Pre-transplant end-stage renal disease-related immune risk profile in kidney transplant recipients predicts post-transplant infections.

BACKGROUND: End-stage renal disease (ESRD) is associated with premature aging of the T-cell system. Nevertheless, the clinical significance of pre-transplant ESRD-related immune senescence is unknown. METHODS: We studied whether immune risk phenotype (IRP), a typical feature of immune senescence, may affect post-transplant infectious complications. A total of 486 patients were prospectively studied during the first year post transplant. IRP was defined as positive cytomegalovirus serology with at least 1 of the following criteria: CD4/CD8 ratio <1 and/or CD8 T-cell count >90th percentile. RESULTS: We found that 47 patients (9.7%) had pre-transplant IRP. IRP+ patients did not differ from IRP- patients for any clinical characteristics, but exhibited more pronounced immune senescence. Both opportunistic infections (43% vs. 6%, P < 0.001) and severe bacterial infection (SBI) (40% vs. 25%, P = 0.028) were more frequent in IRP(+) patients. In multivariate analysis, IRP was predictive of both opportunistic infection (hazard ratio [HR] 2.97 [95% confidence interval {CI} 1.53-5.76], P = 0.001), and SBI (HR 2.33 [95% CI 1.34-3.92], P = 0.008). Acute rejection rates were numerically much lower in IRP+ patients. A total of 418 patients (86%) had biological evaluation 1 year post transplant. Among 41 IRP+ patients, 35 (85%) remained IRP+ 1 year post transplant. CONCLUSION: Pre-transplant IRP is associated with an increased risk of post-transplant infection.

Contribution of Raman spectroscopy in nephrology: a candidate technique to detect hydroxyethyl starch of third generation in osmotic renal lesions.

BACKGROUND AND OBJECTIVES: HydroxyEthyl Starch (HES) has been one of the most commonly used colloid volume expanders in intensive care units for over 50 years. The first and second generation HES, with a high molecular weight (≥200 kD) and a high degree of substitution (≥0.5), has been associated with both renal dysfunction and osmotic nephrosis-like lesions in histological studies. Recently, third generation HES (130 kD/<0.5) has also been shown to impair renal function in critically ill adult patients although tubular accumulation of HES has never been proven in the human kidney. Our objective was to demonstrate the potential of Raman micro-imaging to bring out the presence of third generation-HES in the kidney of patients having received the volume expander. DESIGN: Four biopsies presenting osmotic nephrosis-like lesions originated from HES-administrated patients with impaired renal function were compared with HES-negative biopsies (n = 10) by Raman microspectroscopy. RESULTS: The first step was dedicated to the identification of a specific vibration of HES permitting the detection of the cellular and tissue accumulation of the product. This specific vibration at 480 cm(-1) is assigned to a collective mode of the macromolecule; it is located in a spectral region with a limited contribution from biological materials. Based on this finding, HES distribution within tissue sections was investigated using Raman micro-imaging. Determination of HES positive pixels permitted us to clearly distinguish positive cases from HES-free biopsies (proportions of positive pixels from the total number of pixels: 23.48% ± 28 vs. 0.87% ± 1.2; p = 0.004). CONCLUSIONS: This study shows that Raman spectroscopy is a candidate technique to detect HES in kidney tissue samples currently manipulated in nephrology departments. In addition, on the clinical aspect, our approach suggests that renal impairment related to third generation HES administration is associated with osmotic nephrosis-like lesions and HES accumulation in the kidney.

ATG-induced accelerated immune senescence: clinical implications in renal transplant recipients.

Persistent ATG-induced CD4(+) T cell lymphopenia is associated with serious clinical complications. We tested the hypothesis that ATG induces accelerated immune senescence in renal transplant recipients (RTR). Immune senescence biomarkers were analyzed at transplant and one-year later in 97 incident RTR -62 patients receiving ATG and 35 receiving anti-CD25 mAb (α-CD25). This consisted in: (i) thymic output; (ii) bone marrow renewal of CD34(+) hematopoietic progenitor cells (CD34(+) HPC) and lymphoid (l-HPC) and myeloid (m-HPC) progenitor ratio; (iii) T cell phenotype; and (iv) measurement of T cell relative telomere length (RTL) and telomerase activity (RTA). Clinical correlates were analyzed with a 3 year follow-up. Thymic output significantly decreased one-year posttransplant in ATG-treated patients. ATG was associated with a significant decrease in l-HPC/m-HPC ratio. Late stage differentiated CD57(+) /CD28(-) T cells increased in ATG-treated patients. One-year posttransplant T cell RTL and RTA were consequently lower in ATG-treated patients. ATG is associated with accelerated immune senescence. Increased frequency of late differentiated CD4(+) T cell frequency at transplantation tended to be predictive of a higher risk of subsequent opportunistic infections and of acute rejection only in ATG-treated patients but this needs confirmation. Considering pretransplant immune profile may help to select those patients who may benefit from ATG to prevent severe infections and acute rejection.

