Prevalence of infertility and pregnancy loss among individuals with kidney disease in the Hispanic Community Health Study/Study of Latinos.

BACKGROUND: Hispanic/Latino individuals are less likely to receive optimal treatment for chronic kidney disease than non-Hispanic whites. This may be particularly detrimental for women of reproductive age as chronic kidney disease increases risk for infertility, menstrual irregularities, and pregnancy loss. While these maternal outcomes have been associated with advanced chronic kidney disease, their occurrence in early chronic kidney disease is unclear. OBJECTIVES/DESIGN: Using baseline (2008-2011) and second study visit (2014-2017) data from the Hispanic Community Health Study/Study of Latinos, we retrospectively assessed the prevalence of chronic kidney disease as well as the association between chronic kidney disease and self-reported infertility, cessation of menses, hysterectomy, and nonviable pregnancy loss (experienced at less than 24 weeks gestation) in women of reproductive age (18-45 years). METHODS: Multivariable survey logistic regression analyses determined the unadjusted and multivariable-adjusted prevalence odds ratios with 95% confidence intervals between chronic kidney disease and the separate outcomes. RESULTS: Among 2589 Hispanic/Latino women included (mean age = 31.4 years), 4.6% were considered to have chronic kidney disease. In adjusted analyses, women with chronic kidney disease did not have a significantly increased odds of infertility (odds ratio = 1.02, 95% confidence interval = 0.42-2.49), cessation of menses (odds ratio = 1.25, 95% confidence interval = 0.52-3.04), or hysterectomy (odds ratio = 1.17, 95% confidence interval = 0.61-2.25) compared to those without chronic kidney disease. In those with chronic kidney disease, the adjusted odds of a nonviable pregnancy loss occurring after baseline visit were increased (odds ratio = 2.11, 95% confidence interval = 0.63-7.02) but not statistically significance. CONCLUSION: The presence of early stage chronic kidney disease did not confer a significant risk of infertility, cessation of menses, or nonviable pregnancy loss.

The Hispanic Community Health Study/Study of Latinos is a population-based study of over 16,000 Hispanic/Latino individuals throughout the United States. Within this cohort, we assessed the prevalence of chronic kidney disease in women of reproductive age (18­45 years old) and the associations between kidney disease and infertility, cessation of menses, and nonviable pregnancy loss (loss occurring before the 24th week of pregnancy). We found that kidney disease affected 1 in 20 women of reproductive age and those with kidney disease were more likely to have obesity, diabetes, and hypertension. Compared to those without kidney disease, the presence of kidney disease did not increase risk of infertility, cessation of menses, or nonviable pregnancy loss.

Characteristics and Outcomes of Patients With Pregnancy-Related End-Stage Kidney Disease.

Importance: The incidence of pregnancy-related acute kidney injury is increasing and is associated with significant maternal morbidity including progression to end-stage kidney disease (ESKD). Little is known about characteristics and long-term outcomes of patients who develop pregnancy-related ESKD. Objectives: To examine the characteristics and clinical outcomes of patients with pregnancy-related ESKD and to investigate associations between pre-ESKD nephrology care and outcomes. Design, Setting, and Participants: This was a cohort study of 183 640 reproductive-aged women with incident ESKD between January 1, 2000, and November 20, 2020, from the US Renal Data System and maternal data from births captured in the US Centers for Disease Control and Prevention publicly available natality data. Data were analyzed from December 2022 to June 2023. Exposure: Pregnancy-related primary cause of ESKD, per International Classification of Diseases, Ninth Revision (ICD-9) and ICD-10 codes reported at ESKD onset by the primary nephrologist on Centers for Medicare and Medicaid Services form 2728. Main Outcomes Measures: Multivariable Cox proportional hazards and competing risk models were constructed to examine time to (1) mortality, (2) access to kidney transplant (joining the waiting list or receiving a live donor transplant), and (3) receipt of transplant after joining the waitlist. Results: A total of 341 patients with a pregnancy-related primary cause of ESKD were identified (mean [SD] age 30.2 [7.3]). Compared with the general US birthing population, Black patients were overrepresented among those with pregnancy-related ESKD (109 patients [31.9%] vs 585 268 patients [16.2%]). In adjusted analyses, patients with pregnancy-related ESKD had similar or lower hazards of mortality compared with those with glomerulonephritis or cystic kidney disease (adjusted hazard ratio [aHR], 0.96; 95% CI, 0.76-1.19), diabetes or hypertension (aHR, 0.49; 95% CI, 0.39-0.61), or other or unknown primary causes of ESKD (aHR, 0.60; 95% CI, 0.48-0.75). Despite this, patients with pregnancy-related ESKD had significantly lower access to kidney transplant compared with those with other causes of ESKD, including (1) glomerulonephritis or cystic kidney disease (adjusted subhazard ratio [aSHR], 0.51; 95% CI, 0.43-0.66), (2) diabetes or hypertension (aSHR, 0.81; 95% CI, 0.67-0.98), and (3) other or unkown cause (aSHR, 0.82; 95% CI, 0.67-0.99). Those with pregnancy-related ESKD were less likely to have nephrology care or have a graft or arteriovenous fistula placed before ESKD onset (nephrology care: adjusted relative risk [aRR], 0.47; 95% CI, 0.40-0.56; graft or arteriovenous fistula placed: aRR, 0.31; 95% CI, 0.17-0.57). Conclusion and Relevance: In this study, those with pregnancy-related ESKD had reduced access to transplant and nephrology care, which could exacerbate existing disparities in a disproportionately Black population. Increased access to care could improve quality of life and health outcomes among these young adults with high potential for long-term survival.

