Long-term changes in cardiac remodelling in prevalent kidney graft recipients.

BACKGROUND: Approximately 15% of kidney transplant (KT) recipients develop de novo heart failure after KT. There are scarce data reporting the long-term changes in cardiac structure and function among KT recipients. Despite the improvement in renal function, transplant-related complications as well as immunosuppressive therapy could have an impact on cardiac remodelling during follow-up. We aimed to describe the long-term changes in echocardiographic parameters in prevalent KT recipients and identify the clinical and laboratory factors associated with these changes. METHODS: A centralised blinded review of two echocardiographic examinations after KT (on average after 17 and 39 months post-KT respectively) was performed among 80 patients (age 50.4 ± 16.2, diabetes 13.8% pre-KT), followed by linear regression to identify clinico-biological factors related to echocardiographic changes. RESULTS: Left atrial volume index (LAVI) increased significantly (34.2 ± 10.8 mL/m2vs. 37.6 ± 15.0 mL/m2, annualised delta 3.1 ± 11.4 mL/m2/year; p = 0.034) while left ventricular ejection fraction (LVEF) decreased (62.1 ± 9.0% vs. 59.7 ± 9.9%, annualised delta -2.7 ± 13.6%/year; p = 0.04). Male sex (ß = 8.112 ± 2.747; p < 0.01), pre-KT hypertension (ß = 9.725 ± 4.156; p < 0.05), graft from expanded criteria donor (ß = 3.791 ± 3.587; p < 0.05), and induction by anti-thymocyte globulin (ß = 7.920 ± 2.974; p = 0.01) were associated with an increase in LAVI during follow-up. Higher haemoglobin (>12.9 g/dL) at the time of the first echocardiography (ß = 6.029 ± 2.967; p < 0.05) and ACEi/ARB therapy (ß = 8.306 ± 3.161; p < 0.05) were associated with an increase in LVEF during follow-up. CONCLUSION: This study confirms the existence of long-term cardiac remodelling after KT despite dialysis cessation, characterised by an increase in LAVI and a decrease in LVEF. A better management of anaemia and using ACEi/ARB therapy may prevent such remodelling.

Study of the association between serum levels of kynurenine and cardiovascular outcomes and overall mortality in chronic kidney disease.

Background: Kynurenine is a protein-bound uremic toxin. Its circulating levels are increased in chronic kidney disease (CKD). Experimental studies showed that it exerted deleterious cardiovascular effects. We sought to evaluate an association between serum kynurenine levels and adverse fatal or nonfatal cardiovascular events and all-cause mortality in CKD patients. Methods: The CKD-REIN study is a prospective cohort of people with CKD having an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m². Baseline frozen samples of total and free fractions of kynurenine and tryptophan were measured using a validated liquid chromatography tandem mass spectrometry technique. Cause-specific Cox models were used to estimate hazard ratios (HRs) for each outcome. Results: Of the 2406 included patients (median age: 68 years; median eGFR: 25 ml/min/1.73 m2), 52% had a history of cardiovascular disease. A doubling of serum-free kynurenine levels was associated with an 18% increased hazard of cardiovascular events [466 events, HR (95%CI):1.18(1.02,1.33)], independently of eGFR, serum-free tryptophan level or other uremic toxins, cardioprotective drugs, and traditional cardiovascular risk factors. Serum-free kynurenine was significantly associated with non-atheromatous cardiovascular events [HR(95%CI):1.26(1.03,1.50)], but not with atheromatous cardiovascular events [HR(95%CI):1.15(0.89,1.50)]. The association of serum-free kynurenine with cardiovascular mortality was also independently significant [87 events; adjusted HR(95%CI):1.64(1.10,2.40)]. However, the association of serum-free kynurenine with all-cause mortality was no more significant after adjustment on serum-free tryptophan [311 events, HR(95%CI):1.12(0.90, 1.40)]. Conclusions: Our findings imply that serum-free kynurenine, independently of other cardiovascular risk factors (including eGFR), is associated with fatal or nonfatal cardiovascular outcomes, particularly non-atheromatous cardiovascular events; in patients with CKD. Strategies to reduce serum kynurenine levels should be evaluated in further studies.

