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1.
Am J Kidney Dis ; 2020 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-32359822

RESUMO

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.

2.
J Hypertens ; 38(6): 1064-1071, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32371796

RESUMO

BACKGROUND: Arterial stiffness influences the contour of the digital pressure pulse wave. METHOD: Here, we investigated whether the digital pulse propagation index (DPPI), based on the digital pressure pulse wave, DPPI is associated with cardiovascular events, heart failure, and mortality in a large population-based cohort. Between 2001 and 2003, DPPI was measured with a PortaPres noninvasive hemodynamic monitoring device (FinaPres Medical Systems, Amsterdam, The Netherlands) in participants of the Prevention of Renal and Vascular End-stage Disease study, a community-based cohort. We assessed the main determinants of the DPPI and investigated associations of DPPI with cardiovascular events and mortality. RESULTS: The study included 5474 individuals. Mean age was 52.3 ±â€Š11.8 years and 50.5% was male. Median baseline DPPI was 5.81 m/s (interquartile range 5.47-6.20). Higher age, mean arterial blood pressure, body height, heart rate, current smoking, and lower HDL cholesterol levels and waist circumference were independent determinants of the DPPI (r = 0.43). After adjustment for heart rate, highlogDPPI was associated with all-cause mortality [hazard ratio: 1.67, 95% confidence interval (1.55-1.81) per SD; P < 0.001], cardiovascular mortality [hazard ratio 1.95 (1.72-2.22); P < 0.001], and incident heart failure with reduced ejection fraction [hazard ratio 1.81 (1.60-2.06); P < 0.001]. These associations remained independent upon further adjustment for confounders. Optimal cutoff values for DPPI ranged between 6.1 and 6.3 m/s for all endpoints. After multivariable adjustment, DPPI was no longer associated with coronary artery disease events or cerebrovascular events. CONCLUSION: The DPPI is associated with an increased risk of development of new onset heart failure with reduced ejection fraction and all-cause and cardiovascular mortality, but not with coronary artery events or cerebrovascular events.

3.
BMC Med ; 18(1): 130, 2020 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-32456645

RESUMO

BACKGROUND: Serum free thiols (R-SH, sulfhydryl groups) reliably reflect systemic oxidative stress. Since serum free thiols are rapidly oxidized by reactive species, systemic oxidative stress is generally associated with reduced serum free thiol levels. Free thiols associate with favorable disease outcomes in many patient cohorts, and the current hypothesis is that oxidative stress might also play an important role in cardiovascular disease. In this study, we aimed to establish the role of serum free thiols in the general population by investigating their relationship with the risk of cardiovascular (CV) events and all-cause mortality. METHODS: Participants (n = 5955) of the Prevention of REnal and Vascular ENd-stage Disease (PREVEND) cohort study from the general population were included. At baseline, serum levels of free thiols were quantified and adjusted to total protein levels. Protein-adjusted serum free thiol levels were studied for their associations with clinical and biochemical parameters, as well as with the risk of CV events and all-cause mortality. RESULTS: The mean protein-adjusted serum free thiol level was 5.05 ± 1.02 µmol/g of protein. Protein-adjusted serum free thiols significantly predicted the risk of CV events, even after adjustment for potential confounding factors (hazard ratio [HR] per doubling 0.68 [95% confidence interval [CI] 0.47-1.00], P = 0.048). Similarly, protein-adjusted serum free thiols were significantly predictive of the risk of all-cause mortality (HR per doubling 0.66 [95% CI 0.44-1.00], P = 0.050). Stratified analyses revealed lower HRs for subjects with a lower body mass index (BMI), without hypertension, and without diabetes. Conversely, HRs were lower in subjects with albuminuria. CONCLUSIONS: In this large population-based cohort study, serum free thiols significantly predicted the risk of CV events and all-cause mortality. Our results highlight the potential significance and clinical applicability of serum free thiols since they are amendable to therapeutic intervention.

