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Advances in kidney genomics in the past 20 years has opened the door for more precise diagnosis of kidney disease and identification of new and specific therapeutic agents. Despite these advances, an imbalance exists between low-resource and affluent regions of the world. Individuals of European ancestry from the United States, United Kingdom, and Iceland account for 16% of the world's population, but represent more than 80% of all genome-wide association studies. South Asia, Southeast Asia, Latin America, and Africa together account for 57% of the world population but less than 5% of genome-wide association studies. Implications of this difference include limitations in new variant discovery, inaccurate interpretation of the effect of genetic variants in non-European populations, and unequal access to genomic testing and novel therapies in resource-poor regions. It also further introduces ethical, legal, and social pitfalls, and ultimately may propagate global health inequities. Ongoing efforts to reduce the imbalance in low-resource regions include funding and capacity building, population-based genome sequencing, population-based genome registries, and genetic research networks. More funding, training, and capacity building for infrastructure and expertise is needed in resource-poor regions. Focusing on this will ensure multiple-fold returns on investments in genomic research and technology., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Kidney involvement is common in coronavirus disease-2019 (COVID-19), and our understanding of the effects of COVID-19 on short- and long-term kidney outcomes has evolved over the course of the pandemic. Initial key questions centered on the spectrum and degree of acute kidney injury (AKI) in patients hospitalized with severe COVID-19. Investigators worldwide have explored the association between COVID-19-associated AKI and short-term outcomes, including inpatient mortality and disease severity. Even as treatments evolved, vaccinations were developed, and newer viral variants arose, subsets of patients were identified as at continued high risk for major adverse kidney outcomes. In this review, we explore key topics of continued relevance including the following: (1) a comparison of COVID-19-associated AKI with AKI developing in other clinical settings; (2) the ongoing controversy over kidney tropism in the setting of COVID-19 and the potential for competitive binding of the severe acute respiratory syndrome coronavirus 2 virus with angiotensin converting enzyme-2 to prevent viral cell entry; and (3) the identification of high-risk patients for adverse outcomes to inform long-term outpatient management. Patients at particularly high risk for adverse kidney outcomes include those with APOL1 high-risk genotype status. Biomarkers of injury, inflammation, tubular health, and repair measured in both the blood and urine may hold prognostic significance., (Copyright © 2022. Published by Elsevier Inc.)

