Association of Rosuvastatin Use with Risk of Hematuria and Proteinuria.

BACKGROUND: Despite reports of hematuria and proteinuria with rosuvastatin use at the time of its approval by the US Food and Drug Association (FDA), little postmarketing surveillance exists to assess real-world risk. Current labeling suggests dose reduction (maximum daily dose of 10 mg) for patients with severe CKD. METHODS: Using deidentified electronic health record data, we analyzed 152,101 and 795,799 new users of rosuvastatin and atorvastatin, respectively, from 2011 to 2019. We estimated inverse probability of treatment-weighted hazard ratios (HRs) of hematuria, proteinuria, and kidney failure with replacement therapy (KFRT) associated with rosuvastatin. We reported the initial rosuvastatin dose across eGFR categories and evaluated for a dose effect on hematuria and proteinuria. RESULTS: Overall, we identified 2.9% of patients with hematuria and 1.0% with proteinuria during a median follow-up of 3.1 years. Compared with atorvastatin, rosuvastatin was associated with increased risk of hematuria (HR, 1.08; 95% confidence interval [95% CI], 1.04 to 1.11), proteinuria (HR, 1.17; 95% CI, 1.10 to 1.25), and KFRT (HR, 1.15; 95% CI, 1.02 to 1.30). A substantial share (44%) of patients with eGFR <30 ml/min per 1.73 m2 was prescribed high-dose rosuvastatin (20 or 40 mg daily). Risk was higher with higher rosuvastatin dose. CONCLUSIONS: Compared with atorvastatin, rosuvastatin was associated with increased risk of hematuria, proteinuria, and KFRT. Among patients with eGFR <30 ml/min per 1.73 m2, 44% were prescribed a rosuvastatin daily dose exceeding the FDA's recommended 10 mg daily dose. Our findings suggest the need for greater care in prescribing and monitoring rosuvastatin, particularly in patients who receive high doses or who have severe CKD.

High incidence of proliferative and membranous nephritis in SLE patients with low proteinuria in the Accelerating Medicines Partnership.

OBJECTIVE: Delayed detection of LN associates with worse outcomes. There are conflicting recommendations regarding a threshold level of proteinuria at which biopsy will likely yield actionable management. This study addressed the association of urine protein:creatinine ratios (UPCR) with clinical characteristics and investigated the incidence of proliferative and membranous histology in patients with a UPCR between 0.5 and 1. METHODS: A total of 275 SLE patients (113 first biopsy, 162 repeat) were enrolled in the multicentre multi-ethnic/racial Accelerating Medicines Partnership across 15 US sites at the time of a clinically indicated renal biopsy. Patients were followed for 1 year. RESULTS: At biopsy, 54 patients had UPCR <1 and 221 had UPCR ≥1. Independent of UPCR or biopsy number, a majority (92%) of patients had class III, IV, V or mixed histology. Moreover, patients with UPCR <1 and class III, IV, V, or mixed had a median activity index of 4.5 and chronicity index of 3, yet 39% of these patients had an inactive sediment. Neither anti-dsDNA nor low complement distinguished class I or II from III, IV, V or mixed in patients with UPCR <1. Of 29 patients with baseline UPCR <1 and class III, IV, V or mixed, 23 (79%) had a UPCR <0.5 at 1 year. CONCLUSION: In this prospective study, three-quarters of patients with UPCR <1 had histology showing class III, IV, V or mixed with accompanying activity and chronicity despite an inactive sediment or normal serologies. These data support renal biopsy at thresholds lower than a UPCR of 1.

Safety of procuring research tissue during a clinically indicated kidney biopsy from patients with lupus: data from the Accelerating Medicines Partnership RA/SLE Network.

