Comparison of eGFR Equations to Guide Dosing of Medications for Kidney Transplant Recipients.

BACKGROUND: Clinicians caring for kidney transplant recipients (KTRs) most commonly use estimated glomerular filtration rate (eGFR) to guide medication dosing as it is the most readily available measure of kidney function. Which eGFR equations provide the most accurate medication dosing guidance for KTRs remains uncertain. METHODS: We studied 415 stable KTRs in Canada and New Zealand. Participants completed same-day measurements of creatinine and cystatin C and measured GFR (diethylenetriaminepentaacetic acid). Chronic Kidney Disease Epidemiology Collaboration, European Kidney Function Consortium, and transplant-specific eGFR equations were compared with both Cockcroft-Gault creatinine clearance (CrCl) and measured GFR. eGFR equations were assessed both indexed to a standardized body surface area (BSA) of 1.73 m2 (milliliter per minute per 1.73 m2, as is conventional reporting from most clinical laboratories) and nonindexed (milliliter per minute) accounting for actual BSA. The primary outcome was the proportion of medication dosing discordance relative to Cockcroft-Gault CrCl or measured GFR for 8 commonly prescribed medications. Stratified analyses were performed on the basis of obesity status. RESULTS: Nonindexed eGFR equations (milliliter per minute) resulted in substantially lower medication dosing discordance compared with indexed eGFR equations (milliliter per minute per 1.73 m2). These findings were most pronounced among KTRs with obesity, in whom underdosing was frequent. When compared with Cockcroft-Gault CrCl, the lowest proportion of discordance was found with the nonindexed 2023 transplant-specific equation. When compared with measured GFR, the lowest proportion of discordance was found with the nonindexed 2021 Chronic Kidney Disease Epidemiology CollaborationCr/CysC equation. CONCLUSIONS: Nonindexed eGFR values accounting for actual BSA should be used by clinicians for medication dosing in KTRs. These findings may inform KT providers about which eGFR equations provide the safest, most accurate medication dosing guidance for KTRs.

Time to Benefit of Surgery vs Targeted Medical Therapy for Patients With Primary Aldosteronism: A Meta-analysis.

CONTEXT: Primary aldosteronism (PA) is one of the most common causes of secondary hypertension, but the comparative outcomes of targeted treatment remain unclear. OBJECTIVE: To compare the clinical outcomes in patients treated for primary aldosteronism over time. METHODS: Medline and EMBASE were searched. Original studies reporting the incidence of mortality, major adverse cardiovascular outcomes (MACE), progression to chronic kidney disease, or diabetes following adrenalectomy vs medical therapy were selected. Two reviewers independently abstracted data and assessed study quality. Standard meta-analyses were conducted using random-effects models to estimate relative differences. Time to benefit meta-analyses were conducted by fitting Weibull survival curves to estimate absolute risk differences and pooled using random-effects models. RESULTS: 15 541 patients (16 studies) with PA were included. Surgery was consistently associated with an overall lower risk of death (hazard ratio [HR] 0.34, 95% CI 0.22-0.54) and MACE (HR 0.55, 95% CI 0.36-0.84) compared with medical therapy. Surgery was associated with a significantly lower risk of hospitalization for heart failure (HR 0.48 95% CI 0.34-0.70) and progression to chronic kidney disease (HR 0.62 95% CI 0.39-0.98), and nonsignificant reductions in myocardial infarction and stroke. In absolute terms, 200 patients would need to be treated with surgery instead of medical therapy to prevent 1 death after 12.3 (95% CI 3.1-48.7) months. CONCLUSION: Surgery is associated with lower all-cause mortality and MACE than medical therapy for PA. For most patients, the long-term surgical benefits outweigh the short-term perioperative risks.

Impaired Renal Function and Major Cardiovascular Events in Young Adults.