Infections Following Kidney Transplantation After Exposure to Immunosuppression for Treatment of Glomerulonephritis.

RATIONALE & OBJECTIVE: Kidney transplant patients with glomerulonephritis (GN) as their native disease commonly have received pretransplant immunosuppression (PTI). This may contribute to the immunosuppression burden potentially increasing the risk for infections after transplantation. STUDY DESIGN: Single-center, retrospective cohort study. SETTING & PARTICIPANTS: Recipients of a kidney transplant from January 2005 until May 2020 at a tertiary care university teaching hospital. EXPOSURE: Patients with GN as their native kidney disease who received PTI for treatment of GN (n=184) were compared with nondiabetic recipients of kidney transplants who did not receive PTI (n = 579). OUTCOME: First occurrence after transplantation of an infection outcome, either viral (BK or cytomegalovirus [CMV] infection) or bacterial. ANALYTICAL APPROACH: Cox regression analysis adjusted for age at transplant, sex, race, donor type, year of transplant surgery, dialysis vintage, receipt of T-cell depleting induction, and CMV transplant status. RESULTS: Over a median follow-up period of 5.7 years, patients with GN PTI were not at an increased risk for developing any first viral infection compared with controls (adjusted HR [AHR] 0.69 [95% CI, 0.52-0.91]) nor at increased risk for specific viral infections: BK infection 19.6% vs 26.3% (AHR 0.72 [95% CI, 0.50-1.05]) or CMV infection, 24.5% vs 29.0% (AHR, 0.76 [95% CI, 0.54-1.07]), respectively. There was also no increased risk of developing a first bacterial infection: 54.5% vs 57.5% (AHR, 0.90 [95% CI, 0.71-1.13]). These findings of no increased risk for infection were independent of the type of PTI used (cyclophosphamide, rituximab, mycophenolate mofetil, or calcineurin inhibitor) or the type of T-cell depleting induction therapy (alemtuzumab or antithymocyte globulin) administered. LIMITATIONS: Single-center study, no data on methylprednisone use for PTI, unmeasured confounding. CONCLUSIONS: Use of PTI for the treatment of GN was not associated with an increased risk of viral (BK or CMV) or bacterial infection after transplantation. Additional surveillance for infection after transplantation for patients who received PTI may not be necessary. PLAIN-LANGUAGE SUMMARY: Many kidney transplant patients have glomerular disease as the cause of kidney failure. These patients may be exposed to immunosuppression before transplantation, which could increase the risk for infections after receipt of a transplanted kidney. We identified kidney transplant recipients at a university teaching hospital who received immunosuppression before transplant for the treatment of glomerular kidney disease. We examined their risk for infection after transplantation by comparing it with the risk among transplant patients who were not exposed to immunosuppression before transplant. We observed no increased risk for infection after exposure to prior immunosuppression. Therefore, patients exposed to significant amounts of immunosuppression before transplantation may not require special surveillance or medication adjustment for fear of infection after their receipt of a kidney transplant.