OBJECTIVES: In lupus nephritis the pathological diagnosis from tissue retrieved during kidney biopsy drives treatment and management. Despite recent approval of new drugs, complete remission rates remain well under aspirational levels, necessitating identification of new therapeutic targets by greater dissection of the pathways to tissue inflammation and injury. This study assessed the safety of kidney biopsies in patients with SLE enrolled in the Accelerating Medicines Partnership, a consortium formed to molecularly deconstruct nephritis. METHODS: 475 patients with SLE across 15 clinical sites in the USA consented to obtain tissue for research purposes during a clinically indicated kidney biopsy. Adverse events (AEs) were documented for 30 days following the procedure and were determined to be related or unrelated by all site investigators. Serious AEs were defined according to the National Institutes of Health reporting guidelines. RESULTS: 34 patients (7.2%) experienced a procedure-related AE: 30 with haematoma, 2 with jets, 1 with pain and 1 with an arteriovenous fistula. Eighteen (3.8%) experienced a serious AE requiring hospitalisation; four patients (0.8%) required a blood transfusion related to the kidney biopsy. At one site where the number of cores retrieved during the biopsy was recorded, the mean was 3.4 for those who experienced a related AE (n=9) and 3.07 for those who did not experience any AE (n=140). All related AEs resolved. CONCLUSIONS: Procurement of research tissue should be considered feasible, accompanied by a complication risk likely no greater than that incurred for standard clinical purposes. In the quest for targeted treatments personalised based on molecular findings, enhanced diagnostics beyond histology will likely be required.

Thrombotic microangiopathy versus class IV lupus nephritis in systemic lupus erythematosus.

BACKGROUND: Kidney involvement is common in patients with systemic lupus erythematosus (SLE). This study investigates the clinical and prognostic characteristics of thrombotic microangiopathy (TMA) compared to class IV lupus nephritis in SLE patients. METHODS: A retrospective review of patients who underwent kidney biopsy, with a primary diagnosis of SLE and TMA between June 2006 and September 2018 was conducted. Those patients were subsequently compared to patients with class IV lupus nephritis between January 2018 and December 2018. Demographics, laboratory, and serological data at the time of biopsy were abstracted. RESULTS: Among 214 SLE patients records screened, 27 were included in the final analysis. Eight patients had lupus-related TMA without evidence of active lupus nephritis, while 19 patients had class IV lupus nephritis without evidence of TMA. TMA patients had significantly higher lactate dehydrogenase levels (718 ± 499 vs. 264 ± 107.7 U/L, p = 0.009), serum C3 (100.6 ± 39.3 vs. 65.8 ± 27 mg/dL, p = 0.049), white blood cell count (14743.8 ± 7933.3 vs. 5807.9 ± 2053.2 × 10E3/uL, p < 0.001), and total bilirubin (0.8 ± 0.5 vs. 0.3 ± 0.1 mg/dL, p = 0.007) in addition to significantly lower platelet counts (158.4 ± 88.6 vs. 240.3 ± 100.3 × 10E3/uL, p = 0.03), and haptoglobin (68.8 ± 116.1 vs. 166.8 ± 95.4 mg/dL, p = 0.03). After a median follow-up time of 53 weeks, 3 patients with TMA were dialysis-dependent (37.5%), compared with none in class IV lupus nephritis patients (p = 0.002). CONCLUSIONS: TMA-associated SLE has worse prognosis compared to class IV lupus nephritis. An array of laboratory and pathological findings may be of value in discriminating between those two entities.

Operational Recommendations for Scarce Resource Allocation in a Public Health Crisis.

The coronavirus disease 2019 pandemic may require rationing of various medical resources if demand exceeds supply. Theoretical frameworks for resource allocation have provided much needed ethical guidance, but hospitals still need to address objective practicalities and legal vetting to operationalize scarce resource allocation schemata. To develop operational scarce resource allocation processes for public health catastrophes, including the coronavirus disease 2019 pandemic, five health systems in Maryland formed a consortium-with diverse expertise and representation-representing more than half of all hospitals in the state. Our efforts built on a prior statewide community engagement process that determined the values and moral reference points of citizens and health-care professionals regarding the allocation of ventilators during a public health catastrophe. Through a partnership of health systems, we developed a scarce resource allocation framework informed by citizens' values and by general expert consensus. Allocation schema for mechanical ventilators, ICU resources, blood components, novel therapeutics, extracorporeal membrane oxygenation, and renal replacement therapies were developed. Creating operational algorithms for each resource posed unique challenges; each resource's varying nature and underlying data on benefit prevented any single algorithm from being universally applicable. The development of scarce resource allocation processes must be iterative, legally vetted, and tested. We offer our processes to assist other regions that may be faced with the challenge of rationing health-care resources during public health catastrophes.

Low-Level Proteinuria in Systemic Lupus Erythematosus.

