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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., (Copyright © 2020 Elsevier Inc. All rights reserved.)

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 m 2 (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., (© 2018 Asian Pacific Society of Nephrology.)

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 m 2 . 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&#95;02&#95;07&#95;CJASNPodcast&#95;19&#95;03&#95;.mp3., (Copyright © 2019 by the American Society of Nephrology.)

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., (© 2019 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.)

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 m 2 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., (© 2018 by the American Diabetes Association.)

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.

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., (© 2018 Nordic Federation of Societies of Obstetrics and Gynecology.)

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.

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., (© 2017 Royal College of Obstetricians and Gynaecologists.)

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., (© 2015 Asian Pacific Society of Nephrology.)

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., (Copyright © 2016 by the American Society of Nephrology.)

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., (© 2015 Asian Pacific Society of Nephrology.)

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., (© 2015 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.)

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.

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.

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.

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., (Copyright © 2014 Elsevier Inc. All rights reserved.)

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).

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.

Although proteinuria is highly prevalent in obese individuals, the association between proteinuria and low body weight is equivocal. In this study we determine whether low body weight is more strongly associated with proteinuria compared with normal weight. The association between body mass index (BMI) and proteinuria was examined in a cross-sectional study of 62,582 asymptomatic individuals aged 20-70 years without known kidney diseases recruited, based on the results of medical checkups in 1999. We also examined the incidence of recurrent or nonrecurrent proteinuria in an 8-year longitudinal analysis of 12,493 individuals without proteinuria at baseline. The prevalence of proteinuria showed a J-shaped relationship with BMI. Multivariate regression analysis showed that BMI of 27.0 kg/m(2) and above or 18.9 kg/m(2) and less was significantly associated with proteinuria relative to BMI 21.0-22.9 kg/m(2), even after adjusting for relevant cardiometabolic risk factors. In the longitudinal study, similar J-shaped relationships between the incident rates of proteinuria and baseline BMI groups were observed at post-baseline checkups. Baseline BMI 27.0 kg/m(2) and above was associated with significantly greater risk for recurrent and nonrecurrent proteinuria, whereas BMI 18.9 kg/m(2) and less was only associated with nonrecurrent proteinuria. Thus, obesity and low body weight may be associated with different types of proteinuria independent of cardiometabolic risk factors.

Objective: To examine racial/ethnic differences in the prevalence of diabetic kidney disease (DKD), with and without proteinuria, in an outpatient health care organization., Research Design and Methods: We examined electronic health records for 15,683 persons of non-Hispanic white (NHW), Asian (Asian Indian, Chinese, and Filipino), Hispanic, and non-Hispanic black (NHB) race/ethnicity with type 2 diabetes and no prior history of kidney disease from 2008 to 2010. We directly standardized age- and sex-adjusted prevalence rates of proteinuric DKD (proteinuria with or without low estimated glomerular filtration rate [eGFR]) or nonproteinuric DKD (low eGFR alone). We calculated sex-specific odds ratios of DKD in racial/ethnic minorities (relative to NHWs) after adjustment for traditional DKD risk factors., Results: Racial/ethnic minorities had higher rates of proteinuric DKD than NHWs (24.8-37.9 vs. 24.8%) and lower rates of nonproteinuric DKD (6.3-9.8 vs. 11.7%). On adjusted analyses, Chinese (odds ratio 1.39 for women and 1.56 for men), Filipinos (1.57 for women and 1.85 for men), Hispanics (1.46 for women and 1.34 for men), and NHBs (1.50 for women) exhibited significantly (P < 0.01) higher odds of proteinuric DKD than NHWs. Conversely, Chinese, Hispanic, and NHB women and Hispanic men had significantly lower odds of nonproteinuric DKD than NHWs., Conclusions: We found novel racial/ethnic differences in DKD among patients with type 2 diabetes. Racial/ethnic minorities were more likely to have proteinuric DKD and less likely to have nonproteinuric DKD. Future research should examine diverse DKD-related outcomes by race/ethnicity to inform targeted prevention and treatment efforts and to explore the etiology of these differences.

Background and Objectives: FSGS histologic variants have correlated with outcomes in retrospective studies. The FSGS Clinical Trial provided a unique opportunity to study the clinical impact of histologic variants in a well defined prospective cohort with steroid-resistant primary FSGS., Design, Setting, Participants, & Measurements: Renal biopsies of 138 FSGS Clinical Trial participants aged 2-38 years enrolled from 2004 to 2008 were analyzed using the Columbia classification by core pathologists. This study assessed the distribution of histologic variants and examined their clinical and biopsy characteristics and relationships to patient outcomes., Results: The distribution of histologic variants was 68% (n=94) FSGS not otherwise specified, 12% (n=16) collapsing, 10% (n=14) tip, 7% (n=10) perihilar, and 3% (n=4) cellular. Individuals with not otherwise specified FSGS were more likely to have subnephrotic proteinuria (P=0.01); 33% of teenagers and adults had tip or collapsing variants compared with 10% of children, and subjects with these variants had greater proteinuria and hypoalbuminemia than not otherwise specified patients. Tip variant had the strongest association with white race (86%) and the lowest pathologic injury scores, baseline creatinine, and rate of progression. Collapsing variant had the strongest association with black race (63%, P=0.03) and the highest pathologic injury scores (P=0.003), baseline serum creatinine (P=0.003), and rate of progression. At 3 years, 47% of collapsing, 20% of not otherwise specified, and 7% of tip variant patients reached ESRD (P=0.005)., Conclusions: This is the first prospective study with protocol-defined immunomodulating therapies confirming poor renal survival in collapsing variant and showing better renal survival in tip variant among steroid-resistant patients.

