Factors associated with changes in echocardiographic parameters following kidney transplantation.

BACKGROUND: Chronic kidney disease leads to cardiac remodelling of multifactorial origin known as "uraemic cardiomyopathy", the reversibility of which after kidney transplantation (KT) remains controversial. Our objectives were to assess, in the modern era, changes in echocardiographic parameters following KT and identify predictive clinical and biological factors associated with echocardiographic changes. METHODS: One hundred six patients (mean age 48 ± 16, 73% male) who underwent KT at the University Hospital of Nancy between 2007 and 2018 were retrospectively investigated. Pre- and post-KT echocardiography findings (8.6 months before and 22 months after KT on average, respectively) were centralised, blind-reviewed and compared. RESULTS: A majority of patients (60%) had either a left ventricular (LV) ejection fraction < 50%, at least moderately abnormal LV mass index or left atrial (LA) dilatation at pretransplanted echocardiography. After KT, LV remodelling and diastolic doppler indices did not significantly change whereas LA volume index (LAVI) increased (35.9 mL/m2 post-KT vs. 30.9 mL/m2 pre-KT, p = 0.006). Advancing age, cardiac valvular disease, delayed graft function, lower post-KT haemoglobin, and more severe post-KT hypertension were associated with higher LAVI after KT. Higher post-KT serum creatinine, more severe post-KT hypertension and lower pre-KT blood calcium levels were associated with a deterioration in LAVI after KT. DISCUSSION/CONCLUSION: Adverse remodelling of the left atrial volume occurred after KT, predominantly in patients with lower pre-KT blood calcium, poorer graft function and post-KT hypertension. These results suggest that a better management of modifiable factors such as pre-KT hyperparathyroidism or post-KT hypertension could limit post-KT cardiac remodelling.

Antibiotic therapy in case of positive cultures of kidney transplant preservation fluid: a nationwide survey of prescribing practices.

Our survey aimed to describe current prescribing practices for perioperative antibiotic prophylaxis in French kidney transplant centers. We conducted a nationwide cross-sectional clinical vignette-based survey that we sent via email to hospital practitioners involved in perioperative management of kidney transplant patients (KTR). Nearly half of practitioners contacted (182/427, 42.6%) were respondents. A total of 167 getting enough kidney transplant activity were eligible for the survey. The response rate was 50.7% (68/134) among interns and 33.8% (99/293) among seniors. Positive perfusion fluids (PF) cultures for methicillin-susceptible Staphylococcus aureus were associated with antibiotic prescribing in 35% of cases, with no difference in prescribing in patients with diabetes, obesity, or delayed graft function. Antibiotic prescribing was most frequent with Pseudomonas aeruginosa (67%) and Klebsiella pneumoniae strains producing extended spectrum ß-lactamases (57%). About 77%, 16%, and 13% of respondents, respectively, reported the existence of local practice guidelines for surgical antibiotic prophylaxis, a standardized approach for antibiotic prescribing in case of positive kidney transplant PF cultures, and local practice guidelines for systematical antibiotic prophylaxis in the early post-transplant period. In France, antibiotic prophylaxis practices in the perioperative kidney transplant period are very heterogeneous. To prevent unnecessary prescribing and bacterial resistance, evidence-based practice guidelines should be developed.

Microbiological epidemiology of preservation fluids in transplanted kidney: a nationwide retrospective observational study.

OBJECTIVES: Kidney transplant recipients are at high-risk for donor-derived infections in the early post-transplant period. Transplant preservation fluid (PF) samples are collected for microbiological analysis. In case of positive PF cultures, the risk for the recipient is unknown and there is no consensus for prescribing prophylactic antibiotics. This nationwide observational study aimed to determine the epidemiology of bacterial and fungal agents in kidney transplant PF cultures and identify risk factors associated with positive PF cultures. METHODS: We performed a retrospective observational study on the following data collected from a national database between October 2015 and December 2016: characteristics of donor, recipient, transplantation, infection in donor and PF microbiological data. RESULTS: Of 4487 kidney transplant procedures, including 725 (16.2%, 725/4487) from living donors, 20.5% had positive PF cultures (living donors: 1.8%, 13/725; deceased donors: 24.1%, 907/3762). Polymicrobial contamination was found in 59.9% (485/810) of positive PF cultures. Coagulase-negative staphylococci (65.8%, 533/810) and Enterobacteriaceae (28.0%, 227/810) were the most common microorganisms. Factors associated with an increased risk of positive PF cultures in multivariable analysis were (for deceased-donor kidney transplants): intestinal perforation during procurement (OR 4.4, 95% CI 2.1-9.1), multiorgan procurement (OR 1.4, 95% CI 1.1-1.7) and en bloc transplantation (OR 2.5, 95% CI 1.3-4.9). Use of perfusion pump and donor antibiotic therapy were associated with a lower risk of positive PF cultures (OR 0.4, 95% CI 0.3-0.5 and OR 0.6, 95% CI 0.5-0.7, respectively). CONCLUSION: In conclusion, 24% of deceased-donor PF cultures were positive, and PF contamination during procurement seemed to be the major cause.