Rationale & Objectives: Preeclampsia, which disproportionately affects Black women, is a leading cause of preterm delivery and risk for future hypertension and chronic kidney disease (CKD). Apolipoprotein L1 (APOL1) kidney risk alleles, common among Black individuals, contribute substantially to CKD disparities. Given the strong link between preeclampsia and CKD, we investigated whether maternal and fetal APOL1 risk alleles can jointly influence preeclampsia risk, and explored potential modifiers of the association between APOL1 and preeclampsia., Study Design: Nested case-control study., Setting & Participants: 426 Black mother-infant pairs (275 African Americans and 151 Haitians) from the Boston Birth Cohort., Exposure: Maternal and fetal APOL1 risk alleles., Outcomes: Preeclampsia., Analytical Approach: Logistic regression models with adjustment for demographic characteristics were applied to analyze associations between fetal and maternal APOL1 risk alleles and risk of preeclampsia and to investigate the effects of modification by maternal country of origin., Results: Fetal APOL1 risk alleles tended to be associated with an increased risk of preeclampsia, which was not statistically significant in the total genotyped population. However, this association was modified by maternal country of origin (P<0.05 for interaction tests): fetal APOL1 risk alleles were significantly associated with an increased risk of preeclampsia among African Americans under recessive (odds ratio [OR], 3.6 [95% CI, 1.3-9.7]; P=0.01) and additive (OR, 1.7 [95% CI, 1.1-2.6]; P=0.01) genetic models but not in Haitian Americans. Also, maternal-fetal genotype discordance at the APOL1 locus was associated with a 2.6-fold higher risk of preeclampsia (P<0.001) in African Americans., Limitations: Limited sample size in stratified analyses; self-reported maternal country of origin; pre-pregnancy estimated glomerular filtration rate (eGFR) and proteinuria data in mothers were not collected; unmeasured confounding social and/or environmental factors; no replication study., Conclusions: This study supports the hypothesis that fetal APOL1 kidney risk alleles are associated with increased risk for preeclampsia in a recessive mode of inheritance in African Americans and suggests that maternal-fetal genotype discordance is also associated with this risk. These conclusions underscore the need to better understand maternal-fetal interaction and their genetic and environmental factors as contributors to ethnic disparities in preeclampsia., (Copyright © 2020 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Rationale & Objective: Recent studies in the human immunodeficiency virus (HIV)-infected population have suggested that there are genetic predispositions to the development of chronic kidney disease (CKD) in this context. We investigated the association of genetic polymorphisms of the genes encoding apolipoprotein L1 (APOL1), transforming growth factor β1 (TGF-β1; a profibrotic cytokine), and heme oxygenase 1 (HMOX1) with prevalent CKD among adults with and without HIV infection., Study Design: Case-control study., Setting & Participants: West African adults including 217 HIV-infected patients with CKD (HIV + /CKD + group), 595 HIV-infected patients without CKD (HIV + /CKD - group), 269 with CKD and no HIV infection (HIV - /CKD + group), and 114 with neither CKD nor HIV (HIV - /CKD - group)., Exposure: The genetic polymorphisms with reference single-nucleotide polymorphism (rs) identification numbers rs1800469 (TGF-β1), rs1800470 (TGF-β1), rs121918282 (TGF-β1); rs60910145 (APOL1 G1 risk allele), rs73885319 (APOL1 G1 risk allele), rs71785313 (APOL1 G2 risk allele), and rs743811 (HMOX1); HIV., Outcome: CKD., Analytical Approach: Single-nucleotide polymorphism (SNP) genotyping of rs1800469 (TGF-β1), rs1800470 (TGF-β1), rs121918282 (TGF-β1); rs60910145 (APOL1), rs73885319 (APOL1), rs71785313 (APOL1), and rs743811 (HMOX1) was performed. Hardy-Weinberg equilibrium was evaluated for all SNPs, and minor allele frequencies were reported. A case-control analysis was performed, and multivariable logistic regression was used to control for potential confounders., Results: Minor allele frequencies for TGF-β1 (rs1800469, rs1800470, and rs1800471), APOL1 (rs60910145, rs73885319, and rs71785313), and HMOX1 (rs743811) were 0.25, 0.46, 0.46, 0.44, 0.45, 0.17, and 0.14, respectively. Among HIV-positive individuals, only TGF-β1 rs1800470 (GG vs AA), APOL1 (in the recessive model), and hypertension were associated with prevalent CKD (adjusted ORs of 0.44 [95% CI, 0.20-0.97], 2.54 [95% CI, 1.44-4.51], and 2.17 [95% CI, 1.35-3.48], respectively). No SNP polymorphisms were associated with prevalent CKD among HIV-negative individuals., Limitations: The lack of histopathology data for proper categorization of the type of HIV-related nephropathy., Conclusions: APOL1 polymorphisms were highly prevalent in this population and among adult patients infected with HIV and were associated with increased CKD risk. The TGF-β1 (rs1800470) polymorphism was associated with reduced risk, and HMOX1 polymorphisms were unassociated with CKD., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Nephrotic syndrome (NS) is one of the most challenging conditions to manage and treat, partly because we lack a specific molecular understanding of its pathogenesis and progression. This limits our ability to provide targeted therapy or precise prognostications. Fortunately, genomic discovery in NS and its translation to genomic-informed medicine is allowing us to improve our understanding of the molecular anatomy of NS and our ability to care for patients with NS. In this Core Curriculum, we review the specific genes and loci discovered in childhood NS, specifically NS of Mendelian origin, APOL1-associated NS in black patients, HLA region variants associated with steroid-sensitive NS, their biological impacts, prevalence across populations, and clinical correlates. We also review the fundamentals of genetic architecture of human disease, technologies, and analytic strategies that currently exist to discover disease-related genetic variations. A facility with the concepts and vocabulary of modern genomics and ability to interpret results of genetic studies are essential skills for nephrologists caring for children with NS. As such, we hope to empower them to understand the literature in this area, appropriately order genetic tests and accurately interpret the results, and consider how they may participate in or drive the next wave of genomic discoveries in NS., (Copyright © 2019 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