Polypharmacy in US Medicare beneficiaries with antineutrophil cytoplasmic antibody vasculitis.

BACKGROUND: Treatment requirements of antineutrophil cytoplasmic autoantibody vasculitis (AV) and high comorbidity burden among patients with AV may lead to higher potential for polypharmacy and its associated adverse outcomes, including adverse drug events, nonadherence, drug-drug interactions, and higher costs. Medication burden and risk factors associated with polypharmacy in patients with AV have not been well-characterized. OBJECTIVE: To characterize medication burden and examine prevalence of and risk factors for polypharmacy in the first year after diagnosis with AV. METHODS: We conducted a retrospective cohort study using 2015-2017 Medicare claims to identify incident cases of AV. We counted the number of unique generic products dispensed to patients in each of the 4 quarters after diagnosis and categorized medication count as high (≥10 medications), moderate (5-9 medications), or minimal or no polypharmacy (<5 medications). We used multinomial logistic regression to examine associations of predisposing, enabling, and medical need factors with having high or moderate polypharmacy. RESULTS: In 1,239 Medicare beneficiaries with AV, high or moderate polypharmacy was most common in the first quarter after diagnosis (83.7%), with 43.2% taking 5 - 9 medications and 40.5% taking at least 10. The odds of high polypharmacy were greater in all quarters for patients with eosinophilic granulomatosis with polyangiitis compared with granulomatosis with polyangiitis, ranging from 2.02 (95% CI = 1.18 - 3.46) in the third quarter to 2.96 (95% CI = 1.64-5.33) in the second quarter. Older age, diabetes, chronic kidney disease, obesity, a higher Charlson Comorbidity Index score, coverage with Medicaid/Part D low-income subsidy, and living in areas with low education or persistent poverty were risk factors for high or moderate polypharmacy. CONCLUSIONS: Medicare beneficiaries with newly diagnosed AV experienced a high medication burden, with more than 40% taking at least 10 medications and the highest rates among those with eosinophilic granulomatosis with polyangiitis. Patients with AV may benefit from medication therapy management interventions to manage complex drug regimens and reduce risks associated with polypharmacy. DISCLOSURES: Dr Derebail receives personal fees from Travere Therapeutics, Pfizer, Bayer, Forma Therapeutics, UpToDate, outside of the submitted work. The content is solely the responsibility of the authors and does not represent the official views of the National Institutes of Health or the Department of Veterans Affairs. Dr Thorpe receives royalties from SAGE Publishing for activities unrelated to the submitted work. This research is supported by internal funds from the University of North Carolina, as well as the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under award number R21AI160606 (PI: C. Thorpe).

Emerging Therapies and Advances in Sickle Cell Disease with a Focus on Renal Manifestations.

The underlying mechanisms of disease in sickle cell disease (SCD) contribute to a multifaceted nephropathy, commonly manifested as albuminuria. In severe SCD genotypes ( e.g. , Hemoglobin SS [HbSS]), albuminuria and CKD are major predictors of mortality in this population. Therefore, the monitoring and management of renal function is an intrinsic part of comprehensive care in SCD. Management of nephropathy in SCD can be accomplished with SCD-directed therapies and/or CKD-directed therapies. In the past 5 years, novel disease-modifying and palliative therapies have been approved in SCD to target aspects of the disease, such as anemia, inflammation, and vasculopathy. Along with conventional hydroxyurea and chronic transfusion, l -glutamine, crizanlizumab, and voxelotor have all been shown to mitigate some adverse effect of SCD, and their effect on nephropathy is being investigated. CKD-directed therapies such as renin-angiotensin-aldosterone system blockers have long been used in SCD nephropathy; however, more complete long-term studies on benefits are needed. Given the effect of renal disease on survival, further assessment of the mechanisms and efficacy of these SCD-directed or CKD-directed therapeutic agents is essential.

Pregnancy History and Kidney Disease Progression Among Women Enrolled in Cure Glomerulonephropathy.

