End-stage Renal Disease In African Americans Research Articles

Emerging Ethical Challenges in Living Kidney Donation

Living-donor kidney transplantation (LDKT) offers the best medical outcomes in terms of graft and patient survival for end-stage renal disease (ESRD) patients. LDKT involves a medically and psychologically suitable individual willingly agreeing to donate a kidney to a loved one or stranger. It is a unique situation in which a healthy person consents to having a medical procedure for another person’s benefit. LDKT raises numerous ethical issues, particularly with respect to voluntary consent, risks and benefits, and vulnerability. In recent years, the discovery of APOL1, a gene associated with increased risk of chronic kidney disease and ESRD in African Americans, and unique situations arising from requests to undergo living donation from persons who are not traditionally healthy or have social circumstances that may challenge influence-free, informed decision making have challenged the ethics of LDKT. In this article, we discuss the ethical issues surrounding three emerging situations in LDKT: living kidney donors with life-limiting illness, incarcerated living kidney donors, and APOL1 genotyping in the context of living donor candidate evaluation.

Genome-wide association studies suggest that APOL1-environment interactions more likely trigger kidney disease in African Americans with nondiabetic nephropathy than strong APOL1–second gene interactions

African Americans carrying two apolipoprotein L1 gene (APOL1) renal risk variants have a high risk for nephropathy. However, only a minority develops end-stage renal disease (ESRD). Hence, modifying factors likely contribute to initiation of kidney disease such as endogenous (HIV infection) or exogenous (interferon treatment) environmental modifiers. In this report, genome-wide association studies and a meta-analysis were performed to identify novel loci for nondiabetic ESRD in African Americans and to detect genetic modifiers in APOL1-associated nephropathy. Two African American cohorts were analyzed, 1749 nondiabetic ESRD cases and 1136 controls from Wake Forest and 901 lupus nephritis (LN)-ESRD cases and 520 controls with systemic lupus erythematosus but lacking nephropathy from the LN-ESRDConsortium. Association analyses adjusting for APOL1 G1/G2renal-risk variants were completed and stratified by APOL1 risk genotype status. Individual genome-wide association studies and meta-analysis results of all 2650 ESRD cases and 1656 controls did not detect significant genome-wide associations with ESRD beyond APOL1. Similarly, no single nucleotide polymorphism showed significant genome-wide evidence of an interaction with APOL1 risk variants. Thus, although variants with small individual effects cannot be ruled out and are likely to exist, our results suggest that APOL1-environment interactions may be of greater clinical importance in triggering nephropathy in African Americans than APOL1 interactions with other single nucleotide polymorphisms.

APOL1‐like gene insertion associated with increased blood pressure in the African Green Monkey

End stage renal disease affects 660,000 adults in the United States and disproportionally affects people of African descent. Studies have identified two alleles in the apolipoprotein L1 (APOL1) gene that are expressed in high frequency in African‐ American populations and may contribute to a 4–5 fold increased incidence of end stage renal disease (ESRD) in this demographic. The African Green Monkey (AGM, Chlorocebus aethiops sabaeus) is an Old World monkey species that develops spontaneous hypertension and is indigenous from the regions of Africa from which the two APOL1 alleles are known to exist in humans. We have recently reported that the AGM exhibits renal glomerular and vascular pathologies in conjunction with significant spontaneous hypertension. Furthermore, we report elsewhere that this spontaneous hypertension in the AGM is associated with significant proteinuria even when the animals are prehypertensive; suggesting that altered renal glomerular and/or tubular function in regulating protein excretion may precede the development of spontaneous hypertension in the AGM. This study hypothesized that gene sequence changes in the APOL1‐like gene region may be expressed in the AGM and are associated with increased blood pressure and altered renal function, similar to the human population. DNA was extracted from whole blood or frozen tissue in 44 adult males and the APOL1‐like gene region was sequenced. Bioinformatic analysis identified a 6 nucleotide insertion at base 329 that was positively associated with increased systolic blood pressures (p<0.05). Within the cohort, 2 animals were found to be homozygous for the sequenced insertion (mean ± SE SBP: 206.6±0.1 mmHg), 10 animals were heterozygous (SBP: 136.6±14.6 mmHg), and 32 animals did not have the insertion (SBP: 135.7± 7 mmHg). This data suggests that the insertion in the APOL1‐like gene may affect blood pressure regulation (and/or kidney function) in the AGM, providing a novel and exciting nonhuman primate model to study the progression of ESRD in a non‐human primate species that expresses variations within the APOL1 gene, which is known to correlate with early onset ESRD in African Americans. Ongoing studies are focused on increasing the AGM cohort size, adding normotensive and hypertensive females to the sequenced cohort, and collection of renal functional data on all sequenced animals to determine the effect of the APOL1‐like insertion on kidney function and blood pressure regulation in the AGM.Support or Funding InformationFunding provided by Biomedical Science Research Group, LLC.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Effect of α -Lipoic Acid on Oxidative Stress in End-Stage Renal Disease Patients Receiving Intravenous Iron.