[Robotic-assisted laparoscopic living donor nephrectomy: Study in donors and recipients from 155 cases]. / Néphrectomie laparoscopique assistée par robot dans le cadre du donneur-vivant : étude chez les donneurs et les receveurs à partir de 155 cas.

AIM: To evaluate morbidity and renal function of the donor and recipient during a robotic-assisted laparoscopic nephrectomy procedure. PATIENTS AND METHODS: It is a retrospective study of 155 consecutive patients by robot-assisted laparoscopy in the living donor. Mean operating time, warm ischemia time, blood loss, complications according to the Clavien classification and evolution of creatinine clearance were analyzed in the donors. Recovery of graft function, complications and changes in creatinine clearance were observed in recipients. RESULTS: The mean operating time was 176 (±23) minutes. The mean warm ischemia time was 4.8 (±0.6) minutes. Twenty seven complications were noted. The loss of renal function was 19% at 5 years in donors. Renal recovery was immediate for 153 recipients. Two were delayed due to sepsis. Two patients lost their graft at 15 and 18 months. Seventeen complications have been identified. The mean kidney function of the recipients is measured at 63ml/min at 5 years. CONCLUSION: Robotic-assisted laparoscopic nephrectomy procedure appears to provide the donor with low morbidity and a moderate decrease in creatinine clearance at 19% at 5 years. Morbidity is also low in recipients with very satisfactory 5-year mean renal function. The technique should promote donation. LEVEL OF EVIDENCE: 4.

Obesity phenotype and patient-reported outcomes in moderate and severe chronic kidney disease: a cross-sectional study from the CKD-REIN cohort study.

PURPOSE: To evaluate the association between obesity phenotypes and health-related quality of life (HRQoL) in non-dialysis-dependent CKD patients. METHODS: Data from the national CKD-REIN cohort which included 3033 patients with stage 3-4 CKD were used. Patients were divided into three groups: non-obese (NO) patients (BMI < 30 kg/m2), metabolically healthy obese (MHO) (BMI ≥ 30 kg/m2 and ≤ 1 criterion NCEP/ATP III), and metabolically unhealthy obese (MUO) (BMI ≥ 30 kg/m2 and ≥ 2 criteria NCEP/ATP III). HRQoL was measured by the KDQOL-36™ which comprised three disease-specific dimensions: symptoms, effects, and burden and two summaries scores: physical (PCS) and mental (MCS). We used a mixed effect model with adjustment on sociodemographic characteristics and comorbidities. RESULTS: A total of 2693 patients completed the self-administered questionnaires. MHO patients accounted for 3.4% of the cohort and for 12% of obese patients. In the NO group, average HRQoL scores were 77.2 ± 15.9 for symptoms, 83.5 ± 16.5 for effects, 76.8 ± 22.7 for burden, 43.5 ± 9.7 for PCS, and 47.9 ± 7.0 for MCS. In the multivariate analysis, scores were similar in MHO and NO patients, but significantly different with those in MUO patients: symptoms (- 0.7; p = 0.71 vs. - 3.0; p = 0.0025), effects (+ 1.2; p = 0.57 vs. - 4.3; p < 0.0001), burden (+ 2.7; p = 0.31 vs. - 3.6; p = 0.0031), and PCS (- 0.6; p = 0.58 vs. - 4.3; p < 0.0001). MCS was not associated with obesity phenotypes. CONCLUSIONS: This study demonstrated an association between obesity phenotypes and QoL in non-dialysis-dependent CKD patients. MUO patients had worse QoL than NO and MHO patients even after adjustment on comorbidities.

