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1.
Kidney Int ; 96(3): 728-737, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31301887

RESUMO

Recent European guidelines suggest using the kidney failure risk equation (KFRE) and mortality risk equation for kidney disease (MREK) to guide decisions on whether elderly patients with chronic kidney disease should be referred early for dialysis preparation. However, the concurrent use of the two risk equations has not been validated. To do so we evaluated 1,188 individuals over five years with estimated glomerular filtration rate (eGFR) under 45ml/min/1.73m2 and age over 65 years from the Norwegian population based HUNT study. Forty-two patients started renal replacement therapy and 462 died as their first clinical event. The KFRE was well calibrated (mean risk estimate 4.9% vs observed 3.5%) with high diagnostic accuracy (C-statistics 0.93). The MREK underestimated death risk in those with lower risk (mean risk estimate 30.1% vs observed 38.9%) and had moderate diagnostic accuracy (C-statistics 0.71). Only 31 individuals had estimated end stage kidney disease (ESRD) risk greater than death risk, and most experienced ESRD before death. Only two of 598 patients over 80 years old, and ten of 1,063 with eGFR 25-45ml/min/1.73m2 at baseline experienced ESRD. Decision curve analysis demonstrated that for risk adverse patients, deferring ESRD preparation may be appropriate until predicted ESRD risk exceeds predicted death risk. For those preferring a more aggressive approach, referral when eGFR is under 25 ml/min/1.73m2 may be beneficial if age remains under 80 years. Thus, the risk of ESRD is low compared to the risk of death in many older patients with chronic kidney disease stage 3b or worse, and combination of predicted ESRD and death risks, eGFR levels, age, and the patient`s valuations of harm and benefit can be helpful for deciding when to start dialysis preparations.

2.
Nat Commun ; 10(1): 1847, 2019 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-31015462

RESUMO

Chronic kidney disease (CKD) is a growing health burden currently affecting 10-15% of adults worldwide. Estimated glomerular filtration rate (eGFR) as a marker of kidney function is commonly used to diagnose CKD. We analyze eGFR data from the Nord-Trøndelag Health Study and Michigan Genomics Initiative and perform a GWAS meta-analysis with public summary statistics, more than doubling the sample size of previous meta-analyses. We identify 147 loci (53 novel) associated with eGFR, including genes involved in transcriptional regulation, kidney development, cellular signaling, metabolism, and solute transport. Additionally, sex-stratified analysis identifies one locus with more significant effects in women than men. Using genetic risk scores constructed from these eGFR meta-analysis results, we show that associated variants are generally predictive of CKD with only modest improvements in detection compared with other known clinical risk factors. Collectively, these results yield additional insight into the genetic factors underlying kidney function and progression to CKD.


Assuntos
Loci Gênicos , Estudo de Associação Genômica Ampla , Taxa de Filtração Glomerular/genética , Insuficiência Renal Crônica/genética , Feminino , Carga Global da Doença , Humanos , Rim/fisiopatologia , Masculino , Prognóstico , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/fisiopatologia , Medição de Risco/métodos , Fatores de Risco , Fatores Sexuais
3.
BMJ ; 364: k5301, 2019 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-30630856