Oxidative stress is associated with increased risk of cardiovascular disease in end-stage renal disease (ESRD) patients. Intravenous (IV) iron has been shown to increase oxidative stress. The aim of the study was to evaluate changes in oxidative stress markers following administration of IV sodium ferric gluconate (SFG) to ESRD patients with and without administration of the antioxidant, α-lipoic acid. This is an open-label, crossover study. 125 mg of IV SFG was administered during control (C) and intervention (I) visits. During the I visit, 600 mg of α-lipoic acid was given orally prior to IV SFG. Blood samples were collected at defined time periods for F2-isoprostane (FIP), lipid hydroperoxide (LHP), malondialdehyde (MDA), and iron indices. We recruited ten African-American ESRD subjects: 50% male; mean age 45 ± 9 years; mean hemoglobin 13 ± 1 g/dL; ferritin 449 ± 145 ng/mL; transferrin saturation 27 ± 4%. There were no significant differences in iron indices between the two visits after IV SFG. MDA, FIP, and LHP increased significantly for both C and I visits with a greater increase in the I group. Administration of IV SFG results in an acute rise in oxidative stress in ESRD patients. In contrast to previous studies, administration of α-lipoic acid was associated with a greater increase in oxidative stress.

Understanding the relationship between trust in health care and attitudes toward living donor transplant among African Americans with end‐stage renal disease

Transplantation is the favored therapy for patients with end-stage renal disease (ESRD). Unfortunately, demand for available organs far outpaces the supply. African Americans are disproportionately affected by the ever-widening gap between organ supply and demand. Additionally, structural, biological, and social factors contribute to feelings of unease some African Americans may feel regarding living donor transplant (LDT). The present research examines the relationship between trust in health care and attitudes toward LDT among African American ESRD patients. We hypothesized that lower trust in health care would be significantly associated with negative attitudes toward LDT, and that this relationship would be moderated by patient attitudes toward dialysis. Data were collected from August 2011 to April 2012 as part of a larger study. Measures included trust (of doctors, racial equity of treatment, and hospitals) and attitudes toward both LDT and dialysis. Bivariate analysis revealed that trust in one's doctor, hospital, and in racial equity in health care was significantly correlated with attitudes toward LDT (r = 0.265; r = 0.131; and r = 0.202, respectively). Additionally, attitudes toward dialysis moderated the relationships between Trust in Doctors/Attitudes toward LDT and Trust in Racial equity of treatment/Attitudes toward LDT. Findings suggest a strong relationship between trust in health care and attitudes toward LDT. These findings also shed light on how dialysis experiences are related to the relationship between trust in health care and attitudes toward LDT.

Relevance of the ACTN4 Gene in African-Americans with Non-Diabetic End-Stage Renal Disease

