligible. The results obtained for the determination of tagitinin C in the crude ether extract from aerial parts of T. diversifolia by LC and FT-IR spectroscopic method agreed well: 0.76+/-0.02 and 0.773+/-0.009, of tagitinin C in dried plant respectively.

Fibroadenomas of the breast have been reported in female renal graft recipients and associated with the use of cyclosporin A (CsA). We report the case of a young patient given CsA who developed multiple bilateral fibroadenomas of the breasts 3 years after renal transplantation, leading to bilateral mastectomy. We discuss the association of CsA with fibroadenomas, the mechanisms by which the drug can act and review the literature. Based on these observations, an early conversion from CsA to tacrolimus should be considered; further observations are needed to assess the reversibility of the breast(s) lesions after such immunosuppressive regimen switch.

A simple, rapid and reliable reversed-phase high-performance liquid chromatographic method for the determination of tagitinin C, an anti-plasmodial sesquiterpene lactone isolated from the aerial parts of Tithonia diversifolia, has been developed. The assay has been used to quantify tagitinin C in various extracts of the aerial parts of T. diversifolia.

Background: Aristolochic acid nephropathy (AAN) is a rapidly progressive interstitial nephropathy linked to the exposure to aristolochic acid (AA) and characterized by extensive fibrosis and urothelial atypia. Although the fibrotic process has been documented in extrarenal tissues, the involvement of the peritoneum, as well as the efficacy of peritoneal dialysis in AAN patients, remain uncertain., Methods: The structure of the peritoneal membrane and the expression of basic fibroblast growth factor (bFGF), collagen type III, endothelial nitric oxide synthase (eNOS), and aquaporin-1 (AQP1) were investigated in peritoneal biopsies from an index AAN patient, four other AAN patients, four regular peritoneal dialysis patients, and two controls. Similar methods were used to investigate a rabbit model of AAN after intraperitoneal exposure to high-dose AA. AA-DNA adducts were screened by 32P-postlabeling analysis., Results: The AAN patients had renal failure, renal fibrosis, and urothelial atypia. The peritoneum of AAN patients had a normal structure, lacked cellular atypia, and, in comparison with regular peritoneal dialysis patients and controls, did not show abnormal regulation of fibrotic and endothelial markers. Furthermore, specific AA-DNA adducts were not identified in the peritoneum of AAN patients. In contrast, AA-DNA adducts were detected in peritoneal and kidney tissues of all exposed rabbits, and one of them developed a malignant mesothelioma., Conclusion: These data demonstrate the lack of fibrotic and vascular alterations and the absence of cellular atypia in the peritoneum from AAN patients. Thus, peritoneal dialysis should not be discouraged in these patients. Nevertheless, studies in a rabbit model of high-dose AA exposure may suggest a potential risk of peritoneal malignancy.

Background: Progressive bone loss consistently complicates renal transplantation (TP) in patients given an immunosuppression including prednisolone. The adjunction of cyclosporine in the immunosuppressive regimen does not reverse the negative impact of renal TP on the skeleton. The post-transplant effect of tacrolimus on bone mass is still unknown., Methods: We evaluated the evolution of bone mineral density (BMD) and various biochemical markers over the first 12 months following renal TP in 23 patients given an immunosuppression combining tacrolimus and low-dose prednisolone. BMD of lumbar spine, total hip and hip subregions was measured by dual-energy X-ray absorptiometry within the first 15 days and 1 year after TP., Results: At the time of TP, the average BMD was low in both the lumbar spine and the hip. After TP, a normalization of serum creatinine and a decrease in serum phosphate and iPTH levels occurs. Serum alkaline phosphatase level significantly rose transiently within the first 6 months and decreased thereafter. At 1 year post TP, BMD remained unchanged in the lumbar and in the trochanter subregions and rose in the other sites. BMD increased by at least 2% in 8, 13, 10 and 10 out of the 23 patients in the lumbar, neck, trochanter and total hip subregions, respectively. No correlation was found between evolution in BMD and age, sex, dialysis duration, level of hyperparathyroidism, prednisolone and tacrolimus cumulative intake and prescription of calcium, vitamin D or hormone replacement therapy., Conclusions: An immunosuppression combining tacrolimus and low-dose prednisolone might avoid the usual post-TP bone loss. Further randomized double-blind studies evaluating a larger cohort of patients should be undertaken to compare the effect of cyclosporine and tacrolimus on bone mass.

