Diagnostic performance of [(18)F]fluorodeoxyglucose positron emission tomography-computed tomography in cyst infection in patients with autosomal dominant polycystic kidney disease.

Cyst infection is a common complication of autosomal dominant polycystic kidney disease (ADPKD). Diagnosis is challenging with standard imaging techniques. We aimed to evaluate the diagnostic performance of [(18)F]fluorodeoxyglucose positron emission tomography-computed tomography (18-FDG PET-CT) for the diagnosis of cyst infections among ADPKD patients, in comparison with computed tomography (CT) and magnetic resonance imaging (MRI). All APKD patients who underwent 18-FDG PET-CT for suspected cyst infection between 2006 and 2013 in a French teaching hospital were included. Diagnosis of cyst infection was retained a posteriori on an index of clinical suspicion. 18-FDG PET-CT findings were was considered to be positive in cases of cyst wall hypermetabolism. CT or MRI findings were were considered to be positive in cases of cyst wall thickening (and enhancement if contrast medium was injected) and infiltration of the adjacent fat. A control group of ADPKD patients with 18-FDG PET-CT performed for other reasons was included. Thirty-two 18-FDG PET-CT scans were performed in 24 ADPKD patients with suspected cyst infection. A diagnosis of cyst infection was retained in 18 of 32 cases: 14 with positive 18-FDG PET-CT findings, and four false negatives. There were no false positives and no hypermetabolism of cyst walls in nine ADPKD control patients. 18-FDG PET-CT had a sensitivity of 77%, a specificity of 100%, and a negative predictive value of 77%. 18-FDG PET-CT allowed a differential diagnosis in three patients. In contrast, CT had a sensitivity of 7% and a negative predictive value of 35% (p <0.001 vs. 18-FDG PET-CT). Only eight MRI scans were performed. The diagnostic performance of 18-FDG PET-CT is superior to that of CT in cyst infections, for comparable radiation doses and with no injection of nephrotoxic contrast medium, in ADPKD patients.

Survival of patients with ANCA-associated vasculitis on chronic dialysis: data from the French REIN registry from 2002 to 2011.

BACKGROUND: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) can lead to end-stage renal disease in patients with renal involvement. OBJECTIVE: This study evaluated the survival of AAV patients on chronic dialysis in France. METHODS: Between 2002 and 2011, a total of 425 AAV patients started chronic dialysis and were registered in the Renal Epidemiology and Information Network. We analysed survival censored for renal transplantation, recovery of renal function and loss to follow-up. AAV patients were compared with 794 matched non-AAV patients on chronic dialysis. RESULTS: A total of 166 (39%) patients with microscopic polyangiitis and 259 (61%) patients with granulomatosis with polyangiitis were registered. Within a median follow-up of 23 months, 58 (14%) patients received a renal allograft and 19 (4%) recovered renal function. Median survival on dialysis was 5.35 years (95% CI, 4.4-6.3) and survival rates at 3 months, 1, 3 and 5 years were 96%, 85%, 68% and 53%, respectively. A total of 143 (41%) patients died after a median of 16 months. Causes of death were cardiovascular (29%), infections (20%), malnutrition (13%), malignancies (4%), AAV relapse (2%), miscellaneous (14%) and unknown (18%). Multivariate logistic regression identified three independent risk factors associated with AAV patients' mortality: age (HR = 1.05/year, P < 0.001), peripheral artery disease (HR = 2.62, P = 0.003) and frailty (HR = 2.43, P < 0.001). Survival of AAV patients did not differ from non-AAV controls, but infectious mortality was higher in AAV patients (20% vs. 8%, P < 0.001). CONCLUSION: Survival of AAV patients in chronic dialysis, although poor, was comparable to survival of non-AAV controls on dialysis. There was a similar burden of cardiovascular mortality, but higher infectious mortality.

Immune reconstitution inflammatory syndrome mimicking relapsing cryptococcal meningitis in a renal transplant recipient.