Background: African-Americans (AAs) are predisposed to non-diabetic (non-DM) end-stage renal disease (ESRD), and studies have shown a genetic component to this risk. Rare mutations in ACTN4 (α-actinin-4), an actin-binding protein expressed in podocytes, cause familial focal segmental glomerulosclerosis. Methods: We assessed the contribution of coding variants in ACTN4 to non-DM ESRD risk in AAs. Nineteen exons, 2,800 bases of the promoter and 392 bases of the 3′ untranslated region of ACTN4 were sequenced in 96 AA non-DM ESRD cases and 96 non-nephropathy controls (384 chromosomes). Sixty-seven single-nucleotide polymorphisms (SNPs) including 51 novel SNPs were identified. The SNPs comprised 33 intronic, 21 promoter, 12 exonic, and one 3′ variant. Sixty-two of the SNPs were genotyped in 296 AA non-DM ESRD cases and 358 non-nephropathy controls. Results: One SNP, rs10404257, was associated with non-DM ESRD (p < 1.0E–4, odds ratio, OR = 0.76; confidence interval, CI = 0.59–0.98; additive model). Forty-seven SNPs had minor allele frequencies <5%. These SNPs were segregated into risk and protective SNPs, and each category was collapsed into a single marker, designated by the presence or absence of any rare allele. The presence of any rare allele at a risk SNP was significantly associated with non-DM ESRD (p = 0.001, dominant model). The SNPs with the strongest evidence for association (n = 20) were genotyped in an independent set of 467 non-DM ESRD cases and 279 controls. Although rs10404257 was not associated in this replication sample, when the samples were combined, rs10404257 was modestly associated (p = 0.032, OR = 0.78, CI = 0.63–0.98; dominant model). SNPs were tested for interaction with markers in the APOL1 gene, previously associated with non-DM ESRD in AAs, and rs10404257 was modestly associated (p = 0.0261, additive model). Conclusions: This detailed evaluation of ACTN4 variation revealed limited evidence of association with non-DM ESRD in AAs.

Sickle cell trait is not independently associated with susceptibility to end-stage renal disease in African Americans

Conflicting reports exist as to whether sickle cell trait is a risk factor for the progression of nephropathy. In order to determine whether African Americans with sickle cell trait are at increased risk for kidney disease, we assessed the genetic association between sickle cell trait and end-stage renal disease (ESRD). Hemoglobin S, non-muscle myosin heavy chain 9 (MYH9), and apolipoprotein L1 (APOL1) risk variants were genotyped in 3258 unrelated African Americans: 1085 with non-diabetic ESRD, 996 with type 2 diabetes-associated ESRD, and 1177 controls. Since APOL1 is strongly associated with ESRD in African Americans, interactions between APOL1 and MYH9 risk variants and hemoglobin S were assessed using case-only and case-control centered two-way logistic regression interaction analyses. The sickle cell trait genotype frequencies were 8.7% in non-diabetic ESRD, 7.1% in type 2 diabetes-ESRD, and 7.2% in controls. There was no age-, gender-, and admixture-adjusted significance for sickle cell trait association with non-diabetic ESRD (odds ratio 1.16); type 2 diabetes-ESRD (odds ratio 1.01); or all-cause ESRD (combined non-diabetic and type 2 diabetic-ESRD patients compared to the controls; odds ratio 1.05) in dominant models. In addition, no evidence of APOL1 or MYH9 interactions with sickle cell trait was detected. Hence, sickle cell trait is not associated with diabetic or non-diabetic ESRD in a large sample of African Americans.

Comparison of Measured GFR, Serum Creatinine, Cystatin C, and Beta-Trace Protein to Predict ESRD in African Americans With Hypertensive CKD

Identification of persons with chronic kidney disease (CKD) who are at highest risk to progress to end-stage renal disease (ESRD) is necessary to reduce the burden of kidney failure. The relative utility of traditional markers of kidney function, including estimated glomerular filtration rate (eGFR) and serum creatinine level, and emerging markers of kidney function, including cystatin C and beta-trace protein (BTP) levels, to predict ESRD and mortality has yet to be established. Randomized clinical trial followed by an observational cohort study. 865 African American individuals with hypertensive CKD enrolled in a clinical trial of 2 levels of blood pressure control and 3 different antihypertensive drugs as initial therapy and subsequently followed by an observational cohort study. Quintile of measured GFR (mGFR) by iothalamate clearance, serum creatinine, serum creatinine-based eGFR, cystatin C, and BTP values. Incidence of ESRD and mortality. 246 participants reached ESRD during a median follow-up of 102 months. The incidence rate of ESRD was higher with higher quintiles of each marker. The association between higher BTP level and ESRD was stronger than those for the other markers, including mGFR. All markers remained significantly associated with ESRD after adjustment for mGFR and relevant covariates (all P < 0.05), with BTP level retaining the strongest association (HR for highest vs lowest quintile, 5.7; 95% CI, 2.2-14.9). Associations with the combined end point of ESRD or mortality (n = 390) were weaker, but remained significant for cystatin C (P = 0.05) and BTP levels (P = 0.004). The ability of these markers to predict ESRD and mortality in other racial and ethnic groups and in individuals with CKD due to other causes is unknown. Plasma BTP and cystatin C levels may be useful adjuncts to serum creatinine level and mGFR in evaluating risk of progression of kidney disease.