RESUMO

OBJECTIVE: To evaluate the associations between adiposity measures (body mass index, waist circumference, and waist-to-height ratio) with decline in glomerular filtration rate (GFR) and with all cause mortality. DESIGN: Individual participant data meta-analysis. SETTING: Cohorts from 40 countries with data collected between 1970 and 2017. PARTICIPANTS: Adults in 39 general population cohorts (n=5 459 014), of which 21 (n=594 496) had data on waist circumference; six cohorts with high cardiovascular risk (n=84 417); and 18 cohorts with chronic kidney disease (n=91 607). MAIN OUTCOME MEASURES: GFR decline (estimated GFR decline ≥40%, initiation of kidney replacement therapy or estimated GFR <10 mL/min/1.73 m2) and all cause mortality. RESULTS: Over a mean follow-up of eight years, 246 607 (5.6%) individuals in the general population cohorts had GFR decline (18 118 (0.4%) end stage kidney disease events) and 782 329 (14.7%) died. Adjusting for age, sex, race, and current smoking, the hazard ratios for GFR decline comparing body mass indices 30, 35, and 40 with body mass index 25 were 1.18 (95% confidence interval 1.09 to 1.27), 1.69 (1.51 to 1.89), and 2.02 (1.80 to 2.27), respectively. Results were similar in all subgroups of estimated GFR. Associations weakened after adjustment for additional comorbidities, with respective hazard ratios of 1.03 (0.95 to 1.11), 1.28 (1.14 to 1.44), and 1.46 (1.28 to 1.67). The association between body mass index and death was J shaped, with the lowest risk at body mass index of 25. In the cohorts with high cardiovascular risk and chronic kidney disease (mean follow-up of six and four years, respectively), risk associations between higher body mass index and GFR decline were weaker than in the general population, and the association between body mass index and death was also J shaped, with the lowest risk between body mass index 25 and 30. In all cohort types, associations between higher waist circumference and higher waist-to-height ratio with GFR decline were similar to that of body mass index; however, increased risk of death was not associated with lower waist circumference or waist-to-height ratio, as was seen with body mass index. CONCLUSIONS: Elevated body mass index, waist circumference, and waist-to-height ratio are independent risk factors for GFR decline and death in individuals who have normal or reduced levels of estimated GFR.


Assuntos
Adiposidade , Índice de Massa Corporal , Taxa de Filtração Glomerular , Falência Renal Crônica/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estatura , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mortalidade , Fatores de Risco , Circunferência da Cintura
4.
Am J Kidney Dis ; 2018 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-30348535

RESUMO

RATIONALE & OBJECTIVE: Chronic kidney disease (CKD) is complicated by abnormalities that reflect disruption in filtration, tubular, and endocrine functions of the kidney. Our aim was to explore the relationship of specific laboratory result abnormalities and hypertension with the estimated glomerular filtration rate (eGFR) and albuminuria CKD staging framework. STUDY DESIGN: Cross-sectional individual participant-level analyses in a global consortium. SETTING & STUDY POPULATIONS: 17 CKD and 38 general population and high-risk cohorts. SELECTION CRITERIA FOR STUDIES: Cohorts in the CKD Prognosis Consortium with data for eGFR and albuminuria, as well as a measurement of hemoglobin, bicarbonate, phosphorus, parathyroid hormone, potassium, or calcium, or hypertension. DATA EXTRACTION: Data were obtained and analyzed between July 2015 and January 2018. ANALYTICAL APPROACH: We modeled the association of eGFR and albuminuria with hemoglobin, bicarbonate, phosphorus, parathyroid hormone, potassium, and calcium values using linear regression and with hypertension and categorical definitions of each abnormality using logistic regression. Results were pooled using random-effects meta-analyses. RESULTS: The CKD cohorts (n=254,666 participants) were 27% women and 10% black, with a mean age of 69 (SD, 12) years. The general population/high-risk cohorts (n=1,758,334) were 50% women and 2% black, with a mean age of 50 (16) years. There was a strong graded association between lower eGFR and all laboratory result abnormalities (ORs ranging from 3.27 [95% CI, 2.68-3.97] to 8.91 [95% CI, 7.22-10.99] comparing eGFRs of 15 to 29 with eGFRs of 45 to 59mL/min/1.73m2), whereas albuminuria had equivocal or weak associations with abnormalities (ORs ranging from 0.77 [95% CI, 0.60-0.99] to 1.92 [95% CI, 1.65-2.24] comparing urinary albumin-creatinine ratio > 300 vs < 30mg/g). LIMITATIONS: Variations in study era, health care delivery system, typical diet, and laboratory assays. CONCLUSIONS: Lower eGFR was strongly associated with higher odds of multiple laboratory result abnormalities. Knowledge of risk associations might help guide management in the heterogeneous group of patients with CKD.

