ABSTRACT
RATIONALE & OBJECTIVE: The national kidney allocation system (KAS) implemented in December 2014 in the United States redefined the start of waiting time from the time of waitlisting to the time of kidney failure. Waitlisting has declined post-KAS, but it is unknown if this is due to transplant center practices or changes in dialysis facility referral and evaluation. The purpose of this study was to assess the impact of the 2014 KAS policy change on referral and evaluation for transplantation among a population of incident and prevalent patients with kidney failure. STUDY DESIGN: Cohort study. SETTING & PARTICIPANTS: 37,676 incident (2012-2016) patients in Georgia, North Carolina, and South Carolina identified within the US Renal Data System at 9 transplant centers and followed through December 2017. A prevalent population of 6,079 patients from the same centers receiving maintenance dialysis in 2012 but not referred for transplantation in 2012. EXPOSURE: KAS era (pre-KAS vs post-KAS). OUTCOME: Referral for transplantation, start of transplant evaluation, and waitlisting. ANALYTICAL APPROACH: Multivariable time-dependent Cox models for the incident and prevalent population. RESULTS: Among incident patients, KAS was associated with increased referrals (adjusted HR, 1.16 [95% CI, 1.12-1.20]) and evaluation starts among those referred (adjusted HR, 1.16 [95% CI, 1.10-1.21]), decreased overall waitlisting (adjusted HR, 0.70 [95% CI, 0.65-0.76]), and lower rates of active waitlisting among those evaluated compared to the pre-KAS era (adjusted HR, 0.81 [95% CI, 0.74-0.90]). Among the prevalent population, KAS was associated with increases in overall waitlisting (adjusted HR, 1.74 [95% CI, 1.15-2.63]) and active waitlisting among those evaluated (adjusted HR, 2.01 [95% CI, 1.16-3.49]), but had no significant impact on referral or evaluation starts among those referred. LIMITATIONS: Limited to 3 states, residual confounding. CONCLUSIONS: In the southeastern United States, the impact of KAS on steps to transplantation was different among incident and prevalent patients with kidney failure. Dialysis facilities referred more incident patients and transplant centers evaluated more incident patients after implementation of KAS, but fewer evaluated patients were placed onto the waitlist. Changes in dialysis facility and transplant center behaviors after KAS implementation may have influenced the observed changes in access to transplantation.
Subject(s)
Kidney Failure, Chronic , Kidney Transplantation , Humans , United States/epidemiology , Kidney Failure, Chronic/diagnosis , Kidney Failure, Chronic/epidemiology , Kidney Failure, Chronic/surgery , Cohort Studies , Waiting Lists , Referral and Consultation , KidneyABSTRACT
Although research shows that minorities exhibit higher levels of medical mistrust, perceived racism, and discrimination in healthcare settings, the degree to which these underlying sociocultural factors preclude end-stage renal disease (ESRD) patients from initiating kidney transplant evaluation is unknown. We telephone surveyed 528 adult ESRD patients of black or white race referred for evaluation to a Georgia transplant center (N = 3) in 2014-2016. We used multivariable logistic regression to examine associations between sociocultural factors and evaluation initiation, adjusting for demographic, clinical, and socioeconomic characteristics. Despite blacks (n = 407) reporting higher levels of medical mistrust (40.0% vs 26.4%, P < .01), perceived racism (55.5% vs 18.2%, P < .01), and experienced discrimination (29.0% vs 15.7%, P < .01) than whites (n = 121), blacks were only slightly less likely than whites to initiate evaluation (49.6% vs 57.9%, P = .11). However, after adjustment, medical mistrust (odds ratio [OR]: 0.59; 95% confidence interval [CI]: 0.39, 0.91), experienced discrimination (OR: 0.62, 95% CI: 0.41, 0.95), and perceived racism (OR: 0.61; 95% CI: 0.40, 0.92) were associated with lower evaluation initiation. Results suggest that sociocultural disparities exist in early kidney transplant access and occur despite the absence of a significant racial disparity in evaluation initiation. Interventions to reduce disparities in transplantation access should target underlying sociocultural factors, not just race.