The occurrence of a post-renal transplant syndrome of lower limbs joint pain has been reported extensively over the last decade. Clinical examination of the symptomatic joints is often unremarkable and magnetic resonance imaging reveals abnormalities of the bone marrow suggestive of edema and/or hemorrhage. The main striking features of this syndrome are the spontaneous resolution of the symptoms within a few weeks as well as of the marrow abnormalities. This syndrome has been attributed to cyclosporine, given in the immunosuppression regimen or to epiphyseal impactions. We here document the occurrence of this syndrome in 5 kidney graft recipients given a tacrolimus-based immunosuppression.

Pasteurella multocida is a rare cause of peritonitis in peritoneal dialysis patients with only 10 cases reported in the literature so far. All cases were observed in patients with close contact with cats, usually with a direct puncture of the dialysis tubing. We report a case of Pasteurella multocida peritonitis in a patient maintained under continuous cycling peritoneal dialysis (CCPD), who had frequent and close contact with cats. Patients should be made aware of this potential complication and advised to keep domestic animals away from the location of their peritoneal exchanges.

A 37-year-old patient underwent two successive renal transplantations 7 months apart. He remained dialysis dependent. Early biopsy of both grafts revealed widespread calcium oxalate deposition suggestive of acute oxalate nephropathy. Several causes of oxalate nephropathy, including primary oxalosis and an increased intake of oxalic acid precursors, were excluded. Two years later, the identification of steatorrhea with radiologic signs of chronic pancreatitis led to the hypothesis of enteric hyperoxaluria. Surprisingly, 11 months after the second transplantation, graft function improved progressively allowing interruption of dialysis. Three years later, renal function is stable. The causes and prevention of acute oxalate-induced graft failure are highlighted. Subclinical evidence of enteric hyperoxaluria should be looked for and appropriate therapy instituted as early as possible. The possibility of a late recovery of renal function warrants attentive patience from attending physicians., (Copyright 2002 by the National Kidney Foundation, Inc.)

X-Linked nephrogenic diabetes insipidus (NDI), which accounts for 90% of inherited cases of NDI, is caused by mutations in the AVPR2 gene that encodes the arginine vasopressin (AVP) receptor type 2 (V2R). The V2R mediates the antidiuretic action of AVP in principal cells of the collecting duct. To date, only three AVPR2 mutations (P322S, D85N, and G201D) have been associated with a mild NDI phenotype, and intrafamilial phenotype variability has not been reported in affected males. We describe a novel Belgian family with X-linked NDI caused by substitution of a histidine for an arginine at position 137 (R137H) of AVPR2. This mutation has been identified in two brothers and their mother. The R137H mutation results in a failure of V2R to stimulate adenylate cyclase and has been associated consistently with severe NDI and the inability to increase urinary osmolality to greater than plasma osmolality during water deprivation and/or infusion of 1-desamino-8-d-arginine vasopressin. Detailed examination of the two affected brothers showed the typical NDI phenotype in the 45-year-old proband, whereas a milder clinical phenotype associated with significant urinary concentrating ability during water deprivation was documented in the 33-year-old brother. Thus, in this family, the R137H mutation is associated with either a mild or severe NDI phenotype. Mechanisms that might account for these findings include genetic and/or environmental modifiers., (Copyright 2002 by the National Kidney Foundation, Inc.)

