Comparative risks and predictors of preeclamptic pregnancy in the Eastern, Western and developing world.

Preeclampsia (PE) is a complication of pregnancy characterized by hypertension (HTN-Preg), and often proteinuria. If not managed promptly, PE could lead to eclampsia and seizures. PE could also lead to intrauterine growth restriction (IUGR) and prematurity at birth. Although PE is a major cause of maternal and fetal morbidity and mortality, the underlying mechanisms are unclear. Also, there is a wide variability in the incidence of PE, ranging between 2 and 8% of pregnancies in the Eastern, Western and Developing world, suggesting regional differences in the risk factors and predictors of the pregnancy-related disorder. Several demographic, genetic, dietary and environmental factors, as well as maternal circulating biomarkers have been associated with PE. Demographic factors such as maternal race and ethnicity could play a role in PE. Specific genetic polymorphisms have been identified in PE. Maternal age, parity, education and socioeconomic status could be involved in PE. Dietary fat, protein, calcium and vitamins, body weight, and environmental factors including climate changes and air pollutants could also play a role in PE. Several circulating cytoactive factors including anti-angiogenic factors and cytokines have also been associated with PE. Traditional midwifery care is a common practice in local maternity care units, while advanced perinatal care and new diagnostic tools such as uterine artery Doppler velocimetry have been useful in predicting early PE in major medical centers. These PE risk factors, early predictors and diagnostic tools vary vastly in different regions of the Eastern, Western and Developing world. Further understanding of the differences in the demographic, genetic, dietary and environmental factors among pregnant women in different world regions should help in designing a region-specific cluster of risk factors and predictors of PE, and in turn provide better guidance for region-specific tools for early detection and management of PE.

Serum Metabolomic Alterations Associated with Proteinuria in CKD.

BACKGROUND AND OBJECTIVES: Data are scarce on blood metabolite associations with proteinuria, a strong risk factor for adverse kidney outcomes. We sought to investigate associations of proteinuria with serum metabolites identified using untargeted profiling in populations with CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Using stored serum samples from the African American Study of Kidney Disease and Hypertension (AASK; n=962) and the Modification of Diet in Renal Disease (MDRD) study (n=620), two rigorously conducted clinical trials with per-protocol measures of 24-hour proteinuria and GFR, we evaluated cross-sectional associations between urine protein-to-creatinine ratio and 637 known, nondrug metabolites, adjusting for key clinical covariables. Metabolites significantly associated with proteinuria were tested for associations with CKD progression. RESULTS: In the AASK and the MDRD study, respectively, the median urine protein-to-creatinine ratio was 80 (interquartile range [IQR], 28-359) and 188 (IQR, 54-894) mg/g, mean age was 56 and 52 years, 39% and 38% were women, 100% and 7% were black, and median measured GFR was 48 (IQR, 35-57) and 28 (IQR, 18-39) ml/min per 1.73 m2. Linear regression identified 66 serum metabolites associated with proteinuria in one or both studies after Bonferroni correction (P<7.8×10-5), 58 of which were statistically significant in a meta-analysis (P<7.8×10-4). The metabolites with the lowest P values (P<10-27) were 4-hydroxychlorthalonil and 1,5-anhydroglucitol; all six quantified metabolites in the phosphatidylethanolamine pathway were also significant. Of the 58 metabolites associated with proteinuria, four were associated with ESKD in both the AASK and the MDRD study. CONCLUSIONS: We identified 58 serum metabolites with cross-sectional associations with proteinuria, some of which were also associated with CKD progression. PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2019_02_07_CJASNPodcast_19_03_.mp3.

Baseline characteristics of the autosomal-dominant polycystic kidney disease sub-cohort of the KoreaN cohort study for outcomes in patients with chronic kidney disease.

