Simulation-based learning in nephrology.

Simulation is a technique to replace and amplify real experiences with guided ones that evoke or replicate substantial aspects of the real world in a fully interactive fashion. In nephrology (a particularly complex specialty), simulation can be used by patients, nurses, residents, and attending physicians alike. It allows one to learn techniques outside the stressful environment of care such as central venous catheter placement, arteriovenous fistula management, learning about peritoneal dialysis, or performing a kidney biopsy. Serious games and virtual reality are emerging methods that show promise. Simulation could also be important in relational aspects of working in a team or with the patient. The development of simulation as a teaching tool in nephrology allows for maintaining high-quality training for residents, tailored to their future practice, and minimizing risks for patients. Additionally, this education helps nephrologists maintain mastery of technical procedures, making the specialty attractive to younger generations. Unfortunately, the inclusion of simulation training programmes faces occasional logistical or funding limitations that universities must overcome with the assistance and innovation of teaching nephrologists. The impact of simulation-based teaching on clinical outcomes needs to be investigated in clinical studies.

Assessment of epidemiology and outcomes of adult patients with kidney-limited thrombotic microangiopathies.

Thrombotic microangiopathies (TMA) are usually associated with hematological features (RH-TMA). The epidemiology of TMA limited to kidneys (RL-TMA) is unclear Therefore, patients with TMA and native kidney biopsies were identified during 2009-2022 in 20 French hospitals and results evaluated. RL-TMA was present in 341/757 (45%) patients and associated with lower creatinine levels (median 184 vs 346 µmol/L) than RH-TMA. RL-TMA resulted from virtually all identified causes, more frequently from anti-VEGF treatment and hematological malignancies but less frequently from shigatoxin-associated hemolytic uremic syndrome (HUS), systemic sclerosis, gemcitabine and bacterial infection, and even less frequently when three or more causes/triggers were combined (RL-TMA: 5%; RH-TMA: 12%). RL-TMA was associated with significantly lower major cardiovascular events (10% vs 20%), kidney replacement therapy (23% vs 43%) and death (12% vs 20%) than RH-TMA during follow-up (median 28 months). Atypical HUS (aHUS) was found in 326 patients (RL-TMA: 43%, RH-TMA: 44%). Among the 69 patients with proven complement-mediated aHUS, eculizumab (anti-C5 therapy) was used in 43 (62%) (RL-TMA: 35%; RH-TMA: 71%). Among the 257 other patients with aHUS, including 51% with RL-TMA, eculizumab was used in 29 but with unclear effects of this treatment. Thus, RL-TMA represents a very high proportion of patients with TMA and results from virtually all known causes of TMA and includes 25% of patients with complement-mediated aHUS. Adverse outcomes of RL-TMA are lower compared to RH-TMA but remain significant. Anti-C5 therapy was rarely used in RL-TMA, even in proven complement-mediated aHUS, and its effects remain to be assessed.

Effect of comorbidities on healthcare expenditures for patients on kidney replacement therapy considering the treatment modality and duration in a French cohort.

End-stage kidney disease (ESKD) is associated with a substantial economic burden. In France, the cost of care for such patients represents 2.5% of the total French healthcare expenditures but serves less than 1% of the population. These patients' healthcare expenditures are high because of the specialized and complex treatment needed as well as the presence of multiple comorbidities. This study aims to describe and assess the effect of comorbidities on healthcare expenditures (direct medical cost and non-medical costs including transportation and compensatory allowances) for patients with ESKD in France while considering the modality and duration of renal replacement therapy (RRT). This study included adults who started RRT for the first time between 2012 and 2014 in France and were followed for 5 years. Generalized linear models were built to predict mean monthly cost (MMC) by integrating first the time duration in the cohort, then patient characteristics and finally the duration of use of each treatment modalities. Comorbidities with the highest effect on MMC were inability to walk (+ 1435€), active cancer (+ 593€), HIV positivity (+ 507€) and diabetes (+ 396€). These effects vary according to age or treatment modalities. This study confirms the importance of considering patient characteristics, comorbidities and type of RRT when assessing healthcare expenditures for patients with ESKD.

Thrombotic microangiopathies after kidney transplantation in modern era: nosology based on chronology.