4.
Kidney Int ; 97(6): 1117-1129, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32409237

RESUMO

The worldwide burden of kidney disease is rising, but public awareness remains limited, underscoring the need for more effective communication by stakeholders in the kidney health community. Despite this need for clarity, the nomenclature for describing kidney function and disease lacks uniformity. In June 2019, Kidney Disease: Improving Global Outcomes (KDIGO) convened a Consensus Conference with the goal of standardizing and refining the nomenclature used in the English language to describe kidney function and disease, and of developing a glossary that could be used in scientific publications. Guiding principles of the conference were that the revised nomenclature should be patient-centered, precise, and consistent with nomenclature used in the KDIGO guidelines. Conference attendees reached general consensus on the following recommendations: (i) to use "kidney" rather than "renal" or "nephro-" when referring to kidney disease and kidney function; (ii) to use "kidney failure" with appropriate descriptions of presence or absence of symptoms, signs, and treatment, rather than "end-stage kidney disease"; (iii) to use the KDIGO definition and classification of acute kidney diseases and disorders (AKD) and acute kidney injury (AKI), rather than alternative descriptions, to define and classify severity of AKD and AKI; (iv) to use the KDIGO definition and classification of chronic kidney disease (CKD) rather than alternative descriptions to define and classify severity of CKD; and (v) to use specific kidney measures, such as albuminuria or decreased glomerular filtration rate (GFR), rather than "abnormal" or "reduced" kidney function to describe alterations in kidney structure and function. A proposed 5-part glossary contains specific items for which there was general agreement. Conference attendees acknowledged limitations of the recommendations and glossary, but they considered standardization of scientific nomenclature to be essential for improving communication.

5.
Artigo em Inglês | MEDLINE | ID: mdl-32124925

RESUMO

BACKGROUND: Fibroblast growth factor 23 (FGF23), a phosphate-regulating hormone that increases early in the course of chronic kidney disease (CKD), is associated with disease progression in patients with established CKD. Here we aimed to investigate the association between plasma FGF23 and new-onset CKD in the general population. METHODS: We included 5253 individuals without CKD who participated in the Prevention of Renal and Vascular Endstage Disease study, a prospective, population-based cohort. Multi-variable Cox regression was used to study the association of plasma C-terminal FGF23 with new-onset CKD, defined as a combined endpoint of estimated glomerular filtration rate (eGFR) <60 mL/min/ 1.73 m2, urinary 24-h albumin excretion (UAE) >30 mg/24 h or both, or with all-cause mortality. RESULTS: The median baseline FGF23 was 68 [interquartile range (IQR) 56-85] RU/mL, eGFR was 95 ± 13 mL/min/1.73 m2 and UAE was 7.8 (IQR 5.8-11.5) mg/24 h. After follow-up of 7.5 (IQR 7.2-8.0) years, 586 participants developed CKD and 214 participants died. A higher FGF23 level was associated with new-onset CKD, independent of risk factors for kidney disease and parameters of bone and mineral homoeostasis {fully adjusted hazard ratio (HR) 1.25 [95% confidence interval (CI) 1.10-1.44] per doubling of FGF23; P = 0.001}. In secondary analyses, FGF23 was independently associated with new-onset eGFR <60 mL/min/1.73 m2 [adjusted HR 1.28 (95% CI 1.00-1.62); P = 0.048] or with UAE >30 mg/24 h [adjusted HR 1.24 (95% CI 1.06-1.45); P = 0.01] individually. A higher FGF23 level was also associated with an increased risk of all-cause mortality [fully adjusted HR 1.30 (95% CI 1.03-1.63); P = 0.03]. CONCLUSIONS: High FGF23 levels are associated with an increased risk of new-onset CKD and all-cause mortality in this prospective population-based cohort, independent of established CKD risk factors.

6.
Am J Kidney Dis ; 2020 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-32171640

RESUMO

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.

7.
Nephrol Dial Transplant ; 35(Supplement_1): i33-i42, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32003836

RESUMO

This year the medical community was pleasantly surprised by the results of the first large outcome trial that primarily examined the renal effects of the sodium-glucose cotransporter 2 (SGLT2) inhibitor canagliflozin (CANA) in subjects with diabetes and impaired kidney function. The Evaluation of the Effects of Canagliflozin on Renal and Cardiovascular Outcomes in Participants With Diabetic Nephropathy (CREDENCE) trial showed that CANA, relative to placebo, reduces the risk for end-stage renal disease, doubling of creatinine or renal death by 34% [hazard ratio 0.66 (95% confidence interval 0.53-0.81]. These effects were consistent across baseline estimated glomerular filtration rate (eGFR) and haemoglobin A1c subgroups. In this review we combine the results of the CREDENCE trial with those of several cardiovascular outcome trials with SGLT2 inhibitors and show that, unexpectedly, patients with lower eGFR levels may have greater benefit with respect to cardiovascular outcome than patients with normal kidney function. The cardio- and renoprotective effects of SGLT2 inhibitors seem to be independent of their glucose-lowering effects, as shown in several post hoc analyses. In this review we discuss the alleged mechanisms of action that explain the beneficial effects of this novel class of drugs. Moreover, we discuss whether these findings indicate that this class of drugs may also be beneficial in non-diabetic chronic kidney diseases.

