Risk prediction to inform surveillance of chronic kidney disease in the US Healthcare Safety Net: a cohort study.

BackgroundThe capacity of electronic health record (EHR) data to guide targeted surveillance in chronic kidney disease (CKD) is unclear. We sought to leverage EHR data for predicting risk of progressing from CKD to end-stage renal disease (ESRD) to help inform surveillance of CKD among vulnerable patients from the healthcare safety-net.MethodsWe conducted a retrospective cohort study of adults (n = 28,779) with CKD who received care within 2 regional safety-net health systems during 1996-2009 in the Western United States. The primary outcomes were progression to ESRD and death as ascertained by linkage with United States Renal Data System and Social Security Administration Death Master files, respectively, through September 29, 2011. We evaluated the performance of 3 models which included demographic, comorbidity and laboratory data to predict progression of CKD to ESRD in conditions commonly targeted for disease management (hypertension, diabetes, chronic viral diseases and severe CKD) using traditional discriminatory criteria (AUC) and recent criteria intended to guide population health management strategies.ResultsOverall, 1730 persons progressed to end-stage renal disease and 7628 died during median follow-up of 6.6 years. Performance of risk models incorporating common EHR variables was highest in hypertension, intermediate in diabetes and chronic viral diseases, and lowest in severe CKD. Surveillance of persons who were in the highest quintile of ESRD risk yielded 83-94 %, 74-95 %, and 75-82 % of cases who progressed to ESRD among patients with hypertension, diabetes and chronic viral diseases, respectively. Similar surveillance yielded 42-71 % of ESRD cases among those with severe CKD. Discrimination in all conditions was universally high (AUC ≥0.80) when evaluated using traditional criteria.ConclusionsRecently proposed discriminatory criteria account for varying risk distribution and when applied to common clinical conditions may help to inform surveillance of CKD in diverse populations

Race/ethnicity and disease severity in IgA nephropathy

BACKGROUND: Relatively few U.S.-based studies in chronic kidney disease have focused on Asian/Pacific Islanders. Clinical reports suggest that Asian/Pacific Islanders are more likely to be affected by IgA nephropathy (IgAN), and that the severity of disease is increased in these populations. METHODS: To explore whether these observations are borne out in a multi-ethnic, tertiary care renal pathology practice, we examined clinical and pathologic data on 298 patients with primary glomerular lesions (IgAN, focal segmental glomerulosclerosis, membranous nephropathy and minimal change disease) at the University of California San Francisco Medical Center from November 1994 through May 2001. Pathologic assessment of native kidney biopsies with IgAN was conducted using Haas' classification system. RESULTS: Among individuals with IgAN (N = 149), 89 (60%) were male, 57 (38%) white, 53 (36%) Asian/Pacific Islander, 29 (19%) Hispanic, 4 (3%) African American and 6 (4%) were of other or unknown ethnicity. The mean age was 37 ± 14 years and median serum creatinine 1.7 mg/dL. Sixty-six patients (44%) exhibited nephrotic range proteinuria at the time of kidney biopsy. The distributions of age, gender, mean serum creatinine, and presence or absence of nephrotic proteinuria and/or hypertension at the time of kidney biopsy were not significantly different among white, Hispanic, and Asian/Pacific Islander groups. Of the 124 native kidney biopsies with IgAN, 10 (8%) cases were classified into Haas subclass I, 12 (10%) subclass II, 23 (18%) subclass III, 30 (25%) subclass IV, and 49 (40%) subclass V. The distribution of Haas subclass did not differ significantly by race/ethnicity. In comparison, among the random sample of patients with non-IgAN glomerular lesions (N = 149), 77 (52%) patients were male, 51 (34%) white, 42 (28%) Asian/Pacific Islander, 25 (17%) Hispanic, and 30 (20%) were African American. CONCLUSIONS: With the caveats of referral and biopsy biases, the race/ethnicity distribution of IgAN differs significantly from that of other major glomerulonephridities. However, among individuals undergoing native kidney biopsy, we see no evidence of a race/ethnicity association with severity of disease in IgAN by clinical and IgAN-specific histopathologic criteria. Further studies are needed to identify populations at higher risk for progressive disease in IgAN

The effect of frequent hemodialysis on nutrition and body composition: frequent Hemodialysis Network Trial.

We investigated the effects of frequency of hemodialysis on nutritional status by analyzing the data in the Frequent Hemodialysis Network Trial. We compared changes in albumin, body weight, and composition among 245 patients randomized to six or three times per week in-center hemodialysis (Daily Trial) and 87 patients randomized to six times per week nocturnal or three times per week conventional hemodialysis, performed largely at home (Nocturnal Trial). In the Daily Trial, there were no significant differences between groups in changes in serum albumin or the equilibrated protein catabolic rate by 12 months. There was a significant relative decrease in predialysis body weight of 1.5 ± 0.2 kg in the six times per week group at 1 month, but this significantly rebounded by 1.3 ± 0.5 kg over the remaining 11 months. Extracellular water (ECW) decreased in the six times per week compared with the three per week hemodialysis group. There were no significant between-group differences in phase angle, intracellular water, or body cell mass (BCM). In the Nocturnal Trial, there were no significant between-group differences in any study parameter. Any gain in 'dry' body weight corresponded to increased adiposity rather than muscle mass but was not statistically significant. Thus, frequent in-center hemodialysis reduced ECW but did not increase serum albumin or BCM while frequent nocturnal hemodialysis yielded no net effect on parameters of nutritional status or body composition