5.
Kidney Int ; 93(6): 1432-1441, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29656901

RESUMO

The incidence of renal replacement therapy varies across countries. However, little is known about the epidemiology of chronic kidney disease (CKD) outcomes. Here we describe progression and mortality risk of patients with CKD but not on renal replacement therapy at outpatient nephrology clinics across Europe using individual data from nine CKD cohorts participating in the European CKD Burden Consortium. A joint model assessed the mean change in estimated glomerular filtration rate (eGFR) and mortality risk simultaneously, thereby accounting for mortality risk when estimating eGFR decline and vice versa, while also correcting for the measurement error in eGFR. Results were adjusted for important risk factors (baseline eGFR, age, sex, albuminuria, primary renal disease, diabetes, hypertension, obesity and smoking) in 27,771 patients from five countries. The adjusted mean annual eGFR decline varied from 0.77 (95% confidence interval 0.45, 1.08) ml/min/1.73m2 in the Belgium cohort to 2.43 (2.11, 2.75) ml/min/1.73m2 in the Spanish cohort. As compared to the Italian PIRP cohort, the adjusted mortality hazard ratio varied from 0.22 (0.11, 0.43) in the London LACKABO cohort to 1.30 (1.13, 1.49) in the English CRISIS cohort. These results suggest that the eGFR decline showed minor variation but mortality showed the most variation. Thus, different health care organization systems are potentially associated with differences in outcome of patients with CKD within Europe. These results can be used by policy makers to plan resources on a regional, national and European level.

6.
Eur Heart J ; 39(17): 1535-1542, 2018 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-29554312

RESUMO

Aims: Both hypo- and hyperkalaemia can have immediate deleterious physiological effects, and less is known about long-term risks. The objective was to determine the risks of all-cause mortality, cardiovascular mortality, and end-stage renal disease associated with potassium levels across the range of kidney function and evaluate for consistency across cohorts in a global consortium. Methods and results: We performed an individual-level data meta-analysis of 27 international cohorts [10 general population, 7 high cardiovascular risk, and 10 chronic kidney disease (CKD)] in the CKD Prognosis Consortium. We used Cox regression followed by random-effects meta-analysis to assess the relationship between baseline potassium and adverse outcomes, adjusted for demographic and clinical characteristics, overall and across strata of estimated glomerular filtration rate (eGFR) and albuminuria. We included 1 217 986 participants followed up for a mean of 6.9 years. The average age was 55 ± 16 years, average eGFR was 83 ± 23 mL/min/1.73 m2, and 17% had moderate- to-severe increased albuminuria levels. The mean baseline potassium was 4.2 ± 0.4 mmol/L. The risk of serum potassium of >5.5 mmol/L was related to lower eGFR and higher albuminuria. The risk relationship between potassium levels and adverse outcomes was U-shaped, with the lowest risk at serum potassium of 4-4.5 mmol/L. Compared with a reference of 4.2 mmol/L, the adjusted hazard ratio for all-cause mortality was 1.22 [95% confidence interval (CI) 1.15-1.29] at 5.5 mmol/L and 1.49 (95% CI 1.26-1.76) at 3.0 mmol/L. Risks were similar by eGFR, albuminuria, renin-angiotensin-aldosterone system inhibitor use, and across cohorts. Conclusions: Outpatient potassium levels both above and below the normal range are consistently associated with adverse outcomes, with similar risk relationships across eGFR and albuminuria.

7.
EBioMedicine ; 26: 68-77, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29128444

RESUMO

Chronic kidney disease (CKD) is a public health problem with very high prevalence and mortality. Yet, there is a paucity of effective treatment options, partly due to insufficient knowledge of underlying pathophysiology. We combined metabolomics (GCMS) with kidney gene expression studies to identify metabolic pathways that are altered in adults with non-diabetic stage 3-4 CKD versus healthy adults. Urinary excretion rate of 27 metabolites and plasma concentration of 33 metabolites differed significantly in CKD patients versus controls (estimate range-68% to +113%). Pathway analysis revealed that the citric acid cycle was the most significantly affected, with urinary excretion of citrate, cis-aconitate, isocitrate, 2-oxoglutarate and succinate reduced by 40-68%. Reduction of the citric acid cycle metabolites in urine was replicated in an independent cohort. Expression of genes regulating aconitate, isocitrate, 2-oxoglutarate and succinate were significantly reduced in kidney biopsies. We observed increased urine citrate excretion (+74%, p=0.00009) and plasma 2-oxoglutarate concentrations (+12%, p=0.002) in CKD patients during treatment with a vitamin-D receptor agonist in a randomized trial. In conclusion, urinary excretion of citric acid cycle metabolites and renal expression of genes regulating these metabolites were reduced in non-diabetic CKD. This supports the emerging view of CKD as a state of mitochondrial dysfunction.