The presence of 2 apolipoprotein L1 gene (APOL1) risk variants is associated with increased risk for chronic kidney disease and end-stage kidney disease. Inferior allograft outcomes following transplantation with kidneys from donors with 2 risk variants have also been reported. These data, coupled with anecdotal case reports and a recent cohort study of living donors, raise important questions about the potential increased kidney disease risk for living donors with APOL1 risk variants and the need for testing as part of the standard living donor evaluation process. We identify a series of questions that are central to the development of clinical policy regarding APOL1 testing of potential living kidney donors given the current uncertainty over the clinical implications of having 2 risk variants. We explore the ethical challenges that arise when determining when and to whom APOL1 testing should be offered, what potential donors should be told about APOL1 testing, how test results should be used to determine suitability for donation, if and when recipients should have access to results, and how clinical policy regarding APOL1 testing should be established., (Copyright © 2019 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Essential hypertension is a clinical diagnosis based on the presence of an elevated systemic blood pressure on physical examination without a clear inciting cause. It has multiple etiologies and is not a homogeneous disorder. Hypertension contributes to the development and progression of atherosclerotic cardiovascular diseases, and antihypertensive treatment reduces the risk of fatal and nonfatal myocardial infarction, stroke, and congestive heart failure. Although hypertension is frequently present in nondiabetic individuals with low levels of proteinuria and chronic kidney disease, reducing blood pressures in this population does not reliably slow nephropathy progression. Many of these patients with recent African ancestry have the primary kidney disease "solidified glomerulosclerosis" that is strongly associated with renal-risk variants in the apolipoprotein L1 gene (APOL1). This kidney disease contributes to secondarily elevated blood pressures. The APOL1-associated spectrum of nondiabetic nephropathy also includes proteinuric kidney diseases, idiopathic focal segmental glomerulosclerosis, collapsing glomerulopathy, severe lupus nephritis, and sickle cell nephropathy. This article reviews relationships between mild to moderate essential hypertension and chronic kidney disease with a focus on the role of APOL1 in development of hypertension. Available evidence strongly supports that APOL1 renal-risk variants associate with glomerulosclerosis in African Americans, which then causes secondary hypertension, not with essential hypertension per se., (Copyright © 2019 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Nephrotic syndrome is the most common glomerular disease in children. There is wide variation in the incidence of nephrotic syndrome in different populations, with a higher incidence in children of South Asian descent. However, nephrotic syndrome with a more indolent course and poor prognosis is more common in African American children. The disparity in the prevalence and severity of nephrotic syndrome is likely due to complex interactions between environmental and biological factors. Recent advances in genome science are providing insight into some of the biological factors that may explain these disparities. For example, risk alleles in the gene encoding apolipoprotein L1 (APOL1) have been established as the most important factor in the high incidence of chronic glomerular diseases in African Americans. Conversely, the locus for childhood steroid-sensitive nephrotic syndrome in the gene encoding major histocompatibility complex-class II-DQ-alpha 1 (HLA-DQA1) is unlikely to be the explanation for the high incidence of steroid-sensitive nephrotic syndrome in Asian children because the same variants are equally common in whites and African Americans. There is a need for collaborative large-scale studies to identify additional risk loci to explain disparities in disease incidence and response to therapy. Findings from such studies have the potential to lead to the identification of new therapeutic targets for nephrotic syndrome., (Copyright © 2018 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Pediatric-onset chronic kidney disease (CKD) is as relevant to adults as it is to children. Congenital anomalies of the kidney and urinary tract may have a significant impact on health from birth or during childhood or may not manifest until adulthood. Many acquired kidney diseases start to appear in late childhood and adolescence. The propensity for more rapid progression of CKD to end-stage kidney disease in adults of African ancestry, as well as disparities in access to kidney transplantation and allograft longevity, have been well documented for decades. Similar disparate patterns are seen in children, and we now know that there are a range of biological and nonbiological risk factors for the development and progression of CKD in people of African descent that are pertinent to CKD in children. In some cases, it is unclear whether there are effective potential interventions, whereas in other situations, there are opportunities to improve outcomes., (Copyright © 2018 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Genetic methodologies are improving our understanding of the pathophysiology in diverse diseases. Breakthroughs have been particularly impressive in nephrology, for which marked disparities exist in rates and etiologic classifications of end-stage kidney disease between African Americans and European Americans. Discovery of the apolipoprotein L1 gene (APOL1) association with focal segmental glomerulosclerosis, human immunodeficiency virus (HIV)-associated nephropathy, lupus nephritis, sickle cell nephropathy, and solidified glomerulosclerosis, as well as more rapid failure of transplanted kidneys from donors with APOL1 renal-risk genotypes, has improved our understanding of nondiabetic nephropathy. Environmental factors acting through natural selection in sub-Saharan African populations likely underlie this association. This article describes the discovery of chromosome 22q renal-risk variants and their worldwide distribution, reviews the epidemiology and pathology of APOL1-associated nephropathies, and explores several proposed mechanisms of kidney injury identified in cell culture and animal models. Detection of APOL1 associations with kidney diseases and delineation of injury pathways brings hope for effective treatment for these kidney diseases., (Copyright © 2018 National Kidney Foundation, Inc. All rights reserved.)