BACKGROUND: Cardiovascular (CV) disease in young adults (aged 18-39 years) is on the rise. Whether subclinical reductions in kidney function (ie, estimated glomerular filtration rate [eGFR] above the current threshold for chronic kidney disease but below age-expected values) are associated with elevated CV risk is unknown. OBJECTIVES: The goal of this study was to examine age-specific associations of subclinical eGFR reductions in young adults with major adverse cardiovascular events (MACEs) and MACE plus heart failure (MACE+). METHODS: A retrospective cohort study of 8.7 million individuals (3.6 million aged 18-39 years) was constructed using linked provincial health care data sets from Ontario, Canada (January 2008-March 2021). Cox models were used to examine the association of categorized eGFR (50-120 mL/min/1.73 m2) with MACE (first of CV mortality, acute coronary syndrome, and ischemic stroke) and MACE+, stratified according to age (18-39, 40-49, and 50-65 years). RESULTS: In the study cohort (mean age 41.3 years; mean eGFR 104.2 mL/min/1.73 m2; median follow-up 9.2 years), a stepwise increase in the relative risk of MACE and MACE+ was observed as early as eGFR <80 mL/min/1.73 m2 in young adults (eg, for MACE, at eGFR 70-79 mL/min/1.73 m2, ages 18-30 years: 2.37 events per 1,000 person years [HR: 1.31; 95% CI: 1.27-1.40]; ages 40-49 years: 6.26 events per 1,000 person years [HR: 1.09; 95% CI: 1.06-1.12]; ages 50-65 years: 14.9 events per 1,000 person years [HR: 1.07; 95% CI: 1.05-1.08]). Results persisted for each MACE component and in additional analyses (stratifying according to past CV disease, accounting for albuminuria at index, and using repeated eGFR measures). CONCLUSIONS: In young adults, eGFR below age-expected values were associated with an elevated risk for MACE and MACE+, warranting age-appropriate risk stratification, proactive monitoring, and timely intervention.

Risk of venous thromboembolism or hemorrhage among individuals with chronic kidney disease on prophylactic anticoagulant after hip or knee arthroplasty.

Chronic kidney disease (CKD) confers a high risk of thrombosis and bleeding. However, little evidence exists regarding the optimal choice of postoperative thromboprophylaxis in these patients. We conducted a population-based, retrospective cohort study among adults ≥66 years old with CKD undergoing hip or knee arthroplasty who had filled an outpatient prophylactic anticoagulant prescription between 2010 and 2020 in Ontario, Canada. The primary outcomes of venous thrombosis (VTE) and hemorrhage were identified by validated algorithms using relevant diagnoses and billing codes. Overlap-weighted cause-specific Cox proportional hazard models were used to examine the association of direct oral anticoagulants (DOAC) on the 90-day risk of VTE and hemorrhage compared with low-molecular-weight heparin (LMWH). A total of 27 645 patients were prescribed DOAC (N = 22 943) or LMWH (N = 4702) after arthroplasty. Rivaroxaban was the predominant DOAC (94.5%), while LMWH mainly included enoxaparin (67%) and dalteparin (31.5%). DOAC users had higher eGFRs, fewer co-morbidities, and surgery in more recent years compared to LMWH users. After weighing, DOAC (compared with LMWH) was associated with a lower risk of VTE (DOAC: 1.5% vs. LMWH: 2.1%, weighted hazard ratio [HR] 0.75, 95% confidence interval [CI] 0.59-0.94) and a higher risk of hemorrhage (DOAC: 1.3% vs. LMWH: 1.0%, weighted HR 1.44, 95% CI 1.04-1.99). Additional analyses including a more stringent VTE defining algorithm, different eGFR cut-offs, and limiting to rivaroxaban and enoxaparin showed consistent findings. Among elderly adults with CKD, DOAC was associated with a lower VTE risk and a higher hemorrhage risk compared to LMWH following hip or knee arthroplasty.

A Health Survey-Based Prediction Equation for Incident CKD.

BACKGROUND: Prediction tools that incorporate self-reported health information could increase CKD awareness, identify modifiable lifestyle risk factors, and prevent disease. We developed and validated a survey-based prediction equation to identify individuals at risk for incident CKD (eGFR <60 ml/min per 1.73 m2), with and without a baseline eGFR. METHODS: A cohort of adults with an eGFR ≥70 ml/min per 1.73 m2 from Ontario, Canada, who completed a comprehensive general population health survey between 2000 and 2015 were included (n=22,200). Prediction equations included demographics (age, sex), comorbidities, lifestyle factors, diet, and mood. Models with and without baseline eGFR were derived and externally validated in the UK Biobank (n=15,522). New-onset CKD (eGFR <60 ml/min per 1.73 m2) with ≤8 years of follow-up was the primary outcome. RESULTS: Among Ontario individuals (mean age, 55 years; 58% women; baseline eGFR, 95 (SD 15) ml/min per 1.73 m2), new-onset CKD occurred in 1981 (9%) during a median follow-up time of 4.2 years. The final models included lifestyle factors (smoking, alcohol, physical activity) and comorbid illnesses (diabetes, hypertension, cancer). The model was discriminating in individuals with and without a baseline eGFR measure (5-year c-statistic with baseline eGFR: 83.5, 95% confidence interval [CI], 82.2 to 84.9; without: 81.0, 95% CI, 79.8 to 82.4) and well calibrated. In external validation, the 5-year c-statistic was 78.1 (95% CI, 74.2 to 82.0) and 66.0 (95% CI, 61.6 to 70.4), with and without baseline eGFR, respectively, and maintained calibration. CONCLUSIONS: Self-reported lifestyle and health behavior information from health surveys may aid in predicting incident CKD. PODCAST: This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast.aspx?p=CJASN&e=2023_01_10_CJN05650522.mp3.