Subject(s)
Ethnicity/psychology , Healthcare Disparities , Kidney Failure, Chronic/diagnosis , Kidney Transplantation/statistics & numerical data , Socioeconomic Factors , Trust , Cross-Sectional Studies , Evaluation Studies as Topic , Female , Follow-Up Studies , Humans , Kidney Failure, Chronic/psychology , Kidney Failure, Chronic/surgery , Kidney Transplantation/psychology , Male , Middle Aged , Prognosis , TelephoneABSTRACT
Variability in transplant access exists, but barriers to referral and evaluation are underexplored due to lack of national surveillance data. We examined referral for kidney transplantation evaluation and start of the evaluation among 34 857 incident, adult (18-79 years) end-stage kidney disease patients from 690 dialysis facilities in the United States Renal Data System from January 1, 2012 through August 31, 2016, followed through February 2018 and linked data to referral and evaluation data from nine transplant centers in Georgia, North Carolina, and South Carolina. Multivariable-adjusted competing risk analysis examined each outcome. The median within-facility cumulative percentage of patients referred for kidney transplantation within 1 year of dialysis at the 690 dialysis facilities in Network 6 was 33.7% (interquartile range [IQR]: 25.3%-43.1%). Only 48.3% of referred patients started the transplant evaluation within 6 months of referral. In multivariable analyses, factors associated with referral vs evaluation start among those referred at any time differed. For example, black, non-Hispanic patients had a higher rate of referral (hazard ratio [HR]: 1.22; 95% confidence interval [CI]: 1.18-1.27), but lower evaluation start among those referred (HR: 0.93; 95% CI: 0.88-0.98), vs white non-Hispanic patients. Barriers to transplant varied by step, and national surveillance data should be collected on early transplant steps to improve transplant access.
Subject(s)
Kidney Failure, Chronic , Kidney Transplantation , Adult , Humans , Kidney Failure, Chronic/surgery , North Carolina/epidemiology , Referral and Consultation , Renal Dialysis , United StatesABSTRACT
Human leukocyte antigen G (HLA-G), a nonclassic HLA class Ib molecule involved in the maintenance of maternal tolerance to semiallogeneic fetal tissues during pregnancy, has emerged as a potential therapeutic target to control allograft rejection. We demonstrate here that the level of soluble HLA-G dimer was higher in a group of 90 patients with a functioning renal allograft compared with 40 patients who rejected (RJ) their transplants. The HLA-G dimer level was not affected by demographic status. One of the potential mechanisms in tissue-organ allograft rejection involves the induction of granzymes and perforin, which are the main effector molecules expressed by CD8+ cytotoxic T lymphocytes and function to destroy allogeneic transplants. Using genomics and molecular and cellular analyses of cells from T-cell-mediated RJ and nonrejected kidney transplant patients, cells from leukocyte Ig-like receptor B1 (LILRB1) transgenic mice, humanized mice, and genetically engineered HLA-G dimer, we demonstrated a novel mechanism by which HLA-G dimer inhibits activation and cytotoxic capabilities of human CD8+ T cells. This mechanism implicated the down-regulation of Granzyme B expression and the essential involvement of LILRB1. Thus, HLA-G dimer has the potential to be a specific and effective therapy for prevention of allograft rejection and prolongation of graft survival.-Ajith, A., Portik-Dobos, V., Nguyen-Lefebvre, A. T., Callaway, C., Horuzsko, D. D., Kapoor, R., Zayas, C., Maenaka, K., Mulloy, L. L., Horuzsko, A. HLA-G dimer targets Granzyme B pathway to prolong human renal allograft survival.