Association between kidney retransplantation and survival according to age in the French national cohort of dialysis patients.

The mean age of patients returning to dialysis after a first kidney transplantation (KT) has increased in the past decades. We aimed to assess the association between second KT (2KT) and survival according to age at the time of return to dialysis. Data of 5334 patients registered in the French Renal Epidemiology and Information Network (REIN) (mean age 56.6 ± 13.6 years) who returned to dialysis after a first KT were collected. The association of 2KT with death was assessed using a propensity score-based analysis taking into account baseline and follow-up variables. In relisted patients (3272 patients, 61.3%), retransplantation was associated with better overall survival in comparison with patients who remained in dialysis (adjusted HR 0.75 [0.63-0.89], p = .0009). The survival advantage conferred by retransplantation gradually declined with increasing age (adjusted HR 0.41 [0.24-0.70] in patients <50, HR 0.94 (0.69-1.27) in patients aged 70 or older, p for interaction 0.034 for age considered as a continuous variable). 2KT is associated with better survival as opposed to remaining on dialysis after a first kidney graft failure. Nevertheless, this survival benefit is age dependent and diminishes with increasing age. The risk/benefit ratio should be comprehensively assessed in the oldest patients when relisting is considered.

Minimally Invasive and Open Donor Nephrectomy: Lessons Learned From a French Multicenter Experience.

BACKGROUND: We evaluated different techniques of donor nephrectomy. METHODS: Outcomes of 4 surgical approaches (open surgery [OS], standard laparoscopy [SL], hand-assisted laparoscopy [HAL], and robot-assisted la`paroscopy [RAL]) were compared. RESULTS: A total of 264 nephrectomies were performed: 65 in the OS group, 65 in the SL group, 65 in the HAL group, and 69 in RAL group. Operative time was longer for the RAL group (P < .001) with a mean time of 202 minutes (RAL), 182 minutes (OS), 173 minutes (SL), and 157 minutes (HAL). Complications (P = .002) and consumption of morphine derivates (P = .31) were lower for the RAL group (P = .0002). The visual analog scale pain scores (P = .002), hospital stay (P = .023), and time to return to full activities (P = .79) were higher for OS. CONCLUSIONS: The 4 different nephrectomy surgical approaches had similar favorable results. The robot-assisted technique presented as an alternative option, with low incidence of complications, less pain, and results comparable to the other techniques.

Is a treat-to-target approach to lipid-lowering therapy appropriate in patients with chronic kidney disease? A prospective French cohort study.

BACKGROUND: Whereas European guidelines recommend adjusting lipid-lowering therapy (LLT) to meet prespecified targets ('treat-to-target') for low-density lipoprotein cholesterol (LDL-C), other guidelines do not ('fire and forget'). In a large observational prospective cohort, we sought to evaluate which strategy could be associated with better cardiovascular outcomes in chronic kidney disease (CKD). METHODS: In CKD-REIN, patients (CKD stages 3 and 4) on LLT were categorized according to achievement of LDL-C targets for high and very high cardiovascular risk (< 2.6 and < 1.8 mmol/L, respectively) at baseline. Primary outcome was fatal/non-fatal atheromatous cardiovascular disease (CVD). Secondary outcomes were non-atheromatous CVD, atheromatous or non-atheromatous CVD, and major adverse cardiovascular events. RESULTS: The population comprised 1521 patients (68 ± 12 years, 31% women, mean estimated glomerular filtration rate [eGFR] 35 mL/min/1.73 m2). Overall, 523 (34%) met their LDL-C targets at baseline. Median follow-up was 2.9 years (interquartile range 2.2-3.0). Incidence rates per 100 patient-years were 6.2% (95% confidence interval [CI] 5.5-7.0) for atheromatous CVD, 9.2% (8.3-10.1) for non-atheromatous CVD, 15.2% (14.0-16.4) for atheromatous/non-atheromatous CVD, and 6.3% (5.5-7.1) for major adverse cardiovascular events. Corresponding rates in patients who achieved targets were 6.6%, 9.8%, 16.1%, and 6.3%, respectively. Target achievement was not associated with risk of fatal/non-fatal atheromatous CVD (adjusted hazard ratio 1.04, 95% CI 0.76-1.44, p = 0.77) or fatal/non-fatal atheromatous or non-atheromatous CVD (0.98, 0.78-1.23, p = 0.91). CONCLUSIONS: These findings do not appear to support a treat-to-target approach in CKD patients on LLT, and may favor the hypothesis of an advantage of fire-and-forget. Randomized trials are needed to confirm this theory.