AIM: The aim of this study was to describe the baseline characteristics of autosomal-dominant polycystic kidney disease (ADPKD) in a cohort of Korean patients with chronic kidney disease (CKD). METHODS: From April 2011 to February 2016, patients with CKD stage 1-5 (pre-dialysis) were enrolled as an ADPKD sub-cohort of the KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease. Baseline characteristics, the correlation of kidney and liver volume and kidney function and the factors associated with kidney function were analysed. RESULTS: A total of 364 ADPKD patients with a mean estimated glomerular filtration rate (eGFR) of 68.1 ± 33.3 mL/min per 1.73 m2 (50.5% male with a mean age of 47.0 ± 10.6 years) were enrolled from nine hospitals in Korea. Initially, 55.8% of the patients were asymptomatic, and pain was the most common symptom (12.9%); 87.6 and 77.5% of the patients had hypertension and hepatic cysts, respectively. The height-adjusted total kidney volumes (htTKV) were higher in male patients than in female patients. In contrast, the height-adjusted total liver volumes were higher in female patients than in male patients. The decrease rate of eGFR depending on Log(htTKV) was larger in the group aged between 41 and 50 years than the other age groups. Older age, a higher 24-h urine protein excretion, larger htTKV and hyperuricemia were independently associated with lower eGFR, whereas using febuxostat was independently associated with higher eGFR. CONCLUSION: This sub-cohort will provide clinical characteristics and outcomes of Korean ADPKD patients, which can be compared with those of other previous cohorts. We have identified factors associated with advanced-stage CKD in Korean patients with ADPKD.

First identification of PODXL nonsense mutations in autosomal dominant focal segmental glomerulosclerosis.

Recently, a novel heterozygous missense mutation c.T1421G (p. L474R) in the PODXL gene encoding podocalyxin was identified in an autosomal dominant focal segmental glomerulosclerosis (AD-FSGS) pedigree. However, this PODXL mutation appeared not to impair podocalyxin function, and it is necessary to identify new PODXL mutations and determine their causative role for FSGS. In the present study, we report the identification of a heterozygous nonsense PODXL mutation (c.C976T; p. Arg326X) in a Chinese pedigree featured by proteinuria and renal insufficiency with AD inheritance by whole exome sequencing (WES). Total mRNA and PODXL protein abundance were decreased in available peripheral blood cell samples of two affected patients undergoing hemodialysis, compared with those in healthy controls and hemodialysis controls without PODXL mutation. We identified another novel PODXL heterozygous nonsense mutation (c.C1133G; p.Ser378X) in a British-Indian pedigree of AD-FSGS by WES. In vitro study showed that, human embryonic kidney 293T cells transfected with the pEGFP-PODXL-Arg326X or pEGFP-PODXL-Ser378X plasmid expressed significantly lower mRNA and PODXL protein compared with cells transfected with the wild-type plasmid. Blocking nonsense-mediated mRNA decay (NMD) significantly restored the amount of mutant mRNA and PODXL proteins, which indicated that the pathogenic effect of PODXL nonsense mutations is likely due to NMD, resulting in podocalyxin deficiency. Functional consequences caused by the PODXL nonsense mutations were inferred by siRNA knockdown in cultured podocytes and podocalyxin down-regulation by siRNA resulted in decreased RhoA and ezrin activities, cell migration and stress fiber formation. Our results provided new data implicating heterozygous PODXL nonsense mutations in the development of FSGS.

Urine Complement Proteins and the Risk of Kidney Disease Progression and Mortality in Type 2 Diabetes.