Assuntos
Metabolômica , Mitocôndrias/metabolismo , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/genética , Ácido Aconítico/metabolismo , Idoso , Biópsia , Ciclo do Ácido Cítrico/genética , Feminino , Regulação da Expressão Gênica/genética , Humanos , Isocitratos/metabolismo , Ácidos Cetoglutáricos/metabolismo , Rim/metabolismo , Rim/patologia , Masculino , Redes e Vias Metabólicas/genética , Pessoa de Meia-Idade , Mitocôndrias/genética , Insuficiência Renal Crônica/patologia , Insuficiência Renal Crônica/urina , Ácido Succínico/metabolismo
9.
J Hypertens ; 34(10): 2081-9, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27442788

RESUMO

OBJECTIVE: Knowledge on how changing risk factors influence the progression of albuminuria over time is still limited. Furthermore, large population-based cohorts are needed to study the association between albuminuria change and mortality risk in nondiabetic study participants. METHODS: We evaluated changes of albuminuria in 6282 nondiabetic individuals from the Norwegian population-based Nord-Trøndelag Health study. Using three albumin/creatinine ratios (ACR), we studied the influence of cardiovascular risk factors on ACR change from baseline to follow-up 11 years later. We evaluated the next 8-year mortality risk by using flexible parametric methods to identify nonlinear main effects and their two-way interactions. RESULTS: Mean albuminuria increased significantly over 11 years (1.82-3.02 mg/mmol, P < 0.0001), but two-thirds of individuals had stable levels (ΔACR -1.40 to 1.40 mg/mmol). Higher age, ACR, and SBP as well as smoking and lower glomerular filtration rate at baseline were associated with increasing albuminuria. Study participants in the upper quartile of the increasing group had mean adjusted hazard ratio 1.31 (P = 0.004) for all-cause mortality compared with those with stable ACR. Those with decreasing ACR also had increased mortality, but the risk was strongly attenuated when adjusting for comorbidity. It also decreased the first 3 years before increasing. There was a strong interaction between baseline ACR and ΔACR. Increasing albuminuria had strongest effect on mortality in study participants with moderately increased baseline values. CONCLUSION: Both increasing and decreasing albuminuria are significant independent predictors of mortality in nondiabetic individuals, but must be interpreted in light of baseline values. Cutoffs and clinical usefulness in nondiabetic study participants should be further investigated.


Assuntos
Albuminúria/mortalidade , Albuminúria/urina , Doenças Cardiovasculares/urina , Creatinina/urina , Fatores Etários , Idoso , Albuminúria/etiologia , Pressão Sanguínea , Doenças Cardiovasculares/mortalidade , Feminino , Seguimentos , Taxa de Filtração Glomerular , Humanos , Masculino , Pessoa de Meia-Idade , Noruega/epidemiologia , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , Fumar/epidemiologia , Fatores de Tempo
10.
Kidney Int ; 90(3): 665-73, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27344204

RESUMO

Surveillance of chronic kidney disease (CKD) prevalence over time and information on how changing risk factors influence this trend are needed to evaluate the effects of general practice and public health interventions. Because very few studies addressed this, we studied the total adult population of a demographically stable county representative of Norway using cross-sectional studies 10 years apart (Nord-Trøndelag Health Study (HUNT)2 and Nord-Trøndelag Health Study (HUNT)3, 65,237 and 50,586 participants, respectively). Thorough quality-control procedures and comparisons of methods over time excluded analytical drift, and multiple imputations of missing data combined with nonattendance weights contributed to unbiased estimates. CKD prevalence remained stable in Norway from 1995 through 1997 (11.3%) to 2006 through 2008 (11.1%). The association of survey period with CKD prevalence was modified by a strong decrease in blood pressure, more physical activity, and lower cholesterol levels. Without these improvements, a 2.8, 0.7, and 0.6 percentage points higher CKD prevalence could have been expected, respectively. In contrast, the prevalence of diabetes and obesity increased moderately, but the proportion of diabetic patients with CKD decreased significantly (from 33.4% to 28.6%). A CKD prevalence of 1 percentage point lower would have been expected without these changes. Thus, CKD prevalence remained stable in Norway for more than a decade in association with marked improvements in blood pressure, lipid levels, and physical activity and despite modest increases in diabetes and obesity.