8.
J Hypertens ; 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-32053524

RESUMO

BACKGROUND:: Arterial stiffness influences the contour of the digital pressure pulse wave. METHOD:: Here, we investigated whether the digital pulse propagation index (DPPI), based on the digital pressure pulse wave, DPPI is associated with cardiovascular events, heart failure, and mortality in a large population-based cohort. Between 2001 and 2003, DPPI was measured with a PortaPres noninvasive hemodynamic monitoring device (FinaPres Medical Systems, Amsterdam, The Netherlands) in participants of the Prevention of Renal and Vascular End-stage Disease study, a community-based cohort. We assessed the main determinants of the DPPI and investigated associations of DPPI with cardiovascular events and mortality. RESULTS:: The study included 5474 individuals. Mean age was 52.3 ±â€Š11.8 years and 50.5% was male. Median baseline DPPI was 5.81 m/s (interquartile range 5.47-6.20). Higher age, mean arterial blood pressure, body height, heart rate, current smoking, and lower HDL cholesterol levels and waist circumference were independent determinants of the DPPI (r = 0.43). After adjustment for heart rate, highlogDPPI was associated with all-cause mortality [hazard ratio: 1.67, 95% confidence interval (1.55-1.81) per SD; P < 0.001], cardiovascular mortality [hazard ratio 1.95 (1.72-2.22); P < 0.001], and incident heart failure with reduced ejection fraction [hazard ratio 1.81 (1.60-2.06); P < 0.001]. These associations remained independent upon further adjustment for confounders. Optimal cutoff values for DPPI ranged between 6.1 and 6.3 m/s for all endpoints. After multivariable adjustment, DPPI was no longer associated with coronary artery disease events or cerebrovascular events. CONCLUSION:: The DPPI is associated with an increased risk of development of new onset heart failure with reduced ejection fraction and all-cause and cardiovascular mortality, but not with coronary artery events or cerebrovascular events.

9.
PLoS One ; 15(2): e0228490, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32023312

RESUMO

OBJECTIVE: Research into dietary factors associated with hypertension has focused on the sodium component of salt. However, chloride has distinct physiological effects that may surpass the effect of sodium on blood pressure. This study aims to separate the specific effects of chloride and sodium intake on blood pressure. METHODS: We studied 5673 participants from the Prevention of Renal and Vascular End-Stage Disease(PREVEND) study. Urinary chloride(uCl) and sodium(uNa) were measured in two 24-hour collections. We used generalized-linear-regression to evaluate the relation of uCl and uNa with baseline blood pressure and Cox-proportional-hazards-analysis to assess the association with hypertension. Multicollinearity was assessed with Ridge regression. RESULTS: Baseline 24-hour uCl was 135±39mmol and uNa was 144±54mmol. The correlation between uCl and uNa was high (Pearson's r = 0.96). UCl and uNa had similar non-significant positive and linear associations with blood pressure. In 3515 normotensive patients, 1021 patients developed hypertension during a median follow-up of 7.4 years. UCl and uNa had a comparable but non-significant J-shaped effect on the risk of hypertension. Adding both uCl and uNa to the same model produced instability, demonstrated by Ridge coefficients that converged or changed sign. The single index of uNa minus uCl showed a non-significant higher risk of hypertension of 2% per 10mmol/24-hour difference (HR1.02, 95%CI 0.98-1.06). CONCLUSION: UCl and uNa had similar positive but non-significant associations with blood pressure and risk of hypertension and their effects could not be disentangled. Hence, the alleged adverse effects of high salt intake could be due to sodium, chloride or both. This encourages further study into the effect of chloride in order to complement dietary recommendations currently focused on sodium alone.