Impact of sex and glucose-lowering treatments on hypoglycaemic symptoms in people with type 2 diabetes and chronic kidney disease. The French Chronic Kidney Disease - Renal Epidemiology and Information Network (CKD-REIN) Study.

AIM: To describe current practices of glucose-lowering treatments in people with diabetes and chronic kidney disease (CKD), the associated glucose control and hypoglycaemic symptoms, with an emphasis on sex differences. METHODS: Among the 3033 patients with CKD stages 3-5 recruited into the French CKD-REIN study, 645 men and 288 women had type 2 diabetes and were treated by glucose-lowering drugs. RESULTS: Overall, 31% were treated only with insulin, 28% with combinations of insulin and another drug, 42% with non-insulin glucose-lowering drugs. In CKD stage 3, 40% of patients used metformin, 12% at stages 4&5, similar for men and women; in CKD stage 3, 53% used insulin, similar for men and women, but at stages 4&5, 59% of men and 77% of women used insulin. Patients were reasonably well controlled, with a median HbA1c of 7.1% (54mmol/mol) in men, 7.4% (57mmol/mol) in women (P=0.0003). Hypoglycaemic symptoms were reported by 40% of men and 59% of women; they were not associated with the estimated glomerular filtration rate, nor with albuminuria or with HbA1c in multivariable analyses, but they were more frequent in people treated with insulin, particularly with fast-acting and pre-mixed insulins. CONCLUSION: Glucose-lowering treatment, HbA1c and hypoglycaemic symptoms were sex dependent. Metformin use was similar in men and women, but unexpectedly low in CKD stage 3; its use could be encouraged rather than resorting to insulin. Hypoglycaemic symptoms were frequent and need to be more closely monitored, with appropriate patient-education, especially in women.

Impact of reduced exposure to calcineurin inhibitors on the development of de novo DSA: a cohort of non-immunized first kidney graft recipients between 2007 and 2014.

BACKGROUND: In low-immunological risk kidney transplant recipients (KTRs), reduced exposure to calcineurin inhibitor (CNI) appears particularly attractive for avoiding adverse events, but may increase the risk of developing de novo Donor Specific Antibodies (dnDSA). METHODS: CNI exposure was retrospectively analyzed in 247 non-HLA immunized first KTRs by taking into account trough levels (C0) collected during follow-up. Reduced exposure to CNI was defined as follows: C0 less than the lower limit of the international targets for ≥50% of follow-up. RESULTS: During a mean follow-up of 5.0 ± 2.0 years, 39 patients (15.8%) developed dnDSA (MFI ≥1000). Patients with DSA were significantly younger (46.6 ± 13.8 vs. 51.7 ± 14.0 years, p = 0.039), received more frequently poorly-matched grafts (59% with 6-8 A-B-DR-DQ HLA mismatches vs. 34.6%, p = 0.016) and had more frequently a reduced exposure to CNI (92.3% vs. 62.0%, p = 0.0002). Reduced exposure to CNI was associated with an increased risk of dnDSA (multivariable HR = 9.77, p = 0.002). Reduced exposure to CNI had no effect on patient survival, graft loss from any cause including death, or post-transplant cancer. CONCLUSIONS: Even in a low-immunological risk population, reduced exposure to CNI is associated with increased risk of dnDSA. Benefits and risks of under-immunosuppression must be carefully evaluated before deciding on CNI minimization.

Evaluation of Subclinical Fluid Overload Using Lung Ultrasound and Estimated Plasma Volume in the Postoperative Period Following Kidney Transplantation.