BACKGROUND: Thrombotic microangiopathies (TMAs) are rare but can be severe in kidney transplant. recipients (KTR). METHODS: We analysed the epidemiology of adjudicated TMA in consecutive KTR during the. 2009-2021 period. RESULTS: TMA was found in 77/1644 (4.7%) KTR. Early TMA (n = 24/77 (31.2%); 1.5% of all KTR) occurred during the first two weeks ((median, IQR) 3 [1-8] days). Triggers included acute antibody-mediated rejection (ABMR, n = 4) and bacterial infections (n = 6). Graft survival (GS) was 100% and recurrence rate (RR) was 8%. Unexpected TMA (n = 31/77 (40.2%); 1.5/1000 patient-years) occurred anytime during follow-up (3.0 (0.5-6.2) years). Triggers included infections (EBV/CMV: n = 10; bacterial: n = 6) and chronic active ABMR (n = 5). GS was 81% and RR was 16%. Graft-failure associated TMA (n = 22/77 (28.6%); 2.2% of graft losses) occurred after 8.8 (4.9-15.5) years). Triggers included acute (n = 4) or chronic active (n = 14) ABMR, infections (viral: n = 6; bacterial: n = 5) and cancer (n = 6). 15 patients underwent transplantectomy. RR was 27%. Atypical (n = 6) and typical (n = 2) haemolytic and uremic syndrome, and isolated CNI toxicity (n = 4) were rare. Two-third of biopsies presented TMA features. CONCLUSIONS: TMA are mostly due to ABMR and infections; causes of TMA are frequently combined. Management often is heterogenous. Our nosology based on TMA timing identifies situations with distinct incidence, causes and prognosis.

A Universal Bleeding Risk Score in Native and Allograft Kidney Biopsies: A French Nationwide Cohort Study.

BACKGROUND: The risk of bleeding after percutaneous biopsy in kidney transplant recipients is usually low but may vary. A pre-procedure bleeding risk score in this population is lacking. METHODS: We assessed the major bleeding rate (transfusion, angiographic intervention, nephrectomy, hemorrhage/hematoma) at 8 days in 28,034 kidney transplant recipients with a kidney biopsy during the 2010-2019 period in France and compared them to 55,026 patients with a native kidney biopsy as controls. RESULTS: The rate of major bleeding was low (angiographic intervention: 0.2%, hemorrhage/hematoma: 0.4%, nephrectomy: 0.02%, blood transfusion: 4.0%). A new bleeding risk score was developed (anemia = 1, female gender = 1, heart failure = 1, acute kidney failure = 2 points). The rate of bleeding varied: 1.6%, 2.9%, 3.7%, 6.0%, 8.0%, and 9.2% for scores 0 to 5, respectively, in kidney transplant recipients. The ROC AUC was 0.649 (0.634-0.664) in kidney transplant recipients and 0.755 (0.746-0.763) in patients who had a native kidney biopsy (rate of bleeding: from 1.2% for score = 0 to 19.2% for score = 5). CONCLUSIONS: The risk of major bleeding is low in most patients but indeed variable. A new universal risk score can be helpful to guide the decision concerning kidney biopsy and the choice of inpatient vs. outpatient procedure both in native and allograft kidney recipients.

De novo and relapsing necrotizing vasculitis after COVID-19 vaccination.

We describe five cases of severe necrotizing vasculitis following the RNA-based vaccine for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), including four relapsing anti neutrophil cytoplasmic antibodies (ANCA) vasculitis, 27 days (1-60) after vaccination and one patient with quiescent chronic hepatitis B and de novo polyarteritis nodosa (PAN) 21 days after vaccination. Ten other cases were reported to the French national pharmacovigilance database: six patients with ANCA-associated vasculitis and four patients with PAN (first symptoms 19 days on average after vaccination). Five of these 10 patients developed kidney dysfunction. In conclusion, coronavirus disease 2019 (COVID-19) vaccines can be associated with de novo or recurrent ANCA vasculitis or PAN. Attention should be paid to patients with known ANCA vasculitis or patients with a history of hepatitis B infection.

What is the impact of blood pressure on neurological symptoms and the risk of ESKD in primary and secondary thrombotic microangiopathies based on clinical presentation: a retrospective study.