Immune reconstitution inflammatory syndrome (IRIS) is a rare entity that has been described recently in solid organ transplant (SOT) recipients. IRIS is characterized by an exuberant and dysregulated immune response following treatment of opportunistic infections. We describe here the case of a kidney transplant recipient who developed cryptococcal meningitis that was efficiently treated with antifungal therapy and decreased immunosuppression regimen. Eight months later, a paradoxical worsening of neurological symptoms and neuroradiological findings led to the diagnosis of IRIS. A short course of high-dose steroid therapy allowed complete resolution of neurological symptoms. This report highlights the challenge for physicians to distinguish IRIS from a relapsing cryptococcal infection. Clinical improvement of cryptococcosis-associated IRIS by anti-inflammatory drugs needs to be confirmed among SOT recipients.

Nocardia carnea infection in a kidney transplant recipient.

We report an unusual case of Nocardia carnea brain and lung abscesses in a 54-year-old kidney transplant recipient. Our case was confirmed by molecular detection despite negative cultures. The patient recovered using prolonged cotrimoxazole treatment.

Cytomegalovirus risk factors in renal transplantation with modern immunosuppression.

BACKGROUND: Immunosuppressive regimens have lowered the rate of kidney rejection, but with increasing immunodeficiency-related complications. New cytomegalovirus (CMV) prophylaxis also has become available. The impact of these 2 developments on CMV diseases has not been well evaluated. We conducted a randomized trial comparing a drug regimen common in the 1980s, cyclosporin A (CsA) with azathioprine (Aza), with a drug combination used most today, tacrolimus (Tac) with mycophenolate mofetil (MMF), and we analyzed CMV risk factors in kidney transplant patients. METHODS: The 300 patients included in the trial underwent the same universal prophylaxis and preemptive therapy. CMV events and risk factors were prospectively recorded. RESULTS: With preventive and preemptive strategies combined for 3 months, CMV replication was detected in 32.6% and CMV disease in 18.1% of patients. Multivariate analysis on risk factors for CMV disease were CMV donor (D)/recipient (R) matching and first month renal function (risk ratio [95% confidence interval]: 1.02 [1.01; 1.04]; P=0.011), but not the immunosuppressive regimen (P=0.35). The D+/R- combination increased the risk of CMV disease by a factor of 9 (P<0.0001) when compared with D-/R- status, and a factor of 3.5 (P<0.0001) when compared with all CMV-positive recipients. Despite the 50% rate of CMV disease in the D+/R- group, no asymptomatic CMV replication was detected with the preemptive strategy. CONCLUSIONS: With modern immunosuppression, a sequential quadritherapy with Tac/MMF, and a 3-month CMV prevention strategy, the risk for CMV disease remains close to that with CsA/Aza. A CMV-negative recipient transplanted from a CMV-positive donor (D+/R-) remains a major risk factor, calling for better CMV prophylaxis or matching in negative recipients. Preemptive strategy thus appeared inefficient for this high-risk group. Transplant recipients with altered renal function should also be considered at risk.

Kidney transplantation decreases the level and procoagulant activity of circulating microparticles.

Microparticles (MP) are important players in cardiovascular disorders. Renal transplantation significantly improves the survival of hemodialyzed patients, in part because cardiovascular disease (CVD) progression is lessened. We hypothesized that the beneficial effect of renal transplantation on cardiovascular outcome might involve decreased levels of circulating MP. We evaluated the kinetics of MP subpopulations and their procoagulant activity (MP-PCA) in 52 patients before and 3, 6, 9 and 12 months after graft with reference to 50 healthy controls and we evaluated the impact of cardiovascular complications. During the follow-up, the increased levels of MP observed before graft were significantly decreased and reached normal values with different kinetics according to their cellular origin whereas MP-PCA remained significantly higher than in controls. From multivariate analysis, the levels of MP were negatively correlated with renal function. At 12 months, the decrease in MP and MP-PCA was more pronounced in patients without history of CVD than those with. In conclusion, we demonstrated that renal graft is associated with decreased levels of MP levels and MP-PCA, even more pronounced so in patients without history of CVD. Therefore, we suggest that MP lowering could be involved in the vascular dysfunction improvements reported after transplantation.

Contact allergies in haemodialysis patients: a prospective study of 75 patients.