Bone loss, a recognized complication of renal transplantation (TP), is mainly attributed to steroids. The effect of other immunosuppressive agents on patients' bone mass is difficult to distinguish from that of steroids. In this study, we evaluate the evolution of bone mass density over the first 12 months following renal TP in two groups of patients given either low-dose steroids with tacrolimus ( n=7) or normal-dose steroids and cyclosporine ( n=19). Bone mineral density (BMD) of the lumbar spine, total hip, and hip subregions and total-body bone mineral content (BMC) were measured by dual-energy X-ray absorptiometry within the first 15 days, and 1 year after TP. Biological markers of bone turnover (serum calcium, phosphate, total alkaline phosphatase activity, intact parathyroid hormone, bone-specific alkaline phosphatase, calcitriol, and urinary pyridinolines) were regularly measured during follow-up. After TP, renal function improved rapidly in all patients. One year after TP, bone mass had decreased significantly in the cyclosporine group in all investigated sites. By contrast it had increased in the tacrolimus group. In order to compare the evolution of bone mass in patients given similar amounts of steroids, the cyclosporine group was subdivided in tertiles according to the 1-year cumulative oral intake of prednisolone. A significant bone loss was still observed in the low-steroid cyclosporine subgroup but not in the tacrolimus group, despite the similar steroids intake (3.5+/-0.5 g and 2.7+/-1 g, respectively). Bone gain in the tacrolimus group occurred despite a previous longer dialysis duration and a higher number of postmenopausal women who were not receiving hormone substitutes. Long-term evaluation of bone density (3-5 years post-TP) confirmed the bone gain in the tacrolimus patients. Interestingly, the profile of the biological markers of bone turnover appeared better in patients prescribed tacrolimus than in those given cyclosporine, though the differences did not reach statistical significance. Weconclude that tacrolimus associated with low-dose steroids might better preserve bone mass after renal TP than cyclosporine and normal doses of steroids.

The serum concentration of leptin, an hormone secreted by adipocytes, is increased in obese and chronic renal failure patients. To determine the influence of peritoneal dialysis (PD) therapy on serum leptin levels, we analyzed its concentration in 23 patients on PD for an average of 26.8 +/- 7.1 months and compared it to that of 18 patients with chronic renal failure (creatinine clearance: 49.1 +/- 8.8 ml/min) and of 35 healthy control subjects. Leptin level was also reevaluated in 11 PD patients 9.3 +/- 1 months after the initial analysis. Finally, circadian leptin production was determined in 4 patients on automated PD (APD). Serum leptin was significantly higher in PD (31.9 +/- 7.8 ng/ml) than in chronic renal failure patients (15.2 +/- 5.9 ng/ml) and in healthy control subjects (9.6 +/- 1.1 ng/ml). Serum leptin level was significantly correlated with BMI in all three groups (except in PD males) and with the percentage of fat mass in both male and female PD patients. It did not correlate in PD patients with serum albumin concentration, free fat mass, residual diuresis, time on PD and characteristics of peritoneal permeability. At the second determination, serum leptin level had significantly increased in the PD patients although their respective BMI and serum creatinine concentration had remained virtually unchanged. Finally, in APD patients, the highest leptin level was observed at 08.00 a.m. These results demonstrate that serum leptin level is increased in PD patients and that it progressively rises under PD therapy. The circadian leptin production is delayed in APD patients probably suggesting a negative effect of the nocturnal glucose load on the regulation of its secretion.

Background: Physical activity (PA) level of end-stage renal disease (ESRD) patients after renal transplantation (TP) is a largely unexplored field, although it is an important component of quality of life., Methods: Using the Baecke self-administered and the Five-City Project 7-day PA recall questionnaires, PA level was estimated in 32 consecutive ESRD patients (12 males, 20 females; mean age 45.9+/-13.1 years; mean dialysis duration 23.5+/-21.8 months) admitted for renal TP and to whom no exercise programme of any kind was proposed. PA were recorded 1, 3, 6, 12 and 60 months after TP., Results: Immediate pre-TP PA level of renal transplant candidates was between 18 and 35% less than that of age-matched healthy subjects (P < 0.05), depending on gender and questionnaire. After an immediate decrease in PA level 1 month post-TP, mean PA level increased and reached a plateau 1 year after TP. This gain in PA capacity reached 30%, as compared with pre-TP values (P = 0.06 to P < 0.01). During the fifth year after TP, the mean level of PA was unchanged. A more qualitative analysis, allowed by the sub-score comparisons, showed that although the occupational status of the patients remained the same, they participated significantly more in moderate and even high intensity PA (leisure, sports, household chores) after TP., Conclusions: Most renal graft recipients are spontaneously more active after TP, an observation consistent with a better quality of life. Therefore, they should be advised precisely about how to resume more strenuous activities such as sports in order to avoid cardiac or musculoskeletal disorders in relation to their weakened pre-TP condition.