Assuntos
Pressão Sanguínea , Cloretos/urina , Hipertensão/fisiopatologia , Sódio/urina , Cloretos/administração & dosagem , Feminino , Humanos , Hipertensão/dietoterapia , Hipertensão/urina , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Sódio/administração & dosagem
10.
Clin Nephrol ; 93(6): 310-311, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32000888
12.
JAMA Netw Open ; 3(1): e1919274, 2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31940038

RESUMO

Importance: Higher plasma concentrations of vitamin B12 have been associated with mortality in elderly and hospitalized populations, including patients with chronic kidney disease, but the association of plasma concentrations of vitamin B12 with mortality in the general population remains unclear. Objective: To investigate the association of plasma concentrations of vitamin B12 with all-cause mortality. Design, Setting, and Participants: This longitudinal cohort study used post hoc analysis to examine data from participants of the Prevention of Renal and Vascular End-stage Disease Study in Groningen, the Netherlands. Participants included individuals who completed the second screening visit beginning January 1, 2001, excluding those who were missing values of vitamin B12 plasma concentrations or used vitamin B12 supplementation. Follow-up time was defined between the beginning of the second screening round to end of follow-up on January 1, 2011. Data analysis was conducted from October 2, 2018, to February 22, 2019. Exposures: Plasma vitamin B12 concentration level. Main Outcomes and Measures: Death as recorded by the Central Bureau of Statistics of Groningen, the Netherlands. Results: A total of 5571 participants (mean [SD] age, 53.5 [12.0] years; 2830 [50.8%] men) were included in analyses. Median (interquartile range) plasma concentration of vitamin B12 was 394.42 (310.38-497.42) pg/mL. During the median (interquartile range) of 8.2 (7.7-8.9) years of follow-up, 226 participants (4.1%) died. According to quartiles of the distribution of plasma vitamin B12 concentration levels, mortality rates were 33.8 deaths per 10 000 person-years for the quartile with the lowest plasma concentration of vitamin B12 and 65.7 deaths per 10 000 person-years for the quartile with the highest plasma concentration of vitamin B12. After adjustment for multiple clinical and laboratory variables, Cox regression analyses found a significant association between higher vitamin B12 plasma concentration level and increased risk of all-cause mortality (hazard ratio per 1-SD increase, 1.25 [95% CI, 1.06-1.47]; P = .006). Conclusions and Relevance: These findings suggest that higher levels of plasma concentrations of vitamin B12 were associated with increased risk of all-cause mortality after adjusting for age, sex, renal function, and other clinical and laboratory variables. The mechanisms underlying this association remain to be established.

13.
Am J Kidney Dis ; 75(1): 84-104, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31473020

RESUMO

The US Food and Drug Administration (FDA) and European Medicines Agency (EMA) are currently willing to consider a 30% to 40% glomerular filtration rate (GFR) decline as a surrogate end point for kidney failure for clinical trials of kidney disease progression under appropriate conditions. However, these end points may not be practical for early stages of kidney disease. In March 2018, the National Kidney Foundation sponsored a scientific workshop in collaboration with the FDA and EMA to evaluate changes in albuminuria or GFR as candidate surrogate end points. Three parallel efforts were presented: meta-analyses of observational studies (cohorts), meta-analyses of clinical trials, and simulations of trial design. In cohorts, after accounting for measurement error, relationships between change in urinary albumin-creatinine ratio (UACR) or estimated GFR (eGFR) slope and the clinical outcome of kidney disease progression were strong and consistent. In trials, the posterior median R2 of treatment effects on the candidate surrogates with the clinical outcome was 0.47 (95% Bayesian credible interval [BCI], 0.02-0.96) for early change in UACR and 0.72 (95% BCI, 0.05-0.99) when restricted to baseline UACR>30mg/g, and 0.97 (95% BCI, 0.78-1.00) for total eGFR slope at 3 years and 0.96 (95% BCI, 0.63-1.00) for chronic eGFR slope (ie, the slope excluding the first 3 months from baseline, when there might be acute changes in eGFR). The magnitude of the relationships of changes in the candidate surrogates with risk for clinical outcome was consistent across cohorts and trials: a UACR reduction of 30% or eGFR slope reduction by 0.5 to 1.0mL/min/1.73m2 per year were associated with an HR of ∼0.7 for the clinical outcome in cohorts and trials. In simulations, using GFR slope as an end point substantially reduced the required sample size and duration of follow-up compared with the clinical end point when baseline eGFR was high, treatment effects were uniform, and there was no acute effect of the treatment. We conclude that both early change in albuminuria and GFR slope fulfill criteria for surrogacy for use as end points in clinical trials for chronic kidney disease progression under certain conditions, with stronger support for change in GFR than albuminuria. Implementation requires understanding conditions under which each surrogate is likely to perform well and restricting its use to those settings.