Urgent-start dialysis in patients referred early to a nephrologist-the CKD-REIN prospective cohort study.

BACKGROUND: The lack of a well-designed prospective study of the determinants of urgent dialysis start led us to investigate its individual- and provider-related factors in patients seeing nephrologists. METHODS: The Chronic Kidney Disease Renal Epidemiology and Information Network (CKD-REIN) is a prospective cohort study that included 3033 patients with CKD [mean age 67 years, 65% men, mean estimated glomerular filtration rate (eGFR) 32 mL/min/1.73 m2] from 40 nationally representative nephrology clinics from 2013 to 2016 who were followed annually through 2020. Urgent-start dialysis was defined as that 'initiated imminently or <48 hours after presentation to correct life-threatening manifestations' according to the Kidney Disease: Improving Global Outcomes 2018 definition. RESULTS: Over a 4-year (interquartile range 3.0-4.8) median follow-up, 541 patients initiated dialysis with a known start status and 86 (16%) were identified with urgent starts. The 5-year risks for the competing events of urgent and non-urgent dialysis start, pre-emptive transplantation and death were 4, 17, 3 and 15%, respectively. Fluid overload, electrolytic disorders, acute kidney injury and post-surgery kidney function worsening were the reasons most frequently reported for urgent-start dialysis. Adjusted odds ratios for urgent start were significantly higher in patients living alone {2.14 [95% confidence interval (CI) 1.08-4.25] or with low health literacy [2.22 (95% CI 1.28-3.84)], heart failure [2.60 (95% CI 1.47-4.57)] or hyperpolypharmacy [taking >10 drugs; 2.14 (95% CI 1.17-3.90)], but not with age or lower eGFR at initiation. They were lower in patients with planned dialysis modality [0.46 (95% CI 0.19-1.10)] and more nephrologist visits in the 12 months before dialysis [0.81 (95% CI 0.70-0.94)] for each visit. CONCLUSIONS: This study highlights several patient- and provider-level factors that are important to address to reduce the burden of urgent-start dialysis.

Living kidney donor evaluation for all candidates with normal estimated GFR for age.

Multiple days assessments are frequent for the evaluation of candidates to living kidney donation, combined with an early GFR estimation (eGFR). Living kidney donation is questionable when eGFR is <90 ml/min/1.73 m2 (KDIGO guidelines) or 80 ml/min/1.73 m2 (most US centres). However, age-related GFR decline results in a lower eGFR for older candidates. That may limit the number of older kidney donors. Yet, continuing the screening with a GFR measure increases the number of eligible donors. We hypothesized that in-depth screening should be proposed to all candidates with a normal eGFR for age. We compared the evolution of eGFR after donation between three groups of predonation eGFR: normal for age (Sage ) higher than 90 or 80 ml/min/1.73 m2 (S90 and S80, respectively); across three age groups (<45, 45-55, >55 years) in a population of 1825 French living kidney donors with a median follow-up of 5.9 years. In donors younger than 45, postdonation eGFR, absolute- and relative-eGFR variation were not different between the three groups. For older donors, postdonation eGFR was higher in S90 than in S80 or Sage but other comparators were identical. Postdonation eGFR slope was comparable between all groups. Our results are in favour of in-depth screening for all candidates to donation with a normal eGFR for age.

Characteristics of T- and NK-cell Lymphomas After Renal Transplantation: A French National Multicentric Cohort Study.