Germline Mutations in RASA1 Are Not Found in Patients with Klippel-Trenaunay Syndrome or Capillary Malformation with Limb Overgrowth.

The RASA1 gene encodes p120RASGAP, a multidomain cytoplasmic protein that acts as a negative regulator of the RAS signalling pathway. Heterozygous loss-of-function RASA1 mutations were identified in patients with Parkes Weber syndrome and multifocal capillary malformations. This syndrome is characterised by a capillary blush on an extremity, arteriovenous microfistulas, and bony and soft tissue hypertrophy. The aim of this study was to test RASA1 in 2 disorders characterised by asymmetric limb enlargement and vascular malformations, namely Klippel-Trenaunay syndrome and regional capillary malformation with overgrowth. We did not identify any clear pathogenic change in these patients. Thus, besides clinical and radiological criteria, RASA1 testing constitutes an additional tool to differentiate Parkes Weber syndrome of capillary malformation-arteriovenous malformation (CM-AVM) from overlapping disorders.

[Time course of digital pressure during dialysis sessions in chronic hemodialysis patients. Prospective observational study of 49 patients]. / Évolution de la pression digitale pendant une séance de dialyse chez 49 patients.

OBJECTIVES: To describe and compare the evolution of digital pressure on both hands during a dialysis session in patients without digital ischemia, and to identify the parameters influencing the digital pressure. MATERIALS: Patients with an upper limb vascular access were prospectively included. Digital systolic pressure on the third finger of both hands measured by photoplethysmography and brachial systolic pressure were recorded before dialysis (H0) and every hour (from H1 to H4). RESULTS: Among 53 patients, 49 were included (exclusions: one surgery for ischemia, one hand tremor, two no consent). None of them had digital ischemia. Digital pressure homolateral to the vascular access was significantly lower compared with controlateral side before and during dialysis. Digital pressure significantly decreased on both sides during dialysis. Brachial pressure decreased significantly compared to H0. Only the brachial pressure decrease was correlated with the decrease of digital pressure. The digital pressure was less than 30 mmHg in six patients. No evidence of digital ischemia was reported after a 6-month follow-up. CONCLUSION: To our knowledge, this is the first study showing a significant decrease of digital pressure in both hands during hemodialysis in patients without digital ischemia. Further studies are necessary to investigate which parameters can affect digital pressure and to look for clinical consequence of this measurement.

Comparison of C4d detection on erythrocytes and PTC-C4d to histological signs of antibody-mediated rejection in kidney transplantation.

C4d on erythrocytes (EC4d), C4d peritubular capillary deposition (PTC-C4d) staining and histology were compared in a cross-sectional cohort of 146 renal allograft biopsies (132 patients). EC4d levels paralleled PTC-C4d staining, but were more predictive of peritubular capillaritis (PTC). Donor-specific antibodies (DSA), PTC-C4d, EC4d and PTC were analyzed in an independent longitudinal follow-up cohort (96 biopsies, 76 patients). Seventy-six samples were PTC and EC4d concordant, 11 positive and 65 negative, 7 PTC-EC4d+ and 13 PTC+EC4d-. EC4d levels were related to DSA occurrence. With ABMR defined by PTC and DSA, all apparently discordant patients, EC4d negative, were correctly reassigned comparing EC4d level curves with rejection kinetics, with positive EC4d samples predating biopsy or late biopsies compared with ABMR flare-ups. All EC4d-positive patients without PTC or DSA had permanent high EC4d levels unrelated to rejection. EC4d was more abundant in PTC-positive (mean = 108.5%± 3.4; n = 50) than PTC-negative samples (mean = 88.1%± 1.3; n= 96; p < 0.0001). Sensitivity, specificity, positive predictive value and negative predictive value of PTC-C4d and EC4d for PTC were, respectively, 75%, 79%; 64%, 76% (p < 0.05); 28%, 46% (p < 0.05) and 93%, 94%. Values were similar for DSA. A noninvasive blood test, EC4d, and particularly longitudinally monitoring EC4d levels, may increase surrogate ABMR testing options.