BACKGROUND: The impact of blood pressure on neurological symptoms and risk of end-stage kidney disease (ESKD) is unknown in primary and secondary thrombotic microangiopathies (TMAs). METHODS: We measured baseline systolic (SBP) and diastolic (DBP) BP in consecutive 563 patients with adjudicated primary and secondary TMAs, and assessed its association with the risk of ESKD. RESULTS: Normal BP, grade 1, 2 and 3 hypertension were present in 243 (43.1%), 132 (23.4%), 101 (17.9%) and 88 (15.6%), respectively. Significant BP differences were noted in relation to the cause of TMA: highest BP values were found in patients with atypical hemolytic-uremic syndrome (aHUS), pregnancy, transplantation and auto-immune-related TMAs. Normal BP or grade 1 hypertension was found in 17/18 (94.4%) patients with thrombotic thrombocytopenic patients (only 1/18 (5.6%) had a SBP value>150 mmHg). In contrast, BP values could not differentiate isolated "essential" malignant hypertension (MH) from MH associated with aHUS (isolated MH (n=15): BP (median (IQR)): 220 (182-249)/132 (101-150) mmHg; MH with aHUS (n=5): BP: 223 (196-245)/131 (111-144) mmHg). The risk of vigilance disturbances (6.9%, 15.0%, 25.0%, respectively), epileptic seizures (1.5%, 4.0%, 12.5%, respectively) and posterior reversible encephalopathy syndrome (0.76%, 2.97%, 6.82%, respectively) increased with increasing baseline BP values from grade 1 to grade 3 hypertension. ESKD occurred in 35/563 (6.2%) patients (1.23%, 2.27%, 11.9% and 19.3% of patients with normal BP, grade 1, 2 and 3 hypertension, respectively). As compared to patients with normal BP (<120/139 mmHg), grade 1, grade 2 and grade 3 hypertension were associated with a greater risk of ESKD in univariate (OR: 1.91 [0.83-4.40], 13.2 [3.56-48.9] and 34.8 [9.31-130], respectively) and multivariate (OR: 0.89 [0.30-2.69], 7.00 [1.57-31.3] and 19.7 [4.53-85.2], respectively) analyses. The association between BP and the risk of ESRD was unchanged after adjustment on eculizumab use (OR: 3.46 [1.41-8.49], 17.7 [4.44-70.0] and 70.6 [8.61-579], respectively). Patients with MH, regardless of its cause, had a greater risk of ESKD (OR: 26.4 [10.0-69.8] vs other patients). CONCLUSIONS: Baseline BP differs in primary and secondary TMAs. High BP reduces the neurological tolerance of TMAs and is a powerful independent risk factor of ESKD, even after adjustment on TMA's cause.

Major Bleeding of Transjugular Native Kidney Biopsies. A French Nationwide Cohort Study.

INTRODUCTION: The risk of bleeding associated with transjugular kidney biopsies is unclear, and which patients are the best candidates for this route is unknown. METHODS: This was a retrospective cohort study comparing proportion of bleeding associated with transjugular versus percutaneous native kidney biopsies in all patients in France in the 2010-2019 period. Major bleeding at day 8 (i.e., blood transfusions, hemorrhage/hematoma, angiographic intervention, nephrectomy) and risk of death at day 30 were assessed, and we used a bleeding risk score initially developed for the percutaneous route. RESULTS: Our analysis included 60,331 patients (transjugular route: 5305; percutaneous route: 55,026 patients). The observed proportion of major bleeding varied widely (transjugular vs. percutaneous): 0.4% versus 0.5% for the lowest risk scores (0-4) to 19.1% versus 30.8% for the highest risk scores (≥35). Transjugular was more frequently used than percutaneous route (39% vs. 24%) when the risk score was ≥20 (15,133/60,331; 25% of all patients). Transjugular was associated with a lower risk of major bleeding than percutaneous route in multivariate analyses (odds ratio [OR]: 0.88 [0.78-0.99]), especially for scores ≥20 (OR: 0.83 [0.72-0.96], (i.e., 25% of patients). Major bleeding was associated with an increased risk of death both for transjugular (OR: 1.77 [1.00-3.14]) and percutaneous (OR: 1.80 [1.43-2.28]) routes. CONCLUSIONS: The transjugular route is independently associated with a lower risk of bleeding than the percutaneous route, especially in high-risk patients identified by a preprocedure risk score ≥20 (i.e., 25% of patients). Major bleeding is associated with an increased risk of death for both routes.

Establishing a Core Outcome Set for Autosomal Dominant Polycystic Kidney Disease: Report of the Standardized Outcomes in Nephrology-Polycystic Kidney Disease (SONG-PKD) Consensus Workshop.