The conundrum of increased burden of end-stage renal disease in Asians

The conundrum of increased burden of end-stage renal disease in Asians.BackgroundFew cohort studies have examined the risk of end-stage renal disease (ESRD) among Asians compared with whites and blacks.MethodsTo compare the incidence of ESRD in Asians, whites, and blacks in Northern California, we examined sociodemographic and clinical data on 299,168 adults who underwent a screening health checkup at Kaiser Permanente between 1964 and 1985. Incident cases of ESRD were ascertained by matching patient identifiers with the nationally comprehensive United States Renal Data System ESRD registry.ResultsOverall, 1346 cases of ESRD occurred during 7,837,310 person-years of follow-up. The age-adjusted rate of ESRD (per 100,000 person-years) was 14.0 [95% confidence interval (CI) 10.5-18.5] among Asians, 7.9 (95% CI 6.5-9.5) among whites, and 43.4 (95% CI 36.6-51.4)] among blacks. Controlling for age, gender, educational attainment, diabetes, prior myocardial infarction, serum creatinine, systolic and diastolic blood pressure, proteinuria, hematuria, cigarette smoking, serum total cholesterol, and body mass index increased the risk of ESRD in Asians relative to whites from 1.69 to 2.08 (95% CI 1.61-2.67). By contrast, adjustment for the same covariates decreased the risk of ESRD in blacks relative to whites from 5.30 to 3.28 (95% CI 2.91-3.69).ConclusionFactors contributing to the excess ESRD risk in Asians relative to whites extend beyond usually considered sociodemographic and comorbidity disparities. Strategies aimed at examining novel risk factors for kidney disease and efforts to increase awareness of kidney disease among Asians may reduce ESRD incidence in this high-risk group

INSIG2 gene rs7566605 polymorphism is associated with severe obesity in Japanese

The single nucleotide polymorphism (SNP) rs7566605 in the upstream region of the insulin-induced gene 2 (INSIG2) is associated with the obesity phenotype in many Caucasian populations. In Japanese, this association with the obesity phenotype is not clear. To investigate the relationship between rs7566605 and obesity in Japanese, we genotyped rs7566605 from severely obese subjects [n = 908, body mass index (BMI) ≥ 30 kg/m2] and normal-weight control subjects (n = 1495, BMI < 25 kg/m2). A case–control association analysis revealed that rs7566605 was significantly associated with obesity in Japanese. The P value in the minor allele recessive mode was 0.00020, and the odds ratio (OR) adjusted for gender and age was 1.61 [95% confidential interval (CI) = 1.24–2.09]. Obesity-associated phenotypes, which included the level of BMI, plasma glucose, hemoglobin A1c, total cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol, and blood pressure, were not associated with the rs7566605 genotype. Thus, rs7566605 in the upstream region of the INSIG2 gene was found to be associated with obesity, i.e., severe obesity, in Japanese

A Comprehensive Sequence and Disease Correlation Analyses for the C-Terminal Region of CagA Protein of Helicobacter pylori

Chronic Helicobacter pylori infection is known to be associated with the development of peptic ulcer, gastric cancer and gastric lymphoma. Currently, the bacterial factors of H. pylori are reported to be important in the development of gastroduodenal diseases. CagA protein, encoded by the cagA, is the best studied virulence factor of H. pylori. The pathogenic CagA protein contains a highly polymorphic Glu-Pro-Ile-Tyr-Ala (EPIYA) repeat region in the C-terminal. This repeat region is reported to be involved in the pathogenesis of gastroduodenal diseases. The segments containing EPIYA motifs have been designated as segments A, B, C, and D; however the classification and disease relation are still unclear. This study used 560 unique CagA sequences containing 1,796 EPIYA motifs collected from public resources, including 274 Western and 286 East Asian strains with clinical data obtained from 433 entries. Fifteen types of EPIYA or EPIYA-like sequences are defined. In addition to four previously reported major segment types, several minor segment types (e.g., segment B′, B′′) and more than 30 sequence types (e.g., ABC, ABD) were defined using our classification method. We confirm that the sequences from Western and East Asian strains contain segment C and D, respectively. We also confirm that strains with two EPIYA segment C have a greater chance of developing gastric cancer than those with one segment C. Our results shed light on the relationships between the types of CagAs, the country of origin of each sequence type, and the frequency of gastric disease

Predictors of End-stage Renal Disease in the Urban Poor

Thesis (Master's)--University of Washington, 2012Background: Despite the disproportionate burden of end-stage renal disease (ESRD) among traditionally underserved populations, the influence of social and clinical factors on incident ESRD in the urban poor is poorly understood. We sought to examine the prognostic values of social and clinical factors on risk of progression of established chronic kidney disease (CKD) to ESRD in the urban poor. Methods: We studied 15,353 individuals with moderate to advanced CKD who had received ambulatory care within a large public health system in northern California during 1996-2005. The primary outcome was progression to ESRD through December 31, 2005 as ascertained by the US Renal Data System registry. Results: Overall, 559 cases of ESRD occurred during 55,538 person-years of follow-up. In this public healthcare setting, among traditional predictors of ESRD, younger age, male sex, non-white race-ethnicity, Medicaid or Medicare health insurance coverage, diabetes, lower kidney function, higher proteinuria, lower hemoglobin level and lower serum albumin concentration were significantly associated with a higher adjusted risk of progression to ESRD (PConclusions: In the urban healthcare safety net, we found no evidence that social factors including homelessness, substance abuse, non-English language status, or chronic viral diseases were associated with a higher risk of ESRD. Our results highlight the importance of addressing traditional risk factors for progressive CKD to reduce the disproportionate burden of ESRD among disadvantaged populations