Genetic testing is used for screening, diagnosis, and prognosis of diseases consistent with a genetic cause and to guide drug therapy to improve drug efficacy and avoid adverse effects (pharmacogenomics). This In Practice review aims to inform about DNA-related genetic test availability, interpretation, and recommended clinical actions based on results using evidence from clinical guidelines, when available. We discuss challenges that limit the widespread use of genetic information in the clinical care setting, including a small number of actionable genetic variants with strong evidence of clinical validity and utility, and the need for improving the health literacy of health care providers and the public, including for direct-to-consumer tests. Ethical, legal, and social issues and incidental findings also need to be addressed. Because our understanding of genetic factors associated with disease and drug response is rapidly increasing and new genetic tests are being developed that could be adopted by clinicians in the short term, we also provide extensive resources for information and education on genetic testing., (Copyright © 2018 National Kidney Foundation, Inc. All rights reserved.)

Recent advances in genetics of renal disease have deepened our understanding of progressive kidney disease. Here, we review genetic variants that are of particular importance to progressive glomerular disease that result in end-stage kidney disease (ESKD). Some of the most striking findings relate to APOL1 genetic variants, seen exclusively in individuals of sub-Saharan African descent, that create a predisposition to particular renal disorders, including focal segmental glomerulosclerosis and arterionephrosclerosis. We also review the genetics of cardiovascular disease in ESKD and note that little work has been published on the genetics of other ESKD complications, including anemia, bone disease, and infections. Deeper understanding of the genetics of ESKD and its complications may lead to new therapies that are tailored to an individual patient's genetic profile or are discovered based on genetic approaches that identify novel pathways of renal cell injury and repair., (Published by Elsevier Inc.)

Background: Few data exist for the genetic variants underlying the risk for steroid-sensitive nephrotic syndrome (SSNS) in children. The objectives of this study were to evaluate HLA-DQA1 and APOL1 variants as risk factors for SSNS in African American children and use classic HLA antigen types and amino acid inference to refine the HLA-DQA1 association., Study Design: Case-control study., Setting & Participants: African American children with SSNS or steroid-resistant nephrotic syndrome (SRNS) were enrolled from Duke University and centers participating in the Midwest Pediatric Nephrology Consortium., Factor: Genetic variants in HLA-DQA1 (C34Y [rs1129740]; F41S [rs1071630]) and APOL1 high-risk alleles., Outcomes: SSNS and SRNS., Measurements: Direct sequencing for the HLA-DQA1 and APOL1 variants in 115 African American children (65 with SSNS and 50 with SRNS). Imputation of classic HLA alleles and amino acids was done in 363 South Asian children., Results: The 2 HLA-DQA1 variants were significantly associated with SSNS in African American children (C34Y: P=5.7 × 10 -11 ; OR, 3.53; 95% CI, 2.33-5.42; F41S: P=1.2 × 10 -13 ; OR, 4.08; 95% CI, 2.70-6.28), but not with SRNS (C34Y: P=0.6; F41S: P=0.2). APOL1 high-risk variants were not associated with SSNS (P=0.5) but showed significant associations with SRNS (P=1.04 × 10 -7 ; OR, 4.17; 95% CI, 2.23-7.64). HLA-DQA1*0201, HLA-DQB1*0201, and HLA-DRB1*0701 were the classic HLA alleles with the most significant associations with SSNS risk. The most significantly associated amino acid positions were HLA-DQα1 56 and 76 (both P=2.8 × 10 -7 ). Conditional analysis revealed that these variants most likely account for the observed association., Limitations: Modest sample size and limited statistical power to detect small to moderate effect sizes. Children studied may not be representative of all African American children in the United States., Conclusions: HLA-DQA1 is a risk locus for SSNS, but not SRNS, in African American children, consistent with its role in SSNS risk in children of European, Asian, and African ancestries. There is little evidence of a significant role for the APOL1 high-risk alleles in childhood SSNS in African American children. Refinement of the HLA-DQA1 association identified the critical classic HLA antigen types and amino acids of the HLA-DQ α1 molecule., (Copyright © 2017 National Kidney Foundation, Inc. All rights reserved.)