OBJECTIVE: We examined the association of urine complement proteins with progression to end-stage renal disease (ESRD) or death in people with type 2 diabetes and proteinuric diabetic kidney disease (DKD). RESEARCH DESIGN AND METHODS: Using targeted mass spectrometry, we quantified urinary abundance of 12 complement proteins in a predominantly Mexican American cohort with type 2 diabetes and proteinuric DKD (n = 141). The association of urine complement proteins with progression to ESRD or death was evaluated using time-to-event analyses. RESULTS: At baseline, median estimated glomerular filtration rate (eGFR) was 54 mL/min/1.73 m2 and urine protein-to-creatinine ratio 2.6 g/g. Sixty-seven participants developed ESRD or died, of whom 39 progressed to ESRD over a median of 3.1 years and 40 died over a median 3.6 years. Higher urine CD59, an inhibitor of terminal complement complex formation, was associated with a lower risk of ESRD (hazard ratio [HR] [95% CI per doubling] 0.50 [0.29-0.87]) and death (HR [95% CI] 0.56 [0.34-0.93]), after adjustment for demographic and clinical covariates, including baseline eGFR and proteinuria. Higher urine complement components 4 and 8 were associated with lower risk of death (HR [95% CI] 0.57 [0.41-0.79] and 0.66 [0.44-0.97], respectively); higher urine factor H-related protein 2, a positive regulator of the alternative complement pathway, was associated with greater risk of death (HR [95% CI] 1.61 [1.05-2.48]) in fully adjusted models. CONCLUSIONS: In a largely Mexican American cohort with type 2 diabetes and proteinuric DKD, urine abundance of several complement and complement regulatory proteins was strongly associated with progression to ESRD and death.

Disease severity of proliferative lupus nephritis in Maghrebians.

Objective To study the influence of Maghrebian ethnicity on lupus nephritis. Methods We retrospectively reviewed the files of a cohort of 194 patients with proliferative lupus nephritis followed in seven lupus centres belonging to three groups: Europeans living in Belgium/France (E; n = 111); Maghrebians living in Europe, in casu Belgium/France (ME; n = 43); and Maghrebians living in Morocco (MM; n = 40). Baseline presentation was compared between these three groups but complete long-term outcome data were available only for E and ME patients. Results At presentation, the clinical and pathological characteristics of lupus nephritis did not differ between E, ME and MM patients. Renal relapses were more common in ME patients (54%) than in E patients (29%) ( P < 0.01). Time to renal flare and to end-stage renal disease was shorter in ME patients compared to E patients ( P < 0.0001 and P < 0.05, respectively). While proteinuria measured at month 12 accurately predicted a serum creatinine value of less than 1 mg/dl at 7 years in E patients, this was not the case in the ME group, in whom serum creatinine at month 12 performed better. Conclusion Despite a similar disease profile at onset, the prognosis of lupus nephritis is more severe in Maghrebians living in Europe compared to native Europeans, with a higher relapse rate.

The effect of ethnicity on the performance of protein-creatinine ratio in the prediction of significant proteinuria in pregnancies at risk of or with established hypertension: an implementation audit and cost implications.

INTRODUCTION: The replacement of 24-h urine collection by protein-creatinine ratio (PCR) for the diagnosis of preeclampsia has been recently recommended. However, the literature is conflicting and there are concerns about the impact of demographic characteristics on the performance of PCR. MATERIAL AND METHODS: This was an implementation audit of the introduction of PCR in a London Tertiary obstetric unit. The performance of PCR in the prediction of proteinuria ≥300 mg/day was assessed in 476 women with suspected preeclampsia who completed a 24-h urine collection and an untimed urine sample for PCR calculation. Multivariate logistic regression was used to assess the independent predictors of significant proteinuria. RESULTS: In a pregnant population, ethnicity and PCR are the main predictors of ≥300 mg proteinuria in a 24-h urine collection. A PCR cut-off of 30 mg/mmol would have incorrectly classified as non-proteinuric, 41.4% and 22.9% of black and non-black women, respectively. Sensitivity of 100% is achieved at cut-offs of 8.67 and 20.56 mg/mmol for black and non-black women, respectively. Applying these levels as a screening tool to inform the need to perform a 24-h urine collection in 1000 women, would lead to a financial saving of €2911 in non-black women and to an additional cost of €3269 in black women. CONCLUSIONS: Our data suggest that a move from screening for proteinuria with a 24-h urine collection to screening with urine PCR is not appropriate for black populations. However, the move may lead to cost-saving if used in the white population with a PCR cut-off of 20.5.

Short-term effects of dietary supplementation with amino acids in dogs with proteinuric chronic kidney disease.