BACKGROUND: Haemodialysis exposes patients to many potentially sensitizing allergens. OBJECTIVES: The primary objective of this study was to evaluate the prevalence of delayed hypersensitivity in a population of haemodialysis patients. Secondary objectives were to identify the possible risk factors for contact sensitization and to propose a series of skin tests adapted to haemodialysis patients. METHODS: A prospective monocentric study was carried out in a nonselected population of haemodialysis patients. For each patient, medical history of atopy and allergic contact dermatitis, ongoing treatments (including topical ones), presence of eczema at the site of vascular access for haemodialysis were recorded. Allergological investigation included delayed hypersensitivity tests (European Environmental and Contact Dermatitis Research Group battery, tests GERDA, additional list and a battery of antiseptics and other dialysis-specific allergens) and latex skin prick test. RESULTS: Seventy-five patients (41 men, 34 women, mean age of 65 years old), with a mean 3.8 years under dialysis, were included. Nineteen patients (25%) had at least one positive skin test and 13 (17%) a positive patch test to at least one allergen relative to dialysis process including eight tests to lidocaine-prilocaine cream and three to povidone-iodine. Tests results seemed clinically relevant since nine patients had localized pruritus at the fistula site and six patients active eczema around it. CONCLUSION: Contact sensitizations are frequent in haemodialysis patients and are linked to vascular access conditioning especially the use of lidocaine-prilocaine cream. Designing a specific test battery could help to diagnose the potential allergens and subsequently to give advice to avoid contact with sensitizing agents.

Impact of immunosuppressive treatment on endothelial biomarkers after kidney transplantation.

Endothelial dysfunction occurs in hemodialysis and kidney-transplanted patients and can be enhanced by immunosuppressive therapy. Circulating endothelial cells (CEC), endothelial microparticles (EMP) and sVCAM-1 provide information on endothelium activation and damage. We compared the impact of two immunosuppressive regimens (CsA/Aza vs. Tac/MMF) on the kinetics of CEC, EMP and sVCAM-1 levels in 52 patients, both before graft and 3, 6, 9 and 12 months after graft, in reference to 50 healthy controls. CEC, EMP and sVCAM-1 levels were significantly decreased 1 year after transplantation (M12) as compared to pretransplant values. At M12, CEC and sVCAM-1 levels were significantly higher than those of controls whereas EMP reached normal values. Nine months postgraft, lower CEC and normalized EMP levels were found in patients receiving cyclosporine microemulsion/ azathioprine (CsA/Aza) when compared to patients treated with tacrolimus/ mycophenolate mofetil (Tac/MMF). Multivariate analysis evidenced positive correlations between CEC and history of cardiovascular diseases and between EMP and cytomegalovirus infection at M12. In conclusion, our combined analysis of endothelial injury markers confirms the favorable impact of renal transplantation on endothelium, and show that CEC levels discriminate treatment-associated endothelial toxicity. These results enlighten the potential of these noninvasive blood biomarkers in indexing vascular injury and optimize therapeutic options.

Early IgG glomerulonephritis recurrence in a kidney transplant recipient.

We report a second case of mesangial IgG glomerulonephritis recurrence after kidney allograft transplantation. Mesangial IgG glomerulonephritis is considered a distinct glomerulonephritis. To date, only 1 recurrence after transplantation has been reported. In the present case, recurrence occurred 3 months after transplantation, following an acute rejection episode. Three sequential graft biopsies describe the onset of glomerular lesions.

Lymphoma-associated hemophagocytic syndrome: a rare cause of severe prerenal acute renal failure.

We report on a 79-year-old woman having hemophagocytosis and capillary hyperpermeability syndrome who presented with anuric prerenal acute renal failure. The patient eventually died of a hypovolemic shock. Post-mortem biopsies evidenced a highly aggressive B cell intravascular lymphoma without amyloidosis. Physicians should be aware of the risk of anuric prerenal acute renal failure in the course of lymphoma-associated hemophagocytic syndrome.

The uremic solute indoxyl sulfate induces oxidative stress in endothelial cells.