Aim: The serum immunoglobulin A (IgA)/C3 ratio has been shown to be a good predictor of histological lesions and prognosis for patients with IgA nephropathy (IgAN) in Japanese. But its validity in the Chinese population is unclear. We sought to explore the long-term outcomes of IgAN, its clinical and histopathological predictors in Chinese patients. In particular, the role of serum IgA/C3 ratio in the course of IgAN was addressed., Methods: A total of 217 biopsy-diagnosed IgAN patients were recruited into this prospective cohort with a mean follow-up of 36 months (25-75th percentile, 27-48). Sociodemographics, serum IgA/C3 level, other clinical examinations and Lee's histological grade were measured. The patients with a decline of estimated glomerular filtration rate (eGFR) > 50% or developing end-stage renal disease (ESRD) were defined as progression., Results: A total of 21 patients was found to progress (9.7%). In multivariate analysis, renal end point of IgAN was significantly predicted by proteinuria ≥1 g/day (relative risk (RR) = 2.65, 95% confidence interval (CI) 1.01-7.68), hypertension (RR = 3.15, 95% CI 1.07-9.29), higher Lee's histological grade (RR = 4.67, 95% CI 1.43-15.25) and serum IgA/C3 ratio ≥ 3.32 (RR = 4.31, 95% CI 1.33-13.96)., Conclusion: A proportion of patients with IgAN developed end stage renal disease in a Chinese group. In addition to some traditional risk factors, we also confirmed that IgA/C3 ratio is a useful predictor of poor outcomes of IgAN in Chinese patients., (© 2012 The Authors. Nephrology © 2012 Asian Pacific Society of Nephrology.)

Renal biopsy is an important method of diagnosis and prognosis in children and adolescents with renal diseases, and there are few studies describing the histopathologic alterations in renal biopsies in these age groups. The aim of this study was to evaluate the incidence of morphologic alterations described in renal biopsies carried out in children and adolescents. Patients aged between 1 month and 18 years were observed from 1996 to 2010 and were separated into 3 age groups: 0 to 6 (group 1, n = 29), 6 to 12 (group 2, n = 31), and 13 to 18 (group 3, n = 77) years. Morphologic alterations were evaluated according to light microscopy, immunofluorescence, and electron microscopy findings. The most common glomerulopathies observed in these different age groups were as follows: group 1-podocytopathy (34.78%), hereditary proteinurias 5 (21.73%), lupus nephritis (13.04%), and Berger disease (8.69%); group 2-podocytopathy (44.44%), acute diffuse glomerulonephritis (22.22%), Berger disease (11.11%), and Alport syndrome or thin membrane disease (11.11%); and group 3-lupus nephritis (22.85%), podocytopathy (20.00%), Berger disease (15.71%), and membranous glomerulopathies (11.42%). This study allows for better knowledge of the prevalence of nephropathies in children and adolescents and shows that a well-supported early diagnosis is indispensable for a more adequate treatment of patients with renal diseases., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background and Objectives: The African American Study of Kidney Disease Trial identified risk factors for CKD progression and suggested that GFR level may modify the association between these risk factors and CKD progression or death., Design, Setting, Participants, & Measurements: Enrollment in the African American Study of Kidney Disease Trial occurred between June of 1995 and September of 2001, with median follow-up of 48.6 months. Among 1094 patients with hypertensive kidney disease in the trial, this study tested whether the association between six previously identified risk factors for CKD progression (or death) and a composite clinical outcome (progression of CKD, ESRD, or death) depends on level of GFR. Multivariate Cox regression was used to control for other baseline risk factors., Results: After controlling for baseline risk factors, only proteinuria was more closely associated with the composite clinical outcome at lower levels of GFR (P value for interaction term=0.002); increased hazards of the clinical composite outcome associated with a doubling of proteinuria ranged from 30% (95% confidence interval=21%-39%) with a GFR of 50 to 55% (95% confidence interval=40%-72%) with a GFR of 25., Conclusions: The magnitude of the association between proteinuria and CKD progression, ESRD, or death in the African American Study of Kidney Disease Trial cohort depends on the level of GFR; proteinuria is a stronger independent predictor of the composite clinical outcome at lower levels of GFR. This finding reinforces that African Americans with proteinuria and lower GFR represent a population at particularly high risk for adverse outcomes.

Background: In the present investigation we extracted data on hypertensive patients with chronic kidney disease (CKD) who were enrolled in 3 studies - 2 studies of the angiotensin receptor blocker (ARB) olmesartan medoxomil (OLM), lasting 12 weeks and 2 years, respectively, and one of the calcium channel blocker (CCB) azelnidipine (AZ) lasting 12 weeks - to assess the effects of OLM and AZ on blood pressure (BP), estimated glomerular filtration rate (eGFR) and proteinuria in hypertensive patients with CKD in the setting of daily clinical practice., Methods: The 3 studies followed open prospective cohort designs that represented daily clinical practice in Japan. Patients with CKD at baseline were selected. Change of BP, eGFR and proteinuria on OLM therapy or AZ therapy were analyzed., Results: At 12 weeks, OLM (n=1,317) and AZ (n=952) therapies exhibited similar BP-lowering effects. AZ led to a significantly (p=0.0069) greater increase of eGFR compared with OLM, while OLM tended to improve proteinuria to a greater extent than AZ. Treatment with OLM for 2 years (n=109) significantly improved proteinuria but did not alter eGFR., Conclusion: This study shows that OLM and AZ reduced BP and proteinuria without decreasing eGFR in Japanese hypertensive patients with CKD in the setting of daily clinical practice.