[Treatment of macroglossia due to acromegaly]. / Behandeling van macroglossie ten gevolge van acromegalie.

A 61-years-old woman had macroglossia due to acromegaly with complaints of dyspneu at a lying sleeping position and complaints of speech and dysphagia. At the age of 55 years she was diagnosed with acromegaly induced by a adenoma of the pituitary gland, which had been removed surgically. The treatment of macroglossia included tongue reduction, removal of the remaining mandibular teeth with severe periodontal attachment loss, huge reduction of the residual alveolar ridge, immediate implant insertion, fabrication of implant-supported overdentures, and logopedic treatment. The speech improved significantly and the patient could sleep again in a lying position. Clinically, acromegaly is diagnosed on clinical signs, such as the morphology and the protrusion of the tongue. Often, macroglossia is a secondary symptom of a systemic disease, needing causal treatment. If surgical reduction of the tongue is indicated, also enlargement of the oral cavity should be considered.

Preventing graft thrombosis after renal transplantation: a multicenter survey of clinical practice.

BACKGROUND: Renal allograft vascular thrombosis is a complication that often results in graft loss. Since there are no guidelines on immediate postoperative thromboprophylaxis, we performed a telephone survey of clinical practice in all renal transplantation centers in France. METHODS: Each center considered 4 cases relating to renal transplant candidates on dialysis with an increasing risk of thrombosis: Case 1: patient with no identified risk factors; Case 2: patient with an earlier incidence of deep vein thrombosis; Case 3: patient with ischemic heart disease on antiplatelet therapy; Case 4: patient with atrial fibrillation taking a vitamin K antagonist (VKA) with lupus nephritis syndrome. RESULTS: The treatments proposed by the centers (%) were: Case 1: No anticoagulation therapy (57.1%), calcium heparin at prophylactic doses (P-dose) (40%), or unfractionated heparin (UFH); (P-dose; 2.9%). Case 2: No anticoagulation therapy (34.3%), calcium heparin (P-dose; 51.4%), or UFH (P-dose; 5.7%). Case 3: (A) Interruption of aspirin (65.7%), and either no anticoagulation therapy (21.7%) or substitution of aspirin by calcium heparin (P-dose; 56.6%) or by UFH (P-dose; 8.7%). (B) No interruption of aspirin (34.3%), and either no additional prophylaxis (58.3%) or calcium heparin (P-dose; 33.3%). Case 4: Interruption of VKA (100%), and UFH at a curative dose (68.6%), UFH (P-dose; 14.3%), or calcium heparin (P-dose; 11.4%). CONCLUSIONS: Practices varied widely in the absence of studies of sufficiently high power. There is a need for a preoperative classification of thrombotic and hemorrhagic risk among renal transplant candidates and for consensus guidelines.

[What tests are necessary before registration on the kidney transplant waiting list?]. / Quelles explorations faut-il réaliser avant l'inscription sur une liste de transplantation rénale ?

Before registering a patient on the kidney transplant waiting list, the medical file should be carefully studied looking for factors that may complicate the transplantation. Knowledge of the patient's history and the clinical examination will guide the choice of complementary examinations. The objectives of pretransplantation explorations are : 1) preventing graft rejection ; 2) ensuring that arterial and venous anastomoses are possible ; 3) ensuring that urine can be drained ; 4) preventing post-transplantation infections ; 5) not performing a transplantation on a subject with cancer ; and 6) avoiding any post-transplantation cardiovascular events. The list of the necessary explorations for renal transplantation should be as simple as possible so that registration on the transplant waiting list is not delayed, while being as complete as possible to prevent any complications that may compromise the results. It should be individualized to each patient.

[Anticoagulation after renal transplantation: a multicenter survey on clinical practice]. / Quelle thromboprophylaxie après transplantation rénale ? Enquête sur la prévention des thromboses du greffon en France.

