In advanced chronic kidney disease, obesity may bring a survival advantage, but many transplant centres demand weight loss before wait-listing for kidney graft. The case here described regards a ...71-year-old man, with obesity-related glomerulopathy; referral data were: weight 110 kg, Body Mass Index (BMI) 37 kg/m², serum creatinine (sCr) 5 mg/dL, estimated glomerular filtration rate (eGFR) 23 mL/min, blood urea nitrogen (BUN) 75 mg/dL, proteinuria 2.3 g/day. A moderately restricted, low-protein diet allowed reduction in BUN (45-55 mg/dL) and good metabolic and kidney function stability, with a weight increase of 6 kg. Therefore, he asked to be enrolled in a weight-loss program to be wait-listed (the two nearest transplant centres required a BMI below 30 or 35 kg/m²). Since previous low-calorie diets were not successful and he was against a surgical approach, we chose a qualitative, ad libitum coach-assisted diet, freely available in our unit. In the first phase, the diet is dissociated; he lost 16 kg in 2 months, without need for dialysis. In the second maintenance phase, in which foods are progressively combined, he lost 4 kg in 5 months, allowing wait-listing. Dialysis started one year later, and was followed by weight gain of about 5 kg. He resumed the maintenance diet, and his current body weight, 35 months after the start of the diet, is 94 kg, with a BMI of 31.7 kg/m², without clinical or biochemical signs of malnutrition. This case suggests that our patients can benefit from the same options available to non-CKD (chronic kidney disease) individuals, provided that strict multidisciplinary surveillance is assured.
Delayed graft function (DGF) is an early complication of kidney transplantation (KT) associated with increased risk of early loss of graft function. DGF increases using kidneys from extended criteria ...donors (ECD). NGAL is a 25KDa protein proposed as biomarker of acute kidney injury. The aim of this study was to investigate the role of NGAL as an early and accurate indicator of DGF and Tacrolimus (Tac) toxicity and as a mediator of tissue regeneration in KT from ECD.
We evaluated plasma levels of NGAL in 50 KT patients from ECD in the first 4 days after surgery or after Tac introduction.
Plasma levels of NGAL at day 1 were significantly higher in DGF group. In the non DGF group, NGAL discriminated between slow or immediate graft function and decreased more rapidly than serum creatinine. NGAL increased after Tac introduction, suggesting a role as marker of drug toxicity. In vitro, hypoxia and Tac induced NGAL release from tubular epithelial cells (TEC) favoring an autocrine loop that sustains proliferation and inhibits apoptosis (decrease of caspases and Bax/Bcl-2 ratio).
NGAL is an early and accurate biomarker of graft function in KT from ECD favoring TEC regeneration after ischemic and nephrotoxic injury.
Various prediction models have been developed to predict the risk of kidney failure in patients with CKD. However, guideline-recommended models have yet to be compared head to head, their validation ...in patients with advanced CKD is lacking, and most do not account for competing risks.
To externally validate 11 existing models of kidney failure, taking the competing risk of death into account, we included patients with advanced CKD from two large cohorts: the European Quality Study (EQUAL), an ongoing European prospective, multicenter cohort study of older patients with advanced CKD, and the Swedish Renal Registry (SRR), an ongoing registry of nephrology-referred patients with CKD in Sweden. The outcome of the models was kidney failure (defined as RRT-treated ESKD). We assessed model performance with discrimination and calibration.
The study included 1580 patients from EQUAL and 13,489 patients from SRR. The average
statistic over the 11 validated models was 0.74 in EQUAL and 0.80 in SRR, compared with 0.89 in previous validations. Most models with longer prediction horizons overestimated the risk of kidney failure considerably. The 5-year Kidney Failure Risk Equation (KFRE) overpredicted risk by 10%-18%. The four- and eight-variable 2-year KFRE and the 4-year Grams model showed excellent calibration and good discrimination in both cohorts.
Some existing models can accurately predict kidney failure in patients with advanced CKD. KFRE performed well for a shorter time frame (2 years), despite not accounting for competing events. Models predicting over a longer time frame (5 years) overestimated risk because of the competing risk of death. The Grams model, which accounts for the latter, is suitable for longer-term predictions (4 years).
ABSTRACT
Background
We explore longitudinal trajectories of clinical indicators, patient-reported outcomes, and hospitalizations, in the years preceding death in a population of older patients with ...advanced chronic kidney disease (CKD).
Methods
The EQUAL study is a European observational prospective cohort study with an incident eGFR <20 ml/min per 1.73 m2 and ≥65 years of age. The evolution of each clinical indicator was explored using generalized additive models during the 4 years preceding death.
Results
We included 661 decedents with a median time to death of 2.0 years (IQR 0.9–3.2). During the years preceding death, eGFR, Subjective Global Assessment score, and blood pressure declined, with accelerations seen at 6 months preceding death. Serum hemoglobin, hematocrit, cholesterol, calcium, albumin, and sodium values declined slowly during follow-up, with accelerations observed between 6 and 12 months preceding death. Physical and mental quality of life declined linearly throughout follow-up. The number of reported symptoms was stable up to 2 years prior to death, with an acceleration observed at 1 year prior to death. The rate of hospitalization was stable at around one hospitalization per person year, increasing exponentially at 6 months preceding death.
