Lymphomatoid granulomatosis treated successfully with rituximab in a renal transplant patient.

Lymphomatoid granulomatosis (LYG) in renal transplant recipients is rare multisystemic angiocentric lymphoproliferative disorder with significant malignant potential. Here, we describe LYG in a 70-year-old renal allograft recipient who, 4 years after transplantation, on tacrolimus and mycophenolate mofetil and prednisone maintenance immunosuppression, complained of low-grade fever, persistent headache and gait disturbance. The MRI of the brain revealed diffuse periventricular cerebral and cerebellar contrast-enhanced lesions. The CT scan of the thorax showed multiple pulmonary nodular opacities in both lung fields. The patient was diagnosed LYG based on the cerebral biopsy showing perivascular infiltration of CD20-positive B-lymphocytes with granulomatous lesions and immunofluorescence staining with anti-EBV antibodies. With careful reduction of the immunossuppression combined with the use of rituximab, our patient showed a complete disappearance of LYG, and she is clinically well more than 4 years after the diagnosis, with good kidney function. No recurrence has been observed by radiological imaging until now. This is the first report of a durable (>4 years) complete remission of LYG after treatment with rituximab in renal transplantation.

[Is clinical judgment a suitable method to select marginal allograft for transplantation? A single centre experience]. / Le seul jugement clinique peut-il être utilisé pour accepter un greffon marginal? Expérience d'un centre de transplantation.

In order to deal with the organ shortage, the use of organs from marginal donors has emerged as an obvious option. The decision to accept a kidney from an expanded criteria donor is left to the transplantation centre. This study was carried out to evaluate whether clinical judgment is a suitable method to decline a kidney from a marginal donor. This was a retrospective study of the outcome of marginal kidneys rejected by our centre between 1st January 2000 and 31st December 2006 but accepted by another centre. The decision to refuse a marginal kidney was based on the clinical judgment of the nephrologists on call. Kidney refusal was retrospectively considered as a "mistaken decision" when the kidney was transplanted in another centre and when the estimated GFR was above 60 mL/min/1.73 m(2) one year after transplantation. The DD score was calculated retrospectively for every rejected kidney. During the study period, 304 kidneys were not accepted for transplantation. Of these 304 kidneys, 55 marginal kidneys were not accepted by the nephrologists on call. Among these 55 marginal kidneys, 44 were accepted and transplanted in another centre. Early graft loss occurred in 2/44 recipients. Death censored allograft survival at one and two years was retrospectively 98 and 93%. Kidney refusal was considered as a "mistaken decision" for 12/44 rejected kidneys. Of these 12 rejected kidneys, only two could have been considered as marginal kidneys by the DD score, as compared with 27/30 of the remaining rejected kidneys. Our study shows that clinical judgment alone is not a suitable method for selecting marginal donors. Proven definitions of "marginal donor", available to physicians when the medical decision has to be made, may help nephrologists in their clinical practice.

[Failed transplant patients: dialysis initiation and short-term outcome]. / Dialyse après échec de transplantation. Conditions de prise en charge initiale et évolution à court terme.

UNLABELLED: This study was carried out to evaluate dialysis initiation of failed transplant patient and the short-term outcome of these patients on dialysis. PATIENTS AND METHOD: We conducted a retrospective study of transplanted patients from one centre returning in dialysis after allograft failure. Those patients were transplanted between 31st October 1986 and 3rd March 2004. Patients who experienced allograft failure after 6 months on transplantation were included in the study. RESULTS: Among 600 transplanted patients, 92 patients restarted dialysis after allograft failure. Of the 92 failed transplant patients, 69 had a graft survival of more than 6 months. The mean glomerular filtration rate at dialysis initiation was 13+/-5mL per minute. At time of dialysis initiation, patients had mean haemoglobin level at 80.7+/-10.7g/L, and mean serum albumin level at 34+/-6g/L. Urgent dialysis was needed for 39 over 57 patients. Fourteen over 58 patients had no vascular access or peritoneal catheter at dialysis initiation. Fifty-six over 69 patients were treated by haemodialysis. Of the 13 patients treated by peritoneal dialysis 7 were on PD before transplantation whereas 49 over 57 haemodialysis patients were treated by haemodialysis before transplant failure (p<0.05). Immunosuppressive therapy was stopped during the first year following transplantation failure in 52 over 69 patients and 36 over 69 patients underwent transplantectomy. Thirteen over 56 patients presented a least one cardiovascular events after transplantation failure. CONCLUSION: Unplanned dialysis initiation is frequent in failed transplant patients, in whom an early dialysis start is probably mandatory.