BACKGROUND: Endothelial dysfunction and oxidative stress are matters of concern in patients with chronic renal failure (CRF). Uremic solutes retained in these patients could be involved in these processes. Notably, the protein-bound uremic solute indoxyl sulfate induces endothelial dysfunction in vitro, and has shown pro-oxidant effects. OBJECTIVE: To demonstrate that indoxyl sulfate is a potential mediator of oxidative stress in endothelial cells in vitro. METHODS: Indoxyl sulfate-induced oxidative stress in human umbilical vein endothelial cells (HUVEC) was studied by measuring reactive oxygen specie (ROS) production by cytofluorimetry, by analyzing the involvement of the pro-oxidative enzymes NAD(P)H oxidase, xanthine oxidase, and NO synthase, and by measuring the levels of the non-enzymatic antioxidant glutathione. RESULTS: We showed that indoxyl sulfate induced a significant production of ROS in HUVEC, with or without human serum albumin. We then investigated the role of pro-oxidative enzymes and measured the levels of the antioxidant glutathione. The NAD(P)H oxidase inhibitors, DPI, and apocynin, inhibited ROS production, whereas inhibitors of xanthine oxidase, NO synthase, and mitochondrial ROS had no effect. Interestingly, indoxyl sulfate strongly decreased the levels of glutathione, one of the most active antioxidant systems of the cell. In addition, the ROS production mediated by indoxyl sulfate was inhibited by the antioxidants vitamin C, vitamin E, and NAC. CONCLUSION: The uremic solute indoxyl sulfate enhances ROS production, increases NAD(P)H oxidase activity, and decreases glutathione levels in endothelial cells. Thus, indoxyl sulfate induces oxidative stress by modifying the balance between pro- and antioxidant mechanisms in endothelial cells.

Elevation of circulating endothelial microparticles in patients with chronic renal failure.

BACKGROUND: Chronic renal failure patients are at high risk of cardiovascular events and display endothelial dysfunction, a critical element in the pathogenesis of atherosclerosis. Upon activation, the endothelium sheds microparticles, considered as markers of endothelial dysfunction that also behave as vectors of bioactive molecules. AIM: To measure plasma levels of endothelial microparticles (EMPs) in chronic renal failure patients (CRF), either undialyzed or hemodialyzed (HD), and to investigate the ability of uremic toxins to induce EMP release in vitro. METHODS: Circulating EMPs were numerated by flow cytometry, after staining of platelet-free plasma with phycoerythrin (PE)-conjugated anti-CD144 (CD144+ EMP) or anti-CD146 (CD146+ EMP) monoclonal antibodies. Platelet MP (CD41+ PMP), leukocyte MP (CD45+ leukocyte microparticles (LMP)), and annexin-V+ MPs were also counted. In parallel, MPs were counted in supernatant of human umbilical vein endothelial cells incubated with uremic toxins [oxalate, indoxyl sulfate, p-cresol, and homocysteine (Hcy)], at concentrations found in patients. RESULTS AND CONCLUSIONS: CD144+ EMP and CD146+ EMP levels were significantly higher in CRF and HD patients than in healthy subjects. Furthermore, annexin-V+ MPs were elevated in both groups of uremic patients, and CD41+ PMP and CD45+ LMP were increased in CRF and HD patients, respectively. In vitro, p-cresol and indoxyl sulfate significantly increased both CD146+ and annexin-V+ EMP release. Increased levels of circulating EMP in CRF and HD patients represent a new marker of endothelial dysfunction in uremia. The ability of p-cresol and indoxyl sulfate to increase EMP release in vitro suggests that specific uremic factors may be involved in EMP elevation in patients.

Kelley-Seegmiller syndrome due to a new variant of the hypoxanthine-guanine phosphoribosyltransferase (I136T) encoding gene (HPRT Marseille).

A patient with hyperuricaemia and gouty arthritis due to a new variant of hypoxanthine-guanine phosphoribosyltransferase is described. The mutation (I136T, HPRT Marseille) is in the phosphoribosylpyrophosphate-binding region of the gene and leads to almost total loss of enzyme activity in erythrocytes, with 5% in lymphocytes. Nevertheless, the patient showed no neurological abnormality.

[Review of quality of life instruments used in end-stage renal disease]. / Qualité de vie et insuffisance rénale chronique terminale: le point sur les différents questionnaires existants.