Subject(s)
Granzymes/metabolism , HLA-G Antigens/metabolism , Adult , Animals , Antigens, CD/metabolism , CD8-Positive T-Lymphocytes/metabolism , Concanavalin A/pharmacology , Female , Flow Cytometry , Graft Rejection , Graft Survival , Humans , Kidney Transplantation , Leukocyte Immunoglobulin-like Receptor B1/antagonists & inhibitors , Leukocyte Immunoglobulin-like Receptor B1/metabolism , Mice , Real-Time Polymerase Chain Reaction , T-Lymphocytes/metabolismABSTRACT
BACKGROUND: Racial disparities persist in access to kidney transplantation. Racial differences in preemptive referral, or referral prior to dialysis start, may explain this discrepancy. METHODS: Patient-level data on kidney transplant referrals (2005-2012) from all Georgia transplant centers were linked to the United States Renal Data System to examine racial disparities in preemptive referral, waitlisting, and living donor transplant. Adjusted logistic regression and Cox proportional hazard models determined the associations between race (African American vs white) and preemptive referral, and placement on the waitlist and receipt of a living donor kidney, respectively. RESULTS: Among 7752 adults referred for transplant evaluation, 20.38% (n = 1580) were preemptively referred. The odds of African Americans being preemptively referred for transplant evaluation were 37% (OR = 0.63; [95% CI: 0.55 0.71]) lower than white patients. Among preemptively referred patients, there was no racial difference (African Americans compared to white patients. HR = 0.96; [95% CI: 0.88, 1.04]) in waitlisting. However, African Americans were 70% less likely than white patients to receive a living donor transplant (HR = 0.30; [95% CI: 0.21, 0.42]). CONCLUSION: Racial disparities in transplant receipt may be partially explained by disparities in preemptive referral. Interventions to reduce racial disparities in kidney transplant access may need to be targeted earlier in the disease process.
Subject(s)
Health Services Accessibility , Healthcare Disparities , Kidney Failure, Chronic/surgery , Kidney Transplantation/statistics & numerical data , Living Donors/supply & distribution , Referral and Consultation/statistics & numerical data , Waiting Lists , Adolescent , Adult , Aged , Female , Follow-Up Studies , Humans , Male , Middle Aged , Prognosis , Renal Dialysis , Tissue and Organ Procurement , Young AdultABSTRACT
Clinical outcomes are generally worse for black vs nonblack renal allograft recipients. In BENEFIT and BENEFIT-EXT, recipients were randomized to belatacept more intense-based, belatacept less intense-based, or cyclosporine-based immunosuppression. At year 7, belatacept was associated with superior graft survival vs cyclosporine in BENEFIT (recipients of living or standard criteria deceased donor kidneys); belatacept was associated with similar graft survival vs cyclosporine in BENEFIT-EXT (recipients of extended criteria donor kidneys). In both studies, renal function was superior for belatacept-treated vs cyclosporine-treated patients. Seven-year outcomes were examined by race post hoc in each study. The effect of race and treatment on time to death or graft loss was compared using Cox regression. The interaction between treatment and race was also considered. Glomerular filtration rate (GFR) was estimated from months 1 to 84 using a repeated-measures model. In total, 8.3% (55/666) and 13.1% (71/543) of patients in BENEFIT and BENEFIT-EXT, respectively, were black. Time to death or graft loss was similar in blacks and nonblacks. For both subgroups, estimated mean GFR increased over 7 years for belatacept, but declined for cyclosporine. Outcomes were similar in belatacept-treated black and nonblack patients. Due to the small number of black patients, these results must be interpreted with caution.