Introduction: Preeclampsia increases the risk for future chronic kidney disease (CKD). Among those diagnosed with CKD, it is unclear whether a prior history of preeclampsia, or other complications in pregnancy, negatively impact kidney disease progression. In this longitudinal analysis, we assessed kidney disease progression among women with glomerular disease with and without a history of a complicated pregnancy. Methods: Adult women enrolled in the Cure Glomerulonephropathy study (CureGN) were classified based on a history of a complicated pregnancy (defined by presence of worsening kidney function, proteinuria, or blood pressure; or a diagnosis of preeclampsia, eclampsia, or hemolysis, elevated liver enzymes, and low platelets [HELLP] syndrome), pregnancy without these complications, or no pregnancy history at CureGN enrollment. Linear mixed models were used to assess estimated glomerular filtration rate (eGFR) trajectories and urine protein-to-creatinine ratios (UPCRs) from enrollment. Results: Over a median follow-up period of 36 months, the adjusted decline in eGFR was greater in women with a history of a complicated pregnancy compared to those with uncomplicated or no pregnancies (-1.96 [-2.67, -1.26] vs. -0.80 [-1.19, -0.42] and -0.64 [-1.17, -0.11] ml/min per 1.73 m2 per year, P = 0.007). Proteinuria did not differ significantly over time. Among those with a complicated pregnancy history, eGFR slope did not differ by timing of first complicated pregnancy relative to glomerular disease diagnosis. Conclusions: A history of complicated pregnancy was associated with greater eGFR decline in the years following glomerulonephropathy (GN) diagnosis. A detailed obstetric history may inform counseling regarding disease progression in women with glomerular disease. Continued research is necessary to better understand pathophysiologic mechanisms by which complicated pregnancies contribute to glomerular disease progression.

Tobacco exposure in adults and children with proteinuric glomerulopathies: a NEPTUNE cohort study.

BACKGROUND: Tobacco exposure has been recognized as a risk factor for cardiovascular disease (CVD) and progression of kidney disease. Patients with proteinuric glomerulopathies are at increased risk for cardiovascular morbidity and mortality. Multiple studies have linked tobacco exposure to CVD and chronic kidney disease, but the relationships between smoking and proteinuric glomerulopathies in adults and children have not been previously explored. METHODS: Data from the Nephrotic Syndrome Study Network (NEPTUNE), a multi-center prospective observational study of participants with proteinuric glomerulopathies, was analyzed. 371 adults and 192 children enrolled in NEPTUNE were included in the analysis. Self-reported tobacco exposure was classified as non-smoker, active smoker, former smoker, or exclusive passive smoker. Baseline serum cotinine levels were measured in a sub-cohort of 178 participants. RESULTS: The prevalence of active smokers, former smokers and exclusive passive smoking among adults at baseline was 14.6%, 29.1% and 4.9%, respectively. Passive smoke exposure was 16.7% among children. Active smoking (reference non-smoking) was significantly associated with greater total cholesterol among adults (ß 17.91 95% CI 0.06, 35.76, p = 0.049) while passive smoking (reference non-smoking) was significantly associated with greater proteinuria over time among children (ß 1.23 95% CI 0.13, 2.33, p = 0.03). Higher cotinine levels were associated with higher baseline eGFR (r = 0.17, p = 0.03). CONCLUSION: Tobacco exposure is associated with greater risk for CVD and worse kidney disease outcomes in adults and children with proteinuric glomerulopathies. Preventive strategies to reduce tobacco exposure may help protect against future cardiovascular and kidney morbidity and mortality in patients with proteinuric glomerulopathies.

PRTN3 variant correlates with increased autoantigen levels and relapse risk in PR3-ANCA versus MPO-ANCA disease.

A GWAS of patients with anti-neutrophil cytoplasmic antibodies (ANCAs) found an association between proteinase-3 ANCA (PR3-ANCA) and a single nucleotide polymorphism (rs62132293) upstream of PRTN3, encoding PR3. The variant (G allele) was shown to be an expression quantitative trait locus in healthy controls, but the clinical impact remains unknown. Longitudinally followed patients with ANCA and healthy controls were genotyped. Gene expression was quantified by real-time quantitative PCR from leukocyte RNA. Plasma PR3 was quantified by ELISA. Among patients, variant carriers had elevated leukocyte PRTN3 expression compared with noncarriers (C/G vs. C/C and G/G vs. C/C). Healthy controls had low PRTN3 regardless of genotype. Myeloperoxidase (MPO) expression did not differ by genotype. PRTN3 expression correlated with circulating PR3, and variant carriers had higher plasma PR3 compared with noncarriers. Among variant carriers, there was an increased risk of relapse in patients with PR3-ANCA versus MPO-ANCA. The risk allele marked by rs62132293 is clinically significant as it is associated with increased autoantigen and may, in part, explain increased relapse in PR3-ANCA. Our results underscore the role of autoantigen availability in ANCA vasculitis.