AIM: B-lines count measured with lung ultrasound (LUS) quantifies extravascular lung water and is validated in the setting of acute cardiac failure or chronic dialysis. Patients are often kept in moderately overhydrated states during the early postoperative period following kidney transplantation (KT). We described congestion changes during the early postoperative period following KT and the feasibility of LUS in this setting. METHODS: LUS (28 scanning-points method) and inferior vena cava (IVC) measurements were routinely performed in 36 patients after KT. Estimated plasma volume (ePV) was calculated from hemoglobin and hematocrit levels. RESULTS: No patient had >15 B-lines during the hospital stay. B-lines slightly increased until Day 4 after KT (Day 1, 1.7 ± 1.7; Day 4, 2.5 ± 2.5) and decreased up to Day 10 (1.4 ± 2.2; P vs Day 4 <.05). More B-lines were observed in patients aged older than 60 (P = .01 at Day 4) whereas IVC diameter and ePV were similar. In patients older than 60, B-lines had weak correlation with body weight variation (r = 0.64; P < .05), IVC diameters (r = 0.59 at Day 4 and r = 0.58 at Day 10; P < .05) but a strong correlation with ePV (r = 0.93 at Day 14; P < .05). B-line changes from Day 1 to Day 10 correlated with IVC diameter changes (r = 0.62; P < .05). CONCLUSION: LUS identifies subtle congestion changes during the early postoperative period following KT. The hyperhydration strategy usually followed during this period does not result in overt pulmonary congestion as assessed by LUS, even in older recipients.

Targets for adapting intravenous iron dose in hemodialysis: a proof of concept study.

BACKGROUND: Intravenous iron is widely used to control anemia in dialysis patients and limits costs related to erythropoiesis-stimulating agents (ESA). Current guidelines do not clearly set upper limits for serum ferritin (SF) and transferrin saturation (TSAT). International surveys such as the Dialysis Outcomes and Practice Patterns Study (DOPPS) showed that this lack of upper limits potentially led nephrologists to prescribe iron infusions even for patients with a high SF. Recent publications have suggested a risk of short- and long-term adverse effects related to iron overload. We conducted a proof of concept study to assess the impact of reducing intravenous iron administration. METHODS: In a prospective 8-month study conducted in a hospital dialysis unit, we assessed the impact of a strategy designed to reduce iron infusions. Instead of the usual strategy targeting 30-50% TSAT irrespective of SF, intravenous iron was administered if and only if TSAT was below 20% and SF below 200 µg/L. Routine practices for ESA remained unchanged: hemoglobin target 10-12 g/dL; ESA delivered monthly and dose corrected by 25% as necessary; ESA discontinued temporarily if hemoglobin >13 g/dL; methoxy polyethylene glycol-epoetin beta generally used. Tests were ordered monthly to monitor hemoglobin. Intravenous iron was administered weekly and ESA monthly. Baseline and 6-month TSAT, SF and hemoglobin levels were compared. RESULTS: Six-month data were available for 45 patients (31 M/14 F; 67.6 ± 14.0 y; 53.9 ± 85.7 months on dialysis). Patients experienced the following comorbidities: ischemic heart disease (n = 29, 44%), diabetes mellitus (n = 14; 31%), malignant disease (n = 11; 24%), transplantation (n = 11; 24%) and severe heart failure (n = 6; 13%). The mean weekly dose of iron declined from 77.8 ± 87.6 to 24.4 ± 52.9 mg per patient (p = 0.0003). SF decreased from 947.7 ± 1056.4 to 570.7 ± 424.4 µg/L (p = 0.0001), and TSAT from 41.5 ± 22.4 to 32.6 ± 13.7% (p = 0.01). Hemoglobin levels remained stable (11.13 ± 1.05 vs. 11.00 ± 1.16 g/dL, p = 0.54) as did ESA dose (126.4 ± 91.9 vs. 108.2 ± 112.7 µg/28 days, p = 0.07). CONCLUSIONS: Our study suggests that a regular hemoglobin level can be maintained using regular ESA doses combined with intravenous iron doses adapted to TSAT and SF thresholds lower than those used in routine practice. This strategy reduces the risk of iron overload.

Anti-Donor HLA Antibody Response After Pancreatic Islet Grafting: Characteristics, Risk Factors, and Impact on Graft Function.