Subject(s)
Abatacept/administration & dosage , Cyclosporine/administration & dosage , Ethnicity/statistics & numerical data , Graft Rejection/drug therapy , Immunosuppressive Agents/administration & dosage , Kidney Failure, Chronic/surgery , Kidney Transplantation/methods , Black or African American/statistics & numerical data , Female , Follow-Up Studies , Glomerular Filtration Rate , Graft Rejection/epidemiology , Graft Survival/drug effects , Humans , Incidence , Kidney Function Tests , Male , Middle Aged , Postoperative Complications , Prognosis , Risk Factors , Survival Rate , Time Factors , Transplant Recipients/statistics & numerical dataABSTRACT
BACKGROUND: The Reducing Disparities in Access to kidNey Transplantation Community Study (RaDIANT) was an End-Stage Renal Disease (ESRD) Network 6-developed, dialysis facility-level randomized trial testing the effectiveness of a 1-year multicomponent education and quality improvement intervention in increasing referral for kidney transplant evaluation among selected Georgia dialysis facilities. METHODS: To assess implementation of the RaDIANT intervention, we conducted a process evaluation at the conclusion of the intervention period (January-December 2014). We administered a 20-item survey to the staff involved with transplant education in 67 dialysis facilities randomized to participate in intervention activities. Survey items assessed facility participation in the intervention (fidelity and reach), helpfulness and willingness to continue intervention activities (sustainability), suggestions for improving intervention components (sustainability), and factors that may have influenced participation and study outcomes (context). We defined high fidelity to the intervention as completing 11 or more activities, and high participation in an activity as having at least 75% participation across intervention facilities. RESULTS: Staff from 65 of the 67 dialysis facilities completed the questionnaire, and more than half (50.8%) reported high adherence (fidelity) to RaDIANT intervention requirements. Nearly two-thirds (63.1%) of facilities reported that RaDIANT intervention activities were helpful or very helpful, with 90.8% of facilities willing to continue at least one intervention component beyond the study period. Intervention components with high participation emphasized staff and patient-level education, including in-service staff orientations, patient and family education programs, and patient educational materials. Suggested improvements for intervention activities emphasized addressing financial barriers to transplantation, with financial education materials perceived as most helpful among RaDIANT educational materials. Variation in facility-level fidelity of the RADIANT intervention did not significantly influence the mean difference in proportion of patients referred pre- (2013) and post-intervention (2014). CONCLUSIONS: We found high fidelity to the RaDIANT multicomponent intervention at the majority of intervention facilities, with sustainability of select intervention components at intervention facilities and feasibility for dissemination across ESRD Networks. Future modification of the intervention should emphasize financial education regarding kidney transplantation and amend intervention components that facilities perceive as time-intensive or non-sustainable. TRIAL REGISTRATION: Clinicaltrials.gov number NCT02092727 . Registered 13 Mar 2014 (retrospectively registered).
Subject(s)
Ambulatory Care Facilities/standards , Healthcare Disparities/standards , Kidney Failure, Chronic/therapy , Kidney Transplantation/standards , Referral and Consultation/standards , Renal Dialysis/standards , Aged , Ambulatory Care Facilities/trends , Community Health Services/standards , Community Health Services/trends , Female , Health Personnel/standards , Health Personnel/trends , Healthcare Disparities/trends , Humans , Kidney Failure, Chronic/diagnosis , Kidney Failure, Chronic/epidemiology , Kidney Transplantation/trends , Male , Middle Aged , Referral and Consultation/trends , Renal Dialysis/trendsABSTRACT
Georgia has the lowest kidney transplant rates in the United States and substantial racial disparities in transplantation. We determined the effectiveness of a multicomponent intervention to increase referral of patients on dialysis for transplant evaluation in the Reducing Disparities in Access to kidNey Transplantation Community Study (RaDIANT), a randomized, dialysis facility-based, controlled trial involving >9000 patients receiving dialysis from 134 dialysis facilities in Georgia. In December of 2013, we selected dialysis facilities with either low transplant referral or racial disparity in referral. The intervention consisted of transplant education and engagement activities targeting dialysis facility leadership, staff, and patients conducted from January to December of 2014. We examined the proportion of patients with prevalent ESRD in each facility referred for transplant within 1 year as the primary outcome, and disparity in the referral of black and white patients as a secondary outcome. Compared with control facilities, intervention facilities referred a higher proportion of patients for transplant at 12 months (adjusted mean difference [aMD], 7.3%; 95% confidence interval [95% CI], 5.5% to 9.2%; odds ratio, 1.75; 95% CI, 1.36 to 2.26). The difference between intervention and control facilities in the proportion of patients referred for transplant was higher among black patients (aMD, 6.4%; 95% CI, 4.3% to 8.6%) than white patients (aMD, 3.7%; 95% CI, 1.6% to 5.9%; P<0.05). In conclusion, this intervention increased referral and improved equity in kidney transplant referral for patients on dialysis in Georgia; long-term follow-up is needed to determine whether these effects led to more transplants.