Common DNA sequence variants rarely have a high-risk association with a common disease. When such associations do occur, evolutionary forces must be sought, such as in the association of apolipoprotein L1 (APOL1) gene risk variants with nondiabetic kidney diseases in populations of African ancestry. The variants originated in West Africa and provided pathogenic resistance in the heterozygous state that led to high allele frequencies owing to an adaptive evolutionary selective sweep. However, the homozygous state is disadvantageous and is associated with a markedly increased risk of a spectrum of kidney diseases encompassing hypertension-attributed kidney disease, focal segmental glomerulosclerosis, human immunodeficiency virus nephropathy, sickle cell nephropathy, and progressive lupus nephritis. This scientific success story emerged with the help of the tools developed over the past 2 decades in human genome sequencing and population genomic databases. In this introductory article to a timely issue dedicated to illuminating progress in this area, we describe this unique population genetics and evolutionary medicine detective story. We emphasize the paradox of the inheritance mode, the missing heritability, and unresolved associations, including cardiovascular risk and diabetic nephropathy. We also highlight how genetic epidemiology elucidates mechanisms and how the principles of evolution can be used to unravel conserved pathways affected by APOL1 that may lead to novel therapies. The APOL1 gene provides a compelling example of a common variant association with common forms of nondiabetic kidney disease occurring in a continental population isolate with subsequent global admixture. Scientific collaboration using multiple experimental model systems and approaches should further clarify pathomechanisms further, leading to novel therapies., (Copyright © 2017 Elsevier Inc. All rights reserved.)

End-stage renal disease (ESRD) disproportionately affects African Americans, who are two to four times more likely than European Americans to develop ESRD. Two independent variants of the apolipoprotein L1 (APOL1) gene, G1 and G2, have been associated with a 7- to 10-fold greater risk of developing nondiabetic ESRD in African Americans. Those who inherit two risk variants (G1/G1, G2/G2, or G1/G2) are also more likely to develop ESRD at a younger age and to have progression of chronic kidney disease. Currently, it is not known what proportion of persons with high-risk genotypes will develop ESRD in the general population, the exact mechanism of injury for APOL1-related risk, its relation to environmental exposures, or whether patients with comorbid conditions are more likely to develop ESRD. To address the above uncertainties, research that includes assessment of APOL1 status is needed before guidelines for general testing can be endorsed. Currently, APOL1 testing has been proposed as part of kidney transplant protocols both for living donors and recipients. However, because of uncertainties regarding the clinical implications of APOL1 variants, testing could generate confusion, anxiety, or stigma. Multiple forms of evidence, including the views of community members, are needed to support responsible approaches to providing information about APOL1 status as part of clinical care or in population screening. Informed consent with subsequent counseling regarding the risks and benefits of APOL1 testing should be considered for patients at high risk., (Published by Elsevier Inc.)

Variants of the APOL1 gene, found primarily in individuals of African descent, are associated with various forms of kidney disease and kidney disease progression. Recent studies evaluating the association of APOL1 with cardiovascular disease have yielded conflicting results, and the potential role in cardiovascular disease remains unclear. In this review, we summarize the observational studies linking the APOL1 risk variants with chronic kidney and cardiovascular disease among persons of African descent., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The pathogenesis of many common etiologies of nephropathy has been informed by recent molecular genetic breakthroughs. It now is apparent that the ethnic disparity in the risk for nondiabetic chronic kidney disease between African Americans and European Americans is explained largely by variation in the apolipoprotein L1 gene (APOL1). The presence of two APOL1 renal risk variants markedly increases an individual's risk for kidney disease. In transplantation, kidneys from deceased African Americans with two APOL1 renal risk variants have shorter survival intervals after engraftment, regardless of the ethnicity of the recipient. Precision medicine will transform the clinical practice of nephrology and kidney transplantation, and play an important role in the allocation of kidneys from deceased and living kidney donors with recent African ancestry. This article reviews existing data on APOL1 in deceased-donor and living-donor kidney transplantation. It considers the impact of including APOL1 genotyping in decisions on the allocation and discard of deceased-donor kidneys, as well as the selection of living donors., (Copyright © 2017 Elsevier Inc. All rights reserved.)