OBJECTIVES: Graft thrombosis is a major complication of transplantation. However, there are no recommendation on immediate postoperative thromboprophylaxis after kidney transplantation. We recorded clinical practices in France. MATERIAL AND METHODS: In 29 transplantation centres, four case studies were submitted to the medical kidney transplantation referent (compatible graft from cadaveric donor, without perioperative complication). N(o) 1: Man, 27-years-old, IgA glomerulonephritis, without history of hypercoagulability or cardiovascular risk factor. Hemodialysis since 12months. N(o) 2: Man, 53-years-old, with history of deep venous thrombosis after cholecystectomy 15years before. Membranous nephropathy. Hemodialysis since 10months. N(o) 3: Man, 58-years-old, with history of myocardial infarction. On aspirin therapy. Nephroangiosclerosis and diabetic nephropathy. Peritoneal dialysis since 6months. N(o) 4: Woman, 63-years-old. Atrial fibrillation on vitamin K antagonists therapy. Lupus nephritis without antiphospholipid syndrome. Hemodialysis since 12months. RESULTS: N(o) 1: No anticoagulation therapy (62%), calcium heparin at prophylactic doses (34.5%). N(o) 2: No anticoagulation therapy (38%), calcium heparin at prophylactic doses (44.8%). N(o) 3: 62% interrupted aspirin of whom 22% without any immediate anticoagulation and 55% replaced aspirin with calcium heparin at prophylactic doses. Thirty-eight percent carried on with aspirin of whom 63.6% without other prophylaxis and 27.3% in association with calcium heparin at prophylactic doses. N(o) 4: Unfractionned heparin at curative dose (62%), unfractionned heparin at prophylactic doses (17.2%), calcium heparin at prophylactic doses (13.8%). CONCLUSION: Postoperative anticoagulation after renal transplantation is established as a local dogma rather than evidence-based medicine. Guideline recommendations and standardized protocols for the use of anticoagulation after kidney transplantation should be developed.

A neonate with an intact congenital umbilical appendix: an alternative theory on the etiology of the appendico-umbilical fistula.

Neonatal umbilical anomalies usually represent remains of the vitelline duct or the allantois. We describe a case of an umbilical appendix in a neonate. The vermiform appendix was found to be positioned in the umbilical cord. In a brief literature review we found eight other reports concerning umbilical appendices. In this article we describe a possible embryological explanation for the development of an umbilical appendix, and discuss whether or not the appendiceal umbilical fistulae reported are congenital or iatrogenic. The possible association between an umbilical appendix and different forms of malpositioning and rotation of the gut is also discussed. Protrusion of the neonatal appendix into the umbilical cord represents a different entity of congenital anomalies. It is important to realize that, in the case of an unrecognized umbilical appendix, medical procedures (e.g., canulation or clamping of the umbilicus) may produce an iatrogenic appendico-umbilical fistula. Careful inspection and palpation of the umbilical cord prior to these procedures may prevent a fistula being created. Furthermore, because the possible association between umbilical appendices and different kinds of malpositioning of the gut is so far not wholly elucidated, we recommend further (radiological) investigation in each case of an umbilical appendix. Correct positioning of the bowel needs to be confirmed in order to rule out possible future complications.

Colonic duplications: clinical presentation and radiologic features of five cases.

Diagnosis of colonic duplication can pose a potential problem even for those familiar with gastro-intestinal tract duplications in general but unaware of the condition due to its rarity and its apparently bimodal clinical presentation. In this report of five cases of surgically proven pediatric colonic duplication, we illustrate how the condition manifests clinically and describe the imaging features in an attempt to illustrate this bimodal presentation of the condition. The possible etiology, associated congenital anomalies and modes of clinical presentation are reviewed based on literature review as well as on our own experience.

[Pregnancy after renal transplantation. Obstetrical follow-up and impact on renal graft function]. / Grossesse après transplantation rénale. Suivi obstétrical et retentissement sur le greffon rénal.

OBJECTIVE: The aim of this study is to give the results of our experience about pregnancies among the renal transplantation patients and to assess the impact of the pregnancy on renal graft function. PATIENTS AND METHODS: Twenty pregnancies from 17 renal transplant recipients were analysed and long-term outcome of the renal graft was studied. We analysed the outcomes from clinical and biological data before, during and after pregnancy. RESULTS: Mean patient age was 30.3+/-3.5 years and meantime between transplantation and the onset of pregnancy was 62.4+/-34.5 months. There was no significant difference between the biological data before and after pregnancy. We did not observe any acute rejection. The mean maternal complications were preeclampsia in 35%, low birth weight in 39%, prematurity in 45% and cesarean sections in 55%. There is no impact of the pregnancy on the renal graft during the follow-up (3 years). The follow-up revealed 2 cases of chronic rejection. DISCUSSION AND CONCLUSION: A multi-disciplinary approach of pregnancy in renal recipients and an interval of 2 years after kidney transplantation are necessary. There are more complications during pregnancy without increased risks of graft lose.