[News in peritoneal dialysis]. / Actualités en dialyse péritonéale.

Peritoneal dialysis, like hemodialysis, is a first-line therapy for patients with end-stage renal disease. Progress in medical devices and materials has reduced infectious complications such as peritonitis and catheter exit-site infections and thus decreased morbidity. Peritoneal dialysis fluids are increasingly biocompatible, result in fewer glucose degradation products, protect the peritoneal membrane better and thus improve tolerance. The maintenance of residual renal function, together with better comfort and no pain, help control the fluid and sodium balance. Automated peritoneal dialysis can be performed each night, either autonomously or assisted by a visiting nurse twice a day (to prepare, connect, and disconnect the machine). This treatment can thus be provided to most patients, regardless of their age. Peritoneal dialysis is indicated principally for young people waiting for a kidney transplantation (to preserve their vascular network), elderly patients who wish to remain either at home or in an institution, and patients with cardiac insufficiency, because of the better hemodynamic tolerance. Numerous obstacles, mainly nonmedical, still impede the development of peritoneal dialysis. Patients seen in emergencies start hemodialysis without necessarily receiving any information about peritoneal dialysis. Indeed, neither physicians nor patients receive adequate information.

Long-term evolution of body composition after renal transplantation: 5-year survey.

BACKGROUND: Thanks to advancements in immunosuppression, patients are living longer with kidney transplants, and nonimmunologic factors (particularly nutritional) have become a major source of morbidity and mortality after successful kidney transplantation (KTx). In this current study, we have prospectively assessed, in a cohort of kidney transplant recipients (KTR), the course of some nonimmunologic factors liable to hinder the long-term outcome of KTR. METHODS: Forty-four consecutive KTR with stable functioning grafts received dietary recommendations and were on the lowest effective dose of steroids. Biochemical nutritional markers, C-reactive protein, lipid profile, and body composition determined by dual-energy X-ray absorptiometry were studied over the first year, 2 years, and 5 years after KTx. RESULTS: No patients died during the follow-up. All patients but 2 were considered normotensive. Clinical diabetes developed in 3 patients. Visceral proteins stabilized at a normal range after the first year. Most of the patients normalized their inflammatory status. A significant improvement in lipid profile was observed. Female patients had a significant increase of weight (13.5%), mainly because of an increase in fat mass: 3.4 kg (19.4%) at 1 year and 5.6 kg (29.7%) at 2 years. In male patients, body composition remained stable and close to baseline values. The evolution of bone mass varied according to gender, total corticoid doses, and calcineurin inhibitors. Patients on low doses of steroids normalized their Z-score over the 5-year period. The increase in bone mass (paired t-test, P = .006) was only significant in patients treated with tacrolimus (analysis of variance for repeated measures, P < .001). CONCLUSIONS: Simple measures and dietary intervention to prevent or correct nonimmunologic disorders should permit improvement of long-term morbidity and mortality of KTR without compromising the functional outcome of their transplant.

Assisted peritoneal dialysis. Experience in a French renal department.

BACKGROUND: The French healthcare system offers the possibility of increasing the use of peritoneal dialysis (PD) by involving in patient care nurses who work in the private system. OBJECTIVE: This study was conducted to evaluate the impact of a private home-nurse network on one dialysis program. METHODS: This was a retrospective study of 239 dialysis patients who started dialysis in our center between 1 January 1998 and 31 December 2003. RESULTS: Of these 239 patients, 142 were treated with hemodialysis and 97 with PD during the study period. Among the PD patients, 36 of 97 were treated with assisted PD and 61 of 97 with self-care PD. Assisted-PD patients were older (74 +/- 10 vs 52 +/- 18 years, p < 0.001) and presented more comorbidity (Charlson Comorbidity Index 7 +/- 2.5 vs 4.3 +/- 2.4, p < 0.05) compared with self-care patients. Continuous ambulatory PD was the modality of choice in the assisted group (32/36). Assisted patients were frequently hospitalized (31/36); actuarial survival free of hospitalization at 6 months was 46%. Patients with nurse assistance had a high risk of peritonitis (actuarial survival free of peritonitis: 52% at 1 year). Technique survival was 85% at 6 months and 58% at 1 year. Actuarial patient survival was 90% at 6 months and 83% at 1 year. CONCLUSION: Assisted PD enables increased use of PD in incident dialysis patients. However, in view of the comorbidities of the assisted-PD patients, the need for frequent hospitalization has to be taken into account in such a program.