The omission of outcomes that are of relevance to patients, clinicians, and regulators across trials in autosomal dominant polycystic kidney disease (ADPKD) limits shared decision making. The Standardized Outcomes in Nephrology-Polycystic Kidney Disease (SONG-PKD) Initiative convened an international consensus workshop on October 25, 2018, to discuss the identification and implementation of a potential core outcome set for all ADPKD trials. This article summarizes the discussion from the workshops and the SONG-PKD core outcome set. Key stakeholders including 11 patients/caregivers and 47 health professionals (nephrologists, policy makers, industry, and researchers) attended the workshop. Four themes emerged: "Relevance of trajectory and impact of kidney function" included concerns about a patient's prognosis and uncertainty of when they may need to commence kidney replacement therapy and the lack of an early prognostic marker to inform long-term decisions; "Discerning and defining pain specific to ADPKD" highlighted the challenges in determining the origin of pain, adapting to the chronicity and repeated episodes of pain, the need to place emphasis on pain management, and to have a validated measure for pain; "Highlighting ADPKD consequences" encompassed cyst-related complications and reflected patient's knowledge because of family history and the hereditary nature of ADPKD; and "Risk for life-threatening but rare consequences" such as cerebral aneurysm meant considering both frequency and severity of the outcome. Kidney function, mortality, cardiovascular disease, and pain were established as the core outcomes for ADPKD.

Major Bleeding and Risk of Death after Percutaneous Native Kidney Biopsies: A French Nationwide Cohort Study.

BACKGROUND AND OBJECTIVES: The risk of major bleeding after percutaneous native kidney biopsy is usually considered low but remains poorly predictable. The aim of the study was to assess the risk of major bleeding and to build a preprocedure bleeding risk score. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Our study was a retrospective cohort study in all 52,138 patients who had a percutaneous native kidney biopsy in France in the 2010-2018 period. Measurements included major bleeding (i.e., blood transfusions, hemorrhage/hematoma, angiographic intervention, or nephrectomy) at day 8 after biopsy and risk of death at day 30. Exposures and outcomes were defined by diagnosis codes. RESULTS: Major bleeding occurred in 2765 of 52,138 (5%) patients (blood transfusions: 5%; angiographic intervention: 0.4%; and nephrectomy: 0.1%). Nineteen diagnoses were associated with major bleeding. A bleeding risk score was calculated (Charlson index [2-4: +1; 5 and 6: +2; >6: +3]; frailty index [1.5-4.4: +1; 4.5-9.5: +2; >9.5: +3]; women: +1; dyslipidemia: -1; obesity: -1; anemia: +8; thrombocytopenia: +2; cancer: +2; abnormal kidney function: +4; glomerular disease: -1; vascular kidney disease: -1; diabetic kidney disease: -1; autoimmune disease: +2; vasculitis: +5; hematologic disease: +2; thrombotic microangiopathy: +4; amyloidosis: -2; other kidney diagnosis: -1) + a constant of 5. The risk of bleeding went from 0.4% (lowest score group =0-4 points) to 33% (highest score group ≥35 points). Major bleeding was an independent risk of death (500 of 52,138 deaths: bleeding: 81 of 2765 [3%]; no bleeding: 419 of 49,373 [0.9%]; odds ratio, 1.95; 95% confidence interval, 1.50 to 2.54; P<0.001). CONCLUSIONS: The risk of major bleeding after percutaneous native kidney biopsy may be higher than generally thought and is associated with a twofold higher risk of death. It varies widely but can be estimated with a score useful for shared decision making and procedure choice.

Core Outcome Domains for Trials in Autosomal Dominant Polycystic Kidney Disease: An International Delphi Survey.