Differential effects of MYH9 and APOL1 risk variants on FRMD3 Association with Diabetic ESRD in African Americans.

Single nucleotide polymorphisms (SNPs) in MYH9 and APOL1 on chromosome 22 (c22) are powerfully associated with non-diabetic end-stage renal disease (ESRD) in African Americans (AAs). Many AAs diagnosed with type 2 diabetic nephropathy (T2DN) have non-diabetic kidney disease, potentially masking detection of DN genes. Therefore, genome-wide association analyses were performed using the Affymetrix SNP Array 6.0 in 966 AA with T2DN and 1,032 non-diabetic, non-nephropathy (NDNN) controls, with and without adjustment for c22 nephropathy risk variants. No associations were seen between FRMD3 SNPs and T2DN before adjusting for c22 variants. However, logistic regression analysis revealed seven FRMD3 SNPs significantly interacting with MYH9—a finding replicated in 640 additional AA T2DN cases and 683 NDNN controls. Contrasting all 1,592 T2DN cases with all 1,671 NDNN controls, FRMD3 SNPs appeared to interact with the MYH9 E1 haplotype (e.g., rs942280 interaction p-value = 9.3E−7 additive; odds ratio [OR] 0.67). FRMD3 alleles were associated with increased risk of T2DN only in subjects lacking two MYH9 E1 risk haplotypes (rs942280 OR = 1.28), not in MYH9 E1 risk allele homozygotes (rs942280 OR = 0.80; homogeneity p-value = 4.3E−4). Effects were weaker stratifying on APOL1. FRMD3 SNPS were associated with T2DN, not type 2 diabetes per se, comparing AAs with T2DN to those with diabetes lacking nephropathy. T2DN-associated FRMD3 SNPs were detectable in AAs only after accounting for MYH9, with differential effects for APOL1. These analyses reveal a role for FRMD3 in AA T2DN susceptibility and accounting for c22 nephropathy risk variants can assist in detecting DN susceptibility genes.

Polymorphisms in the nonmuscle myosin heavy chain 9 gene (MYH9) are associated with the progression of IgA nephropathy in Chinese

IgA nephropathy (IgAN) is the leading cause of end-stage renal disease (ESRD) in China considering different compositions of ESRD causes in different ethnicities. A recent genome-wide association study (GWAS) indicated that the MYH9 gene was significantly associated with non-diabetic ESRD in African-Americans and also influenced kidney function in Europeans. Thus, in the present study, we aim to clarify whether MYH9 confers a shared mechanism among different causes of ESRD and to seek possible further insight into our understanding of IgAN by applying GWAS data from ESRD to IgAN. One thousand one hundred and sixteen Chinese, including 527 patients with renal biopsy-proven IgAN and 589 healthy controls, were enrolled in the present study. Four single neucleotide polymorphisms (SNPs) (rs3752462, rs4821480, rs11089788 and rs2413396) reported to be associated with ESRD with the most significance were genotyped by TaqMan assay or a restriction fragment length polymorphism assay for a further case-control study. None of the four SNPs was associated with the susceptibility to IgAN or clinical and pathological characters at the time of renal biopsy. However, estimated glomerular filtration rate decline rate was associated with rs11089788 in the dominant model (P = 0.021). Cox regression showed that rs11089788 (hazard ratio, 3.95; 95% confidence interval, 1.23-12.63; P = 2.1 × 10(-2)) was an independent predictive factor for renal survival. Based on a large Chinese IgAN cohort, we found an association between rs11089788 and prognosis of IgAN, adding to the mounting evidence of MYH9 as an important gene in IgAN to ESRD.