Background: Deterioration of the peritoneal membrane limits the technical survival of peritoneal dialysis (PD). Advanced glycation of the membrane has been incriminated in this evolution. Advanced glycation end products (AGEs) develop under the influence of glucose and of its degradation products, mainly reactive carbonyl compounds (RCOs) such as glyoxal (GO), methylglyoxal (MGO), and 3-deoxyglucosone (3-DG). The present study was undertaken to evaluate the impact of recently developed glucose-free PD fluids on AGE generation., Methods: Recently developed glucose-free PD fluids containing either icodextrin or amino acids were investigated. GO, MGO, and 3-DG [high-performance liquid chromatography (HPLC)] and total RCOs (spectrophotometry) were measured in fresh solutions and in effluents after various dwell duration. The AGE formation potential of PD fluids and effluents was assessed by incubation at 37 degrees C, for one week, with bovine serum albumin and by the eventual measurement of pentosidine (HPLC) and Nepsilon-carboxymethyllysine (CML; gas chromatography/mass spectrometry)., Results: GO, MGO, and 3-DG (P < 0. 001) as well as total RCOs levels (P < 0.01) were significantly lower in icodextrin and amino acid PD fluid than in commercial, heat-sterilized, 1.36% glucose PD fluid. Pentosidine and CML generation were also significantly lower (P < 0.001) in icodextrin and amino acid PD fluid than in conventional 1.36% glucose PD fluid. The levels of total RCOs, however, increased in icodextrin and amino acid PD fluid effluents with dwell time. AGE formation potential rose accordingly, as demonstrated by a parallel increase in the generation of pentosidine and CML during incubation of PD effluents., Conclusion: The present data demonstrate lower RCO contents and AGE formation potential in fresh icodextrin and amino acid PD fluids than in fresh heat-sterilized glucose PD fluids. However, this difference decreases progressively during dwell time, mainly as a result of the influx of total RCOs.

Long-term peritoneal dialysis (PD) is associated with alterations in peritoneal permeability and loss of ultrafiltration. These changes originate from increased peritoneal surface area, but the morphologic and molecular mechanisms involved remain unknown. The hypothesis that modifications of activity and/or expression of nitric oxide synthase (NOS) isozymes might play a role in these modifications, via enhanced local production of nitric oxide, was tested in this study. NOS activities were measured by the L-citrulline assay in peritoneal biopsies from seven control subjects, eight uremic patients immediately before the onset of PD, and 13 uremic patients on short-term (<18 mo, n = 6) or long-term(>18 mo, n = 7) PD. Peritoneal NOS activity is increased fivefold in long-term PD patients compared with control subjects. In uremic patients, NOS activity is positively correlated with the duration of PD. Increased NOS activity is mediated solely by Ca(2+)-dependent NOS and, as shown by immunoblotting, an upregulation of endothelial NOS. The biologic relevance of increased NOS in long-term PD was demonstrated by enhanced nitrotyrosine immunoreactivity and a significant increase in vascular density and endothelial area in the peritoneum. Immunoblotting and immunostaining studies demonstrated an upregulation of vascular endothelial growth factor (VEGF) mostly along the endothelium lining peritoneal blood vessels in long-term PD patients. In the latter, VEGF colocalized with the advanced glycation end product pentosidine deposits. These data provide a morphologic (angiogenesis and increased endothelial area) and molecular (enhanced NOS activity and endothelial NOS upregulation) basis for explaining the permeability changes observed in long-term PD. They also support the implication of local advanced glycation end product deposits and liberation of VEGF in that process.