RATIONALE & OBJECTIVE: Outcomes reported in trials involving patients with autosomal dominant polycystic kidney disease (ADPKD) are heterogeneous and rarely include patient-reported outcomes. We aimed to identify critically important consensus-based core outcome domains to be reported in trials in ADPKD. STUDY DESIGN: An international 2-round online Delphi survey was conducted in English, French, and Korean languages. SETTING & PARTICIPANTS: Patients/caregivers and health professionals completed a 9-point Likert scale (7-9 indicating critical importance) and a Best-Worst Scale. ANALYTICAL APPROACH: The absolute and relative importance of outcomes were assessed. Comments were analyzed thematically. RESULTS: 1,014 participants (603 [60%] patients/caregivers, 411 [40%] health professionals) from 56 countries completed round 1, and 713 (70%) completed round 2. The prioritized outcomes were kidney function (importance score, 8.6), end-stage kidney disease (8.6), death (7.9), blood pressure (7.9), kidney cyst size/growth (7.8), and cerebral aneurysm (7.7). Kidney cyst-related pain was the highest rated patient-reported outcome by both stakeholder groups. Seven themes explained the prioritization of outcomes: protecting life and health, directly encountering life-threatening and debilitating consequences, specificity to ADPKD, optimizing and extending quality of life, hidden suffering, destroying self-confidence, and lost opportunities. LIMITATIONS: Study design precluded involvement from those without access to internet or limited computer literacy. CONCLUSIONS: Kidney function, end-stage kidney disease, and death were the most important outcomes to patients, caregivers, and health professionals. Kidney cyst-related pain was the highest rated patient-reported outcome. Consistent reporting of these top prioritized outcomes may strengthen the value of trials in ADPKD for decision making.

An extension of the RITUX-ERAH study, multicenter randomized clinical trial comparing rituximab to placebo in acute antibody-mediated rejection after renal transplantation.

The treatment of active antibody-mediated rejection (ABMR) is still a matter of debate, the place of rituximab remaining controversial. The French multicenter double-blind RITUX-ERAH study included 38 patients with ABMR in the first year of renal transplantation. All patients received plasma exchanges, intravenous immunoglobulins, and corticosteroids and were randomly assigned rituximab or placebo infusion at day 5. Additional rituximab infusions were allowed. In the intention-to-treat analysis, 12-month graft survival and renal function were not different between the rituximab and placebo groups. Long-term data are needed to conclude. Evaluation of the 7-year outcomes of the RITUX-ERAH study patients according to the rituximab or placebo treatment received. Eleven patients received placebo and 27 at least one infusion of rituximab. Seven years after ABMR, death-censored kidney allograft survival and renal function were not different between the groups. The evolution of anti-HLA sensitization was similar. There was no statistically significant difference in the incidence of infectious or neoplastic complications, but to be noted, seven cancers developed in six patients treated with rituximab (mean period of 44 months post-ABMR). In this cohort, there was no benefit 7 years after ABMR of rituximab in addition to plasma exchanges, intravenous immunoglobulins, and steroids.

Range and Variability of Outcomes Reported in Randomized Trials Conducted in Patients With Polycystic Kidney Disease: A Systematic Review.

RATIONALE & OBJECTIVE: Trials in autosomal dominant polycystic kidney disease (ADPKD) have increased, but their impact on decision making has been limited. Because heterogeneity in reported outcomes may be responsible, we assessed their range and variability in ADPKD trials. STUDY DESIGN: Systematic review. SETTING & STUDY POPULATION: Adult participants in clinical trials in ADPKD. SELECTION CRITERIA FOR STUDIES: We included trials that studied adults and were published in English. For trials that enrolled patients without ADPKD, only those enrolling ≥50% of participants with ADPKD were included. DATA EXTRACTION: We extracted information on all discrete outcome measures, grouped them into 97 domains, and classified them into clinical, surrogate, and patient-reported categories. For each category, we choose the 3 most frequently reported domains and performed a detailed analysis of outcome measures. ANALYTICAL APPROACH: Frequencies and characteristics of outcome measures were described. RESULTS: Among 68 trials, 1,413 different outcome measures were reported. 97 domains were identified; 41 (42%) were surrogate, 30 (31%) were clinical, and 26 (27%) were patient reported. The 3 most frequently reported domains were in the surrogate category: kidney function (54; 79% of trials; using 46 measures), kidney and cyst volumes (43; 63% of trials; 52 measures), and blood pressure (27; 40% of trials, 30 measures); in the clinical category: infection (10; 15%; 21 measures), cardiovascular events (9; 13%; 6 measures), and kidney failure requiring kidney replacement therapy (8; 12%; 5 measures); and in the patient-reported category: pain related to ADPKD (16; 24%; 26 measures), pain for other reasons (11; 16%; 11 measures), and diarrhea/constipation/gas (10; 15%; 9 measures). LIMITATIONS: Outcome measures were assessed for only the top 3 domains in each category. CONCLUSIONS: The outcomes in ADPKD trials are broad in scope and highly variable. Surrogate outcomes were most frequently reported. Patient-reported outcomes were uncommon. A consensus-based set of core outcomes meaningful to patients and clinicians is needed for future ADPKD trials.