Background: Inherited malabsorption of cobalamin (Cbl) causes hematological and neurological abnormalities that can be fatal. Three genes have been implicated in Cbl malabsorption; yet, only about 10% of ~400-500 reported cases have been molecularly studied to date. Recessive mutations in CUBN or AMN cause Imerslund-Gräsbeck Syndrome (IGS), while recessive mutations in GIF cause Intrinsic Factor Deficiency (IFD). IGS and IFD differ in that IGS usually presents with proteinuria, which is not observed in IFD. The genetic heterogeneity and numerous differential diagnoses make clinical assessment difficult., Methods: We present a large genetic screening study of 154 families or patients with suspected hereditary Cbl malabsorption. Patients and their families have been accrued over a period spanning >12  years. Systematic genetic testing of the three genes CUBN, AMN, and GIF was accomplished using a combination of single strand conformation polymorphism and DNA and RNA sequencing. In addition, six genes that were contenders for a role in inherited Cbl malabsorption were studied in a subset of these patients., Results: Our results revealed population-specific mutations, mutational hotspots, and functionally distinct regions in the three causal genes. We identified mutations in 126/154 unrelated cases (82%). Fifty-three of 126 cases (42%) were mutated in CUBN, 45/126 (36%) were mutated in AMN, and 28/126 (22%) had mutations in GIF. We found 26 undescribed mutations in CUBN, 19 in AMN, and 7 in GIF for a total of 52 novel defects described herein. We excluded six other candidate genes as culprits and concluded that additional genes might be involved., Conclusions: Cbl malabsorption is found worldwide and genetically complex. However, our results indicate that population-specific founder mutations are quite common. Consequently, targeted genetic testing has become feasible if ethnic ancestry is considered. These results will facilitate clinical and molecular genetic testing of Cbl malabsorption. Early diagnosis improves the lifelong care required by these patients and prevents potential neurological long-term complications. This study provides the first comprehensive overview of the genetics that underlies the inherited Cbl malabsorption phenotype.

Increased acid excretion may promote renal injury. To evaluate this in African Americans with hypertensive nephrosclerosis, we studied the association between the net endogenous acid production and progression of kidney disease in 632 patients in the AASK trial. Protein and potassium intakes were estimated from 24 h urea nitrogen and potassium excretion, and used to estimate net endogenous acid production, averaged over 2 years, approximating routine intake. The link between net endogenous acid production and the I(125)iothalamate glomerular filtration rate (iGFR) and time to end-stage renal disease or doubling of serum creatinine was analyzed using mixed models and Cox proportional hazards regressions. The trend in higher net endogenous acid production was significantly associated with a faster decline in iGFR over a median of 3.2 years. After adjustment for age, body mass index, baseline iGFR, urine protein-to-creatinine ratio, and randomized treatment group, the trend in higher net endogenous acid production remained significantly associated with a faster decline in iGFR at a rate of 1.01 ml/min per 1.73 m(2) per year faster in the highest compared to the lowest quartile. However, in time-to-event analyses over a median of 7.7 years, the adjusted hazard ratio (1.10) for composite renal events per 25 mEq/day higher net endogenous acid production was not significant. Hence, our findings implicate endogenous acid production as a potential modifiable risk factor for progressive kidney disease.

The angiotensin converting enzyme inhibitors (ACEIs) are a group of pharmaceuticals that are used primarily in treatment of hypertension and congestive heart failure, in some cases as the drugs of first choice. The renin-angiotensin system is activated in response to hypotension, decreased sodium concentration in the distal tubule, decreased blood volume and in renal sympathetic nerve stimulation. This study examines the effects of angiotensin converting enzyme inhibitor (Lisinopril) on blood pressure (BP) 131 ± 2.4 and proteinuria 0.198 ± 0.005 in Kurd hypertensive patients, mean arterial blood pressure and proteinuria excretion were measured weekly along the period of 12 weeks. Lisinopril significantly reduced mean arterial blood pressure, and attenuated proteinuria level in patients subjected to this study in lisinopril 10mg dose dependent manner (p<0.05, n=24). In conclusion, lisinopril is of beneficial of renoprotection and in lowering BP.