Social determinants of health and the transition from advanced chronic kidney disease to kidney failure.

BACKGROUND: The transition from chronic kidney disease (CKD) to kidney failure is a vulnerable time for patients, with suboptimal transitions associated with increased morbidity and mortality. Whether social determinants of health are associated with suboptimal transitions is not well understood. METHODS: This retrospective cohort study included 1070 patients with advanced CKD who were referred to the Ottawa Hospital Multi-Care Kidney Clinic and developed kidney failure (dialysis or kidney transplantation) between 2010 and 2021. Social determinant information, including education level, employment status and marital status, was collected under routine clinic protocol. Outcomes surrounding suboptimal transition included inpatient (versus outpatient) dialysis starts, pre-emptive (versus delayed) access creation and pre-emptive kidney transplantation. We examined the association between social determinants of health and suboptimal transition outcomes using multivariable logistic regression. RESULTS: The mean age and estimated glomerular filtration rate were 63 years and 18 ml/min/1.73 m2, respectively. Not having a high school degree was associated with higher odds for an inpatient dialysis start compared with having a college degree {odds ratio [OR] 1.71 [95% confidence interval (CI) 1.09-2.69]}. Unemployment was associated with higher odds for an inpatient dialysis start [OR 1.85 (95% CI 1.18-2.92)], lower odds for pre-emptive access creation [OR 0.53 (95% CI 0.34-0.82)] and lower odds for pre-emptive kidney transplantation [OR 0.48 (95% CI 0.24-0.96)] compared with active employment. Being single was associated with higher odds for an inpatient dialysis start [OR 1.44 (95% CI 1.07-1.93)] and lower odds for pre-emptive access creation [OR 0.67 (95% CI 0.50-0.89)] compared with being married. CONCLUSIONS: Social determinants of health, including education, employment and marital status, are associated with suboptimal transitions from CKD to kidney failure.

The value of repeat kidney biopsy during an atypical course of membranous nephropathy.

BACKGROUND: The clinical trajectory for patients with primary membranous nephropathy ranges widely from spontaneous remission to a rapid decline in kidney function. Etiologies for rapid progression with membranous nephropathy include concurrent bilateral renal vein thrombosis, malignant hypertension, and crescentic membranous nephropathy. Given the wide heterogeneity in prognosis, timing of immunosuppressive therapy is often challenging and centers around an individual patient's perceived risk for rapidly progressive disease. CASE PRESENTATION: Herein, we describe the clinical course of a young patient who initially developed a typical presentation of membranous nephropathy with consistent kidney biopsy findings. Given clinical stability, a six month observation period was undertaken prior to initiating immunosuppression. Within this observation window, the patient developed community acquired pneumonia followed several weeks later by a sudden, rapid decline in kidney function requiring dialysis. Repeat kidney biopsy revealed post-infectious glomerulonephritis superimposed upon a background of membranous nephropathy. Immunosuppressive therapy resulted in a favorable long-term outcome with normalization of kidney function and remission of nephrotic syndrome. To our knowledge, this is the first report of the simultaneous occurrence of these two glomerular disease processes. CONCLUSION: This case illustrates the value of repeat kidney biopsy during an atypical course of membranous nephropathy. Superimposed glomerular disease processes should be considered during a course of rapidly progressive membranous nephropathy.

Performance of the 2021 Race-Free CKD-EPI Creatinine- and Cystatin C-Based Estimated GFR Equations Among Kidney Transplant Recipients.