Etiology and Outcomes of Thrombotic Microangiopathies.

BACKGROUND AND OBJECTIVES: Thrombotic microangiopathies constitute a diagnostic and therapeutic challenge. Secondary thrombotic microangiopathies are less characterized than primary thrombotic microangiopathies (thrombotic thrombocytopenic purpura and atypical hemolytic and uremic syndrome). The relative frequencies and outcomes of secondary and primary thrombotic microangiopathies are unknown. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted a retrospective study in a four-hospital institution in 564 consecutive patients with adjudicated thrombotic microangiopathies during the 2009-2016 period. We estimated the incidence of primary and secondary thrombotic microangiopathies, thrombotic microangiopathy causes, and major outcomes during hospitalization (death, dialysis, major cardiovascular events [acute coronary syndrome and/or acute heart failure], and neurologic complications [stroke, cognitive impairment, or epilepsy]). RESULTS: We identified primary thrombotic microangiopathies in 33 of 564 patients (6%; thrombotic thrombocytopenic purpura: 18 of 564 [3%]; atypical hemolytic and uremic syndrome: 18 of 564 [3%]). Secondary thrombotic microangiopathies were found in 531 of 564 patients (94%). A cause was identified in 500 of 564 (94%): pregnancy (35%; 11 of 1000 pregnancies), malignancies (19%), infections (33%), drugs (26%), transplantations (17%), autoimmune diseases (9%), shiga toxin due to Escherichia coli (6%), and malignant hypertension (4%). In the 31 of 531 patients (6%) with other secondary thrombotic microangiopathies, 23% of patients had sickle cell disease, 10% had glucose-6-phosphate dehydrogenase deficiency, and 44% had folate deficiency. Multiple causes of thrombotic microangiopathies were more frequent in secondary than primary thrombotic microangiopathies (57% versus 19%; P<0.001), and they were mostly infections, drugs, transplantation, and malignancies. Significant differences in clinical and biologic differences were observed among thrombotic microangiopathy causes. During the hospitalization, 84 of 564 patients (15%) were treated with dialysis, 64 of 564 patients (11%) experienced major cardiovascular events, and 25 of 564 patients (4%) had neurologic complications; 58 of 564 patients (10%) died, but the rates of complications and death varied widely by the cause of thrombotic microangiopathies. CONCLUSIONS: Secondary thrombotic microangiopathies represent the majority of thrombotic microangiopathies. Multiple thrombotic microangiopathies causes are present in one half of secondary thrombotic microangiopathies. The risks of dialysis, neurologic and cardiac complications, and death vary by the cause of thrombotic microangiopathies.

Increased risk of rejection after basiliximab induction in sensitized kidney transplant recipients without pre-existing donor-specific antibodies - a retrospective study.

Depleting induction therapy is recommended in sensitized kidney transplant recipients (KTRs), though the detrimental effect of nondonor-specific anti-HLA antibodies is not undeniable. We compared the efficacy and safety of basiliximab and rabbit anti-thymocyte globulin (rATG) in sensitized KTRs without pre-existing donor-specific antibodies (DSAs). This monocentric retrospective study involved all sensitized KTR adults without pre-existing DSAs (n = 218) who underwent transplantation after June 2007. Patients with basiliximab and rATG therapy were compared for risk of biopsy-proven acute rejection (BPAR) and a composite endpoint (BPAR, graft loss and death) by univariate and multivariate analysis. Patients with basiliximab (n = 60) had lower mean calculated panel reactive antibody than those with rATG (n = 158; 23.7 ± 24.2 vs. 63.8 ± 32.3, P < 0.0001) and more often received a first graft (88% vs. 54%, P < 0.0001) and a transplant from a living donor (13% vs. 2%, P = 0.002). Risks of BPAR and of reaching the composite endpoint were greater with basiliximab than rATG [HR = 3.63 (1.70-7.77), P = 0.0009 and HR = 1.60 (0.99-2.59), P = 0.050, respectively]. Several adjustments did not change those risks [BPAR: 3.36 (1.23-9.16), P = 0.018; composite endpoint: 1.83 (0.99-3.39), P = 0.053]. Infections and malignancies were similar in both groups. rATG remains the first-line treatment in sensitized KTR, even in the absence of pre-existing DSAs.

Identifying patient-important outcomes in polycystic kidney disease: An international nominal group technique study.