BACKGROUND: Posttransplant lymphoproliferative disorders (PTLDs) encompass a spectrum of heterogeneous entities. Because the vast majority of cases PTLD arise from B cells, available data on PTLD of T or NK phenotype (T/NK-cell PTLD) are scarce, which limits the quality of the management of these patients. METHODS: All adult cases of PTLD diagnosed in France were prospectively recorded in the national registry between 1998 and 2007. Crosschecking the registry data with 2 other independent national databases identified 58 cases of T/NK-cell PTLD. This cohort was then compared with (i) the 395 cases of B-cell PTLD from the registry, and of (ii) a cohort of 148 T/NK-cell lymphomas diagnosed in nontransplanted patients. RESULTS: T/NK-cell PTLD occurred significantly later after transplantation and had a worse overall survival than B-cell PTLD. Two subtypes of T/NK-cell PTLD were distinguished: (i) cutaneous (28%) and (ii) systemic (72%), the latter being associated with a worse prognosis. Compared with T/NK-cell lymphomas of nontransplanted patients, overall survival of systemic T/NK-cell PTLD was worse (hazard ratio: 2.64 [1.76-3.94]; P < 0.00001). CONCLUSIONS: This difference, which persisted after adjustment on tumoral mass, histological subtype, and extension of the disease at diagnosis could be explained by the fact that transplanted patients were less intensively treated and responded less to chemotherapy.

Adverse outcomes of proton pump inhibitors in patients with chronic kidney disease: The CKD-REIN cohort study.

AIMS: Long-term use of proton pump inhibitors (PPIs) has been associated with adverse kidney events in the general population, but their impact among chronic kidney disease (CKD) patients is unclear. We studied the prevalence and incidence (new users) of PPI prescriptions and their relation to kidney outcomes and mortality in CKD patients. METHODS: We collected drug prescriptions prospectively in a cohort of 3023 nephrology outpatients with CKD stages 2-5 at inclusion. Hazard ratios (HR, 95% confidence intervals [95% CI]) for acute kidney injury (AKI), end-stage kidney disease (ESKD), and mortality associated with new PPI prescriptions as a time-dependent variable were estimated with cause-specific Cox models in 1940 non-users with eGFR ≥ 15 mL/min/1.73 m2 at baseline, adjusted for comorbidities, laboratory data and drugs. RESULTS: There were 981/3023 (32%) prevalent users (67 ± 13 years, 65% men) at baseline, and 366/3023 (12%) were prescribed PPI (new users) over a median follow-up of 3.9 years (interquartile range, 3-4.2). Among these new users, their median cumulative duration of prescription was 1 year (interquartile range: 0.4-2.3). During follow-up, 354 patients developed ESKD and 216 died before ESKD. The adjusted HRs associated with PPI prescription were 1.74 (95% CI, 1.26-2.40) for ESKD and 2.42 (95% CI, 1.73-3.39) for all-cause mortality. Over the first 3 years of follow-up, 211 AKI events had occurred. The adjusted HR for AKI associated with PPI prescription was 2.89 (95% CI, 1.91-4.38). CONCLUSIONS: Long-term PPI prescription was common in CKD patients. Our results call attention to its potential risks of both acute and chronic kidney failure.

Low incidence of SARS-CoV-2, risk factors of mortality and the course of illness in the French national cohort of dialysis patients.

The aim of this study was to estimate the incidence of COVID-19 disease in the French national population of dialysis patients, their course of illness and to identify the risk factors associated with mortality. Our study included all patients on dialysis recorded in the French REIN Registry in April 2020. Clinical characteristics at last follow-up and the evolution of COVID-19 illness severity over time were recorded for diagnosed cases (either suspicious clinical symptoms, characteristic signs on the chest scan or a positive reverse transcription polymerase chain reaction) for SARS-CoV-2. A total of 1,621 infected patients were reported on the REIN registry from March 16th, 2020 to May 4th, 2020. Of these, 344 died. The prevalence of COVID-19 patients varied from less than 1% to 10% between regions. The probability of being a case was higher in males, patients with diabetes, those in need of assistance for transfer or treated at a self-care unit. Dialysis at home was associated with a lower probability of being infected as was being a smoker, a former smoker, having an active malignancy, or peripheral vascular disease. Mortality in diagnosed cases (21%) was associated with the same causes as in the general population. Higher age, hypoalbuminemia and the presence of an ischemic heart disease were statistically independently associated with a higher risk of death. Being treated at a selfcare unit was associated with a lower risk. Thus, our study showed a relatively low frequency of COVID-19 among dialysis patients contrary to what might have been assumed.