Pancreatic islet grafting restores endogenous insulin production in type 1 diabetic patients, but long-term outcomes remain disappointing as a result of immunological destruction of allogeneic islets. In solid organ transplantation, donor-specific anti-HLA antibodies (DSA) are the first cause of organ failure. This retrospective multicentric study aimed at providing in-depth characterization of DSA response after pancreatic islet grafting, identifying the risk factor for DSA generation and determining the impact of DSA on graft function. Forty-two pancreatic islet graft recipients from the Groupe Rhin-Rhône-Alpes-Genève pour la Greffe d'Ilots de Langerhans consortium were enrolled. Pre- and postgrafting sera were screened for the presence of DSA and their ability to activate complement. Prevalence of DSA was 25% at 3 years postgrafting. The risk of sensitization increased steeply after immunosuppressive drug withdrawal. DSA repertoire diversity correlated with the number of HLA and eplet mismatches. DSA titer was significantly lower from that observed in solid organ transplantation. No detected DSA bound the complement fraction C3d. Finally, in contrast with solid organ transplantation, DSA did not seem to negatively affect pancreatic islet graft survival. This might be due to the low DSA titers, specific features of IgG limiting their ability to activate the complement and/or the lack of allogenic endothelial targets in pancreatic islet grafts.

Temporal Trend and Time-Varying Effect of Preemptive Second Kidney Transplantation on Graft Survival: A 30-Year Single-Center Cohort Study.

BACKGROUND: There are discrepancies regarding the impact of preemptive 2nd kidney transplantation (PSKT) on graft survival. The present study aimed to determine whether the association between PSKT and outcome varies over time and whether this association is era dependent. METHODS: A total of 266 patients underwent SKT (244 non-PSKT, 22 PSKT) in our center from 1985 to 2015. Association between PSKT and graft survival (allograft failure from any cause including death) was assessed with the use of Cox models. RESULTS: During a median follow-up of 6.7 years, 116 events were recorded: 72 returns to dialysis and 44 deaths before return to dialysis. Survival curves diverged up to 5 years (5-year survivals: PSKT, 94.1 ± 5.7%; non-PSKT, 76.8 ± 2.9%) but they converged thereafter (12-year survivals: PSKT, 50.9 ± 15.2%; non-PSKT, 55.5 ± 3.9%). After adjustment for age and living-donor status, PSKT tended to be associated with better graft survival (hazard ratio [HR], 0.18; 95% confidence interval [CI], 0.02-1.27; P = .08) within the first 5 years of SKT but tended to be associated with worse outcome thereafter (HR, 2.36; 95% CI, 0.97-5.72; P = .06; P for interaction with time = .04). In addition, a significant interaction was identified between PSKT and SKT year (P for interaction = .04). In the multivariable model, the estimated HR for PSKT was 2.54 (95% CI, 0.88-7.35; P = .08) in 1990 as opposed to 0.16 (95% CI, 0.02-1.17; P = .07) in 2012. CONCLUSIONS: The effect of PSKT on graft survival varies over time and according to year of the procedure. Although the benefit observed within the first 5 years of SKT appears to fade over time, overall graft survival seemingly improved in more recent years.

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.

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.

Renal safety of ibandronate 6 mg infused over 15 min versus 60 min in breast cancer patients with bone metastases: a randomized open-label equivalence trial.

PURPOSE: The aim of this study was to demonstrate the renal safety equivalence of ibandronate 6 mg infused over 15 min versus 60 min, in patients with bone metastases of breast cancer. PATIENTS AND METHODS: Patients were females having breast cancer with at least one bone metastasis. Exclusion criteria were renal failure (creatinine clearance < 30 mL/min), tooth/jaw disorder or uncontrolled severe disease. Eligible patients were randomly assigned to receive nine ibandronate 6 mg i.v. infusions over either 15 min or 60 min. The primary outcome was the 95% confidence interval (CI) of the difference in creatinine clearance between groups, 28 days after the last infusion. The equivalence margin was ±8 mL/min. RESULTS: Overall 334 patients were randomized (165-15 min infusions vs. 169 to 60 min infusions, 325 (159 vs. 166) were analyzed by intent-to-treat, and 312 (151 vs. 161) were analyzed per protocol. Per protocol, the 15 min-60 min difference in creatinine clearance [95% CI] was -3.00 [-8.18, 2.18]. By intent-to-treat, this difference was-2.91 [-7.99, 2.16]. Death and serious adverse event rates did not differ between groups. Three serious adverse events were considered related to ibandronate: an osteonecrosis of the jaw (15-min group), a pain in jaw and an enamel cracking (60-min group). Two renal failures, reported in the 60 min group, were not considered related to ibandronate. None occurred in the 15 min group. CONCLUSION: Ibandronate may be infused over 15 min without clinically significant consequence on renal safety.