Assuntos
Doenças Cardiovasculares/epidemiologia , Diabetes Mellitus/epidemiologia , Obesidade/epidemiologia , Insuficiência Renal Crônica/epidemiologia , Adulto , Idoso , Albuminúria/urina , Pressão Sanguínea , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/complicações , Estudos Transversais , Inglaterra/epidemiologia , Feminino , Taxa de Filtração Glomerular , Humanos , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Noruega/epidemiologia , Obesidade/complicações , Prevalência , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/urina , Risco Ajustado , Fatores de Risco , Comportamento de Redução do Risco , Inquéritos e Questionários , Estados Unidos/epidemiologia
11.
Curr Diab Rep ; 16(7): 61, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27155611

RESUMO

Despite major improvements in the treatment of patients with diabetes mellitus, many patients still suffer from progressive diabetic kidney disease. More research is needed to improve treatment and to understand why some patients develop complications while others do not. Mitochondrial dysfunction has turned out to be central to the pathogenesis of diabetes, and we will review some new aspects in this field and the potential for treatment. The conventional theory has been that the intracellular surplus of glucose leads to mitochondrial overproduction of superoxide that contributes to general cell damage and activation of deleterious pathways specific for diabetes complications. However, recent data suggests that reduced mitochondrial activity could be the basis for disease progression and complications through increased inflammation and pro-fibrotic factors. Physical exercise is a very strong stimulus to mitochondrial biogenesis, and we now understand many of the underlying signaling pathways. Clinical trials have also shown that training, especially high-intensity training, can delay the onset of diabetes and improve insulin resistance. Furthermore, intermittent fasting and various pharmacological agents are other potential options for stimulating mitochondrial function and reducing the risk of development and progression of diabetic kidney disease.


Assuntos
Nefropatias Diabéticas/metabolismo , Mitocôndrias/metabolismo , Animais , Nefropatias Diabéticas/genética , Nefropatias Diabéticas/terapia , Exercício/fisiologia , Glucose/metabolismo , Humanos , Metaboloma , Espécies Reativas de Oxigênio/metabolismo , Resultado do Tratamento
12.
Nephron ; 133(1): 44-52, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27161102

RESUMO

BACKGROUND: The association between albuminuria and coronary heart disease (CHD) is well-known, but uncertainties related to day-to-day variability and effect modification of gender complicate the risk assessment process. This study evaluates the associations of CHD with albuminuria level in men and women based on the number of urine samples. METHODS: Nine thousand one hundred and fifty-eight adults provided 3 urine samples and were followed for 14 years in the population-based HUNT-2 cohort study. The association of myocardial infarction or coronary death with different albumin-creatinine ratio (ACR) cut-offs, based on gender and number of positive ACRs, were estimated by hazard ratios (HRs) and adjusted for by Framingham variables. RESULTS: Associations between ACR and CHD were similar in men and women. For example, HRs for moderately increased (3.0≤ ACR ≤30.0 mg/mmol) vs. normal albuminuria (ACR <1.0 mg/mmol) were 1.40 (95% CI 1.27-2.03) and 1.61 (95% CI 1.15-1.71) respectively, (psex-equality = 0.3). However, median intra-individual day-to-day ACR coefficient of variation was 22.4% in women vs. 17.5% in men (p < 0.001). Two or 3 positive ACRs were required to establish a significant association with CHD at levels below 4.0 mg/mmol in women, while one positive ACR implied a significant association at all levels in men. Based on receiver-operating-characteristics curves, the Youden index suggested possible equal cut-offs for women (1.12 mg/mmol) and men (0.88 mg/mmol), p = 0.06. CONCLUSIONS: There were no significant gender differences in the association between albuminuria and coronary events. However, women had increased intra-individual albuminuria variability compared to men, necessitating several positive urine samples if mildly increased albuminuria is used in coronary risk evaluation.