Impact of the dialysate acid component on haemodialysis mortality rates.

BACKGROUND: No prospective study has evaluated the long-term effect on mortality of the new acid concentrates added to bicarbonate dialysate. The aim of this pharmacoepidemiological study was to evaluate the association between hydrochloric or citric acid-based dialysate and mortality on haemodialysis (HD). METHODS: This study included 117 796 patients with 3 723 887 months on HD recorded in the national French Renal Epidemiology and Information Network registry. Dialysate acid components were retrospectively reconstructed for each facility. All patients on HD were associated each month with an exposure based on that at their facility of treatment. We took each patient's time-varying exposure into account to calculate the monthly mortality rates for each exposure. Incidence rate ratios (IRRs) for mortality were calculated with a Poisson regression, with acetic acid as the reference. Regressions were adjusted for initial clinical characteristics (age, gender, previous cardiovascular events, active malignancy, diabetes, pulmonary disease, mobility), dialysis technique and location (in-centre, outpatient centre, self-care unit) and ESRD vintage, updated monthly. RESULTS: The crude mortality rate per 1000 patient-months with citric acid {11.5 [95% confidence interval (CI) 11.1-12.0]} was lower than with either acetic acid [12.9 (95% CI 12.8-13.1)] or hydrochloric acid [12.8 (95% CI 12.2-13.5)]. For the 2014-17 period, the IRR for mortality with citric acid [adjusted IRR 0.94 (95% CI 0.90-0.99)] and with hydrochloric acid [adjusted IRR 0.86 (95% CI 0.79-0.94)] were significantly lower than with acetic acid. CONCLUSION: This post-marketing study of long-term exposure to dialysate acidifiers at the patient level found the use of citric and hydrochloric acid-based dialysates, compared with acetic acid, was associated with lower mortality.

Adverse Drug Reactions in Patients with CKD.

BACKGROUND AND OBJECTIVES: Little is known about the burden of adverse drug reactions in CKD. We estimated the incidence of overall and serious adverse drug reactions and assessed the probability of causation, preventability, and factors associated with adverse drug reactions in patients seen by nephrologists. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The Chronic Kidney Disease-Renal Epidemiology and Information Network cohort included 3033 outpatients (65% men) with CKD and eGFR<60 ml/min per 1.73 m2, with follow-up for 2 years. Adverse drug reactions were identified from hospitalization reports, medical records, and participant interviews and finally assessed for causality, preventability, and immediate therapeutic management by experts in pharmacology. RESULTS: Median (interquartile range) age was 69 (60-76) years old; 55% had eGFR≥30 ml/min per 1.73 m2, and 45% had eGFR<30 ml/min per 1.73 m2. Participants were prescribed a median (range) of eight (five to ten) drugs. Over 2 years, 536 patients had 751 adverse drug reactions, 150 (in 125 participants) classified as serious, for rates of 14.4 (95% confidence interval, 12.6 to 16.5) and 2.7 (95% confidence interval, 1.7 to 4.3) per 100 person-years, respectively. Among the serious adverse drug reactions, 32% were considered preventable or potentially preventable; 16 caused death, directly or indirectly. Renin-angiotensin system inhibitors (15%), antithrombotic agents (14%), and diuretics (10%) were the drugs to which the most adverse drug reactions were imputed, but antithrombotic agents caused 34% of serious adverse drug reactions. The drug was discontinued in 71% of cases, at least temporarily. Adjusted hazard ratios for serious adverse drug reaction were significantly higher in patients with eGFR<30 versus ≥30 ml/min per 1.73 m2 (1.8; 95% confidence interval, 1.3 to 2.6), in those prescribed more than ten versus less than five medications (2.4; 95% confidence interval, 1.1 to 5.2), or in those with poor versus good adherence (1.6; 95% confidence interval, 1.4 to 2.4). CONCLUSIONS: Adverse drug reactions are common and sometimes serious in patients with CKD. Many serious adverse drug reactions may be preventable. Some specific pharmacologic classes, particularly antithrombotic agents, are at risk of serious adverse drug reactions. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Chronic Kidney Disease-Renal Epidemiology and Information Network (CKD-REIN), NCT03381950.