Background: Despite improvements in survival with human immunodeficiency virus (HIV) infection, kidney disease remains an important complication. Few studies have evaluated risk factors associated with the development of end-stage renal disease (ESRD) in HIV-infected individuals. We sought to identify traditional and HIV-related risk factors for ESRD in HIV-infected individuals and compare ESRD risk by estimated glomerular filtration rate (eGFR) and proteinuria levels., Study Design: Retrospective cohort study., Setting & Participants: 22,156 HIV-infected veterans without pre-existing ESRD receiving health care in the Veterans' Affairs medical system between 1996 and 2004., Predictors: Hypertension, diabetes, cardiovascular disease, hypoalbuminemia (serum albumin <3.5 mg/dL), CD4 lymphocyte count, HIV viral load, hepatitis C virus coinfection, proteinuria, and eGFR were identified using the Veterans' Affairs electronic record system., Outcomes: ESRD was ascertained by the US Renal Data System., Results: 366 cases of ESRD occurred, corresponding to 3 cases/1,000 person-years. Hypertension (HR, 1.9; 95% CI, 1.5-2.4), diabetes (HR, 1.7; 95% CI, 1.3-2.2), and cardiovascular disease (HR, 2.2; 95% CI, 1.7-2.7) were associated independently with ESRD risk in multivariate-adjusted models, as were CD4 lymphocyte count <200 cells/μL (HR, 1.5; 95% CI, 1.2-2.0), HIV viral load ≥30,000 copies/mL (HR, 2.0; 95% CI, 1.5-2.8), hepatitis C virus coinfection (HR, 1.9; 95% CI, 1.5-2.4), and hypoalbuminemia (HR, 2.1; 95% CI, 1.8-2.5). Compared with persons without chronic kidney disease, defined as eGFR >60 mL/min/1.73 m(2) and no proteinuria, lower eGFR and higher proteinuria categories were associated jointly with exponentially higher ESRD rates, ranging from 6.6 events/1,000 person-years for persons with urine protein excretion of 30-100 mg/dL and eGFR >60 mL/min/1.73 m(2) to 193 events/1,000 person-years for persons with urine protein excretion ≥300 mg/dL and eGFR <30 mL/min/1.73 m(2)., Limitations: Results may not be generalizable to female and nonveteran populations., Conclusions: In HIV-infected persons, ESRD risk appears attributable to a combination of traditional and HIV-related risk factors for kidney disease. Combining eGFR and proteinuria for chronic kidney disease staging is most effective for stratifying the risk of ESRD., (Published by Elsevier Inc.)

Context: Studies addressing the association of metabolic syndrome and insulin resistance with the risks of incident chronic kidney disease (CKD) and the progression of renal function were either lacking or inconclusive., Objective: The aim of this study was to define the effect of metabolic syndrome and insulin resistance on the development of new CKD and the decline in renal function., Design and Setting: A prospective cohort study was conducted at a tertiary university-based hospital in Taiwan., Patients and Other Participants: We studied a total of 1456 Asians 65 or older who were followed for an average of 3.15 yr. Within the cohort, we measured insulin resistance using the homeostasis model assessment formula in 652 nondiabetic participants., Interventions: There were no interventions., Main Outcome Measures: We measured the prevalence and incidence of CKD and the annual decline of the estimated glomerular filtration rate., Results: We found that the adjusted odds ratio for prevalent CKD in association with metabolic syndrome was 1.778 (95% confidence interval, 1.188 to 2.465), the hazard ratio for rapid decline in renal function was 1.042 (0.802-1.355), and the hazard ratio for incident CKD was 1.931 (1.175-3.174). With each one-unit increment of insulin resistance, the odds ratio of prevalent CKD and proteinuria were raised 1.312-fold (1.114 to 1.545) and 1.278-fold (1.098 to 1.488), respectively. Insulin resistance was not associated with incident CKD. Increment of insulin resistance per unit was associated with 1.16-fold (1.06 to 1.26) elevation in the hazard ratios of the decline in renal function., Conclusions: Metabolic syndrome predicts the risks of prevalent and incident CKD, whereas insulin resistance is associated with prevalent CKD and rapid decline in renal function in elderly individuals.

Background: The traditional paradigm of glomerular filtration rate (GFR) progression in patients with chronic kidney disease (CKD) is a steady nearly linear decline over time. We describe individual GFR progression trajectories over 12 years of follow-up in participants in the African American Study of Kidney Disease and Hypertension (AASK)., Study Design: Longitudinal observational study., Setting & Participants: 846 AASK patients with at least 3 years of follow-up and 8 GFR estimates., Measurements: Longitudinal GFR estimates from creatinine-based equations., Predictors: Patient demographic and clinical features., Outcomes: Probability of a nonlinear trajectory and probability of a period of nonprogression calculated for each patient from a Bayesian model of individual estimated GFR (eGFR) trajectories., Results: 352 (41.6%) patients showed a > 0.9 probability of having either a nonlinear trajectory or a prolonged nonprogression period; in 559 (66.1%), the probability was > 0.5. Baseline eGFR > 40 mL/min/1.73 m2 and urine protein-creatinine ratio < 0.22 g/g were associated with a higher likelihood of a nonprogression period. 74 patients (8.7%) had both a substantial period of stable or increasing eGFR and a substantial period of rapid eGFR decrease., Limitations: Clinical trial population; absence of direct GFR measurements., Conclusions: In contrast to the traditional paradigm of steady GFR progression over time, many patients with CKD have a nonlinear GFR trajectory or a prolonged period of nonprogression. These findings highlight the possibility that stable kidney disease progression can accelerate and, conversely, provide hope that CKD need not be relentlessly progressive. These results should encourage researchers to identify time-dependent factors associated with periods of nonprogression and other desirable trajectories., (Copyright © 2012 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Imerslund-Gräsbeck syndrome (IGS) was described just over 50 years ago by Olga Imerslund and Ralph Gräsbeck and colleagues. IGS is caused by specific malabsorption of cobalamin (Cbl) due to bi-allelic mutations in either the cubilin gene (CUBN) or the human amnionless homolog (AMN). Mutations in the two genes are commonly seen in founder populations or in societies with a high degree of consanguineous marriages. One particular mutation in AMN, c.208-2A>G, causing an out-of-frame loss of exon 4 in the mRNA, is responsible for some 15% of IGS cases globally. We present evidence that this founder mutation causes a substantial percentage of cases among diverse ethnicities and that the mutation is as old as human civilization., Methods: Partial genotyping indicated a founder event but its presence in diverse peoples of Arabic, Turkish, Jewish, and Hispanic ancestry suggested that the mutation might be recurrent. We therefore studied the flanking sequence spanning 3.5 Mb to elucidate the origin of the haplotype and estimate the age of the mutation using a Bayesian inference method based on observed linkage disequilibrium., Results: The mutation's distribution, the size of the shared haplotype, and estimates of growth rate and carrier frequency indicated that the mutation was a single prehistoric event. Dating back to the ancient Middle East around 11,600 BC, the mutation predates the advent of writing, farming, and the monotheistic religions of the region., Conclusions: This mutation causes over 50% of the IGS cases among Arabic, Turkish, and Sephardic Jewish families, making it a primary target for genetic screening among diverse IGS cases originating from the Middle East. Thus, rare founder mutations may cause a substantial number of cases, even among diverse ethnicities not usually thought to be related.