Assuntos
Albuminúria/urina , Doença das Coronárias/urina , Urinálise , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
14.
JAMA ; 315(2): 164-74, 2016 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-26757465

RESUMO

IMPORTANCE: Identifying patients at risk of chronic kidney disease (CKD) progression may facilitate more optimal nephrology care. Kidney failure risk equations, including such factors as age, sex, estimated glomerular filtration rate, and calcium and phosphate concentrations, were previously developed and validated in 2 Canadian cohorts. Validation in other regions and in CKD populations not under the care of a nephrologist is needed. OBJECTIVE: To evaluate the accuracy of the risk equations across different geographic regions and patient populations through individual participant data meta-analysis. DATA SOURCES: Thirty-one cohorts, including 721,357 participants with CKD stages 3 to 5 in more than 30 countries spanning 4 continents, were studied. These cohorts collected data from 1982 through 2014. STUDY SELECTION: Cohorts participating in the CKD Prognosis Consortium with data on end-stage renal disease. DATA EXTRACTION AND SYNTHESIS: Data were obtained and statistical analyses were performed between July 2012 and June 2015. Using the risk factors from the original risk equations, cohort-specific hazard ratios were estimated and combined using random-effects meta-analysis to form new pooled kidney failure risk equations. Original and pooled kidney failure risk equation performance was compared, and the need for regional calibration factors was assessed. MAIN OUTCOMES AND MEASURES: Kidney failure (treatment by dialysis or kidney transplant). RESULTS: During a median follow-up of 4 years of 721,357 participants with CKD, 23,829 cases kidney failure were observed. The original risk equations achieved excellent discrimination (ability to differentiate those who developed kidney failure from those who did not) across all cohorts (overall C statistic, 0.90; 95% CI, 0.89-0.92 at 2 years; C statistic at 5 years, 0.88; 95% CI, 0.86-0.90); discrimination in subgroups by age, race, and diabetes status was similar. There was no improvement with the pooled equations. Calibration (the difference between observed and predicted risk) was adequate in North American cohorts, but the original risk equations overestimated risk in some non-North American cohorts. Addition of a calibration factor that lowered the baseline risk by 32.9% at 2 years and 16.5% at 5 years improved the calibration in 12 of 15 and 10 of 13 non-North American cohorts at 2 and 5 years, respectively (P = .04 and P = .02). CONCLUSIONS AND RELEVANCE: Kidney failure risk equations developed in a Canadian population showed high discrimination and adequate calibration when validated in 31 multinational cohorts. However, in some regions the addition of a calibration factor may be necessary.


Assuntos
Modelos de Riscos Proporcionais , Insuficiência Renal Crônica/complicações , Insuficiência Renal/epidemiologia , Medição de Risco , Estudos de Coortes , Progressão da Doença , Humanos , Prognóstico
16.
J Am Soc Nephrol ; 27(7): 2135-47, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26701975

RESUMO

CKD prevalence estimation is central to CKD management and prevention planning at the population level. This study estimated CKD prevalence in the European adult general population and investigated international variation in CKD prevalence by age, sex, and presence of diabetes, hypertension, and obesity. We collected data from 19 general-population studies from 13 European countries. CKD stages 1-5 was defined as eGFR<60 ml/min per 1.73 m(2), as calculated by the CKD-Epidemiology Collaboration equation, or albuminuria >30 mg/g, and CKD stages 3-5 was defined as eGFR<60 ml/min per 1.73 m(2) CKD prevalence was age- and sex-standardized to the population of the 27 Member States of the European Union (EU27). We found considerable differences in both CKD stages 1-5 and CKD stages 3-5 prevalence across European study populations. The adjusted CKD stages 1-5 prevalence varied between 3.31% (95% confidence interval [95% CI], 3.30% to 3.33%) in Norway and 17.3% (95% CI, 16.5% to 18.1%) in northeast Germany. The adjusted CKD stages 3-5 prevalence varied between 1.0% (95% CI, 0.7% to 1.3%) in central Italy and 5.9% (95% CI, 5.2% to 6.6%) in northeast Germany. The variation in CKD prevalence stratified by diabetes, hypertension, and obesity status followed the same pattern as the overall prevalence. In conclusion, this large-scale attempt to carefully characterize CKD prevalence in Europe identified substantial variation in CKD prevalence that appears to be due to factors other than the prevalence of diabetes, hypertension, and obesity.