Health related quality of life (HRQOL) indicators take into account the personal perception of health, and are proposed as an alternative for efficacy indicators in medical and therapeutic decision making. They provide, due to elaboration and validation of a questionnaire, a standardised assessment of the health status perception. This paper provides a review of a variety of HRQOL instruments developed for patients suffering end-stage renal disease (ESRD). Generic instruments are designed to be applicable in general population and disease-targeted instrument are potentially more sensitive to the characteristics of a specific population. Among HRQOL instruments, we found 4 generic questionnaires (the Sickness Impact Profile, the SF 36, the Nottingham Health Profile and the EQ-5D), 3 disease-targeted questionnaires developed for ESRD patient undergoing dialysis (the Kidney Disease Quality of Life instrument, the Kidney Disease Questionnaire and the Choice Health Experience Questionnaire), 1 questionnaire specific for ESRD patients (the HRQOL questionnaire), and 2 specific disease-targeted instruments for renal transplant (the Kidney Transplant Questionnaire and the ESRD Symptom Checklist-Transplantation Module). In France, very few studies on the quality of life of ESRD patients were published; no specific questionnaire validated in French is yet published.

Comparative study on two kidney graft rinsing and preservation solutions in terms of the post-transplantation risk of delayed graft function and cost.

OBJECTIVE: To determine whether Belzer solution (Viaspan, Bristol-Myers Squibb, Brussels, Belgium), which is more expensive than Eurocollins solution, was better at preventing delayed graft function (DGF) and whether it was cost-effective as it could potentially reduce post-transplantation complications. METHOD: The risk of occurrence of complications associated with the use of these two rinsing and preserving solutions was estimated from a survey of 106 patients undergoing renal transplantation between 1 January 1993 and 31 March 1998. Both efficacy and adverse outcomes were recorded along with the costs directly associated with the transplantation procedure in the hospital setting: hospitalization, rinsing and preserving solutions, medical and technical interventions and diagnostic tests. RESULTS: For the 45 kidney grafts rinsed and preserved with Eurocollins (strategy S1: n1 = 45) the cost/graft was estimated at 40 euros. With Viaspan (strategy S2: n2 = 61) the corresponding cost/graft was 424 euros. Logistic regression analysis showed that Viaspan was better than Eurocollins solution (ebeta = 0.437; P = 0.05) in preventing DGF. Overall, S2 was less expensive than S1, from the hospital's perspective. The mean difference per patient was 278 euros, which amounts to a saving of 2% of the total cost per renal transplantation. For rinsing and preserving kidney grafts Belzer solution is therefore preferable to Eurocollins solution.

Tubular lesions and tubular cell adhesion molecules for the prognosis of lupus nephritis.

BACKGROUND: To assess the prognostic value of tubular lesions and cell adhesion molecules' expression, a retrospective study with immunohistochemistry was performed on 152 patients presenting lupus nephritis from January 1985 to December 1999. METHODS: The following clinical parameters were recorded: age, sex, race, time of systemic lupus erythematosus (SLE) diagnosis, time of the biopsy, proteinuria, creatininemia, and renal function at the end of follow-up. All biopsies were re-evaluated according to a tubular grading, an inflammatory grading, the percentage of sclerosed glomeruli, the percentage of crescents, and the current WHO classification. Immunohistochemistry was performed with anti-CD40, anti-CD44, and anti-intercellular adhesion molecule-1 (anti-ICAM-1) antibodies. RESULTS: Patients were 136 women (89.5%) and 16 men with a mean age of 31.2 years +/- 12.8 at the time of biopsy. The mean follow-up period was 94.3 months +/- 64.1. Eighty-eight biopsies (58%) showed various degrees of tubular atrophy. Males (P = 0.001) and tubular grading (P = 0.0001) were linked with renal survival in univariate and multivariate analysis. CD40 (P = 0.01) and ICAM-1 (P = 0.001) tubular expressions were linked with renal survival. ICAM-1 tubular expression provided additional information for the prognosis of the patients with biopsies showing tubular atrophy (P = 0.005) or not (P = 0.05). CONCLUSIONS: Our study shows that tubular lesions are good indicator of lupus nephritis outcome. Furthermore, tubular expression of cell adhesion molecules like ICAM-1 and CD40 also serves to predict the outcome.