APOL1 kidney risk variants lead to high rates of kidney disease in people of recent African ancestry. These risk variants are very common and confer a large increase in risk of kidney disease. This unusual combination of high frequency and large effect size occurs because the risk variants also appear to have beneficial properties. The risk variants show enhanced protective effects against certain pathogens, particularly the trypanosomes that cause African sleeping sickness. Here, we consider the origins and evolution of the primate-only APOL1 gene. Human genetics, mouse models, biochemistry, and comparative genomics suggest that APOL1 is an innate immunity gene and that the risk variants have the potential for heightened immunity that comes at the cost of toxicity to the kidneys. A better understanding of the evolution of APOL1 may help illuminate how APOL1 causes kidney disease in individuals who harbor the high-risk variants., (Copyright © 2017. Published by Elsevier Inc.)

In the face of ever-increasing incidence and prevalence of kidney disease worldwide, the unmet need for new treatments is unprecedented. Precision medicine is defined as the use of modern technologies to identify mechanisms of diseases in individual patients, and thus deploy treatment using tailored, targeted approaches, in the hopes of avoiding unnecessary toxicities and complications. Is there a place for kidney disease therapeutics in this space? If so, what is required to make significant progress toward precision nephrology? To answer these critical questions, we present a series of personalized comments corresponding to the responses offered to these very questions during the Inaugural Glom-NExT Symposium held at Harvard Medical School on October 23, 2014, a national meeting focused exclusively on kidney disease therapeutics., (Copyright © 2016.)

Apolipoprotein L1 (APOL1) genetic variants account for much of the excess risk of chronic and end-stage kidney disease, which results in a significant global health disparity for persons of African ancestry. We estimate the lifetime risk of kidney disease in APOL1 dual-risk allele individuals to be at least 15%. Experimental evidence suggests a direct role of APOL1 in pore formation, cellular injury, and programmed cell death in renal injury. The APOL1 BH3 motif, often associated with cell death, is unlikely to play a role in APOL1-induced cytotoxicity because it is not conserved within the APOL family and is dispensable for cell death in vitro. We discuss two models for APOL1 trypanolytic activity: one involving lysosome permeabilization and another involving colloid-osmotic swelling of the cell body, as well as their relevance to human pathophysiology. Experimental evidence from human cell culture models suggests that both mechanisms may be operative. A systems biology approach whereby APOL1-associated perturbations in gene and protein expression in affected individuals are correlated with molecular pathways may be productive to elucidate APOL1 function in vivo., (Published by Elsevier Inc.)

Variable rates of disease observed between members of different continental population groups may be mediated by inherited factors, environmental exposures, or their combination. This article provides evidence in support of differential allele frequency distributions that underlie the higher rates of nondiabetic kidney disease in the focal segmental glomerulosclerosis spectrum of disease and lower rates of coronary artery calcified atherosclerotic plaque and osteoporosis in populations of African ancestry. With recognition that these and other common complex diseases are affected by biological factors comes the realization that targeted manipulation of environmental exposures and pharmacologic treatments will have different effects based on genotype. The present era of precision medicine will couple one's genetic makeup with specific therapies to reduce rates of disease based on the presence of disease-specific alleles., (Copyright © 2013 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Marked familial aggregation of chronic kidney disease suggests that inherited factors play a major role in nephropathy susceptibility. Molecular genetics analyses have identified a number of genes reproducibly associated with a broad range of renal phenotypes. Most associations show polygenic inheritance patterns with limited effect size. In contrast, genetic association between the apolipoprotein L1 (APOL1) gene and several severe nondiabetic forms of kidney disease in African Americans approach Mendelian inheritance patterns and account for a large proportion of glomerulosclerosis in populations of African ancestry. Emerging data support an important role for APOL1 in the progression of diverse etiologies of kidney disease, in concert with requisite environmental (gene*environment) and inherited (gene*gene) interactions. This article reviews the current status of APOL1-associated nephropathy and discusses research questions under active investigation in the search for a cure for these severe and often progressive kidney diseases., (© 2013 Elsevier Inc. All rights reserved.)