INTRODUCTION: In patients with systemic lupus erythematosus (SLE) without concurrent active urinary sediment or unexplained acute kidney injury (AKI), current guidelines recommend performing a kidney biopsy in those with at least 500 mg/24-hour (European League Against Rheumatism/European Renal Association-European Dialysis and Transplant Association [EULAR/ERA-EDTA]) or 1000 mg/24-hour (American College of Rheumatology [ACR]) proteinuria. To evaluate the relevance of these indications, we studied histopathologic findings in patients with SLE with proteinuria below these cutoffs. METHODS: We retrospectively reviewed the clinical, laboratory and histological characteristics of patients with SLE with <1000 mg/24-hour proteinuria (or mg/g urinary protein-to-creatinine ratio [UPCR]) who underwent their first kidney biopsy between 2003 and 2018. RESULTS: We identified 87 patients with SLE with proteinuria less than 1000 mg/24-hour (or mg/g UPCR); 52 of 87 (60%) with isolated proteinuria, that is, without AKI or active urinary sediment (hematuria). Histologic evidence of lupus nephritis (LN) was present in 40 of 52 (76%). Of the 40 patients with LN, 12 had class I or II, 14 had class III or IV, 8 had class V, 6 had a combined proliferative and membranous LN. Non-lupus diagnoses included focal segmental glomerulosclerosis, acute interstitial nephritis, and others. Patient's age, low C3, low C4, and positivity for anti-double-stranded DNA (anti-dsDNA) antibodies predicted the histological diagnosis of LN on univariate logistic regression; however, a multivariate model including these parameters as independent covariates failed to predict LN. CONCLUSIONS: Patients with SLE with low-level proteinuria may have significant lupus- or non-lupus-related kidney disease with management implications. There was a significant burden of severe forms of LN. The presence of LN was not predicted by laboratory abnormalities. Based on our findings, we suggest current guidelines be revised to expand kidney biopsy indications to include isolated proteinuria of any grade.

The COVID-19 nephrology compendium: AKI, CKD, ESKD and transplantation.

The pandemic of coronavirus disease 2019 (CoVID-19) has been an unprecedented period. The disease afflicts multiple organ systems, with acute kidney injury (AKI) a major complication in seriously ill patients. The incidence of AKI in patients with CoVID-19 is variable across numerous international studies, but the high incidence of AKI and its associated worse outcomes in the critical care setting are a consistent finding. A multitude of patterns and mechanisms of AKI have been elucidated, and novel strategies to address shortage of renal replacement therapy equipment have been implemented. The disease also has had consequences on longitudinal management of patients with chronic kidney disease and end stage kidney disease. Kidney transplant recipients may be especially susceptible to CoVID-19 as a result of immunosuppression, with preliminary studies demonstrating high mortality rates. Increased surveillance of disease with low threshold for testing and adjustment of immunosuppression regimen during acute periods of illness have been recommended.

Interventions Made to Preserve Cognitive Function Trial (IMPCT) study protocol: a multi-dialysis center 2x2 factorial randomized controlled trial of intradialytic cognitive and exercise training to preserve cognitive function.

BACKGROUND: Kidney disease and dialysis significantly impact cognitive function across the age spectrum. Cognitive training (CT) and/or exercise training (ET) are promising approaches to preserve cognitive function among community-dwelling older adults, but have not been tested for cognition preservation in hemodialysis patients of all ages. In this manuscript, we summarize the protocol for the Interventions Made to Preserve Cognitive Function Trial (IMPCT). METHODS: We will perform a 2 × 2 factorial randomized controlled trial (RCT) of eligible adult (≥18 years) hemodialysis initiates (n = 200) to test whether intradialytic CT (brain games on a tablet PC), ET (foot peddlers) and combined CT + ET while undergoing hemodialysis preserves executive function compared to standard of care (SC). Participants will engage in the interventions to which they are randomized for 6 months. The primary objective is to compare, among interventions, the 3-month change in executive function measured using the Trail Making Test A (TMTA) and B (TMTB); specifically, executive function is calculated as TMTB-TMTA to account for psychomotor speed. This primary outcome was selected based on findings from our pilot study. The secondary objectives are to compare the risk of secondary cognitive outcomes, ESKD-specific clinical outcomes, and patient-centered outcomes at 3-months and 6-months. All data collection and interventions are conducted in the dialysis center. DISCUSSION: We hypothesize that receiving intradialytic CT or ET will better preserve executive function than SC but receiving combined CT + ET, will be the most effective intervention. The current trial will be an important step in understanding how intradialytic interventions might preserve cognitive health. TRIAL REGISTRATION: Clinicaltrials.Gov (Date: 8/6/18): # NCT03616535 . Protocol Version: 10 (April 2020). FUNDING: NIDDK R01DK114074.