Conclusions
We identified clinically relevant physiological accelerations in patient trajectories that began ∼6 to 12 months prior to death, which are likely multifactorial in nature, but correlate with a surge in hospitalizations. Further research should focus on how to effectively use this knowledge to inform patient and family expectations, to benefit the planning of (end-of-life) care, and to establish clinical alert systems.
Graphical Abstract
Graphical Abstract
Asymptomatic bacteriuria is frequent in kidney transplant recipients (KTRs). However, there is no consensus on diagnosis or management. We conducted a European survey to explore current practice ...related to the diagnosis and management of asymptomatic bacteriuria in adult KTRs.
A panel of experts from the European Renal Association-European Dialysis Transplant Association/Developing Education Science and Care for Renal Transplantation in European States working group and the European Study Group for Infections in Compromised Hosts of the European Society of Clinical Microbiology and Infectious Diseases designed this cross-sectional, questionnaire-based, self-administered survey. Invitations to participate were e-mailed to European physicians involved in the care of KTRs.
Two hundred and forty-four participants from 138 institutions in 25 countries answered the survey (response rate 30%). Most participants 72% (176/244) said they always screen for asymptomatic bacteriuria in KTRs. Six per cent (15/240) reported never treating asymptomatic bacteriuria with antibiotics. When antimicrobial treatment was used, 24% of the participants (53/224) said they would start with empirical antibiotics. For an episode of asymptomatic bacteriuria caused by a fully susceptible microorganism and despite no contraindications, a majority of participants (121/223) said they would use a fluoroquinolone (n = 56), amoxicillin/clavulanic acid (n = 38) or oral cephalosporins (n = 27).
Screening for and treating asymptomatic bacteriuria are common in KTRs despite uncertainties around the benefits and harms. In an era of antimicrobial resistance, further studies are needed to address the diagnosis and management of asymptomatic bacteriuria in these patients.
Background People with reduced glomerular filtration rate (GFR) often have elevated cardiac troponin T (cTnT) levels. It remains unclear how cTnT levels develop over time in those with chronic kidney ...disease (CKD). The aim of this study was to prospectively study the association between cTnT and GFR over time in older advanced-stage CKD patients not on dialysis. Methods and Results The EQUAL (European Quality Study) study is an observational prospective cohort study in stage 4 to 5 CKD patients aged ≥65 years not on dialysis (incident estimated GFR, <20 mL/min/1.73 m²). The EQUAL cohort used for the purpose of this study includes 171 patients followed in Sweden between April 2012 and December 2018. We used linear mixed models, adjusted for important groups of confounders, to investigate the effect of both measured GFR and estimated GFR on high-sensitivity cTnT (hs-cTnT) trajectory over 4 years. Almost all patients had at least 1 hs-cTnT measurement elevated above the 99th percentile of the general reference population (≤14 ng/L). On average, hs-cTnT increased by 16%/year (95% CI, 13-19;
<0.0001). Each 15 mL/min/1.73 m
lower mean estimated GFR was associated with a 23% (95% CI, 14-31;
<0.0001) higher baseline hs-cTnT and 9% (95% CI, 5-13%;
<0.0001) steeper increase in hs-cTnT. The effect of estimated GFR on hs-cTnT trajectory was somewhat lower than a previous myocardial infarction (15%), but higher than presence of diabetes mellitus (4%) and male sex (5%). Conclusions In CKD patients, hs-cTnT increases over time as renal function decreases. Lower CKD stage (each 15 mL/min/1.73 m
lower) is independently associated with a steeper hs-cTnT increase over time in the same range as other established cardiovascular risk factors.
ABSTRACT
Background
Patients with chronic kidney disease (CKD) are at a higher risk of major adverse cardiovascular events (MACE) compared with the general population, but gender differences in this ...risk, especially in older adults, are not fully known. We aim to identify gender differences in the risk of MACE in older European CKD patients, and explore factors that may explain these differences.
Methods
The European Quality study (EQUAL) is a prospective study on stage 4–5 CKD patients, ≥65 years old, not on dialysis, from Germany, Italy, the Netherlands, Poland, Sweden and the UK. Cox regression and cumulative incidence competing risk curves were used to identify gender differences in MACE risks. Mediation analysis was used to identify variables which may explain risk differences between men and women.
Results
A total of 417 men out of 1134 (37%) and 185 women out of 602 women (31%) experienced at least one MACE, over a follow-up period of 5 years. Women had an 18% lower risk of first MACE compared with men (hazard ratio 0.82; 95% confidence interval 0.69–0.97; P = .02), which was attenuated after adjusting for pre-existing cardiometabolic comorbidities and cardiovascular risk factors. There were no significant gender differences in the risk of recurrent MACE or fatal MACE. The risk difference in MACE by gender was larger in patients aged 65–75 years, compared with patients over 75 years.
Conclusions
In a cohort of older adults with advanced CKD, women had lower risks of MACE. These risk differences were partially explained by pre-existing cardiometabolic comorbidities and cardiovascular risk factors.
Graphical Abstract
Graphical Abstract
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