Precision nephrology identified tumor necrosis factor activation variability in minimal change disease and focal segmental glomerulosclerosis.

The diagnosis of nephrotic syndrome relies on clinical presentation and descriptive patterns of injury on kidney biopsies, but not specific to underlying pathobiology. Consequently, there are variable rates of progression and response to therapy within diagnoses. Here, an unbiased transcriptomic-driven approach was used to identify molecular pathways which are shared by subgroups of patients with either minimal change disease (MCD) or focal segmental glomerulosclerosis (FSGS). Kidney tissue transcriptomic profile-based clustering identified three patient subgroups with shared molecular signatures across independent, North American, European, and African cohorts. One subgroup had significantly greater disease progression (Hazard Ratio 5.2) which persisted after adjusting for diagnosis and clinical measures (Hazard Ratio 3.8). Inclusion in this subgroup was retained even when clustering was limited to those with less than 25% interstitial fibrosis. The molecular profile of this subgroup was largely consistent with tumor necrosis factor (TNF) pathway activation. Two TNF pathway urine markers were identified, tissue inhibitor of metalloproteinases-1 (TIMP-1) and monocyte chemoattractant protein-1 (MCP-1), that could be used to predict an individual's TNF pathway activation score. Kidney organoids and single-nucleus RNA-sequencing of participant kidney biopsies, validated TNF-dependent increases in pathway activation score, transcript and protein levels of TIMP-1 and MCP-1, in resident kidney cells. Thus, molecular profiling identified a subgroup of patients with either MCD or FSGS who shared kidney TNF pathway activation and poor outcomes. A clinical trial testing targeted therapies in patients selected using urinary markers of TNF pathway activation is ongoing.

Malignancy risk in kidney transplant recipients exposed to immunosuppression pre-transplant for the treatment of glomerulonephritis.

BACKGROUND: Kidney transplant patients with glomerulonephritis (GN) as their native disease may receive significant amounts of pre-transplant immunosuppression (PTI), which could increase the risk for development of malignancy post-transplant. METHODS: We conducted a single-center, retrospective study of kidney transplant recipients from January 2005 until May 2020. Patients with GN as their native kidney disease who received PTI for treatment of GN (n = 184) were compared with a control cohort (n = 579) of non-diabetic, non-PTI-receiving kidney transplant patients. We calculated hazard ratios (HR) with 95% confidence intervals (95% CI) for outcomes of first occurrence of solid or hematologic malignancy, non-melanoma skin cancer (NMSC) and post-transplant lymphoproliferative disorder (PTLD). RESULTS: Over a median follow-up of 5.7 years, PTI for GN was associated with significantly increased risk for malignancy compared with controls [13.0%  vs 9.7%, respectively; adjusted HR 1.82 (95% CI 1.10-3.00)], but not for NMSC [10.3% vs 11.4%, respectively; adjusted HR 1.09 (95% CI 0.64-1.83)] or PTLD [3.3% vs 3.1%, respectively; adjusted HR 1.02 (95% CI 0.40-2.61)]. The risk for malignancy was significantly increased in those who received cyclophosphamide [HR 2.59 (95% CI 1.48-4.55)] or rituximab [HR 3.82 (95% CI 1.69-8.65)] pre-transplant, and particularly in those who received both cyclophosphamide and rituximab, but not for calcineurin inhibitors or mycophenolate. CONCLUSION: The use of PTI for treatment of GN, especially cyclophosphamide or even with rituximab, is associated with increased risk for development of solid or hematologic malignancy post-transplant. These data highlight potential risks with treatment of GN and underscore the importance of post-transplant malignancy surveillance in this patient population.

Relevance of Combined Clinicopathologic Phenotype and Antineutrophil Cytoplasmic Autoantibody Serotype in the Diagnosis of Antineutrophil Cytoplasmic Autoantibody Vasculitis.