Subject(s)
Healthcare Disparities/statistics & numerical data , Kidney Transplantation , Patient Selection , Referral and Consultation/statistics & numerical data , Humans , Middle Aged , United StatesABSTRACT
Kidney transplant is not only the best treatment for patients with advanced kidney disease but it also reduces health care expenditure. The management of transplant patients is complex as they require special care by transplant nephrologists who have expertise in assessing transplant candidates, understand immunology and organ rejection, have familiarity with perioperative complications, and have the ability to manage the long-term effects of chronic immunosuppression. This skill set at the intersection of multiple disciplines necessitates additional training in Transplant Nephrology. Currently, there are more than 250,000 patients with a functioning kidney allograft and over 100,000 waitlisted patients awaiting kidney transplant, with a burgeoning number added to the kidney transplant wait list every year. In 2022, more than 40,000 patients were added to the kidney wait list and more than 25,000 received a kidney transplant. The Advancing American Kidney Health Initiative, passed in 2019, is aiming to double the number of kidney transplants by 2030 creating a need for additional transplant nephrologists to help care for them. Over the past decade, there has been a decline in the Nephrology-as well Transplant Nephrology-workforce due to a multitude of reasons. The American Society of Transplantation Kidney Pancreas Community of Practice created a workgroup to discuss the Transplant Nephrology workforce shortage. In this article, we discuss the scope of the problem and how the Accreditation Council for Graduate Medical Education recognition of Transplant Nephrology Fellowship could at least partly mitigate the Transplant Nephrology work force crisis.
Subject(s)
Accreditation , Education, Medical, Graduate , Kidney Transplantation , Nephrology , Humans , Nephrology/education , Nephrologists/education , United States , Fellowships and ScholarshipsABSTRACT
BACKGROUND: Cytomegalovirus (CMV) disease remains an important problem in solid-organ transplant recipients, with the greatest risk among donor CMV-seropositive, recipient-seronegative (D(+)/R(-)) patients. CMV-specific cell-mediated immunity may be able to predict which patients will develop CMV disease. METHODS: We prospectively included D(+)/R(-) patients who received antiviral prophylaxis. We used the Quantiferon-CMV assay to measure interferon-γ levels following in vitro stimulation with CMV antigens. The test was performed at the end of prophylaxis and 1 and 2 months later. The primary outcome was the incidence of CMV disease at 12 months after transplant. We calculated positive and negative predictive values of the assay for protection from CMV disease. RESULTS: Overall, 28 of 127 (22%) patients developed CMV disease. Of 124 evaluable patients, 31 (25%) had a positive result, 81 (65.3%) had a negative result, and 12 (9.7%) had an indeterminate result (negative mitogen and CMV antigen) with the Quantiferon-CMV assay. At 12 months, patients with a positive result had a subsequent lower incidence of CMV disease than patients with a negative and an indeterminate result (6.4% vs 22.2% vs 58.3%, respectively; P < .001). Positive and negative predictive values of the assay for protection from CMV disease were 0.90 (95% confidence interval [CI], .74-.98) and 0.27 (95% CI, .18-.37), respectively. CONCLUSIONS: This assay may be useful to predict if patients are at low, intermediate, or high risk for the development of subsequent CMV disease after prophylaxis. CLINICAL TRIALS REGISTRATION: NCT00817908.