Candidate genes for non-diabetic ESRD in African Americans: a genome-wide association study using pooled DNA

African Americans have increased susceptibility to non-diabetic (non-DM) forms of end-stage renal disease (ESRD) and extensive evidence supports a genetic contribution. A genome-wide association study (GWAS) using pooled DNA was performed in 1,000 African Americans to detect associated genes. DNA from 500 non-DM ESRD cases and 500 non-nephropathy controls was quantified using gel electrophoresis and spectrophotometric analysis and pools of 50 case and 50 control DNA samples were created. DNA pools were genotyped in duplicate on the Illumina HumanHap550-Duo BeadChip. Normalization methods were developed and applied to array intensity values to reduce inter-array variance. Allele frequencies were calculated from normalized channel intensities and compared between case and control pools. Three SNPs had p values of <1.0E-6: rs4462445 (ch 13), rs4821469 (ch 22) and rs8077346 (ch 17). After normalization, top scoring SNPs (n = 65) were genotyped individually in 464 of the original cases and 478 of the controls, with replication in 336 non-DM ESRD cases and 363 non-nephropathy controls. Sixteen SNPs were associated with non-DM ESRD (p < 7.7E-4, Bonferroni corrected). Twelve of these SNPs are in or near the MYH9 gene. The four non-MYH9 SNPs that were associated with non-DM ESRD in the pooled samples were not associated in the replication set. Five SNPs that were modestly associated in the pooled samples were more strongly associated in the replication and/or combined samples. This is the first GWAS for non-DM ESRD in African Americans using pooled DNA. We demonstrate strong association between non-DM ESRD in African Americans with MYH9, and have identified additional candidate loci.

Marriage and End-Stage Renal Disease: Implications for African Americans

African Americans are disproportionately represented among patients with end-stage renal disease (ESRD). ESRD is managed with a strict routine that might include regular dialysis as well as dietary, fluid intake, and other lifestyle changes. In a disease such as this, with such disruptive treatment modalities, marriage, specifically, and its ties to well-being have the potential to significantly affect adherence to medical treatment and lifestyle recommendations as well as downstream health outcomes such as disease progression and mortality. The authors used data from the Dialysis Morbidity and Mortality Study, Wave 2, of the U.S. Renal Data System Database, a prospective study of 4,000 ESRD patients selected from a random sample of 25% U.S. dialysis facilities, to investigate these research questions. They found that married African American ESRD patients had marginally better outcomes on several clinical and psychosocial measures, which they hypothesize may be attributable to the instrumental and emotional support conferred by marriage.

Pilot study of an association between a common variant in the non-muscle myosin heavy chain 9 (MYH9) gene and type 2 diabetic nephropathy in a Taiwanese population

Nowadays diabetic nephropathy (DN) is the most common cause of end-stage renal disease (ESRD). Recent studies have demonstrated that the myosin, heavy chain 9, non-muscle (MYH9) gene is associated with ESRD in African Americans. In this study, we tested the hypothesis that a common single nucleotide polymorphism rs16996677 in the MYH9 gene may contribute to the etiology of DN in type 2 diabetes (T2D) in a Taiwanese population with T2D. There were 180 T2D patients diagnosed with DN and 178 age- and sex-similar T2D without DN controls. Single locus analyses showed no significant main effects of MYH9 rs16996677 on the risk of DN in T2D. The results suggest that the rs16996677 SNP in MYH9 may not contribute to the risk of DN in T2D in Taiwanese T2D patients.

Susceptibility genes in common complex kidney disease

This paper reviews recent efforts to identify genetic variants conferring risk for chronic kidney disease. A brief overview of methods for identifying gene variants is provided, along with genetic associations and new avenues under exploration. The role of renal failure susceptibility genes, including MYH9, ELMO1, UMOD and ACTN4, has become clearer over the past 18 months. The spectrum of MYH9-associated kidney disease, including focal segmental glomerulosclerosis, global glomerulosclerosis and collapsing glomerulopathy, related entities contributing to approximately 43% of end-stage renal disease in African-Americans, has come to light. MYH9 will re-categorize focal segmental glomerulosclerosis and related disorders, and has clarified the relationship between hypertension and kidney disease. MYH9 polymorphisms account for much of the excess risk of HIV-associated nephropathy and nondiabetic kidney disease in African-Americans. Kidney disease associations with ELMO1 and UMOD have been replicated and applications of genome-wide association studies based on expression data are providing novel insights on renal protein expression. These breakthroughs will alter our approach to kidney disease surveillance and lead to new therapeutic options.