[Use of iron in nephrology: Results of a French practical survey]. / Utilisation du fer en néphrologie : enquête sur les pratiques des néphrologues français.

The French-speaking Society of Nephrology, Dialysis and Transplantation conducted, in 2018, a survey among French nephrologists into their iron prescribing habits for patients with chronic kidney disease stages 3 to 5 before dialysis. The results show that 73% of nephrologists use intravenous iron before dialysis stage. When a patient has gastrointestinal symptoms under oral iron therapy, only 48% of nephrologists use intravenous route. The starting thresholds for iron are for 78% of nephrologists a transferrin saturation <20% and for 80% a serum ferritin <100 µg/L. Only 14% start iron when a transferrin saturation <25% or higher and 29% start iron when serum ferritin <200 µg/L or higher. High dosages of iron (500 and 1000 mg) are used by 58% of nephrologists. Finally, about 30% of nephrologists refer to various barriers to intravenous iron prescription, such as cost, unavailability of intravenous iron in their facility or lack of day hospital unit. The correction of iron deficiency without anemia remains controversial. It is performed by only 43% of nephrologists. These results show an improvement of the practices compared to a 2006 survey. However, they indicate a sub-prescription of iron compared to the European recommendations which recommend a starting threshold of iron of transferrin saturation <25% and ferritinemia <200 µg/L in anemic patients not treated with erythropoietin-stimulating agents.

Cost-effectiveness of four living-donor nephrectomy techniques from a hospital perspective.

BACKGROUND: In Europe, transplantation centres use different nephrectomy techniques: open surgery, and standard, hand-assisted and robot-assisted laparoscopies. Few studies have analysed the disparity in costs and clinical outcomes between techniques. Since donors are healthy patients expecting minimum pain and fast recovery, this study aimed to compare the cost-effectiveness of four nephrectomy techniques focusing on early surgical outcomes, an essential in the donation act. METHODS: A micro-costing approach was used to estimate the cost of implementation from a hospital perspective. Estimates took into account sterilization costs for multiple-use equipment, costs for purchasing single-use equipment, staff and analgesics. The study recruited donors in 20 centres in France. Quality of life by EuroQol-5D was assessed preoperatively, and 4 and 90 days post-operatively. Two effectiveness indicators were built: quality-of-life recovery and post-operative pain days averted (PPDA). The study was registered at ClinicalTrials.gov NCT02830568, on 10 June 2010. RESULTS: A total of 264 donors were included; they underwent open surgery (n = 65), and standard (n = 65), hand-assisted (n = 65) and robot-assisted laparoscopies (n = 69). Use of the nephrectomy techniques differed greatly in cost of implementation and immediate post-operative outcomes but not in clinical outcomes at 90 days. At 4 days, hand-assisted laparoscopy provided the lowest cost per quality-of-life recovery unit of effectiveness (%) and PPDA (days) (€2056/40.1%/2.3 days, respectively). Robot-assisted laparoscopy was associated with the best post-operative outcomes but with the highest cost (€3430/59.1%/2.6 days). CONCLUSION: Hand-assisted, standard and robot-assisted laparoscopies are cost-effective techniques compared with open surgery. Hand-assisted surgery is the most cost-effective procedure. Robot-assisted surgery requires more healthcare resource use but enables the best clinical outcome.

Immunosuppression and Graft Rejection in Living-related HLA-identical Renal Transplantation: The RADOVFULL Study.