This retrospective study investigated the impact of amino acid supplementation on body weight, serum albumin, creatinine and urea concentrations, and urine protein-to-creatinine (UPC) ratio in proteinuric dogs with chronic kidney disease (CKD). Forty-six client-owned azotemic dogs with spontaneous proteinuric CKD already on a renal diet and in therapy with enalapril were included. After approximately 1 month of treatment (baseline), 29 dogs received oral amino acid supplementation daily (group A) and 17 dogs did not (group B). The parameters under investigation were determined at baseline and after 4 to 8 weeks in both groups. Compared to baseline, body weight and serum albumin increased (P < 0.01, P < 0.05, respectively) at follow-up in group A, but did not change in group B. Serum creatinine concentration did not change in both groups; urea concentration (P < 0.05) and UPC ratio (P < 0.01) decreased in group B, but not in group A. Supplementation with amino acids increased body weight and serum albumin concentration in these dogs but it might have prevented a decrease in proteinuria and urea concentration.

Effets à court terme de la supplémentation alimentaire avec des acides aminés chez les chiens atteints de la maladie rénale chronique protéinurique. Cette étude rétrospective a étudié l'impact de la supplémentation avec des acides aminés sur le poids corporel, l'albumine sérique, les concentrations de créatinine et d'urée et le rapport protéines/créatinine urinaire (UPC) chez les chiens albuminuriques atteints de maladie rénale chronique (MRC). Quarante-six chiens azotémiques, appartenant à des clients, atteints de MRC albuminurique spontanée consommant déjà une diète rénale et un traitement d'énalapril ont été inclus. Environ 1 mois après le traitement (données de référence), 29 chiens ont reçu une supplémentation quotidienne aux acides aminés (groupe A) et 17 ne l'ont pas reçu (groupe B). Les paramètres à l'étude étaient déterminés aux données de référence et après 4 à 8 semaines dans les deux groupes. Comparativement aux données de référence, le poids corporel et l'albumine sérique ont augmenté (P < 0,01, P < 0,05, respectivement) au suivi dans le groupe A, mais n'ont pas changé dans le groupe B. La concentration de créatinine sérique n'a pas changé dans les deux groupes; la concentration d'urée (P < 0,05) et le rapport d'UPC (P < 0,01) ont baissé dans le groupe B, mais non dans le groupe A. La supplémentation avec des acides aminés a augmenté le poids corporel et la concentration d'albumine sérique chez ces chiens mais elle peut avoir empêché une baisse de la concentration de protéinurie et d'urée.(Traduit par Isabelle Vallières).

Exploring the hypothesis of differential care for African immigrant and native women in France with hypertensive disorders during pregnancy: a qualitative study.

OBJECTIVE: To analyse whether prenatal care trajectories among women with hypertensive disorders during pregnancy in France differ between immigrants from sub-Saharan Africa (SSA) and native French women. DESIGN: Qualitative interview study. SETTING: Three public maternity units in the Paris region. POPULATION: Women born in SSA or in France of French parents and treated for hypertension or pre-eclampsia during their pregnancy. METHODS: A sociologist conducted semi-structured in-depth interviews of 33 women during their postpartum hospitalisation and collected data from their medical files. n'vivo 10 (QSR International) was used for line-by-line coding of the transcriptions, to identify emerging themes. Strauss's concept of illness trajectories was then applied to these data. MAIN OUTCOME MEASURES: Themes derived from interviews. RESULTS: Women reported during the interviews that the blood pressure measurement procedures used by hospital staff varied between the two groups, and their medical records supported this finding. Repeated urinary dipstick testing of proteinuria before laboratory testing was more frequent for African women, as was the failure to further test proteinuria levels requiring additional action. The two groups received similar standardised care after severe complications. Other findings showed that African women were less likely to rely on healthcare services. CONCLUSIONS: These results suggest non-medically justified differential prenatal care between African and native women that may have helped delay the diagnosis of hypertension or pre-eclampsia. This study suggests hypotheses for further quantitative studies to explore the potential involvement of this differential care in the higher frequency of severe complications in this subgroup, concordantly reported in European countries hosting SSA migrants. TWEETABLE ABSTRACT: Differential prenatal care may delay diagnosis of pre-eclampsia among African compared with native French women.