Clinical course of COVID-19 in a liver transplant recipient on hemodialysis and response to tocilizumab therapy: A case report.

The novel coronavirus disease 2019 (COVID-19) is a highly infectious and rapidly spreading disease. There are limited published data on the epidemiology and outcomes of COVID-19 infection among organ transplant recipients. After initial flulike symptoms, progression to an inflammatory phase may occur, characterized by cytokine release rapidly leading to respiratory and multiorgan failure. We report the clinical course and management of a liver transplant recipient on hemodialysis, who presented with COVID-19 pneumonia, and despite completing a 5-day course of hydroxychloroquine, later developed marked inflammatory manifestations with rapid improvement after administration of off-label, single-dose tocilizumab. We also highlight the role of lung ultrasonography in early diagnosis of the inflammatory phase of COVID-19. Future investigation of the effects of immunomodulators among transplant recipients with COVID-19 infection will be important.

A Night Float System in Nephrology Fellowship: A Mixed Methods Evaluation.

Background: Johns Hopkins was an early adopter of an in-house nephrology fellowship night float to improve work-life balance. Our study aimed to elucidate attitudes to guide fellowship structuring. Methods: We performed a mixed-methods study surveying Johns Hopkins fellows, alumni, and faculty and conducting one focus group of current fellows. Surveys were developed through literature review, queried on a five-point Likert scale, and analyzed with t and ANOVA tests. The focus group transcript was analyzed by two independent reviewers. Results: Survey response rates were 14 (100%) fellows, 32 (91%) alumni, and 17 (94%) faculty. All groups felt quality of patient care was good to excellent with no significant differences among groups (range of means [SD], 4.1 [0.7]-4.6 [0.7]; P=0.12), although fellows had a statistically significantly more positive view than faculty on autonomy (4.6 [0.5] versus 4.1 [0.3]; P=0.006). Fellows perceived a positive effect across all domains of night float on the day team experience (range, 4.2 [0.8]-4.6 [0.6]; P<0.001 compared with neutral effect). Focus group themes included patient care, care continuity, professional development, wellness, and structural components. One fellow said, "…my bias is that every program would switch to a night float system if they could." All groups were satisfied with night float with 4.7 [0.5], 4.2 [0.8], and 4.0 [0.9] for fellows, faculty, and alumni, respectively; fellows were most enthusiastic (P=0.03). All three groups preferred night float, and fellows did so unanimously. Conclusions: Night float was well liked and enhanced the perceived daytime fellow experience. Alumni and faculty were positive about night float, although less so, possibly due to concerns for adequate preparation to handle overnight calls after graduation. Night float implementation at other nephrology programs should be considered based on program resources; such changes should be assessed by similar methods.

Correction: HIV Viremia and T-cell Activation Differentially Affect the Performance of Glomerular Filtration Rate Equations Based on Creatinine and Cystatin C.

[This corrects the article DOI: 10.1371/journal.pone.0082028.].

Association of HIV Suppression With Kidney Disease Progression Among HIV-Positive African Americans With Biopsy-Proven Classic FSGS.

BACKGROUND: In the era of combined antiretroviral therapy, classic focal segmental glomerulosclerosis (FSGS) is the most common histopathological finding in African American HIV-positive patients with kidney disease. We sought to determine whether HIV suppression is associated with lower risk of progression to end-stage renal disease (ESRD) among HIV-positive African Americans with biopsy-confirmed classic FSGS. METHODS: HIV-positive African Americans who underwent kidney biopsies at a single tertiary hospital between January 1996 and June 2011 were confirmed as having classic FSGS by the presence of segmental glomerulosclerosis without features of HIV-associated nephropathy. Multivariable Cox proportional hazards models were used to examine the independent association of viral suppression (HIV-RNA < 400 copies per milliliter at biopsy) with time to progression to ESRD. RESULTS: Of the 55 HIV-positive African Americans with classic FSGS, 26 had suppressed viral loads at the time of biopsy. Compared to viremic patients, those who were virally suppressed had a significantly higher mean CD4 cell count (452 vs. 260 cell/mm, respectively; P = 0.02) and median estimated glomerular filtration rate (53.5 vs 35.5 mL/min/1.73 m, respectively; P = 0.002). Adjusting for sex and baseline CD4 cell count, estimated glomerular filtration rate, and proteinuria, those with HIV-RNA levels <400 copies per milliliter at baseline had a 75% lower risk of progressing to ESRD (hazard ratio = 0.25; 95% CI: 0.07 to 0.88) during a median follow-up time of 2.70 years (interquartile range: 0.80-5.15 years). CONCLUSIONS: HIV suppression is associated with significantly lower risk of progression to ESRD among HIV-infected African Americans with classic FSGS, supporting the potential role of combined antiretroviral therapy for this histopathology in addition to HIV-associated nephropathy among HIV-positive individuals.