Renal transplantation in patients with AA amyloidosis nephropathy: results from a French multicenter study.

Although end-stage renal disease related to AA amyloidosis nephropathy is well characterized, there are limited data concerning patient and graft outcome after renal transplantation. We performed a multicentric retrospective survey to assess the graft and patient survival in 59 renal recipients with AA amyloidosis. The recurrence rate of AA amyloidosis nephropathy was estimated at 14%. The overall, 5- and 10-year patient survival was significantly lower for the AA amyloidosis patients than for a control group of 177 renal transplant recipients (p = 0.0001, 0.028 and 0.013, respectively). In contrast, we did not observe any statistical differences in the 5- and 10- year graft survival censored for death between two groups. AA amyloidosis-transplanted patients exhibited a high proportion of infectious complications after transplantation (73.2%). Causes of death included both acute cardiovascular events and fatal septic complications. Multivariate analysis demonstrated that the recurrence of AA amyloidosis on the graft (adjusted OR = 14.4, p = 0.01) and older recipient age (adjusted OR for a 1-year increase = 1.06, p = 0.03) were significantly associated with risk of death. Finally, patients with AA amyloidosis nephropathy are eligible for renal transplantation but require careful management of both cardiovascular and infectious complications to reduce the high risk of mortality.

Long-Term Impact of Cyclosporin Reduction with MMF Treatment in Chronic Allograft Dysfunction: REFERENECE Study 3-Year Follow Up.

Calcineurin inhibitor (CNI) toxicity contributes to chronic allograft nephropathy (CAN). In the 2-year, randomized, study, we showed that 50% cyclosporin (CsA) reduction in combination with mycophenolate mofetil (MMF) treatment improves kidney function without increasing the risk for graft rejection/loss. To investigate the long-term effect of this regimen, we conducted a follow up study in 70 kidney transplant patients until 5 years after REFERENCE initiation. The improvement of kidney function was confirmed in the MMF group but not in the control group (CsA group). Four graft losses occurred, 2 in each group (graft survival in the MMF group 95.8% and 90.9% in control group). One death occurred in the control group. There was no statistically significant difference in the occurrence of serious adverse events or acute graft rejections. A limitation is the weak proportion of patient still remaining within the control group. On the other hand, REFERENCE focuses on the CsA regimen while opinions about the tacrolimus ones are still debated. In conclusion, CsA reduction in the presence of MMF treatment seems to maintain kidney function and is well tolerated in the long term.

[Incidence of chronic kidney disease in general population, EPIRAN study]. / Incidence de l'insuffisance rénale chronique en population générale, étude EPIRAN.

AIMS: To assess incidence of chronic kidney disease in general population and to describe baseline characteristics of incident patients. METHODS: Between 1st/01/04 and 30/06/06 all incident cases of chronic kidney disease in the Nancy district were prospectively identified. New cases were identified from all medical laboratories in this area and determined by a persistently increased serum creatinine level (> or = 150micromol/l, or paediatric levels) for 3 months after the 1st/01/04, and by living in Nancy area. RESULTS: The annual incidence rate of detected chronic kidney disease was 1 per thousand inhabitants (1,3 per thousand for men and 0,7 per thousand for women). Incidents patients were old (mean age: 77 years) and with numerous comorbidities (diabetes: 34 %, cardiac failure: 23 %). More than 30% of incident patients were diagnosed at sever stage of chronic kidney disease (<30ml/min/1,73m(2)). CONCLUSIONS: The annual incidence of diagnosed chronic kidney disease is common: 10 times more than end-stage renal disease in France. Most of these patients are diagnosed in a severe stage of chronic kidney disease whereas they could be detected earlier and benefit from adequate, appropriate and multidisciplinary take care.

[Medical care of chronic kidney disease after kidney transplantation]. / Prise en charge de la maladie rénale chronique après transplantation rénale.

Kidney transplantation is the treatment of choice to enhance survival, morbidity and quality of life perceived by the patient. Despite improvements in short-term outcomes, a gap persists comparing with health of general population. A stringent collaboration between the family physician, the community nephrologists, the transplant center and others specialists is required. Recent recommendations have been published in France.