Structural Predictors of Loss of Renal Function in American Indians with Type 2 Diabetes.

BACKGROUND AND OBJECTIVES: Diabetes is the leading cause of kidney failure in the United States, but early structural determinants of renal function loss in type 2 diabetes are poorly defined. We examined the association between morphometrically determined renal structural variables and loss of renal function in 111 American Indians with type 2 diabetes who volunteered for a research kidney biopsy at the end of a 6-year clinical trial designed to test the renoprotective efficacy of losartan versus placebo. Participants were subsequently followed in an observational study, in which annual measurements of GFR (iothalamate) initiated during the clinical trial were continued. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Renal function loss was defined as ≥40% loss of GFR from the research examination performed at the time of kidney biopsy. Associations with renal function loss were evaluated by Cox proportional hazards regression. Hazard ratios (HRs) were reported per 1-SD increment for each morphometric variable. RESULTS: Of 111 participants (82% women; baseline mean [±SD] age, 46 years old [±10]; diabetes duration, 16 years [±6]; hemoglobin A1c =9.4% [±2.2]; GFR=147 ml/min [±56]; median albumin-to-creatinine ratio, 41 mg/g [interquartile range, 13-158]), 51 (46%) developed renal function loss during a median follow-up of 6.6 years (interquartile range, 3.1-9.0). Fourteen had baseline GFR <90 ml/min, and three had baseline GFR <60 ml/min. Higher mesangial fractional volume (HR, 2.27; 95% confidence interval [95% CI], 1.58 to 3.26), percentage of global glomerular sclerosis (HR, 1.63; 95% CI, 1.21 to 2.21), nonpodocyte cell number per glomerulus (HR, 1.50; 95% CI, 1.10 to 2.05), glomerular basement membrane width (HR, 1.48; 95% CI, 1.05 to 2.08), mean glomerular volume (HR, 1.42; 95% CI, 1.02 to 1.96), and podocyte foot process width (HR, 1.28; 95% CI, 1.03 to 1.60); lower glomerular filtration surface density (HR, 0.62; 95% CI, 0.41 to 0.94); and fewer endothelial fenestrations (HR, 0.68; 95% CI, 0.48 to 0.95) were each associated with GFR decline after adjustment for baseline age, sex, duration of diabetes, hemoglobin A1c, GFR, and treatment assignment during the clinical trial. CONCLUSIONS: Quantitative measures of glomerular structure predict loss of renal function in type 2 diabetes.

High mutation rate of NPHP3 in 18 Chinese infantile nephronophthisis patients.

AIM: The present study was designed to explore mutations of NPHP2 and NPHP3 and clinical features in 18 Chinese infantile nephronophthisis (NPHP) patients. METHODS: Patients were subjected to screen for mutations in both NPHP2 and NPHP3, and clinical data were collected. RESULTS: Eighteen patients from 17 families were included in this study. Eight of 17 (47.1%) patients detected were identified to have mutations in NPHP3, but none had a mutation in NPHP2. Of the patients with NPHP3 mutations, four had compound heterozygous mutations, and the other four harboured single heterozygous mutations. Ten of the NPHP3 mutations were novel. Low molecular weight proteinuria was observed in all 16 detected patients. Renal histology were available in seven children, five patients showed infantile type NPHP features, and the other two patients from the same family showed juvenile type NPHP features. Liver involvement was observed in all patients with NPHP3 mutations and congenital heart disease in two patients harbouring NPHP3 mutation of c.2369 T > C (p.L790P). CONCLUSIONS: In this group of infantile NPHP patients, mutations of NPHP3 were prevalent, whereas mutation of NPHP2 was absent. Genotype to phenotype correlations were observed in patients with NPHP3 mutations and all patients with NPHP3 mutations showed renal-hepatic phenotype.

Validation of chronic kidney disease risk categorization system in Chinese patients with kidney disease: A cohort study.