Introduction: Granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA), 2 major clinicopathologic variants of antineutrophil cytoplasmic autoantibody (ANCA) vasculitides, are mostly associated with proteinase 3 (PR3)-ANCA and myeloperoxidase (MPO)-ANCA, respectively. Less is known regarding the uncommon forms of ANCA vasculitis, PR3-ANCA MPA and MPO-ANCA GPA. Methods: In this cohort study we detailed the clinical presentation and outcome of patients with PR3-ANCA MPA and MPO-ANCA GPA from the Glomerular Disease Collaborative Network (GDCN) inception cohort. Baseline clinical manifestations, relapses, end-stage kidney disease (ESKD), and survival were compared within MPA cases by PR3-ANCA (n = 116) versus MPO-ANCA (n = 173) and within GPA cases by PR3-ANCA (n = 108) versus MPO-ANCA (n = 43). Fisher's exact test and Wilcoxon two sample test were used for comparisons. Proportional hazards models were used to evaluate the development of relapses, ESKD, and death. Results: Patients with PR3-ANCA MPA were younger (53 years vs. 62 years, P = 0.0007) and had increased prevalence of joint involvement (56% vs. 40%, P = 0.0115) and ear, nose, and throat (ENT) involvement (44% vs. 26%, P = 0.002) than MPO-ANCA MPA. Relapses, ESKD, and survival were similar between both MPA subsets. Within the GPA group, patients with MPO-ANCA GPA were older (61 years vs. 46 years, P = 0.0007) and more likely female (56% vs. 35%, P = 0.027) than PR3-ANCA GPA patients. MPO-ANCA GPA was also characterized by less prevalent ENT manifestations (58% vs. 77%, P = 0.028) and neurologic manifestations (5% vs. 25%, P = 0.0029), and increased ESKD and mortality. Conclusions: PR3-ANCA MPA and MPO-ANCA GPA are clinicopathologically distinct subsets of ANCA vasculitis that differ from MPO-ANCA MPA and PR3-ANCA GPA. Although the impact of these differences on the clinical management and outcome warrants further evaluation, these results support the recommendation of including both the phenotypic diagnosis and ANCA serotype in the diagnosis of ANCA vasculitis.

Sickle Cell Disease and the Kidney: Filters Gone Awry.

Throughout the lifespan, the kidney of a person with sickle cell disease is at increased risk of injury to the glomeruli, tubules, and renal vasculature. This injury manifests as urine concentrating defects, enuresis, albuminuria, acute kidney injury, chronic kidney disease, and end-stage kidney disease. The outcomes for patients who progress to end-stage kidney disease are poor and access to organ transplantation is limited. Therefore, identifying risk factors for progression, intervening with renoprotective agents early in life, and improving access to care are vital for sickle cell patients.

Health care costs and utilization prior to diagnosis of antineutrophil cytoplasmic antibody vasculitis in Medicare beneficiaries.

BACKGROUND: Antineutrophil cytoplasmic antibody (ANCA) vasculitis (AV) is a complex group of autoimmune disorders affecting blood vessels in multiple organ systems. Delays in diagnosis are common because AV symptoms can be nonspecific and present heterogeneously. This may result in increased health care utilization in the months preceding diagnosis. OBJECTIVE: To examine whether Medicare beneficiaries with AV experienced increased health care utilization and costs in the year before the first diagnosis recorded in claims, relative to beneficiaries without AV. METHODS: This retrospective cohort study used 2015-2016 Medicare Part A/B claims and Part D prescription drug data. Beneficiaries with newly diagnosed AV were identified by having 1 or more inpatient claims or 2 or more noninpatient claims 7 or more days apart in 2016 with an International Classification of Diseases, Tenth Revision, Clinical Modification code for AV, with no AV claims in the year prior. Beneficiaries with AV were matched 1:1 on age and sex to beneficiaries without any diagnoses for any type of systemic vasculitis in 2016. Beneficiaries with Part A/B coverage (AB, n = 1,460) and Part A/B/D coverage (ABD, n = 3,252) were analyzed separately. We estimated generalized linear mixed models with a negative binomial distribution to compare health care costs and utilization by AV status. RESULTS: Beneficiaries with AV had approximately 3 times higher Medicare Part A/B payments (incidence rate ratio [95% CI]: AB: 2.94 [2.44-3.53]; ABD: 2.95 [2.64-3.29]) and 2.5 times higher beneficiary Part A/B payments (AB: 2.47 [2.14-2.84]; ABD: 2.62 [2.40-2.87]) vs beneficiaries without AV. Beneficiaries with AV experienced significantly higher utilization across all categories, with the largest differences observed in hospital outpatient visits (AB: 2.69 [2.22-3.27]; ABD: 3.08 [2.73-3.47]). CONCLUSIONS: In the year prior to AV diagnosis, Medicare beneficiaries have significantly higher health care costs and utilization than beneficiaries without AV. DISCLOSURES: Dr Huang was supported by the University of North Carolina and GlaxoSmithKline Health Outcomes Fellowship during the time of the study and reports current employment at Horizon Therapeutics, Deerfield, IL. Dr Nguyen received predoctoral funding through a fellowship appointment sponsored by Bristol Myers Squibb during the time of the study and reports current employment at GlaxoSmithKline, Collegeville, PA. Dr Derebail receives personal fees from Travere Therapeutics, Bayer, and UpToDate, outside of the submitted work. The views expressed are those of the authors and do not represent the views of the Department of Veteran Affairs. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Glomerular Hematuria and the Utility of Urine Microscopy: A Review.