14.
J Cereb Blood Flow Metab ; 40(2): 328-340, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30540219

RESUMO

Near-infrared spectroscopy (NIRS) is used to monitor cerebral tissue oxygenation (rSO2) depending on cerebral blood flow (CBF), cerebral blood volume and blood oxygen content. We explored whether NIRS might be a more easy applicable proxy to [15O]H2O positron emission tomography (PET) for detecting CBF changes during hemodialysis. Furthermore, we compared potential determinants of rSO2 and CBF. In 12 patients aged ≥ 65 years, NIRS and PET were performed simultaneously: before (T1), early after start (T2), and at the end of hemodialysis (T3). Between T1 and T3, the relative change in frontal rSO2 (ΔrSO2) was -8 ± 9% (P = 0.001) and -5 ± 11% (P = 0.08), whereas the relative change in frontal gray matter CBF (ΔCBF) was -11 ± 18% (P = 0.009) and -12 ± 16% (P = 0.007) for the left and right hemisphere, respectively. ΔrSO2 and ΔCBF were weakly correlated for the left (ρ 0.31, P = 0.4), and moderately correlated for the right (ρ 0.69, P = 0.03) hemisphere. The Bland-Altman plot suggested underestimation of ΔCBF by NIRS. Divergent associations of pH, pCO2 and arterial oxygen content with rSO2 were found compared to corresponding associations with CBF. In conclusion, NIRS could be a proxy to PET to detect intradialytic CBF changes, although NIRS and PET capture different physiological parameters of the brain.

16.
JAMA ; 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31703124

RESUMO

Importance: Early identification of individuals at elevated risk of developing chronic kidney disease (CKD) could improve clinical care through enhanced surveillance and better management of underlying health conditions. Objective: To develop assessment tools to identify individuals at increased risk of CKD, defined by reduced estimated glomerular filtration rate (eGFR). Design, Setting, and Participants: Individual-level data analysis of 34 multinational cohorts from the CKD Prognosis Consortium including 5 222 711 individuals from 28 countries. Data were collected from April 1970 through January 2017. A 2-stage analysis was performed, with each study first analyzed individually and summarized overall using a weighted average. Because clinical variables were often differentially available by diabetes status, models were developed separately for participants with diabetes and without diabetes. Discrimination and calibration were also tested in 9 external cohorts (n = 2 253 540). Exposures: Demographic and clinical factors. Main Outcomes and Measures: Incident eGFR of less than 60 mL/min/1.73 m2. Results: Among 4 441 084 participants without diabetes (mean age, 54 years, 38% women), 660 856 incident cases (14.9%) of reduced eGFR occurred during a mean follow-up of 4.2 years. Of 781 627 participants with diabetes (mean age, 62 years, 13% women), 313 646 incident cases (40%) occurred during a mean follow-up of 3.9 years. Equations for the 5-year risk of reduced eGFR included age, sex, race/ethnicity, eGFR, history of cardiovascular disease, ever smoker, hypertension, body mass index, and albuminuria concentration. For participants with diabetes, the models also included diabetes medications, hemoglobin A1c, and the interaction between the 2. The risk equations had a median C statistic for the 5-year predicted probability of 0.845 (interquartile range [IQR], 0.789-0.890) in the cohorts without diabetes and 0.801 (IQR, 0.750-0.819) in the cohorts with diabetes. Calibration analysis showed that 9 of 13 study populations (69%) had a slope of observed to predicted risk between 0.80 and 1.25. Discrimination was similar in 18 study populations in 9 external validation cohorts; calibration showed that 16 of 18 (89%) had a slope of observed to predicted risk between 0.80 and 1.25. Conclusions and Relevance: Equations for predicting risk of incident chronic kidney disease developed from more than 5 million individuals from 34 multinational cohorts demonstrated high discrimination and variable calibration in diverse populations. Further study is needed to determine whether use of these equations to identify individuals at risk of developing chronic kidney disease will improve clinical care and patient outcomes.