Case-control studies suggest that African Americans with genetic variants in both copies of APOL1 have increased risk for hypertension-attributable ESRD and focal segmental glomerulosclerosis. Here, we tested these risk variants in the Dallas Heart Study to ascertain the prevalence of APOL1-associated renal disease in a large population-based study and to estimate the contribution of APOL1 risk variants to disparities in renal disease. We determined the genotype of 1825 African Americans and 1042 European Americans. Among participants without diabetes, we identified microalbuminuria in 2.3% of European Americans, 6.0% of African Americans with no or one APOL1 risk allele, and 16.5% of African Americans with two risk alleles. In addition, the proportions of participants with estimated GFR < 60 ml/min per 1.73 m(2) was 1.5% for nondiabetic European Americans, 1.7% for African Americans with no or one APOL1 risk allele, and 6.7% for African Americans with two risk alleles. The APOL1 genotype did not associate with any differences in rates of CKD for study participants with diabetes. Our data suggest that more than 3 million African Americans likely have the high-risk genotype and are at markedly increased risk for nondiabetic CKD. In contrast, African Americans without the risk genotype and European Americans appear to have similar risk for developing nondiabetic CKD.

Purpose: To estimate the long-term cumulative incidence and risk factors for retinal vein occlusion (RVO) in a population-based cohort study of Japanese., Methods: In 1998, a total of 1775 individuals aged 40 years or older underwent a baseline eye examination. Of those, 1369 subjects (77.1%) took part in the follow-up eye examination in 2007 and were enrolled in the present study. Each participant underwent a comprehensive examination. The diagnosis of RVO, including branch (BRVO) and central RVO (CRVO), was determined by grading color fundus photographs. Logistic regression analysis was performed to determine risk factors for RVO., Results: The 9-year cumulative incidence of RVO was 3.0% (2.7% for BRVO and 0.3% for CRVO). The age-specific cumulative incidence of RVO significantly increased with age (P for trend = 0.03). After adjusting for age and sex, higher diastolic blood pressure and chronic kidney disease (CKD) were significantly associated with RVO. In multivariate analysis, higher diastolic blood pressure (per 10 mm Hg) (odds ratio [OR], 1.51; 95% confidence interval [CI], 1.14 to 2.01) and CKD (OR, 2.23; 95% CI, 1.02 to 4.89) remained independently significant risk factors for RVO. In stratified analysis, the risk of RVO was higher in subjects with CKD than that in subjects without CKD in both the nonhypertension and the hypertension groups., Conclusions: These findings suggest that the incidence of RVO is higher in Japanese than that in other Asians and Caucasians, and that higher blood pressure and CKD are independent risk factors for RVO in the Japanese.

Recent studies suggest that correcting low serum bicarbonate levels may reduce the progression of kidney disease; however, few patients with chronic kidney disease have low serum bicarbonate. Therefore, we examined whether higher levels of serum bicarbonate within the normal range (20-30 mmol/l) were associated with better kidney outcomes in the African American Study of Kidney Disease and Hypertension (AASK) trial. At baseline and during follow-up of 1094 patients, the glomerular filtration rates (GFR) were measured by iothalamate clearances and events were adjudicated by the outcomes committee. Mean baseline serum bicarbonate, measured GFR, and proteinuria were 25.1 mmol/l, 46 ml/min per 1.73 m(2), and 326 mg/g of creatinine, respectively. Each 1 mmol/l increase in serum bicarbonate within the normal range was associated with reduced risk of death, dialysis, or GFR event and with dialysis or GFR event (hazard ratios of 0.942 and 0.932, respectively) in separate multivariable Cox regression models that included errors-in-variables calibration. Cubic spline regression showed that the lowest risk of GFR event or dialysis was found at serum bicarbonate levels near 28-30 mmol/l. Thus, our study suggests that serum bicarbonate is an independent predictor of CKD progression. Whether increasing serum bicarbonate into the high-normal range will improve kidney outcomes during interventional studies will need to be considered.

Unlabelled: Chronic vascular diseases constitute a growing global health problem., Objectives: To (a) determine marker positivity for renovascular damage in the total adult population of the Isle of Youth, Cuba; (b) describe marker association with common risk factors for renal and related chronic vascular conditions, and (c) identify best predictors of renovascular damage., Methods: Previous informed consent was obtained, the population studied was 55,646, and subjects were aged ≥20 years. Blood pressure, weight and height were measured and a questionnaire applied. Urine markers for renovascular damage (hematuria, proteinuria and microalbuminuria) were also determined., Results: Positive markers were detected in 21.3%: hematuria (12.6%), microalbuminuria (6.8%), proteinuria (0.9%), and proteinuria + hematuria (0.9%). Risk factors were highly prevalent: 15.1% were aged ≥60 years; 32.3% overweight, 13.9% obese, and 25.1% smokers. Prevalence of high blood pressure (30%), diabetes mellitus (5.4%) and cardiovascular disease (5%) was also high, while cerebrovascular disease registered 0.9%. Markers were more prevalent in older people and in those suffering from diabetes mellitus, high blood pressure, cardiovascular and cerebrovascular disease, overweight or obesity. Risk factor regression tree analysis identified hypertension as the best predictor of renovascular damage., Conclusions: Adult population-wide screening revealed hidden morbidity and permitted better risk stratification. Results serve to inform community-based multidisciplinary and intersectoral disease prevention and management., (Copyright © 2010 S. Karger AG, Basel.)