Assuntos
Insuficiência Renal Crônica/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Europa (Continente)/epidemiologia , Feminino , Humanos , Falência Renal Crônica/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Índice de Gravidade de Doença , Adulto Jovem
17.
Clin Proteomics ; 12(1): 21, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26257595

RESUMO

BACKGROUND: The contrast between a high prevalence of chronic kidney disease (CKD) and the low incidence of end-stage renal disease highlights the need for new biomarkers of progression beyond albuminuria testing. Urinary proteomics is a promising method, but more studies focusing on progression rate and patients with hypertensive nephropathy are needed. RESULTS: We analyzed urine samples with capillary electrophoresis coupled to a mass-spectrometer from 18 well characterized patients with CKD stage 4-5 (of whom six with hypertensive nephropathy) and 17 healthy controls. Classification scores based on a previously developed panel of 273 urinary peptides were calculated and compared to urine albumin dipstick results. Urinary proteomics classified CKD with a sensitivity of 0.95 and specificity of 1.00. Overall diagnostic accuracy (area under ROC curve) was 0.98, which was better than for albuminuria (0.85, p = 0.02). Results for hypertensive nephropathy were similar to other CKD diagnoses. Adding the proteomic score to an albuminuria model improved detection of rapid kidney function decline (>4 ml/min/1.73 m(2) per year) substantially: area under ROC curve increased from 0.762 to 0.909 (p = 0.042), and 38% of rapid progressors were correctly reclassified to a higher risk and 55% of slow progressors were correctly reclassified to a lower risk category. Reduced excretion of collagen types I-III, uromodulin, and other indicators of interstitial inflammation, fibrosis and tubular dysfunction were associated with CKD diagnosis and rapid progression. Patients with hypertensive nephropathy displayed the same findings as other types of CKD. CONCLUSIONS: Urinary proteomic analyses had a high diagnostic accuracy for CKD, including hypertensive nephropathy, and strongly improved identification of patients with rapid kidney function decline beyond albuminuria testing.

18.
Nephrol Dial Transplant ; 30 Suppl 4: iv6-16, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26209739

RESUMO

BACKGROUND: Many publications report the prevalence of chronic kidney disease (CKD) in the general population. Comparisons across studies are hampered as CKD prevalence estimations are influenced by study population characteristics and laboratory methods. METHODS: For this systematic review, two researchers independently searched PubMed, MEDLINE and EMBASE to identify all original research articles that were published between 1 January 2003 and 1 November 2014 reporting the prevalence of CKD in the European adult general population. Data on study methodology and reporting of CKD prevalence results were independently extracted by two researchers. RESULTS: We identified 82 eligible publications and included 48 publications of individual studies for the data extraction. There was considerable variation in population sample selection. The majority of studies did not report the sampling frame used, and the response ranged from 10 to 87%. With regard to the assessment of kidney function, 67% used a Jaffe assay, whereas 13% used the enzymatic assay for creatinine determination. Isotope dilution mass spectrometry calibration was used in 29%. The CKD-EPI (52%) and MDRD (75%) equations were most often used to estimate glomerular filtration rate (GFR). CKD was defined as estimated GFR (eGFR) <60 mL/min/1.73 m(2) in 92% of studies. Urinary markers of CKD were assessed in 60% of the studies. CKD prevalence was reported by sex and age strata in 54 and 50% of the studies, respectively. In publications with a primary objective of reporting CKD prevalence, 39% reported a 95% confidence interval. CONCLUSIONS: The findings from this systematic review showed considerable variation in methods for sampling the general population and assessment of kidney function across studies reporting CKD prevalence. These results are utilized to provide recommendations to help optimize both the design and the reporting of future CKD prevalence studies, which will enhance comparability of study results.


Assuntos
Biomarcadores/análise , Taxa de Filtração Glomerular , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/fisiopatologia , Amostragem , Adulto , Calibragem , Europa (Continente)/epidemiologia , Humanos , Prevalência
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