[Hospitalization of peritoneal dialysis patients: the impact of peritonitis episodes on the hospitalization rate]. / Impact des infections du liquide de dialyse sur le taux d'hospitalisation des patients traités par dialyse péritonéale.

Peritonitis is still a frequent complication in peritoneal dialysis patients. Medical guidelines have been established to manage this infection. These guidelines do not provide any information regarding the requirement for hospitalization. The main objective of this study was to evaluate the impact of peritonitis episode on the hospitalization rate and on the hospitalization duration in a centre where peritoneal dialysis patients were hospitalized in case of peritonitis. This was a retrospective study of incident peritoneal patients over a six years period. Among 101 peritoneal dialysis patients 65% were hospitalized. Two hundred and twenty hospital stays were registered. The total duration of hospital stays was 2091 days. The hospitalization rate was 2 per patient and per year, the hospital duration was 19 days per patient per year. Of the 220 hospital stays, 67 (30%) were due to a peritoneal infection. Peritonitis episodes represent 581/2091 (28%) days of hospitalization. The mean duration of hospitalization for peritonitis was 8.7+/-7 days. Among the patients hospitalized for a peritonitis episode, 57% were assisted by a nurse at home to perform their peritoneal dialysis exchanges. Of the 67 peritonitis episodes, 91% were discharged from the hospital without any complication. This study emphases the fact that peritonitis has an important impact on the hospitalization rate and on the hospitalization duration in peritoneal dialysis patients. In an attempt to decrease the rate of hospitalization, educational programs are clearly needed in order to treat more peritonitis without any hospitalization requirement.

[Optimal use of peritoneal dialysis fluids in type 2 diabetes mellitus patients]. / Utilisation optimale des solutions de dialyse péritonéale chez les diabétiques de type 2.

The glucose side-effects, the main osmotic agent in conventional peritoneal dialysis (PD) solutions, are structural and functional changes of the peritoneal membrane, especially diabetic alterations in the microvasculature. Therefore, hyperpermeability with high small solutes transport and less ultrafiltration necessitates more and more high glucose concentration solutions. Glucose degradation products (PDF) and advanced glycation end-products (AGE) are formed and may induce peritoneal membrane alterations. More biocompatible solutions have to be used with less PDF and physiological pH. Icodextrin containing PD solutions have beneficial effect on sustained ultrafiltration for long dwells in PD, limitating fluid overload common in PD patients above all during peritonitis episodes. Amino acid-based PD solutions contribute to the prevention of malnutrition often observed in the diabetic PD population.

Early loss of two renal grafts obtained from the same donor: role of ecstasy?

Early loss of renal grafts is generally caused by vascular or immunologic complications. We describe two patients who received a kidney transplant from the same donor and lost their grafts during the first posttransplant week. Both cases presented necrotizing graft vasculopathy without inflammatory element. The donor was a 21-year-old woman who regularly used "ecstasy" over a 2-year period. After an extensive work-up to investigate the potential causes of graft loss, we considered the possibility of ecstasy being the cause of these two renal-graft losses.

Impact of automated peritoneal dialysis on initial graft function after renal transplantation.

In this retrospective study, we evaluated the impact of automated peritoneal dialysis (APD) on initial graft function after cadaveric renal transplantation. Each patient on APD was matched for donor age, donor serum creatinine, and cold ischemia time with one control patient on HD. The study sample consisted of 67 cases and 67 controls. The rate of delayed graft function--defined as a need for dialysis within the first week following renal transplantation-was 16% in the APD group and 10% in the HD group [p = nonsignificant (NS)]. The proportion of patients with a creatinine clearance below 10 mL/min 6 days after renal transplantation was 7% in the APD group and 3% in the HD group. Of the 67 APD patients, 12 had slow graft function as compared with 13 of the 67 HD patients (p=NS). Weight changes 3 days after transplantation were +2.1% +/- 3.7% of dry weight in HD patients and -0.1% +/- 4.6% of dry weight in APD patients (p < 0.05). The total amount of fluid infused during the surgical procedure was similar in the two groups (55.8 +/- 14.3 mL/kg vs. 60.7 +/- 14.8 mL/kg). Compared with HD, APD was not associated with a lower rate of delayed graft function.

Serum leptin, body fat, and nutritional markers during the six months post-kidney transplantation.