Polymorphisms in the non-muscle myosin heavy chain 9 gene (MYH9) are strongly associated with end-stage renal disease historically attributed to hypertension in African Americans

African Americans have high incidence rates of end-stage renal disease (ESRD) labeled as due to hypertension. As recent studies showed strong association with idiopathic and HIV-related focal segmental glomerulosclerosis and non-muscle myosin heavy chain 9 (MYH9) gene polymorphisms in this ethnic group, we tested for MYH9 associations in a variety of kidney diseases. Fifteen MYH9 single-nucleotide polymorphisms were evaluated in 175 African Americans with chronic glomerulonephritis-associated ESRD, 696 African Americans reportedly with hypertension-associated ESRD, and 948 control subjects without kidney disease. Significant associations were detected with 14 of the 15 polymorphisms in all 871 non-diabetic patients with ESRD. In hypertension-associated ESRD cases alone, significant associations were found with 13 MYH9 polymorphisms and the previously reported E1 haplotype. Thus, hypertension-associated ESRD in African Americans is substantially related to MYH9 gene polymorphisms and this may explain the poor response to blood pressure control in those diagnosed with hypertensive nephrosclerosis. It is possible that many African Americans classified as having hypertension-associated ESRD have occult MYH9-associated segmental or global glomerulosclerosis. Our study shows that gene-environment and/or gene-gene interactions may initiate kidney disease in genetically susceptible individuals, because African Americans homozygous for MYH9 risk alleles do not universally develop kidney disease.

Association of tibia lead and blood lead with end-stage renal disease: A pilot study of African–Americans

The association between body lead burden and kidney disease remains controversial. Fifty-five African–American end-stage renal disease (ESRD) cases and 53 age- and sex-matched African–American controls without known renal disease were recruited from Tulane University-affiliated dialysis clinics and out-patient clinics, respectively. Blood lead was measured via atomic absorption spectrophotometry and tibia lead (a measure of body lead) was measured via 109Cd-based K shell X-ray fluorescence. Median blood lead levels were significantly higher among ESRD cases (6 μg/dL) compared to their control counterparts (3 μg/dL; P<0.001). Although no participants had overt lead poisoning (blood lead ⩾25 μg/dL), seven cases but no controls had blood lead levels above 10 μg/dL ( P=0.006). The median tibia lead level was 17 micrograms of lead per gram of bone mineral (μg/g) and 13 μg/g among ESRD cases and their control counterparts, respectively ( P=0.134). Four ESRD cases (7%), but no controls, had a tibia lead level above 40 μg/g ( P=0.115) while a similar proportion of cases and controls had tibia lead between 20 and 39 μg/g (33% and 32%, respectively; P=0.726). After adjustment for potential confounders, the odds ratios of ESRD associated with a tibia lead ⩾20 μg/g and each four-fold higher tibia lead (e.g., 5–20 μg/g) were 1.55 (95% CI: 0.55, 4.41) and 1.88 (95% CI: 0.53, 6.68), respectively. These findings support the need for prospective cohort studies of body lead burden and renal disease progression.

African American ESRD patients have a high pre-dialysis prevalence of kidney stones compared to NHANES III

If nephrolithiasis (NL) promotes progression to end stage renal disease (ESRD), requiring renal replacement therapy, one might expect a higher prevalence of pre-ESRD stones among ESRD versus non-ESRD subjects. We compared the prevalence of pre-ESRD stones in an African-American (AA) hemodialysis (HD) population to the estimated stone prevalence in a nationally representative cohort of AA persons as obtained by the Third National Health and Nutrition Survey (NHANES III). Face-to-face questionnaires were administered to a sample of 300 AA HD patients undergoing dialysis therapy at the University of Chicago to determine pre-ESRD NL prevalence. All data on pre-ESRD stone prevalence was confirmed by documented medical history, radiology and laboratory findings, where available. Prevalence of pre-ESRD NL in AA HD patients was 8.3% versus 2.8% in the age, race and sex adjusted NHANES III population (P < 0.001). After adjustment for age and sex, it was estimated that the prevalence of pre-ESRD kidney stones among AA HD patients is significantly higher than the prevalence of kidney stones found in the general AA population.