Unlabelled: A specific method for measurement of nitric oxide synthase enzymatic activity in peritoneal biopsies., Background: Nitric oxide (NO) is synthesized by NO synthase (NOS) isoforms that are expressed in the peritoneum. Thus far, NOS activity in the peritoneum has been assessed by nonspecific methods. We describe the application of a specific method for determination of NOS activity in rat and human peritoneal biopsies., Methods: The L-citrulline assay is based on the stoechiometric production of NO and L-[3H]-citrulline from L-[3H]-arginine by NOS. The assay is technically difficult when applied on small samples with relatively low levels of NOS activity, which required specific procedures for extraction and samples processing. Reaction parameters ensuring assay linearity in the peritoneum were defined. Peritoneum lysates were also used for immunoblot analysis to identify the NOS isoforms involved., Results: A significant NOS activity is detected in the normal peritoneum because of both Ca2+-dependent and Ca2+-independent NOS. The specificity of NOS activity has been demonstrated by various controls, including the NOS inhibitor L-NMMA. Competition experiments with L-valine and amino acid analyses have reasonably excluded the interference of endogenous arginase and L-arginine, which both might underestimate NOS activity. The procedure is sensitive; it detects a high range of NOS activities as well as the appropriate NOS isoforms in various tissues and conditions, as shown by correlations with immunoblot studies., Conclusions: We have adapted and characterized the L-citrulline assay to measure specific NOS activities within the peritoneum. The peritoneum lysate assayed for NOS activity can also be used for characterizing NOS isoform expression by immunoblot analysis.

The loss of ultrafiltration (UF) that accompanies acute peritonitis is a common problem in peritoneal dialysis (PD). It has been suggested that changes in nitric oxide (NO)-mediated vascular tone and permeability might be involved in the loss of UF, whereas channel-mediated water permeability should not be affected. This study used a model of acute peritonitis in rats to characterize changes in PD parameters, in correlation with: (1) expression studies of water channel aquaporin-1 and NO synthase (NOS) isoforms and (2) enzymatic assays for NOS in the peritoneum. Compared with controls, rats with peritonitis had a higher removal of plasma urea, a faster glucose absorption, and a loss of UF. Additional changes, including high protein loss, elevated leukocyte counts in dialysate, positive bacterial cultures, edema, and mononuclear infiltrates, were similar to those observed in PD patients with acute peritonitis. Acute peritonitis in rats induced a major increase in total NOS activity, which was inversely correlated with free-water permeability. The increased NOS activity was mediated by both inducible (Ca2+-independent) and endothelial (Ca2+-dependent) NOS isoforms and was reflected by increased peritoneal staining for nitrotyrosine. In contrast, aquaporin-1 expression was unchanged in rats with peritonitis. These findings cast light on the pathophysiology of permeability changes and loss of UF that characterize acute peritonitis. In particular, these data suggest that a local production of NO, mediated by different NOS isoforms, might play a key role in these changes.

The fate of preexisting benign monoclonal gammopathy after organ transplantation is largely unknown. We report the case of a 47-year-old male kidney graft recipient with a pretransplantation IgG kappa monoclonal gammopathy who developed, 10 years after transplantation, de novo augloid light chain (AL) amyloidosis involving skin and kidney graft. The potential role of heavy immunosuppressive treatment in the development of this complication is discussed. The possible occurrence of AL amyloidosis should be kept in mind when a patient with benign monoclonal gammopathy is evaluated for organ transplantation, as well as when a transplanted patient with pre-existing monoclonal gammopathy develops new onset of proteinuria.

Aquaporin-1 (AQP1) has been claimed to be the molecular counterpart of the transcellular pathway for free-water movement across the peritoneum during peritoneal dialysis. We report the case of a 67-year-old man, on peritoneal dialysis for 11 years, in whom ultrafiltration failure due to an abolition of the transcellular water transfer (documented by a loss of sodium sieving) was associated with an apparently normal expression of AQP1. We suggest that an alteration of AQP1 structure, rather than of its expression, accounts for this observation.