Leptin is a 16-kd protein that is thought to be a regulator of food intake and body weight. Many previous studies have reported elevated serum leptin levels in renal failure. In this study, we investigated the outcome of serum leptin and its relationship to body fat (BF), dietary intake, nutritional, and inflammatory markers after kidney transplantation (KTx). A total of 41 kidney transplant recipients were followed-up prospectively during 6 months posttransplantation. Serum leptin, albumin, transferrin, and C-reactive protein (CRP) were measured at KTx, 15 days, 3, and 6 months later. Dietary intake and BF were determined at KTx, 3, and 6 months later. A decrease in serum leptin was observed early at day 15 after KTx; this decrease was significant only in patients with BF >/= 30% of body weight. The decrease was maintained at 3 and 6 months after KTx. In multivariate analysis, an independent impact of higher percentage BF at KTx on the decrease of serum leptin was observed. Serum leptin correlated positively with BF. Conversely, no correlation was found between changes of serum leptin and changes of dietary intake. Leptin correlated positively with CRP at KTx, but not after normalization of renal function. Changes of serum leptin levels were not correlated with those of serum albumin levels. In summary, hyperleptinemia at KTx is manifest in patients with a high percentage of BF. An early and maintained correction follows KTx. Serum leptin levels did not appear to affect alimentary intake at and after KTx.

Body composition of patients on a very low-protein diet: a two-year survey with DEXA.

BACKGROUND: It has been reported that patients on a very-low-protein diet (VLPD) maintain a satisfactory nutritional status because of a conserved adaptive metabolic response. However, only few studies have examined the course of nutritional status and body composition in the long term (2 years). METHODS: Thirteen stable patients (8 men; age, 55 +/- 12 years; glomerular filtration rate (GFR), 15 +/- 5 mL/min) receiving a VLPD (0.3 g/kg/day protein) supplemented with amino acids and ketoanalogues (SVLPD) were studied for 2 years. A joint visit with a physician and a dietitian and routine blood and urine analyses were performed every month. Dual-energy x-ray absorptiometry (DEXA), which was used to assess modification of body composition, and GFR (urinary 51Cr-EDTA) and urinary urea and creatinine excretion, which were used to assess nutritional status and compliance to the diet, were assessed every 3 months. RESULTS: GFR, albumin, and prealbumin levels remained stable. Urea urinary excretion decreased at 3 months and then slightly increased at 2 years, but the calculated protein intake remained low at 0.38 +/- 0.1 g/kg/day. Energy intake remained close to 30 kcal/kg/day. No significant change was observed for total fat mass or percent fat mass. After an initial decrease, lean body mass stabilized at 6 months and then increased significantly from 6 to 24 months (P =.02, paired t-test); the mean increase during this period was of 2 kg, that is, 4.6%. Urinary creatinine excretion showed the same profile. Total bone mass, lumbar or hip site bone mass, and Z-score significantly decreased from T0 to 1 and 2 years (P <.05). CONCLUSION: This study confirms that a supplemented VLPD is nutritionally safe for a long period, but attention must be paid to bone mass.

[Virological, epidemiological and pathogenic aspects of human polyomaviruses]. / Caractères virologiques, épidémiologiques et pathogéniques des polyomavirus humains.

VIROLOGICAL ASPECTS: Human polyomaviruses (BK virus and JC virus), together with simian polyomaviruses (SV40 virus) share 75% of genomic homology. Their in vivo and in vitro genomes vary. Molecular analyses have identified several genotypes, some of which appear related to the development of viral diseases. Genomic modifications of the regulation area might provide the BKv with a pathogenic aspect thus enhancing the induction of tubulo-interstitial nephropathies in renal transplant recipients. EPIDEMIOLOGY: Human polyomaviruses are ubiquitous and exhibit a sero-prevalence of 60 to 80% in adults. Following a primary infection via the respiratory tract in childhood, these viruses are diffused in the blood using the B-lymphocytes during their latent stage in the urogenital tract. The reactivation that occurs after several years is asymptomatic and urinary excretion of BKv is observed in 4 to 6% of immunocompetent patients. PATHOGENIC POTENTIAL: Human polyomaviruses have a cytopathogenic effect on the urothelium and epithelium of renal transplant recipients. Infection by BKv may provoke hemorrhagic cystitis or urethral stenosis. The JCv is the cause of progressive multifocal leuko-encephalitis. The BKv (and less frequently the JCv) is responsible for tubulo-interstitial nephritis possible leading to renal transplant loss. They also have an oncogenic effect and their implication in the origin of tumours is the subject of many studies.