Background: Few studies have examined the association between obesity and markers of kidney injury in a chronic kidney disease population. We hypothesized that obesity is independently associated with proteinuria, a marker of chronic kidney disease progression., Study Design: Observational cross-sectional analysis., Setting & Participants: Post hoc analysis of baseline data for 652 participants in the African American Study of Kidney Disease (AASK)., Predictors: Obesity, determined using body mass index (BMI)., Measurements & Outcomes: Urine total protein-creatinine ratio and albumin-creatinine ratio measured in 24-hour urine collections., Results: AASK participants had a mean age of 60.2 ± 10.2 years and serum creatinine level of 2.3 ± 1.5 mg/dL; 61.3% were men. Mean BMI was 31.4 ± 7.0 kg/m(2). Approximately 70% of participants had a daily urine total protein excretion rate <300 mg/d. In linear regression analyses adjusted for sex, each 2-kg/m(2) increase in BMI was associated with a 6.7% (95% CI, 3.2-10.4) and 9.4% (95% CI, 4.9-14.1) increase in urine total protein-creatinine and urine albumin-creatinine ratios, respectively. In multivariable models adjusting for age, sex, systolic blood pressure, serum glucose level, uric acid level, and creatinine level, each 2-kg/m(2) increase in BMI was associated with a 3.5% (95% CI, 0.4-6.7) and 5.6% (95% CI, 1.5-9.9) increase in proteinuria and albuminuria, respectively. The interaction between older age and BMI was statistically significant, indicating that this relationship was driven by younger AASK participants., Limitations: May not generalize to other populations; cross-sectional analysis precludes statements regarding causality., Conclusions: BMI is associated independently with urine total protein and albumin excretion in African Americans with hypertensive nephrosclerosis, particularly in younger patients., (Copyright © 2010 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

The etiology and pathogenesis of preeclampsia remain unclear. Little is known about the possible impact of adiponectin gene polymorphisms on the pathogenesis of preeclampsia. In this study, we analyzed the association of two adiponectin single-nucleotide polymorphisms (SNPs) with preeclampsia. One hundred eighty-eight Han Chinese pregnant women were enrolled (81 normal-term, 20 mild preeclampsia and 87 severe cases). Serum adiponectin level, and adiponectin exon 2 SNP +45T/G (rs2241766) genotype and intron 2 SNP +276G/T genotype (rs1501299) and their allele distributions were tested with enzyme-linked immunosorbent assay and PCR-restriction-fragment length polymorphism, respectively. There were no significant differences among the three groups (P>0.05) in genotype distribution or allele frequencies of either SNP. Systolic pressure and 24-h urinary protein were lower in TT homozygotes than those in TG+GG patients at SNP +45T/G in the severe preeclamptic group (P<0.05). Furthermore, blood pressure, serum adiponectin level and 24-h urinary protein were lower in GG homozygotes than those in TG+TT patients at SNP +276G/T in the severe preeclamptic group (P<0.05). The risk of high blood pressure (≥160/110 mm Hg) and of high serum adiponectin in T-allele carriers at +276G/T in the severe preeclamptic group were 5.345 and 5.818 times higher, respectively, compared with GG patients. These data suggest that adiponectin +45T/G and +276G/T polymorphisms are associated with important clinical manifestations of preeclampsia and that polymorphism +276G/T is associated with serum adiponectin level. Taken together, these findings suggest that adiponectin gene polymorphism is involved in the pathogenesis of preeclampsia.

Background and Objectives: Proteinuria is a major determinant of chronic kidney disease. We aimed to characterize the prevalence and correlates of proteinuria in a cohort of HIV-infected and uninfected injection drug users., Design, Setting, Participants, & Measurements: A cross-sectional analysis was performed among 902 injection drug users (273 HIV-infected) in the AIDS Linked to the Intravenous Experience cohort. The primary outcome was proteinuria defined as having a urine protein/creatinine concentration ratio >200 mg/g. Poisson regression with robust variance was used to determine prevalence ratios., Results: Overall, 24.8% of participants had proteinuria; the prevalence was 2.9 times higher among HIV-infected participants (45%) compared with HIV-uninfected participants (16%). In addition, age, health insurance, employment status, hepatitis B and C serostatus, diabetes, and high BP were associated with proteinuria. Neither antiretroviral therapy nor features of illicit drug use history were associated with proteinuria. In multivariate analysis, HIV infection, unemployment, increased age, diabetes, hepatitis C infection, and high BP were significantly associated with a higher prevalence of proteinuria., Conclusions: In an aging, predominantly African-American cohort of injection drug users, we found a striking burden of proteinuria that was strongly associated with HIV status. In addition to being a pathway to ESRD, proteinuria is a potent risk factor for cardiovascular morbidity and mortality. Evaluation of aggressive screening and disease-modification strategies in this high-risk population is warranted.

