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Background: Microalbuminuria is an early sign of kidney disease in people with diabetes and indicates increased risk of cardiovascular disease. We tested whether a urinary proteomic risk classifier (CKD273) score was associated with development of microalbuminuria and whether progression to microalbuminuria could be prevented with the mineralocorticoid receptor antagonist spironolactone. Methods: In this multicentre, prospective, observational study with embedded randomised controlled trial (PRIORITY), we recruited people with type 2 diabetes, normal urinary albumin excretion, and preserved renal function from 15 specialist centres in ten European countries. All participants (observational cohort) were tested with the CKD273 classifier and classified as high risk (CKD273 classifier score >0·154) or low risk (≤0·154). Participants who were classified as high risk were entered into a randomised controlled trial and randomly assigned (1:1), by use of an interactive web-response system, to receive spironolactone 25 mg once daily or matched placebo (trial cohort). The primary endpoint was development of confirmed microalbuminuria in all individuals with available data (observational cohort). Secondary endpoints included reduction in incidence of microalbuminuria with spironolactone (trial cohort, intention-to-treat population) and association between CKD273 risk score and measures of impaired renal function based on estimated glomerular filtration rate (eGFR; observational cohort). Adverse events (particularly gynaecomastia and hyperkalaemia) and serious adverse events were recorded for the intention-to-treat population (trial cohort). This study is registered with the EU Clinical Trials Register (EudraCT 20120-004523-4) and ClinicalTrials.gov (NCT02040441) and is completed. Findings: Between March 25, 2014, and Sept 30, 2018, we enrolled and followed-up 1775 participants (observational cohort), 1559 (88%) of 1775 participants had a low-risk urinary proteomic pattern and 216 (12%) had a high-risk pattern, of whom 209 were included in the trial cohort and assigned to spironolactone (n=102) or placebo (n=107). The overall median follow-up time was 2·51 years (IQR 2·0–3·0). Progression to microalbuminuria was seen in 61 (28%) of 216 high-risk participants and 139 (9%) of 1559 low-risk participants (hazard ratio [HR] 2·48, 95% CI 1·80–3·42; p

Background: The ability of brain natriuretic peptide (BNP) together with other traditional and nontraditional risk factors to predict cardiovascular (CV) mortality in hemodialysis (HD) patients has not been well established. The aim of this prospective study was to determine the predictive cutoff values of baseline measurement of BNP along with the known CV disease risk factors to predict all-cause and CV mortality in HD patients. Methods: BNP concentration before HD was measured in 125 prevalent HD patients (age 53.0 ± 13.5 years, HD vintage 75.2 ± 61.0 months). In addition, several traditional CV risk factors (blood pressure, dyslipidemia, diabetes mellitus, body mass index, left ventricular hypertrophy) and uremia/dialysis-related CV risk factors (anemia, calcium and phosphate impairment, malnutrition, inflammation, ultrafiltration, HD duration, Kt/V) were examined. Results: During the 2-year follow-up, we lost 28 out of 125 patients (22.5%), with CV disease (65.7%) being the main cause of mortality. The cutoff point for BNP, as predictor of the clinical outcome, according to the ROC curve was 1,194 pg/ml for CV mortality with sensitivity and specificity of 63 and 65%, respectively (AUC 0.61 and confidence interval (CI) 95% 0.47–0.75). Kaplan-Meier analysis showed that all-cause (log-rank, p = 0.002) and CV mortality (log-rank, p = 0.001) were the cause of a significantly lower survival in patients with a mean BNP >1,200 pg/ml. The univariate Cox regression analysis found the following factors to be predictors of all-cause mortality: hemoglobin (1.78 mmol/l), albumin (1,200 pg/ml) and cardiac ejection fraction (≤55%). The multivariate Cox regression analyses demonstrated that only CRP ≧10 mg/l with a hazard ratio (HR) 6.82 (CI 95% 1.86–24.9, p = 0.004) and BNP >1,200 pg/ml with HR 5.79 (CI 95% 1.58–21.3, p = 0.004) were predictors of all-cause mortality. BNP >1,200 pg/ml with HR 13.52 (CI 95% 1.68–108.9, p = 0.014) was found to be an even stronger predictor of CV mortality than CRP ≧10 mg/l with HR 6.53 (CI 95% 1.35–31.6, p = 0.020). Conclusions: Our study pointed out that BNP >1,200 pg/ml as a marker of cardiac dysfunction and CRP ≧10 mg/l as a marker of inflammation identify HD patients at increased risk of CV mortality.