Subject(s)
Cytomegalovirus Infections/immunology , Immunity, Cellular , Transplants/adverse effects , Adult , Aged , Antiviral Agents/therapeutic use , Chemoprevention/methods , Cohort Studies , Female , Humans , Immunocompromised Host , Immunosuppressive Agents/adverse effects , Interferon-gamma Release Tests , Leukocytes, Mononuclear/immunology , Male , Middle Aged , Predictive Value of Tests , Risk AssessmentABSTRACT
Purpose of review: The purpose of this review is to describe the Southeastern Kidney Transplant Coalition's mission, vision, goals, and Early Transplant Access registry as an example of a community/academic collaboration dedicated to improving access to transplantation and reducing inequities in transplant access. Recent findings: The barriers and facilitators to referral and evaluation for kidney transplantation are not necessarily the same as for waitlisting and transplantation. Recent findings suggest that inequities in transplant access are multilevel and multifactorial and require continued community engagement to improve access to kidney transplantation across patients, health systems, and populations. Summary: Community-engaged approaches are critical to ensuring that inequities in transplant access - which may vary across regions -- are not only described but are addressed in practice in a sustainable manner.
ABSTRACT
INTRODUCTION: There are pervasive racial disparities in access to living donor kidney transplantation, which for most patients with end-stage renal disease (ESRD) represents the optimal treatment. We previously developed a theory-driven, culturally sensitive intervention for African American (AA) patients with kidney disease called Living ACTS (About Choices in Transplantation and Sharing) as a DVD and booklet, and found this intervention was effective in increasing living donor transplant knowledge. However, it is unknown whether modifying this intervention for a Web-based environment is effective at increasing access to living donor transplantation. METHODS: We describe the Web-based Living ACTS study, a multicenter, randomized controlled study designed to test the effectiveness of a revised Living ACTS intervention in 4 transplant centers in the southeastern United States. The intervention consists of a Web site with 5 modules: Introduction, Benefits and Risks, The Kidney Transplant Process, Identifying a Potential Kidney Donor, and ACT Now (which encourages communication with friends and family about transplantation). RESULTS: This study will enroll approximately 800 patients from the 4 transplant centers. The primary outcome is the percentage of patients with at least 1 inquiry from a potential living donor among patients who receive Living ACTS as compared with those who receive a control Web site. CONCLUSION: The results from this study are expected to demonstrate the effectiveness of an intervention designed to increase access to living donor transplantation among AA individuals. If successful, the Web-based intervention could be disseminated across the >250 transplant centers in the United States to improve equity in living donor kidney transplantation.
ABSTRACT
Acute Page Kidney (APK) phenomenon is a rare cause of secondary hypertension, mediated by activation of renin-angiotensin-aldosterone system (RAAS). Timely intervention is of great importance to prevent any end organ damage from hypertension. We present a unique case of three episodes of APK in the same renal transplant allograft.
ABSTRACT
The relation between the oxidative burst and phenylpropanoid pathways has been studied using the sugarcane cultivar C86-56, which does not release phenolics in agar-base micropropagation systems. In stationary liquid culture, a significant production of phenolic compounds and plant survival were determined in sugarcane plants treated with 5mM H(2)O(2). The spectrophotometer determinations and the gene expression analysis corroborated that releasing of phenolics and soluble θ-quinones was induced during the first 24h of treatment. In comparison with the control treatments, sugarcane plants treated with H(2)O(2) demonstrated differences in the micropropagation-related variables when multiplied in Temporary Immersion Bioreactors (TIBs) supplemented with polyethyleneglycol (PEG 20%). Expression of selected genes related to photosynthesis, ethylene, auxins, oxidative burst, and defense pathways were confirmed during the entire PEG 20% stress in the plants coming from the 5mM H(2)O(2) treatment; whereas, much more heterogeneous expression patterns were evidenced in plants stressed with PEG but not previously treated with H(2)O(2). RT-PCR expression analysis supports the hypothesis that while H(2)O(2) induces the oxidative burst, the phenylpropanoids pathways elicit and maintain the defensive response mechanism in micropropagated sugarcane plants.