Phthalate exposure and odds of bacterial vaginosis among U.S. reproductive-aged women, NHANES 2001-2004.

Endocrine-disrupting chemicals, such as phthalates, are an unexamined potential risk factor for bacterial vaginosis (BV) and warrant investigation because hormones affect BV. We examined the association between phthalate exposure and BV in the National Health and Nutrition Examination Survey, 2001-2004. BV outcomes were defined as intermediate (Nugent score of 4-6) and positive (7-10). Phthalate metabolites, including monoethyl phthalate (MEP), mono-n-butyl phthalate (MnBP), and di(2-ethylhexyl) phthalate (DEHP) metabolites, were measured in urine. Among 854 women with complete data, multinomial logistic regression revealed that concentrations of MnBP (Q4 vs. Q1 OR = 3.01, 95% CI 1.76-5.15, p-trend <0.001) and ΣDEHP metabolites (Q4 OR = 2.55, 95% CI 1.45-4.47, p-trend = 0.03) were associated with Nugent-score BV, although only MnBP was significant after adjustment for confounders. Associations were null after adjustment for urinary creatinine (MnBP Q4 OR = 1.11, 95% CI 0.63-1.96; ΣDEHP Q4 OR = 0.72, 95% CI 0.37-1.39). Future work should further examine these relationships using direct measurements of intravaginal phthalates exposures.

Randomized Evaluation of Heart Failure With Preserved Ejection Fraction Patients With Acute Heart Failure and Dopamine: The ROPA-DOP Trial.

OBJECTIVES: This study sought to compare a continuous infusion diuretic strategy versus an intermittent bolus diuretic strategy, with the addition of low-dose dopamine (3 µg/kg/min) in the treatment of hospitalized patients with heart failure with preserved ejection fraction (HFpEF). BACKGROUND: HFpEF patients are susceptible to development of worsening renal function (WRF) when hospitalized with acute heart failure; however, inpatient treatment strategies to achieve safe and effective diuresis in HFpEF patients have not been studied to date. METHODS: In a prospective, randomized, clinical trial, 90 HFpEF patients hospitalized with acute heart failure were randomized within 24 h of admission to 1 of 4 treatments: 1) intravenous bolus furosemide administered every 12 h; 2) continuous infusion furosemide; 3) intermittent bolus furosemide with low-dose dopamine; and 4) continuous infusion furosemide with low-dose dopamine. The primary endpoint was percent change in creatinine from baseline to 72 h. Linear and logistic regression analyses with tests for interactions between diuretic and dopamine strategies were performed. RESULTS: Compared to intermittent bolus strategy, the continuous infusion strategy was associated with higher percent increase in creatinine (continuous infusion: 16.01%; 95% confidence interval [CI]: 8.58% to 23.45% vs. intermittent bolus: 4.62%; 95% CI: -1.15% to 10.39%; p = 0.02). Low-dose dopamine had no significant effect on percent change in creatinine (low-dose dopamine: 12.79%; 95% CI: 5.66% to 19.92%, vs. no-dopamine: 8.03%; 95% CI: 1.44% to 14.62%; p = 0.33). Continuous infusion was also associated with greater risk of WRF than intermittent bolus (odds ratio [OR]: 4.32; 95% CI: 1.26 to 14.74; p = 0.02); no differences in WRF risk were seen with low-dose dopamine. No significant interaction was seen between diuretic strategy and low-dose dopamine (p > 0.10). CONCLUSIONS: In HFpEF patients hospitalized with acute heart failure, low-dose dopamine had no significant impact on renal function, and a continuous infusion diuretic strategy was associated with renal impairment. (Diuretics and Dopamine in Heart Failure With Preserved Ejection Fraction [ROPA-DOP]; NCT01901809).