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)

Hypertension is associated with more rapid progression of chronic kidney disease. Several studies have shown that treating hypertension in patients with chronic kidney disease and proteinuria may attenuate the decline in glomerular filtration rate.The study evaluates the prevalence of hypertension and its association with chronic kidney disease progression in patients without and with diabetic nephropathy.Patients with CKD stage 2-4 were followed up by a nephrologist for 12-52 months. A total of 137 patients were included in the study, 70 with non-diabetic CKD and 67 with type 2 diabetes and diabetic nephropathy. Demographic and clinical parameters were recorded at initiation and during follow-up. Glomerular filtration rate was estimated by the Cockroft-Gault formula and progression of CKD by the slope of the estimated GFR decline.Out of 70 patients in the non-diabetic group, 34 were males, (mean age 50.37+/-12.2 years). Out of 67 diabetic patients, 30 were (males, mean age 57.8+/-8.4 years). 77% in the non-diabetic group had SBP above 140 mmHg. The higher SBP was associated with older age, (53.16+/-10.8 vs 40.9+/-12.2 years, p0.0001). Diastolic blood pressure above 90 was present in 73%. Pulse pressure above 80 had 5.7% and was associated with older age (p0.02). Progression of chronic kidney disease correlated inversely with age, and positively with diastolic blood pressure and proteinuria (p=0.005, p=0.019 and p=0.02 respectively). Multiple regression analysis showed that only younger age and higher proteinuria were predictive for chronic kidney disease progression (p=0.00002). 6% of pts in the diabetic group had SBP below 140, 19% between 140 and 160, and 75% above 160 mmHg. Diastolic blood pressure below 80 had only 6% of patients, between 80 and 90 had 37% and above 90 mmHg had 57%. Pulse pressure below 80 mmHg had 55% and it was correlated positively with age, p=0.009. Progression of chronic kidney disease in the diabetic group correlated positively with mean arterial pressure, systolic blood pressure and proteinuria, (p=0.017, 0.036 and 0.000000 respectively) and inversely with age (p=0.0003). Multiple regression analysis showed that proteinuria, age and SBP were the only predictors for chronic kidney disease progression in diabetics.Isolated systolic hypertension predominates the older age groups, proteinuria and age significantly correlate with GFR decline in both groups, and SBP is associated with more rapid progression of CKD in the diabetic patients.

Cardiovascular diseases are the most common causes of death among hemodialysis (HD) patients, yet the risk factors for these events have not been well established. Our study objective was to determine predictors of cardiovascular mortality, considering the non-traditional/disease-related and treatment-related/ cardiovascular risk factor in HD patients.Disease-related cardiovascular risk factors, such as anaemia, calcium-phosphate disorders, nutrition-inflammation and treatment/dialysis-related cardiovascular risk factors such as HD dose, using the index Kt/V were analyzed in 214 patients on HD. Mortality was monitored prospectively over a two year period.Fifty-three of the 214 HD patients died during the follow-up period and the main cause of death was cardiovascular events (56.6%), followed by infection/sepsis (26.4%). The patients who died were significantly older than those alive, had significantly lower serum levels of hemoglobin (Hb), albumin and Kt/V. Serum levels of calcium, C-reactive protein (CRP) and fibrinogen were significantly higher in patients who died during the follow-up period. Kaplan-Meier analysis showed that the all cause and cardiovascular mortality was considerably higher in patients with Hb110 g/l, albumin40 g/l, CRP8 mg/l and spKt/V1.2 (log rank, p=0.000/p=0.000, p=0.000/ p=0.001, p=0.000/p=0.000, p=0.000/p=0.000), respectively. No difference in cardiovascular mortality was observed between the fibrinogen4 g/llevels. High CRP, low Hb levels and low spKt/V were significant predictors of all-cause mortality, but low albumin and high fibrinogen levels were not in the Cox proportional hazards analysis. When only cardiovascular mortality was entered into the Cox model, high CRP and low Hb levels were the only significant predictors for mortality.It can be concluded that, inflammation (elevated CRP) and anaemia (decreased Hb), were identified as significant independent non-traditional, disease-related cardiovascular risk factors that predict cardiovascular mortality in HD patients.

Background An improvement in the glomerular filtration rate (GFR) of chronic kidney disease patients has been an underestimated clinical outcome. Although this may be considered as an unexpected disease course, it may provide some insights into possible mechanisms underlying disease remission and/or regression. Therefore, our aim was to identify urinary peptide biomarkers associated with an improvement in estimated GFR (eGFR) over time and to improve patient stratification. Methods Capillary electrophoresis coupled with mass spectrometry (CE-MS) was employed to evaluate the urine peptidome of patients with different types of renal diseases. In total, 376 patients with a slope/year between -1.5% and +1.5% were designated as non-progressors or stable, while 177 patients with a > 5% slope/year were designated as patients with an improved eGFR for state-of-art biomarker discovery and validation. Results We detected 384 significant peptide fragments by comparing the CE-MS data of the stable patients and those with improved renal function in our development cohort. Of these 384, a set of 141 peptides with available amino acid sequence information were used to generate a support vector machine-based classification panel. The biomarker panel was applied to our validation cohort, achieving a moderate area under the curve (AUC) value of 0.85 (81% sensitivity and 81% specificity). The majority of the peptides (78%) from the diagnostic panel arose from different types of collagen. Conclusions We have developed a panel of urinary peptide markers able to discriminate those patients predisposed to improve their kidney function over time and possibly be treated with more specific or less aggressive therapy.