Pietro Manuel Ferraro

CKD Prevalence Varies across the European General Population

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.

Low level exposure to cadmium increases the risk of chronic kidney disease: analysis of the NHANES 1999-2006

BackgroundEnvironmental factors have been associated with the outbreak of chronic kidney disease (CKD). We evaluated the association of Cadmium (Cd) exposure with the risk of CKD in U.S. adults who participated in the 1999-2006 National Health and Nutrition Examination Surveys (NHANES).Methods5426 subjects ≥ 20 years were stratified for values of urinary and blood Cd and a multivariate logistic regression was performed to test the association between blood and urinary Cd, CKD and albuminuria (ALB) after adjustment for age, gender, race/ethnicity, body mass index and smoking habits.ResultsSubjects with urinary Cd > 1 mcg/g and subjects with blood Cd > 1 mcg/L showed a higher association with ALB (OR 1.63, 95% CI 1.23, 2.16; P = 0.001). Subjects with blood Cd > 1 mcg/L showed a higher association with both CKD (OR 1.48, 95% CI 1.01, 2.17; P = 0.046) and ALB (OR 1.41, 95% CI 1.10, 1.82; P = 0.007). An interaction effect on ALB was found for high levels of urinary and blood Cd (P = 0.014).ConclusionsModerately high levels of urinary and blood Cd are associated with a higher proportion of CKD and ALB in the United States population.

Soda and Other Beverages and the Risk of Kidney Stones

BACKGROUND AND OBJECTIVES Not all fluids may be equally beneficial for reducing the risk of kidney stones. In particular, it is not clear whether sugar and artificially sweetened soda increase the risk. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We prospectively analyzed the association between intake of several types of beverages and incidence of kidney stones in three large ongoing cohort studies. Information on consumption of beverages and development of kidney stones was collected by validated questionnaires. RESULTS The analysis involved 194,095 participants; over a median follow-up of more than 8 years, 4462 incident cases occurred. There was a 23% higher risk of developing kidney stones in the highest category of consumption of sugar-sweetened cola compared with the lowest category (P for trend=0.02) and a 33% higher risk of developing kidney stones for sugar-sweetened noncola (P for trend=0.003); there was a marginally significant higher risk of developing kidney stones for artificially sweetened noncola (P for trend=0.05). Also, there was an 18% higher risk for punch (P for trend=0.04) and lower risks of 26% for caffeinated coffee (P for trend<0.001), 16% for decaffeinated coffee (P for trend=0.01), 11% for tea (P for trend=0.02), 31%-33% for wine (P for trend<0.005), 41% for beer (P for trend<0.001), and 12% for orange juice (P for trend=0.004). CONCLUSIONS Consumption of sugar-sweetened soda and punch is associated with a higher risk of stone formation, whereas consumption of coffee, tea, beer, wine, and orange juice is associated with a lower risk.

Combined treatment with renin–angiotensin system blockers and polyunsaturated fatty acids in proteinuric IgA nephropathy: a randomized controlled trial

BACKGROUND Currently, several therapeutic protocols exist for IgA nephropathy (IgAN); results in slowing the progression to end-stage renal disease (ESRD) are variable, but approximately 30-40% of patients require replacement therapy (dialysis or renal transplantation) by 20 years from the onset. The adverse effects brought by the chronic assumption of drugs can be a potential limit. Actually, the most used therapies for IgAN are renin-angiotensin system blockers (RASB), glucocorticoids and immunosuppressive agents. Trials with polyunsaturated fatty acids (PUFA) in IgAN have been done since the first successful attempt by Hamazaki in 1984, resulting in alternate answers, but no trials have ever been done testing the efficacy of combined therapy with RASB and PUFA. METHODS We tested the effect of a 6-month course of PUFA (3 grams/day) in a group of 30 patients with biopsy-proven IgAN and proteinuria already treated with RASB randomized to receive PUFA supplementation or to continue their standard therapy. The primary end-point was the percent reduction of proteinuria from the baseline. Secondary end-points were modifications in glomerular filtration rate (GFR), blood pressure, serum triglycerides and erythrocyturia. RESULTS At the end of the 6-month trial, the percent reduction of proteinuria was 72.9% in the PUFA group and 11.3% in the RASB group (P < 0.001). A reduction of >or=50% of baseline proteinuria was achieved in 80.0% of PUFA patients and 20.0% of RASB patients (P = 0.002). Erythrocyturia was significantly lower in the PUFA group (P = 0.031). No significant changes in renal function, blood pressure and triglycerides were observed. CONCLUSIONS PUFA associated with RASB reduced proteinuria in patients with IgAN more than RASB alone.

Prevalence of CKD in Northeastern Italy: Results of the INCIPE Study and Comparison with NHANES

BACKGROUND AND OBJECTIVES Sufficiently powered studies to investigate the CKD prevalence are few and do not cover southern Europe. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS For the INCIPE study, 6200 Caucasian patients ≥40 years old were randomly selected in northeastern Italy in 2006. Laboratory determinations were centralized. The albumin to creatinine ratio in urine and estimated GFR from calibrated creatinine (SCr) were determined. A comparison with 2001 through 2006 NHANES surveys was performed. RESULTS Prevalence of CKD was 13.2% in northeastern (NE) Italy (age and gender standardized to the U.S. 2007 Caucasian population). Prevalence of CKD in U.S. Caucasians is higher (20.3%), the major difference being in CKD 3. Risk factors for CKD are more prevalent in the United States than in Italy. With use of CKD 3a and 3b stages, CKD prevalence decreased in NE Italy (8.5%) and in the United States (12.8%). CONCLUSIONS The prevalence of CKD is high in NE Italy, but lower than that in the United States. A large part of the difference in CKD prevalence in NE Italy versus that in the United States is due to the different prevalence of CKD 3. The higher prevalence of a number of renal risk factors in persons from the United States explains in part the different dimensions of the CKD problem in the two populations.