AIM: To validate the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines risk stratification system based on the combination of estimated glomerular filtration rate (eGFR) and proteinuria. METHODS: This was a cohort study. A total of 1219 study population were recruited. Estimated GFR and proteinuria measured by using 24 h urine protein excretion rate (PER) were predictors. Adverse outcomes included all-cause mortality (ACM) and end-stage renal disease (ESRD). Follow-up was done by regular visit, telephone interview and electronic medical records. RESULTS: Over a median follow-up of 4.6 years, 153 (12.6%) and 43 (3.5%) patients experienced ESRD and ACM, respectively. On multivariable analysis, the adjusted hazard ratio for ESRD and ACM (compared with patients with eGFR > 60 mL/min per 1.7 m²) was of 29.8 and 3.6 for those with eGFR of 15-29 mL/min per 1.73 m², respectively. The adjusted hazard ratio for ESRD and ACM (compared with patients with PER < 150 mg/24h) was of 15.9 and 3.9 for those with PER > 500 mg/24h. Higher KDIGO guidelines risk categories (indicating lower eGFR or higher proteinuria) were associated with a graded increase in the risk for the ESRD (P < 0.001) and ACM (P < 0.001). Reclassification of KDIGO guidelines risk categories yielded net reclassification improvements for those with ESRD or ACM event (NRIevents ) of 33.3% or 30.2%. CONCLUSION: Lower eGFR and higher proteinuria are risk factors for ESRD and ACM in Chinese patients. The KDIGO guidelines risk categorization system assigned patients who went on to have the event to more appropriate CKD risk categories.

Race, Relationship and Renal Diagnoses After Living Kidney Donation.

BACKGROUND: In response to recent studies, a better understanding of the risks of renal complications among African American and biologically related living kidney donors is needed. METHODS: We examined a database linking U.S. registry identifiers for living kidney donors (1987-2007) to billing claims from a private health insurer (2000-2007 claims) to identify renal condition diagnoses categorized by International Classification of Diseases 9th Revision coding. Cox regression with left and right censoring was used to estimate cumulative incidence of diagnoses after donation and associations (adjusted hazards ratios, aHR) with donor traits. RESULTS: Among 4650 living donors, 13.1% were African American and 76.3% were white; 76.1% were first-degree relatives of their recipient. By 7 years post-donation, after adjustment for age and sex, greater proportions of African American compared with white donors had renal condition diagnoses: chronic kidney disease (12.6% vs 5.6%; aHR, 2.32; 95% confidence interval [95% CI], 1.48-3.62), proteinuria (5.7% vs 2.6%; aHR, 2.27; 95% CI, 1.32-3.89), nephrotic syndrome (1.3% vs 0.1%; aHR, 15.7; 95% CI, 2.97-83.0), and any renal condition (14.9% vs 9.0%; aHR, 1.72; 95% CI, 1.23-2.41). Although first-degree biological relationship to the recipient was not associated with renal risk, associations of African American race persisted for these conditions and included unspecified renal failure and reported disorders of kidney dysfunction after adjustment for biological donor-recipient relationship. CONCLUSIONS: African Americans more commonly develop renal conditions after living kidney donation, independent of donor-recipient relationship. Continued research is needed to improve risk stratification for renal outcomes among African American living donors.

Renal involvement in Chinese patients with Behcet's disease: a report of 16 cases.