[Infective lithiasis]. / Lithiases d'infection.

"Infection Lithiasis" refers to calculi that occur with persistent urinary tract infection. Stones composed of magnesium ammonium phosphate (struvite) and carbonate apatite, called "triple phosphate" stones, are the more common type of infection lithiasis. These stones are also called "staghorn" calculi because they may grow rapidly and fill the entire collecting system. They form during urinary infection with urea-splitting micro-organism. They may originate de novo or complicate a lithiasis when pre-existing stones are colonized with urea-splitting bacteria. They represent about 2-3% of stones referred for laboratory analysis. This article reviews the epidemiology, pathogenesis, clinical features, and management of struvite stones. A singular pathologic entity recently described, called "encrusted cystitis or encrusted pyelitis", mainly caused by Corynebacterium urealyticum is also review. Infection lithiases caused by non-urease-producing bacteria may also occur and are examined in this article. Finally, the controversial role of nanobacteria in nephrolithiasis is discussed.

[A child with traumatic hemobilia]. / Een kind met traumatische hemobilie.

A 4-year-old boy was hit by a car travelling at 40 km/h and was admitted 3.5 h later to the department of paediatric surgery. Because he was haemodynamically unstable and needed blood transfusion, the patient underwent an emergency operation. The liver was ruptured in the right lobe. A large haematoma was found in the serosa of the duodenum, along with a Meckel's diverticle, which was left in place. The liver rupture was covered and sealed. One month after the accident the patient was re-admitted, because of abdominal pain and gastrointestinal bleeding. The cause was thought to be the Meckel's diverticle, which was removed later. Two months after the trauma the patient was re-admitted with abdominal pain, again with haematemesis and melaena. The diagnosis of hemobilia was obtained with MRI and angiography, which revealed a ruptured pseudoaneurysm of the ramus dexter of the proper hepatic artery. The patient was successfully treated with embolization. The diagnostic delay was two months, which illustrates the importance of considering the possibility of the diagnosis hemobilia in case of gastrointestinal haemorrhage combined with biliary symptoms.

[Acute appendicitis in children: serious complications when treatment is delayed]. / Appendicitis acuta bij kinderen: ernstige complicaties bij vertraging in de behandeling.

Three children, two boys aged 9 and 6 and a 12-year-old girl, had diffuse abdominal complaints, diarrhoea and a (sub)febrile temperature for several days. On admission, they were found to have a perforated inflamed appendix and peritonitis. Following asystole, intra-abdominal abscesses and an enterocutaneous fistula, the oldest boy showed good recovery after a hospital stay of two months; the girl recovered after one month in hospital following a psoas muscle abscess and two episodes of constrictive pericarditis with threatened tamponade. The younger boy was dead on arrival at the hospital. Appendicitis is not always easy to diagnose. An atypical presentation, very often with diarrhoea, can result in diagnostic delay. Early surgical consultation is mandatory in a child with progressive abdominal pain.

[Haemangiomas and congenital vascular malformations: their classification and diagnosis]. / Hemangiomen en congenitale vasculaire malformaties; classificatie en diagnostiek.

Mulliken and Glowacki's classification of peripheral blood- and lymph-vessel abnormalities is based on their clinical course and cellular characteristics, and is therefore clear to and readily usable by the practising physician. In order to make the diagnostic process more accessible, the Haemangiomas and Congenital Vascular Malformations Nijmegen working group has developed a system of diagnostic guidelines on the basis of this classification. The anamnesis should be directed at the following six distinguishing characteristics: presence of the anomaly at birth, growth, involution, change in volume, pain and outflow. The physical examination is directed at the following five characteristics: the possibility of emptying or pushing aside the anomaly, changes in volume during engorgement, murmur/'thrill'/pulsation, phleboliths, and hyper- or hypotrophy. If a diagnosis still cannot be made, then additional investigations may be carried out. Duplex scanning is usually sufficient for this purpose, after which the nature and extent of the malformation can be determined with MRI. On the basis of the results, the persons involved can be informed as to the prognosis of the malformation and a plan of treatment can be proposed.