[Therapeutic possibilities for polyomavirus infections in renal transplantation]. / Possibilités thérapeutiques des infections à polyomavirus humains en transplantation rénale.

TO IMPROVE THERAPEUTIC MANAGEMENT: The aim is the early detection of polyomavirus infection, before the onset of tubulo-interstitial nephritic lesions, and to reduce viral replication. AT THE STAGE OF POLYOMAVIRUS INFECTION: Treatment relies on the reduction of immunosuppression. Efficacy is controlled by monitoring the decoy cells in the urine and the detection and quantification of the DNA of polyomaviruses in the plasma and urine. AT THE STAGE OF POLYOMAVIRUS DISEASE: The aim is to reduce the viral replication by further decreasing immunosuppression to stabilize renal function and avoid graft rejection. When signs of rejection and viral infection co-exist, cidofovir could be a therapeutic alternative. However, the use of cidofovir remains in the field of clinical research and requires the further development of therapeutic protocols.

[Clinical aspects of human polyomaviruses in renal transplantation]. / Manifestations cliniques des polyomavirus humains en transplantation rénale.

A THREAT FOR RENAL ALLOGRAFT: Human polyomavirus infections (BK virus, JC virus), known for the past 30 years, were considered as common in renal transplantation until the recently reported studies describing the responsibility of BKv (and less JCv) in the occurrence of tubulo-interstitial nephritis in around 5% of renal transplant recipients, with worsening of the renal function leading to graft failure in 10 to 45% of infected patients. Their description coincided with the use of new immunosuppressors (tacrolimus and mycophenolate mofetil) without, however, their responsibility clearly incriminated. EARLY DIAGNOSIS FOR EFFICIENT TREATMENT: The presence of cells infected by the polyomavirus ("decoy cells") in the urine and the detection of BKv or JCv DNA by PCR in the plasma and urine are viral replication markers which strongly suggest the possibility of a polyomavirus nephropathy. TWO CLINICAL VARYING FORMS: Polyomavirus infection is frequent and often asymptomatic. The diagnosis requires the detection of large nucleus "decoy cells" in fresh urine. Polyomavirus renal allograft disease is characterised by the association of decoy cells and renal failure related to a tubulo-interstitial nephropathy and the presence of DNA of the virus in the plasma. The diagnosis requires identification of intra-nuclear viral inclusions in epithelial cells using immunohistochemistry, in situ hybridisation, or electron microscopy techniques. A DIFFICULT DIAGNOSIS: Confusion between interstitial nephritis and acute cellular rejection is the major risk leading to therapeutic error. Risk factors include over-immunosuppression and/or treatment of rejection episodes which could increase viral replication as well as the emergence of mutant BKv strains at the origin of tubulo-interstitial nephritis, leading to acute and chronic dysfunction of the renal transplantation.

Nutrition in hemodialysis patients previously on a supplemented very low protein diet.

BACKGROUND: Nutritional safety of protein-restricted diets in patients with chronic renal failure is controversial. In the present study, we have assessed the evolution of nutritional status after initiation of hemodialysis in patients previously treated by a supplemented very low protein diet (SVLPD). METHODS: Nutritional data were prospectively collected during the first year of hemodialysis from 15 consecutive patients treated with a SVLPD (0.3 g protein/kg/day supplemented with essential amino acids, calcium, iron, and vitamins) and compared to 15 age- and gender-matched end-stage renal disease (ESRD) patients previously on a less-restricted diet (0.90 +/- 0.21 g protein/kg/day) who started hemodialysis during the same period. Dual-energy x-ray absorptiometry (DEXA) was used to assess body composition at 0, 6, and 12 months. Hemodialysis prescriptions, biologic data and 3-day food records were collected every 3 months. RESULTS: Protein intake was higher than 1.2 g/kg/day in both groups as soon as 3 months after the start of hemodialysis. Albumin and prealbumin increased significantly during the first 6 months in all patients. Body mass index (BMI) increased in all patients (+0.97 +/- 1.31 kg/m2; P < 0.001) reflecting a gain in fat mass in the overall population (+2.36 +/- 2.94 kg/m2; P < 0.001) while lean body mass remained stable overall. CONCLUSION: Once on hemodialysis, SVLPD patients rapidly increased protein intake. Nutritional status improved in all patients, with a gain in fat mass in all, and a gain in lean body mass in SVLPD men only. These data indicate that treatment with a SVLPD prior to hemodialysis initiation is nutritionally safe.