Methodology used in studies reporting chronic kidney disease prevalence: a systematic literature review

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 m2 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.

Paradoxical psoriasis in a large cohort of patients with inflammatory bowel disease receiving treatment with anti‐TNF alpha: 5‐year follow‐up study

Psoriasis is an emerging paradoxical side effect in patients with inflammatory bowel disease (IBD) when treated with anti‐TNF alpha. Patients with severe skin lesions unresponsive to topical therapy need to withdraw from treatment.

Cytokines profile in serum of homozygous familial hypercholesterolemia is changed by LDL-apheresis

OBJECTIVE The effects of LDL-apheresis (LDLa) with dextran sulphate on plasma cytokines in 6 homozygous familial hypercholesterolemic (HozFH) patients, were evaluated. METHODS Plasma IL-1α; IL-1ra; IL-4; IL-6; IL-10; IL-12(p40); IL-12(p70); TNF-α, sTNF-R, VEGF, VEGF-R1, E-Selectin (ESEL), and P-Selectin (PSEL) concentrations were measured before and after LDLa on three consecutive sessions for each patient. RESULTS TNF-α was significantly reduced (-60%; P=0.01), while TNF-R was only slightly increased (+15%), although not significantly. Plasma VEGF was significantly reduced (-57%; P=1.87301E-05), while VEGF-R1 was significantly increased (+56%; P=0.05). ESEL and PSEL were reduced but not to a statistically significant extent (-19%, -15%, respectively). IL-1α level was dramatically reduced (-87%; P=0.0001). IL-1ra concentration was only slightly increased in plasma, but not significantly. IL-4 and IL-10 levels were significantly reduced in plasma after apheresis (-50%; P=0.03, and -55%; P=0.004, respectively). On the contrary, IL-6 concentration showed a slight decrease (-8%). Plasma IL-12p40 was significantly increased (+47%; P=0.0004). On the other hand, IL-12p70 was reduced, but the difference (-31%) was not statistically significant. CONCLUSIONS Plasma cytokines imbalance is associated with inflammation and atherogenesis. In this study LDLa changed several circulating cytokines inducing anti-inflammatory and anti-atherogenic changes in cytokines plasma profile in HozFH patients with/without pre-existing angiographically demonstrated coronary heart disease (CHD) and aortic valvular disease (AVD).

Treatment of symptomatic hyperLp(a)lipidemia with LDL-apheresis vs. usual care

BACKGROUND/AIMS To assess LDL-apheresis efficacy to lower Lp(a) and to compare the effects of Usual Medical Care (UMC) a 12-months study was carried out. The incidence of new coronary artery disease (CAD) events/need of revascularization, was also monitored. METHODS Twenty-one patients with hyperLp(a)lipidemia and angiographically documented CAD were randomly assigned to LDL-apheresis every week, or the UMC. RESULTS LDL-apheresis group, averaged an Lp(a) reduction of 57.8+/-9.5% vs. basal values (P<0.001). In the UMC group Lp(a) increased in 1 year to 14.7+/-36.5% (P=0.66). Stepwise multivariate regression analysis for predictors of Lp(a) including: type of treatment, smoking, hypertension, age, age at first cardiovascular event, initial Lp(a), LDL, and BMI values, was performed. Only the type of treatment was co-related (P<0.001): Lp(a) variation (beta)=0.863. The model has R2 adjusted relative risk of 0.725. CONCLUSION LDL-apheresis could be the first line treatment of isolated hyperLp(a)lipidemia when CAD is established. New CAD events/cardiac interventions were not observed.

Familial clustering of medullary sponge kidney is autosomal dominant with reduced penetrance and variable expressivity

Medullary sponge kidney (MSK) is a renal malformation typically associated with nephrocalcinosis and recurrent calcium nephrolithiasis. Approximately 12% of recurrent stone formers have MSK, which is generally considered a sporadic disorder. Since its discovery, three pedigrees have been described in which an apparently autosomal dominant inheritance was suggested. Here, family members of 50 patients with MSK were systematically investigated by means of interviews, renal imaging, and biochemical studies in an effort to establish whether MSK is an inheritable disorder. Twenty-seven MSK probands had 59 first- and second-degree relatives of both genders with MSK in all generations. There were progressively lower mean levels of serum calcium, urinary sodium, pH, and volume, combined with higher serum phosphate and potassium from probands to relatives with bilateral, to those with unilateral, and to those unaffected by MSK. This suggests that most affected relatives have a milder form of MSK than the probands, which would explain why they had not been so diagnosed. Thus, our study provides strong evidence that familial clustering of MSK is common, and has an autosomal dominant inheritance, a reduced penetrance, and variable expressivity.