Subject(s)
Gene Expression , Genes, Plant , Hydrogen Peroxide/metabolism , Phenols/metabolism , Polyethylene Glycols/pharmacology , Saccharum/metabolism , Stress, Physiological/genetics , Bioreactors , Metabolic Networks and Pathways , Osmosis , Oxidation-Reduction , Respiratory Burst , Saccharum/drug effects , Saccharum/genetics , Signal TransductionABSTRACT
Drug-induced liver disease accounts for about 50% of acute or subacute liver failure in the United States. United Network of Organ Sharing (UNOS) data suggest 8%-20% of liver transplantation in this country per year is for fulminant liver failure due to drugs. Even though the most common medication implicated in acute liver injury is acetaminophen (75%), there are numerous other drugs that are responsible for acute and chronic liver injury. A variety of antifungal medications are known to cause a wide range of liver injury from a mild hepatocellular-cholestatic injury pattern to acute/subacute liver failure. Terbinafine is one of the antifungals that have been associated with such liver injuries. We report a case of terbinafine-induced severe liver failure requiring liver transplantation.
Subject(s)
Antifungal Agents/adverse effects , Liver Failure, Acute/chemically induced , Liver Transplantation/methods , Naphthalenes/adverse effects , Acetaminophen/pharmacology , Bile Ducts/pathology , Cholestasis/etiology , Humans , Liver/drug effects , Liver/pathology , Male , Middle Aged , TerbinafineABSTRACT
Patients with sickle cell anemia (SCA) may develop a glomerulopathy with proteinuria and progressive renal insufficiency, leading to ESRD. Albuminuria is a sensitive marker of glomerular damage in this population and precedes the development of renal insufficiency. For determination of the prevalence of glomerular damage in SCA and the clinical correlates of renal insufficiency, 300 adult patients with SCA were studied (hemoglobin SS = 184; and 116 with other sickling hemoglobinopathies: SC, SD, and S-beta thalassemia); albumin excretion rates (AER) and renal function (Cockroft-Gault formula) were determined, and clinical and hematologic evaluations were conducted. In hemoglobin SS disease, increased AER (micro- and macroalbuminuria) occurred in 68% of adult patients, and macroalbuminuria occurred in 26%. In other sickling disorders, increased AER occurs in 32% of adults, and macroalbuminuria occurs in 10%. The development of graded albuminuria was age dependent, so at 40 yr, 40% of patients with SS disease had macroalbuminuria. There were no differences in hematologic parameters (hemoglobin levels, white blood cell count, percentage of reticulocytes, platelet counts, or lactate dehydrogenase levels) between patients with normoalbuminuria and those with micro- or macroalbuminuria. By multivariate analysis, albuminuria correlated with age and serum creatinine in SS disease but not with BP or hemoglobin levels. In other sickling disorders, albuminuria tended to be associated with age but not with hemoglobin or BP levels. The diastolic BP was lower in patients with SCA than in African American control subjects, and the development of renal insufficiency, which was present in 21% of adults with SS disease, was not accompanied by significant hypertension. It is concluded that glomerular damage in adults with SCA is very common, and a majority of patients with SS disease are at risk for the development of progressive renal failure. The development of micro- and macroalbuminuria is not related to the degree of anemia, suggesting that sickle cell glomerulopathy is not solely related to hemodynamic adaptations to chronic anemia. In contrast to other glomerulopathies, the development of systemic hypertension is uncommon in SS disease with renal insufficiency.