AIM: Patients with autosomal dominant polycystic kidney disease (ADPKD) are at increased risk of premature mortality, morbidities and complications, which severely impair quality of life. However, patient-centered outcomes are not consistently reported in trials in ADPKD, which can limit shared decision-making. We aimed to identify outcomes important to patients and caregivers and the reasons for their priorities. METHODS: Nominal group technique was adopted involving patients with ADPKD and caregivers who were purposively selected from eight centres across Australia, France and the Republic of Korea. Participants identified, ranked and discussed outcomes for trials in ADPKD. We calculated an importance score (0-1) for each outcome and conducted thematic analyses. RESULTS: Across 17 groups, 154 participants (121 patients, 33 caregivers) aged 19 to 78 (mean 54.5 years) identified 55 outcomes. The 10 highest ranked outcomes were: kidney function (importance score 0.36), end-stage kidney disease (0.32), survival (0.21), cyst size/growth (0.20), cyst pain/bleeding (0.18), blood pressure (0.17), ability to work (0.16), cerebral aneurysm/stroke (0.14), mobility/physical function (0.12), and fatigue (0.12). Three themes were identified: threatening semblance of normality, inability to control and making sense of diverse risks. CONCLUSION: For patients with ADPKD and their caregivers, kidney function, delayed progression to end-stage kidney disease and survival were the highest priorities, and were focused on achieving normality, and maintaining control over health and lifestyle. Implementing these patient-important outcomes may improve the meaning and relevance of trials to inform clinical care in ADPKD.

Renal function at the time of nephrology referral but not dialysis initiation as a risk for death in patients with diabetes mellitus.

BACKGROUND: Renal patients with diabetes mellitus are at very high risk of death before and after chronic dialysis initiation. Risk factors for death in this population are not clearly identified. METHODS: We performed a retrospective survival analysis in 861 patients with diabetes mellitus consecutively followed up in the 2000-13 period in a nephrology setting. RESULTS: The mean age was 70 ± 10 years [men 65.2%; diabetes duration 13.7 ± 10.3 years; mean estimated glomerular filtration rate (eGFR) 42.4 ± 21.0 mL/min/1.73 m2). During follow-up (median 60 months; up 15 years), 263 patients died (184 before and 79 after dialysis initiation) and 183 started chronic dialysis. In multivariate analyses, age, elevated systolic and low diastolic arterial pressures, peripheral artery disease, cancer, loop diuretic use and atrial fibrillation at baseline and acute kidney injury (AKI), heart failure (HF) and amputation during follow-up were identified as risk factors for death. After adjustments on these parameters, eGFRs at the time of the first outpatient visit-eGFR <45 mL/min/1.73 m2 {hazard ratio [HR] 1.58 [95% confidence interval (CI) 1.15-2.17]}, P = 0.005 and eGFR <30 [HR 1.53 (1.05-2.05)], P = 0.004, but not eGFR <60-were powerful risk factors for death. When initiation of dialysis was entered into the multivariate models, it was not associated with a risk of premature death [HR 1.19 (95% CI 0.91-1.55), P = 0.2069], even in patients >80 years of age [HR 1.08 (95% CI 0.64-1.81), P = 0.7793]. CONCLUSIONS: In patients with diabetes mellitus, high systolic and low diastolic arterial pressure, peripheral artery disease and development of AKI and HF are significant risk factors for death. In addition to these parameters, eGFR <45 mL/min/1.73 m2 at the time of referral is also a powerful risk factor for death.

Range and Consistency of Outcomes Reported in Randomized Trials Conducted in Kidney Transplant Recipients: A Systematic Review.

BACKGROUND: The potential for clinical trials to impact patient care may be limited if the outcomes reported vary by trial and lack direct relevance to patients. Despite the many trials conducted in kidney transplantation, premature death due to cardiovascular disease, infection, and malignancy remains high. We aimed to assess the range and consistency of outcomes reported in trials in kidney transplantation. METHODS: We searched for randomized trials conducted in kidney transplantation. We extracted the outcome measures, classified them into outcome domains, and into categories (clinical, surrogate or patient-reported outcome [PRO]). We assessed the measures used for the top 4 domains. RESULTS: Overall, 397 trials reported 12 047 outcomes measures and time points (median, 19 per trial; interquartile range, 9-42) across 106 different domains, of which 55 (52%) were surrogate, 35 (33%) clinical, and 16 (15%) PRO. The 4 most frequently reported were graft function (322 [81%] trials, 118 outcome measures), acute rejection (234 [59%], 93 measures), graft loss (215 [54%], 48 measures), and mortality (204 [51%], 51 measures). The remaining 102 domains were reported in less than 50% of trials. CONCLUSIONS: Mortality- and graft-related outcome domains were frequently reported and assessed with a multiplicity of measures. Most outcome domains were surrogate outcomes, and the reporting of relevant life-threatening complications and PRO were uncommon. Establishing core outcomes based on the shared priorities of patients/caregivers and health professionals in kidney transplantation may improve the relevance and consistency of outcome reporting in trials to better inform clinical decision making.