17.
Am J Nephrol ; 50(5): 375-385, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31600749

RESUMO

BACKGROUND: Markers currently used to predict the likelihood of rapid disease progression in patients with autosomal dominant polycystic kidney disease (ADPKD) are expensive and time consuming to assess and often have limited sensitivity. New, easy-to-measure markers are therefore needed that alone or in combination with conventional risk markers can predict the rate of disease progression. In the present study, we investigated the ability of tubular damage and inflammation markers to predict kidney function decline. METHODS: At baseline, albumin, immunoglobulin G, kidney injury molecule 1, ß2 microglobulin (ß2MG), heart-type fatty acid-binding protein, neutrophil gelatinase-associated lipocalin, and monocyte chemotactic protein-1 -(MCP-1) were measured in 24-h urine samples of patients participating in a study investigating the therapeutic efficacy of lanreotide in ADPKD. Individual change in estimated glomerular filtration rate (eGFR) during follow-up was calculated using mixed-model analysis taking into account 13 -eGFRs (chronic kidney disease EPIdemiology) per patient. Logistic regression analysis was used to select urinary biomarkers that had the best association with rapidly progressive disease. The predictive value of these selected urinary biomarkers was compared to other risk scores using C-statistics. RESULTS: Included were 302 patients of whom 53.3% were female, with an average age of 48 ± 7 years, eGFR of 52 ± 12 mL/min/1.73 m2, and a height-adjusted total kidney volume (htTKV) of 1,082 (736-1,669) mL/m. At baseline, all urinary damage and inflammation markers were associated with baseline eGFR, also after adjustment for age, sex and baseline htTKV. For longitudinal analyses only patients randomized to standard care were considered (n = 152). A stepwise backward analysis revealed that ß2MG and MCP-1 showed the strongest association with rapidly progressive disease. A urinary biomarker score was created by summing the ranking of tertiles of ß2MG and MCP-1 excretion. The predictive value of this urinary biomarker score was higher compared to that of the Mayo htTKV classification (area under the curve [AUC] 0.73 [0.64-0.82] vs. 0.61 [0.51-0.71], p = 0.04) and comparable to that of the predicting renal outcomes in -ADPKD score (AUC 0.73 [0.64-0.82] vs. 0.65 [0.55-0.75], p = 0.18). In a second independent cohort with better kidney function, similar results were found for the urinary biomarker score. CONCLUSION: Measurement of urinary ß2MG and MCP-1 excretion allows selection of ADPKD patients with rapidly progressive disease, with a predictive value comparable to or even higher than that of TKV or PKD mutation. Easy and inexpensive to measure urinary markers therefore hold promise to help predict prognosis in ADPKD.

18.
Diabetes Care ; 42(11): 2151-2153, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31488569

RESUMO

OBJECTIVE: To study whether fibroblast growth factor 23 (FGF23) is associated with adverse outcomes in patients with type 2 diabetes and normal or mildly impaired kidney function. RESEARCH DESIGN AND METHODS: We analyzed C-terminal FGF23 levels in 310 patients with type 2 diabetes and estimated glomerular filtration rate ≥60 mL/min/1.73 m2. Associations of FGF23 with all-cause mortality and major adverse cardiovascular events (MACE) were studied by Cox regression. RESULTS: During a follow-up of 5.8 years (3.3-6.5), 47 patients developed MACE and 28 patients died. FGF23 was associated with an increased risk of all-cause mortality (age- and sex-adjusted hazard ratio 2.78 [95% CI 1.76-4.40]) and MACE (1.67 [1.12-2.49]). Results were similar after additional adjustment for other potential confounders and were consistent upon replication in an independent cohort. CONCLUSIONS: In patients with type 2 diabetes and normal or mildly impaired kidney function, FGF23 is associated with an increased risk of cardiovascular events and mortality.

20.
Curr Opin Nephrol Hypertens ; 28(6): 519-526, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31449083

RESUMO

PURPOSE OF REVIEW: Chronic kidney disease is a global health problem with few effective therapies available that slow the progression to end-stage renal disease. The established clinical endpoints for renal trials; doubling of serum creatinine or end-stage renal disease, are late manifestations of CKD. This leads to large trials enrolling preferably patients with advanced stages of CKD. The use of valid surrogate biomarkers that substitute a clinical endpoint (surrogate endpoints), can lead to trials of shorter duration that can be performed at earlier stages of CKD. Change in albuminuria has been proposed as surrogate endpoint in CKD. Yet, although albuminuria is a strong risk factor for CKD progression, there is persistent uncertainty about its validity to substitute clinical endpoints. RECENT FINDINGS: New observational studies have demonstrated robust associations between changes in albuminuria and risk of end-stage renal disease. In addition, a meta-analysis of observational studies confirmed the strong association between change in albuminuria and end-stage renal disease. Another meta-analysis of clinical trials showed moderately strong associations between treatment effects on albuminuria and treatment effects on clinical endpoints. These new data support a role for change in albuminuria as surrogate endpoint for clinical trials of progression of CKD. SUMMARY: There is increasing evidence that change in albuminuria is a valid surrogate endpoint for CKD. Implementing albuminuria as surrogate requires proper understanding of the settings in which the surrogate works well.

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