BACKGROUND: We aimed to describe the immunosuppressive regimens and graft rejection rates in living-related HLA-identical (LR HLAid) renal transplantation. METHODS: We performed a retrospective multicenter analysis of the French national database for LR HLAid renal transplantations performed between 2002 and 2012. Univariate and multivariate analysis were performed to determine risk factors for graft rejection in LR HLAid recipients. RESULTS: A total of 27 218 renal transplantations were performed, of whom 163 had a LR HLAid donor. About immunosuppressive treatment, <60% of the cohort had induction therapy with polyclonal or monoclonal antibodies, 28% did not receive calcineurin inhibitors, and 36% did not receive steroids in maintenance. Biopsy-proven acute rejection was diagnosed in 21 patients (12.9%). Rejection occurred on an average of 24 months after transplantation, in 28.5% of the cases after minimization of immunosuppression. Factors associated with rejection were age of recipient (OR, 0.91 [0.84-0.96]; P = 0.003), the body mass index of donors (odds ratio [OR], 1.22 [1.04-1.46]; P = 0.01), and minimization of immunosuppression (OR, 26.2 [5.48-166.6]; P < 0.001). Overall and graft survival rates were not statistically different according to rejection at 1, 5, and 10 years posttransplantation. CONCLUSIONS: Minimization of immunosuppression should be done with caution in LR HLAid renal transplantations.

Unilateral nephrectomy versus renal arterial embolization and technique survival in peritoneal dialysis patients with autosomal dominant polycystic kidney disease.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is a common genetic disorder associated with progressive enlargement of the kidneys and liver. ADPKD patients may require renal volume reduction, especially before renal transplantation. The standard treatment is unilateral nephrectomy. However, surgery incurs a risk of blood transfusion and alloimmunization. Furthermore, when patients are treated with peritoneal dialysis (PD), surgery is associated with an increased risk of temporary or definitive switch to haemodialysis (HD). Unilateral renal arterial embolization can be used as an alternative approach to nephrectomy. METHODS: We performed a multicentre retrospective study to compare the technique of survival of PD after transcatheter renal artery embolization with that of nephrectomy in an ADPKD population. We included ADPKD patients treated with PD submitted to renal volume reduction by either surgery or arterial embolization. Secondary objectives were to compare the frequency and duration of a temporary switch to HD in both groups and the impact of the procedure on PD adequacy parameters. RESULTS: More than 700 patient files from 12 centres were screened. Only 37 patients met the inclusion criteria (i.e. treated with PD at the time of renal volume reduction) and were included in the study (21 embolized and 16 nephrectomized). Permanent switch to HD was observed in 6 embolized patients (28.6%) versus 11 nephrectomized patients (68.8%) (P = 0.0001). Renal artery embolization was associated with better technique survival: subdistribution hazard ratio (SHR) 0.29 [95% confidence interval (CI) 0.12-0.75; P = 0.01]. By multivariate analysis, renal volume reduction by embolization and male gender were associated with a decreased risk of switching to HD. After embolization, a decrease in PD adequacy parameters was observed but no embolized patients required temporary HD; the duration of hospitalization was significantly lower [5 days [interquartile range (IQR) 4.0-6.0] in the embolization group versus 8.5 days (IQR 6.0-11.0) in the surgery group. CONCLUSIONS: Transcatheter renal artery embolization yields better technique survival of PD in ADPKD patients requiring renal volume reduction.

Risk profile, quality of life and care of patients with moderate and advanced CKD: The French CKD-REIN Cohort Study.