AIM: To investigate the clinical and pathological characteristics of renal involvement in Behcet's disease (BD). METHODS: A retrospective analysis was carried out in BD patients complicated with renal damage who were hospitalized in Peking Union Medical College Hospital from June 1998 to July 2012. RESULTS: There were 16 BD patients with renal involvement, accounted for 2.6% of all the 618 hospitalized BD patients. The presentation of renal disease was chronic glomerulonephritis in six patients (including one with nephritic syndrome), renal tubular acidosis in one patient, renal artery stenosis in eight patients and renal vein thrombosis in one patient. Renal biopsy was performed in five patients, three of whom revealed to have minor glomerular lesions, mild mesangial proliferative glomerulonephritis and chronic tubular-interstitial nephropathy, respectively. The other two patients underwent a second biopsy, the one with minor glomerular lesion in the first biopsy was transformed into grade III immunoglobulin A (IgA) nephropathy on Lee's glomerular grading system 6 years later, and the other one who had IgA nephropathy of grade II in the first biopsy was progressed to grade IV 2 years later. Among the nine patients with renal vascular involvement, two underwent surgery, and several received anticoagulant therapy. During the follow-up of 13 patients, the urine protein quantifications were reduced, and renal function remained relatively stable. CONCLUSIONS: Renal damage is relatively uncommon in BD patients. There are various clinical presentations of renal involvement in BD. Routine screening with urinalysis, serum creatinine and imaging studies should be carried out for the early diagnosis of renal involvement in BD.

Mid-life proteinuria and late-life cognitive function and dementia in elderly men: the Honolulu-Asia Aging Study.

BACKGROUND: Impaired renal function has been linked to cognitive impairment. We assessed mid-life proteinuria and late-life cognitive function in elderly Asian men. METHODS: The Honolulu Heart Program is a prospective study that began in 1965 with 8006 Japanese-American men aged 45 to 68 years. Mid-life proteinuria was detected by urine dipstick in 1971 to 1974. The Honolulu-Asia Aging Study began 20 years later, with cognitive assessment by the Cognitive Abilities Screening Instrument (CASI) in 3734 men. Standard criteria were used to classify 8-year incident dementia and subtypes. RESULTS: The age-adjusted incidence of dementia increased significantly from 13.8, to 22.8, to 39.7 per 1000 person years follow-up, among those with no, trace, and positive mid-life proteinuria (P=0.004). Using linear regression adjusting for age, education, APOEε4, stroke, hypertension, systolic blood pressure, diabetes, fasting blood glucose, physical activity, and baseline CASI, those with positive proteinuria had significantly higher annual change in CASI over 8 years follow-up (-1.24, P=0.02) (reference=no proteinuria). Multivariate Cox regression found that positive proteinuria had a significant association with incident all-cause dementia (RR=2.66; 95%CI, 1.09-6.53; P=0.03), but no significant associations with incident Alzheimer disease or vascular dementia. CONCLUSION: Mid-life proteinuria was an independent predictor for late-life incident all-cause dementia and cognitive decline over 8 years.

Kidney diseases in Roma and non-Roma children from eastern Slovakia: are Roma children more at risk?

OBJECTIVES: To compare the occurence of primary renal diseases (PRD) in Roma and non-Roma children. METHODS: Data on all outpatients (n = 921) from a tertiary pediatric nephrology centre (<19 years) in eastern Slovakia were collected. We assessed early signs and symptoms and PRD for Roma and non-Roma children. RESULTS: The proportion of Roma among patients was relatively small regarding early signs like proteinuria but large regarding PRD with gross clinically apparent symptoms (e.g. Alport syndrome, p < 0.01 and systemic lupus erythematosus, p < 0.05). CONCLUSIONS: The overall proportion of Roma children in outpatients with kidney problems is smaller than the estimated proportion of Roma in all children in Slovakia, in particular for early signs, but not for major renal diseases.

Assessment of clinical biochemical parameters in Roma minority residing in eastern Slovakia compared with the majority population.

Roma constitute the largest ethnic minority in Europe and the second largest minority in Slovakia. Their health problems originate mainly from their low socioeconomic status, certain cultural aspects and their health-threatening lifestyle as well as the psycho-social burden arising from poverty and frequent migration. Evaluation of glucose, albumin, triacylglycerol (TAG) and low density lipoprotein cholesterol (LDL-C) concentrations did not reveal any clue about the presumed deteriorated health of the Roma population. Higher proportions of subjects with elevated serum total cholesterol were found in Roma women as compared to both control groups of women (p = 0.027, p = 0.006) and in Roma men as compared to the male control group living in standard conditions. Only the low level of HDL-cholesterol gives a glimpse of their deteriorated health. Significantly lower levels of serum HDL-C were reported in Roma men and women compared to the respondents in both control groups with a p value of p < 0.001. Comparing the ratio of LDL-C/HDL-C yielded significant differences between the number of physiological values in Roma men and men from the control group 1 (p = 0.022) in favour of the control group. When comparing the number of people with physiological values of cholesterols and with worsening TAG parameters at the same time, the increased risk of Roma men compared with men from the control group 1 became evident, with a level of significance of p = 0.023. Evaluation of urine samples pointed to significantly higher concentrations of urinary protein in Roma women compared with women in the control group 1 (p = 0.012).