Aim: To investigate clinicopathological and prognostic differences between adults and children with acute post-streptococcal glomerulonephritis (APSGN)., Methods: A retrospective case series of 112 patients with APSGN was undertaken. Patients were divided into two groups according to age: adults aged more than 17 years and children aged less than 15 years., Results: The incidence of APSGN, especially in adults, has decreased in the past three decades. Children have had a higher incidence of macroscopic haematuria than adults (58.3% vs 32.7%, P < 0.05). Laboratory test showed that red blood cell count of urine sediment in children was more significant. On light microscopy, adults had more global glomerulosclerosis, tubular basement membrane thickening, tubular atrophy and interstitial fibrosis, while children had more glomerular infiltrating neutrophils and monocytes and cellular casts. Immunofluorescence microscopy showed that classical staining was seen more in children. The short-term prognoses were good in both children and adults. But the recovery rate of proteinuria in children was faster than that in adults., Conclusion: Adults with APSGN had similar clinical features as children except that children had more significant haematuria. On pathology, adults had more outstanding chronic changes by light microscopy and more untypical staining by immunofluorescence., (© 2010 The Authors. Nephrology © 2010 Asian Pacific Society of Nephrology.)

Renal involvement in patients with sickle cell disease (SCD) is associated with significant morbidity and mortality. Proteinuria is common in patients with SCD and is a risk factor for future development of renal failure. We sought to identify risk factors, if any, associated with proteinuria in adult Saudi patients with SCD. We studied 67 patients with SCD followed-up at the King Khalid University Hospital, Riyadh, Saudi Arabia. All patients underwent 24-hour urine collection to measure creatinine clearance and to quantify proteinuria. In addition, blood was examined for evaluation of hematological and biochemical parameters. Clinical information was gathered from review of the patients' charts. A urine protein level of more than 0.150 grams/24 hours was considered abnormal. Urine protein was correlated with various clinical and laboratory parameters. Thirty-one males and 36 females were evaluated. The mean age of the cohort was 23.8 (± 7.2) years. Twenty-seven patients (40.3%) had proteinuria of more than 0.150 grams/24 hours. The study group had a mean hemoglobin level of 8.5 (± 2.8) g/dL and mean fetal hemoglobin (HbF) level of 14.4% (± 7.3%). Majority of the patients (61) had hemoglobin SS genotype and six patients had S-ß⁰ thalassemia. None of the parameters evaluated correlated with proteinuria although there was a borderline association with older age and higher systolic blood pressure (P = 0.073 and 0.061 respectively). Hydroxyurea use for more than a year was not beneficial. In conclusion, our study suggests that proteinuria in adult Saudi patients is not associated with any clear identifiable risk factors.

Autosomal dominant polycystic kidney disease (ADPKD) is not well described in black Africans while some data suggesting the disease is exceptional in this race. A retrospective study of patients with ADPKD followed in nephrology department of a teaching hospital in Dakar (January 1, 1995 to December 31, 2005) was therefore undertaken. Prevalence of ADPKD was one in 250. Mean age was 47 + or - 5 years with a predominance of male (57%). High blood pressure (HBP) was present in 68% of patients. Other renal manifestations were flank pain, hematuria and proteinuria. Majority of patients had impaired renal function at time of diagnosis. Extra-renal cysts were essentially found in liver (45.5%), pancreas and seminal vesicles. Main complications: ESRD (51%) occurred within a 6 year mean period, urinary tract infection (13%) and cerebral haemorrhage (2%). HBP control, in general needed 2 or more antihypertensive drugs. Fourteen patients died, ten patients had been on haemodialysis and four others died from uremic complications. In conclusion, ADPKD in black African adults is not rare and probably underdiagnosed. Early HBP and ESRD are likely more frequent than in other races. Earlier ultrasound detection and strategies to preserve renal function should be offered to at-risk individuals to improve outcomes.

Background and Objectives: In our center, systemic lupus erythematosus nephritis is routinely treated with an oral cyclophosphamide (POCY) regimen. POCY is easy to administer and less expensive than intravenous cyclophosphamide (IVCY) as it is currently used in the United States; however, the use of POCY has declined in favor of IVCY. Our experience with POCY suggests that it is well tolerated and consistently associated with good long-term outcomes. Here we report this experience to build a case for maintaining POCY as a therapeutic option in lupus nephritis., Design, Setting, Participants, & Measurements: This is a single-center, retrospective analysis of the outcome of 46 patients who had systemic lupus erythematosus with nephritis and were treated with POCY between 1995 and 2006. POCY was given for 2 to 4 mo at a dosage of 1.0 to 1.5 mg/kg ideal body weight. After completing POCY, the patients received either azathioprine or mycophenolate mofetil., Results: Median follow-up was 23.5 mo, and median duration of POCY was 4 mo (range 1 to 16 mo). Durable complete or partial remission of proteinuria was achieved in 32 (70%) patients, whereas 5 (11%) progressed to ESRD. Outcomes were comparable in black and white individuals. Adverse effects occurred in fewer than 10% of the cohort, and only four patients discontinued POCY., Conclusions: These results suggest that sequential therapy of POCY followed by azathioprine or mycophenolate mofetil is comparable to IVCY regimens but that efficacy may not be affected by race.