Improved survival in HIV-infected African-Americans with ESRD

To determine if there has been improvement in survival of HIV-infected patients with end-stage renal failure subsequent to widespread use of highly active antiretroviral therapy. The United States Renal Data System is a national data system funded by the National Institute of Diabetes and Digestive and Kidney Disease with the Centers for Medicare and Medicaid. Using the United States Renal Data System Standard Analysis Files, we analyzed all African-American end-stage renal failure patients in the United States from 1990-2001. We compared survival rates for patients with HIV disease, sickle cell anemia, diabetes, and all other diagnoses for the time periods 1990-1994 and 1995-2001. The main outcome measure was one- and five-year survival in each cohort. One-year survival of African-American patients with end-stage renal disease and HIV increased from 46.6% during 1990-1994 to 65.1% during 1995-2001 (odds ratio 2.139). One-year survival decreased in the sickle cell group (odds ratio 0.595) and decreased slightly in the diabetic group (odds ratio 0.927) and all others (odds ratio 0.941). Five-year survival in the HIV group increased from 13.3% in 1990-1995 to 30.4% in 1995-2001 (odds ratio 2.847). There was no corresponding increase in survival for the sickle cell group (odds ratio 0.987), the diabetic group (odds ratio 1.06), or all others (odds ratio 1.137). We conclude that survival in African-American end-stage renal disease patients and HIV infection has substantially improved subsequent to introduction of highly active antiretroviral therapy. Our data support aggressive multi-drug treatment of end-stage renal failure patients with HIV infection.

A genome scan for all-cause end-stage renal disease in African Americans

In an attempt to map the genes predisposing to the common, complex aetiologies of end-stage renal disease (ESRD), we performed a genome-wide scan in 1023 individuals with chronic kidney disease (946 dialysis dependent and 77 with advanced chronic renal failure) from 483 African American families. The study sample comprised 563 ESRD-affected sibling pairs, with nephropathy attributed to diabetes mellitus, chronic glomerular disease or hypertension. Multipoint non-parametric linkage (NPL) analysis methods were employed. NPL regression provided modest evidence of linkage to 13q33.3 near D13S796 [log of the odds (LOD) = 1.72], 9q34.3 near D9S1826 (LOD = 1.22), 4p15.32 near D4S2639 (LOD = 1.11) and 1q25.1 near D1S1589 (LOD = 1.01). Adjusting for the evidence of linkage at the other loci using NPL regression analysis provided evidence for linkage to 4p15.32, 9q34.3 and 13q33.3. NPL regression interaction and ordered subset analysis (OSA) suggested that the evidence for linkage to ESRD significantly increased with higher body mass index (BMI) at 13q33.3 (LOD = 4.94 in 61% of families with the highest BMI). Additionally, OSA suggested that linkage significantly improved in the 13% of families with earliest age at ESRD onset (LOD = 3.05 at 2q32.1) and in the 16% of families with latest age at ESRD onset (LOD = 2.47 at 10q26.3). Multipoint single-locus linkage analysis provided modest evidence of linkage to all-cause ESRD in African Americans on 13q33.3, and NPL regression and OSA suggested that evidence for linkage in this region markedly increased in obese families. This region, as well as 9q34.3, 4p15.32 and 1q25.1, should receive priority in the search for loci contributing to ESRD susceptibility in African Americans.

Diabetic nephropathy in African-American patients

Diabetic nephropathy (DN) is the number one cause of end-stage renal disease (ESRD) in the United States and is highly prevalent in African Americans. Since 1997, DN has been the number one cause of ESRD in African Americans. In African Americans, almost all DN is due to type 2 diabetes mellitus (T2DM), and nephropathy may affect female more than male patients. African Americans with T2DM are at increased risk for developing and having progression of DN. Glycemic control, development of albuminuria, family history of renal disease, and control of blood pressure are important risk factors for progression of DN. In addition, cigarette smoking, presence of hepatitis C, and use of thiazolinediones has an impact on renal survival in African Americans. Large vessel complications may be less frequent in African Americans with T2DM, when compared with white persons. Yet, cardiovascular disease and other microvascular complications are very common, and both are dependent on control of blood pressure. Achieving the recommended blood pressure of less than 130/80 mm Hg is essential but requires multiple antihypertensive medications, including an inhibitor of the renin-angiotensin system.