Proteinuria in midlife and 39-year total mortality: the Honolulu Heart Program.

BACKGROUND: Previous population-based studies have shown that proteinuria is an independent predictor of total mortality. However, no studies have examined multiple proteinuria measurements or had a follow-up period longer than two decades. METHODS: Proteinuria was measured by urine dipstick on 6,815 Japanese-American men on two occasions, 6 years apart. Participants were classified into the "no proteinuria" group if both examinations were negative, "transient proteinuria" if either was positive, and "persistent proteinuria" if both were positive and followed for total mortality over 39 years. RESULTS: Prevalence of transient and persistent proteinuria was 6.4% and 1.3%, respectively. Age-adjusted total mortality rates were 41.9, 55.0, and 71.9 per 1000 person-years follow-up for no, transient, and persistent proteinuria groups, respectively (p for trend <.0001). Multivariate Cox proportional hazards models showed increased total mortality risk in a dose-response manner: HR, 1.40; P < .001 and HR, 2.26; P < .001 for transient and persistent proteinuria groups, respectively (using no proteinuria as reference). Stratified analyses showed stronger associations between proteinuria and mortality among those with prevalent cardiovascular diseases compared with those without. CONCLUSIONS: Proteinuria was independently associated with higher total mortality risk over 39 years. This risk was stronger among high-risk populations but also remained significant in low-risk populations. Simple urine dipstick can be a good risk assessment tool in the general population.

U-shaped association between body mass index and proteinuria in a large Japanese general population sample.

BACKGROUND: There is little data on the association between body mass index (BMI) and proteinuria. METHODS: This was a cross-sectional cohort study assessing the association between BMI and proteinuria in a large Japanese population. Using a nationwide health check-up database of 212,251 Japanese aged >20 years with no pre-existing cardiovascular diseases (185,183 men, median age 66 years; 127,068 women, median age 65 years), we examined the association between BMI and proteinuria (≥ 1+ on dipstick). RESULTS: Subjects were divided into 11 subgroups by BMI grading in 1 kg/m(2) intervals from 18.5-27.5 kg/m(2). A BMI of approximately 22 ± 0.5 kg/m(2) was considered optimal for Japanese; therefore, this subgroup was set as a reference when logistic analysis was applied. Age, waist circumference, height, weight, smoking and drinking habits, use of medications such as antihypertensive, antidiabetic, or antihyperlipidemic, as well as proteinuria, estimated glomerular filtration rate (eGFR), chemistry data, and blood pressure levels were significantly different between subgroups in both genders. The odds ratio for proteinuria showed a U-shape in men and women, even after adjustment for significant covariates such as age, waist circumference, systolic blood pressure, eGFR, fasting plasma glucose, triglyceride, low-density lipoprotein, antihypertensive use, antidiabetic use, antihyperlipidemic use, and lifestyle factors (smoking and drinking). Gender differences were also prominent--a BMI <20.4 kg/m(2) was significantly associated with proteinuria in men compared to a BMI <18.4 kg/m(2) in women. On the other hand, a BMI ≥ 25.5 kg/m(2) was also significantly associated with proteinuria in men compared to a BMI ≥ 22.5 kg/m(2) in women. CONCLUSIONS: We found that BMI levels were associated with proteinuria in a U-shaped manner and showed marked gender differences. Health guidance should not only focus on higher BMI subjects, but also on thin subjects, in terms of the prevention of chronic kidney disease.