Background: Although obesity is recognized to be a risk factor for chronic kidney disease (CKD), few studies have reported the association between obesity and CKD in the young population. We investigated the relationship between obesity and renal function including proteinuria in young Japanese., Methods: This cross-sectional study consisted of 16,031 men and 5,746 women aged from 20 to 39 years who received health examinations. The subjects were stratified into four age groups (20-24, 25-29, 30-34, and 35-39 years) or into four groups based on the number of risk factors (hypertension, hyperglycemia, dyslipidemia, and hyperuricemia). The relationship between obesity and risk factors and the relationship between obesity and estimated glomerular filtration rate (eGFR) were analyzed., Results: There were no significant differences in eGFR between obese and nonobese groups, except in the male 35-39 years age group. Body mass index (BMI) in both men and women increased with increase in number of risk factors (P < 0.001). Multivariate analysis revealed that hypertension, hyperglycemia, dyslipidemia, and hyperuricemia were independently associated with obesity. Obesity and the risk factors were independently associated with proteinuria., Conclusion: The present study indicated that obesity was an independent risk factor for proteinuria in healthy subjects younger than 40 years of age. The other risk factors were independently associated with obesity. These findings suggest that obesity causes proteinuria concomitantly with other risk factors such as hypertension, diabetes, and dyslipidemia in young adults.

Objective: To assess whether hydroxychloroquine can delay renal damage development in lupus nephritis patients., Methods: Lupus nephritis patients (n = 256) from the LUpus in MInorities, NAture versus nurture study (n = 635), a multiethnic cohort of African Americans, Hispanics, and Caucasians, age > or =16 years with disease duration < or =5 years at baseline (T0) were studied. Renal damage was defined using the Systemic Lupus International Collaborating Clinics Damage Index (> or =1 of the following lasting at least 6 months: estimated/measured glomerular filtration rate <50%, 24-hour proteinuria > or =3.5 gm and/or end-stage renal disease, regardless of dialysis or transplantation). Patients with renal damage before T0 were excluded (n = 53). The association between hydroxychloroquine use and renal damage (as defined, or omitting proteinuria) was estimated using Cox proportional regression analyses adjusting for potential confounders. Kaplan-Meier survival curves based on hydroxychloroquine intake or the World Health Organization (WHO) class glomerulonephritis were also derived., Results: Sixty-three (31.0%) of the 203 patients included developed renal damage over a mean +/- SD disease duration of 5.2 +/- 3.5 years. The most frequent renal damage domain item was proteinuria. Patients who received hydroxychloroquine (79.3%) exhibited a lower frequency of WHO class IV glomerulonephritis, had lower disease activity, and received lower glucocorticoid doses than those who did not take hydroxychloroquine. After adjusting for confounders, hydroxychloroquine was protective of renal damage occurrence in full (hazard ratio [HR] 0.12, 95% confidence interval [95% CI] 0.02-0.97, P = 0.0464) and reduced (HR 0.29, 95% CI 0.13-0.68, P = 0.0043) models. Omitting proteinuria provided comparable results. The cumulative probability of renal damage occurrence was higher in those who did not take hydroxychloroquine and those classified as WHO class IV glomerulonephritis (P < 0.0001)., Conclusion: After adjusting for possible confounding factors, the protective effect of hydroxychloroquine in retarding renal damage occurrence in systemic lupus erythematosus is still evident.

Background and Objectives: Proteinuria is associated with chronic kidney disease (CKD), and heavy proteinuria predicts a rapid decline in kidney function. However, the epidemiologic distribution of this important biomarker study is not well described in the pediatric CKD population., Design, Setting, Participants & Measurements: This cross-sectional study of North American children with CKD examined the association of proteinuria among the baseline clinical variables in the cohort. Urinary protein-to-creatinine ratios (Up/c) were used to measure level of proteinuria., Results: Of the 419 subjects studied, the median GFR as measured by iohexol disappearance (iGFR) was 42 ml/min per 1.73 m(2), median duration of CKD was six yr, and glomerular diseases accounted for 22% of the CKD diagnoses. Twenty-four percent of children had normal range (Up/c <0.2), 62% had significant, and 14% had nephrotic-range proteinuria (Up/c >2.0). A decrease in iGFR was associated with an increase in Up/c. At any level of GFR, a higher Up/c was associated with a glomerular cause of CKD and non-Caucasian race. Among subjects with a glomerular cause of CKD, Up/c was lower in subjects reporting utilization of renin-angiotensin system (RAS) antagonists (median Up/c = 0.93) compared with those who did not (median Up/c = 3.78)., Conclusions: Proteinuria is associated with level of iGFR, cause of CKD, and race. The longitudinal study design of Chronic Kidney Disease in Children (CKiD) cohort study and the large number of subjects being studied has created an opportunity to better define the association between proteinuria and CKD progression.

We analyzed the association between single nucleotide polymorphisms in IL-12 and IL-18 genes in disease susceptibility and severity of SLE in Thais. A weak association was observed between A allele of the IL-12 gene at the 3' untranslated region in SLE patients with proteinuria (OR = 1.89, 95% CI = 1.05-3.40, P = 0.02, Pc = 0.06). In addition, we found a significant association between C allele of IL-18 (-137) with arthritis (OR = 6.88, 95% CI = 1.54-42.93, P = 0.003, Pc = 0.009). The presence of one C allele (C/C+C/G) was associated with significant OR of 8.72 (95% CI = 1.83-56.71, P = 0.001, Pc = 0.003). Interestingly, we found the combined effect between the G/C genotype of IL-18 (-137) and the A/A genotype of IFNG (+874) gene causing susceptibility of arthritis in SLE patients (OR = 13.22, 95% CI = 1.56-291.66, P = 0.004).