Evaluation of hematuria and microscopic examination of urine sediment are commonly used tools by nephrologists in their assessment of glomerular diseases. Certain morphological aspects of urine red blood cells (RBCs) seen by microscopy may help in identifying the source of hematuria as glomerular or not. Recognized signs of glomerular injury are RBC casts or dysmorphic RBCs, in particular acanthocytes (ring-shaped RBCs with protruding blebs). Despite being a highly operator-dependent test, urine sediment examination revealing these signs of glomerular hematuria has demonstrated specificities and positive predictive values ranging between 90%-100% for diagnosing glomerular disease, although sensitivity can be quite variable. Hematuria is a commonly used tool for diagnosing patients with proliferative glomerulonephritis such as IgA nephropathy, antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, and lupus nephritis, sometimes even as a surrogate for kidney involvement. Studies examining the role for hematuria in monitoring and predicting adverse outcomes in these diseases have shown inconsistent results, possibly due to inconsistent definitions that often fail to consider specific markers of glomerular hematuria such as dysmorphic RBCs, acanthocytes, or RBC casts. A consensus definition of what constitutes glomerular hematuria would help standardize use in future studies and likely improve the diagnostic and prognostic value of hematuria as a marker of glomerulonephritis.

Hyperkalemia and Metabolic Acidosis Occur at a Higher eGFR in Sickle Cell Disease.

Background: People with sickle cell disease (SCD) have an elevated estimated glomerular filtration rate (eGFR) compared with the general population, and this may alter the usual creatinine-based eGFR cutoffs for which physiologic evidence of kidney dysfunction is apparent. This study aimed to identify eGFR thresholds for hyperkalemia and metabolic acidosis in patients with SCD. Methods: This was a cross-sectional analysis of 733 patients with severe (hemoglobin SS or Sß0-thalassemia) SCD genotype, 238 patients with moderate (hemoglobin SC or Sß+-thalassemia) SCD genotype, and 1333 age- and sex-matched African Americans from the National Health and Nutrition Examination Survey (NHANES). The prevalence rates of hyperkalemia and metabolic acidosis were compared by eGFR category. Cutoffs for hyperkalemia and metabolic acidosis were determined using generalized additive models. Results: Hyperkalemia and metabolic acidosis were more common in those with severe SCD genotype (13% and 21%, respectively) compared with the NHANES (0.3% and 5%, respectively); the prevalence rates in the moderate SCD genotype were intermediate for hyperkalemia (3%) and metabolic acidosis (11%). The proportion of patients with hyperkalemia and metabolic acidosis progressively increased with lower eGFR category in both SCD genotype groups. The eGFR thresholds for hyperkalemia and metabolic acidosis were higher in the severe (85 and 91 ml/min per 1.73 m2, respectively) and moderate (52 and 102 ml/min per 1.73 m2, respectively) SCD genotypes compared with the NHANES (34 and 46 ml/min per 1.73 m2). Conclusions: We demonstrate that hyperkalemia and metabolic acidosis are more common and occur at higher eGFR values in patients with SCD compared with age- and sex-matched African Americans, including in eGFR ranges considered to be normal. Future studies using redefined creatinine-based eGFR thresholds for abnormal kidney function may identify high-risk patients for earlier intervention strategies and referral for specialized renal care in SCD.