Background: The French Chronic Kidney Disease-Renal Epidemiology and Information Network (CKD-REIN) cohort study was designed to investigate the determinants of prognosis and care of patients referred to nephrologists with moderate and advanced chronic kidney disease (CKD). We examined their baseline risk profile and experience. Methods: We collected bioclinical and patient-reported information from 3033 outpatients with CKD and estimated glomerular filtration rates (eGFRs) of 15-60 mL/min/1.73 m2 treated at 40 nationally representative public and private facilities. Results: The patients' median age was 69 (60-76) years, 65% were men, their mean eGFR was 33 mL/min/1.73 m2, 43% had diabetes, 24% had a history of acute kidney injury (AKI) and 57% had uncontrolled blood pressure (BP; >140/90 mmHg). Men had worse risk profiles than women and were more likely to be past or current smokers (73% versus 34%) and have cardiovascular disease (59% versus 42%), albuminuria >30 mg/mmol (or proteinuria > 50) (40% versus 30%) (all P < 0.001) and a higher median risk of end-stage renal disease within 5 years, predicted by the kidney failure risk equation {12% [interquartile range (IQR) 3-37%] versus 9% [3-31%], P = 0.008}. During the previous year, 60% of patients reported one-to-two nephrologist visits and four or more general practitioner visits; only 25% saw a dietician and 75% were prescribed five or more medications daily. Physical and mental quality of life (QoL) were poor, with scores <50/100. Conclusions: The CKD-REIN study highlights high-risk profiles of cohort members and identifies several priorities, including improving BP control and dietary counselling and increasing doctors' awareness of AKI, polypharmacy and QoL. Trial registration: ClinicalTrials.gov identifier: NCT03381950.

[Tubulointerstitiel nephritis and Crohn's disease, nephrotoxicity or extraintestinal manifestation of Crohn's disease? About a case]. / Néphrite tubulo-interstitielle et maladie de Crohn, néphrotoxicité ou atteinte extradigestive de la maladie de Crohn ? À propos d'un cas.

Extraintestinal manifestations in inflammatory bowel disease involve most frequently the joints, the skin, the eyes, the liver and the biliary tract. Renal involvement is rare, and manifested as nephrolithiasis, tubulointerstitial nephritis, glomerulonephritis and amyloidosis. In patients with inflammatory bowel disease, renal disease is most frequently due to treatment nephrotoxicity and rarely as a guenine extraintestinal manifestation of inflammatory bowel disease. We are reporting a case of tubulointerstitial nephritis as an extraintestinal manifestation of Crohn's disease and we are explaining the diagnostic difficulty to distinguish this from drug-induced nephrotoxicity.

Ultramarathon and Renal Function: Does Exercise-Induced Acute Kidney Injury Really Exist in Common Conditions?

Background: Increasing ultramarathons participation, investigation into strenuous exercise and kidney function has to be clarified. Study Design: Prospective observational study. Methods and Protocol: The study used data collected among ultra-marathon runners completing the 2017 edition of the 120 km "Infernal trail" race. Samples were collected within 2 h pre-race (start) and immediately post-race (finish). Measurements of serum creatinine (sCr), cystatin C (Cys), creatine kinase, and urine albumin were completed. Acute Kidney Injury (AKI) as defined by the RIFLE criteria. "Risk" of injury was defined as increased serum Creatinine (sCr) × 1.5 or Glomerular Filtration Rate (GFR) decrease >25%. Injury was defined as 2 × sCr or GFR decrease >50%. These two categories of AKI were combined to calculate total incidence at the finish line. GFR was estimated by two methods, using measure of sCr and using measure of cystatin C. Urinary biomarkers [neutrophil gelatinase-associated lipocalin (NGAL)] were also used to define AKI. Outcome results before and after the race were compared by using McNemar test for qualitative data and Wilcoxon signed-rank test for quantitative data, in modified intent-to-treat and per-protocol analyses. Results: A sample of 24 included finishers, with no use of non-steroidal anti-inflammatory drugs (NSAIDs) was studied. Depending the methodology used to calculate GFR, the prevalence of AKI was observed from 0 to 12.5%. Urinary biomarkers of kidney damage were increased following the race but with no significant decrease in GFR. Discussion/Conclusion: Our study showed a very low prevalence of AKI and no evidence that ultra-endurance running can cause important kidney damage in properly hydrated subjects with no use of NSAIDs. Whether the increase in urinary biomarkers of kidney damage following the race reflects structural kidney injury or a simple metabolic adaptation to strenuous exercise needs to be clarified.