Standardised Outcomes in Nephrology-Polycystic Kidney Disease (SONG-PKD): study protocol for establishing a core outcome set in polycystic kidney disease.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is the most common potentially life threatening inherited kidney disease and is responsible for 5-10% of cases of end-stage kidney disease (ESKD). Cystic kidneys may enlarge up to 20 times the weight of a normal kidney due to the growth of renal cysts, and patients with ADPKD have an increased risk of morbidity, premature mortality, and other life-time complications including renal and hepatic cyst and urinary tract infection, intracranial aneurysm, diverticulosis, and kidney pain which impair quality of life. Despite some therapeutic advances and the growing number of clinical trials in ADPKD, the outcomes that are relevant to patients and clinicians, such as symptoms and quality of life, are infrequently and inconsistently reported. This potentially limits the contribution of trials to inform evidence-based decision-making. The Standardised Outcomes in Nephrology-Polycystic Kidney Disease (SONG-PKD) project aims to establish a consensus-based set of core outcomes for trials in PKD (with an initial focus on ADPKD but inclusive of all stages) that patients and health professionals identify as critically important. METHODS: The five phases of SONG-PKD are: a systematic review to identify outcomes that have been reported in existing PKD trials; focus groups with nominal group technique with patients and caregivers to identify, rank, and describe reasons for their choices; qualitative stakeholder interviews with health professionals to elicit individual values and perspectives on outcomes for trials involving patients with PKD; an international three-round Delphi survey with all stakeholder groups (including patients, caregivers, healthcare providers, policy makers, researchers, and industry) to gain consensus on critically important core outcome domains; and a consensus workshop to review and establish a set of core outcome domains and measures for trials in PKD. DISCUSSION: The SONG-PKD core outcome set is aimed at improving the consistency and completeness of outcome reporting across ADPKD trials, leading to improvements in the reliability and relevance of trial-based evidence to inform decisions about treatment and ultimately improve the care and outcomes for people with ADPKD.

Toward Establishing Core Outcome Domains For Trials in Kidney Transplantation: Report of the Standardized Outcomes in Nephrology-Kidney Transplantation Consensus Workshops.

BACKGROUND: Treatment decisions in kidney transplantation requires patients and clinicians to weigh the benefits and harms of a broad range of medical and surgical interventions, but the heterogeneity and lack of patient-relevant outcomes across trials in transplantation makes these trade-offs uncertain, thus, the need for a core outcome set that reflects stakeholder priorities. METHODS: We convened 2 international Standardized Outcomes in Nephrology-Kidney Transplantation stakeholder consensus workshops in Boston (17 patients/caregivers; 52 health professionals) and Hong Kong (10 patients/caregivers; 45 health professionals). In facilitated breakout groups, participants discussed the development and implementation of core outcome domains for trials in kidney transplantation. RESULTS: Seven themes were identified. Reinforcing the paramount importance of graft outcomes encompassed the prevailing dread of dialysis, distilling the meaning of graft function, and acknowledging the terrifying and ambiguous terminology of rejection. Reflecting critical trade-offs between graft health and medical comorbidities was fundamental. Contextualizing mortality explained discrepancies in the prioritization of death among stakeholders-inevitability of death (patients), preventing premature death (clinicians), and ensuring safety (regulators). Imperative to capture patient-reported outcomes was driven by making explicit patient priorities, fulfilling regulatory requirements, and addressing life participation. Specificity to transplant; feasibility and pragmatism (long-term impacts and responsiveness to interventions); and recognizing gradients of severity within outcome domains were raised as considerations. CONCLUSIONS: Stakeholders support the inclusion of graft health, mortality, cardiovascular disease, infection, cancer, and patient-reported outcomes (ie, life participation) in a core outcomes set. Addressing ambiguous terminology and feasibility is needed in establishing these core outcome domains for trials in kidney transplantation.