RATIONALE & OBJECTIVE: Race-free estimated glomerular filtration rate (eGFR) equations incorporating creatinine with and without cystatin C were recently developed and recommended for routine use. However, the performance of these equations among kidney transplant recipients (KTRs) remains unknown. STUDY DESIGN: Cross-sectional study to validate the 2021 race-free Chronic Kidney Disease (CKD) Epidemiology Collaboration (CKD-EPI) eGFR equation based on creatinine alone (eGFRcr) or based on creatinine and cystatin C (eGFRcr-cys) among KTRs. SETTING & PARTICIPANTS: KTRs in stable condition (N = 415) from Canada and New Zealand with same-day measurements of creatinine, cystatin C, and glomerular filtration rate (GFR) using radiolabeled diethylenetriaminepentaacetic acid. TESTS COMPARED: The 2009 CKD-EPI eGFRcr, 2021 CKD-EPI eGFRcr, 2012 CKD-EPI eGFRcr-cys, 2021 CKD-EPI eGFRcr-cys, 2012 CKD-EPI eGFRcys, and Modification of Diet in Renal Disease (MDRD) Study eGFR equations were compared with measured GFR. OUTCOMES: Bias, precision, accuracy, and correct classification by CKD stage. Bias was defined as the difference between estimated and measured GFR. Precision was represented by the interquartile range. Accuracy was defined as the percentages of participants with eGFRs within 10%/20%/30% (P10/P20/P30) of measured GFR, root mean square error, and mean absolute error. RESULTS: 87% of patients studied were White, 3% Black, and 10% other races. Mean measured GFR was 53 ± 19 (SD) mL/min/1.73 m2. The 2009 and 2021 CKD-EPI eGFRcr equations demonstrated similar median bias (-2.3 vs -0.2 mL/min/1.73 m2, respectively), precision (14.5 vs 14.9 mL/min/1.73 m2), and accuracy (P10/P20/P30, 32%/65%/84% vs 33%/63%/84%). The 2012 and 2021 CKD-EPI eGFRcr-cys equations also demonstrated similar median bias (-3.6 vs 0.3 mL/min/1.73 m2, respectively), precision (13.3 vs 14.3 mL/min/1.73 m2), and accuracy (P10/P20/P30, 32%/63%/80% vs 32%/67%/83%). No clear difference in performance was detected between the 2021 CKD-EPI eGFRcr and eGFRcr-cys equations among KTRs. The proportion of correct classification by CKD stage was similar across all eGFR equations. LIMITATIONS: Moderate sample size, few patients had a GFR <30 mL/min/1.73 m2, and the large majority of patients were White. CONCLUSIONS: Among KTRs, the 2021 race-free CKD-EPI eGFR equations perform similarly to the previous CKD-EPI equations that included race correction terms. No significant difference in performance was observed between the 2021 CKD-EPI eGFRcr and eGFRcr-cys equations in the kidney transplant population.

Benefits of Surgical Over Medical Treatment for Unilateral Primary Aldosteronism.

Primary aldosteronism is the most common and modifiable form of secondary hypertension. Left untreated, primary aldosteronism leads high rates of cardiovascular, metabolic, and kidney disease. Therefore, early diagnosis and targeted therapy are crucial to improve long-term patient outcomes. In the case of unilateral primary aldosteronism, surgical adrenalectomy is the guideline-recommended treatment of choice as compared to alternative medical therapies such as mineralocorticoid receptor antagonist medications. Surgical adrenalectomy is not only highly successful in reversing the biochemical abnormalities inherent to primary aldosteronism, but also in mitigating the long-term risks associated with this disease. Indeed, as opposed to medical treatment alone, surgical adrenalectomy offers the potential for disease cure. Within this review article, we review the existing evidence highlighting the benefits of surgical over medical treatment for unilateral primary aldosteronism.

Intravenous albumin for the prevention of hemodynamic instability during sustained low-efficiency dialysis: a randomized controlled feasibility trial (The SAFER-SLED Study).

BACKGROUND: Hemodynamic instability is a frequent complication of sustained low-efficiency dialysis (SLED) treatments in the ICU. Intravenous hyperoncotic albumin may prevent hypotension and facilitate ultrafiltration. In this feasibility trial, we sought to determine if a future trial, powered to evaluate clinically relevant outcomes, is feasible. METHODS: This single-center, blinded, placebo-controlled, randomized feasibility trial included patients with acute kidney injury who started SLED in the ICU. Patients were randomized to receive 25% albumin versus 0.9% saline (control) as 100 mL boluses at the start and midway through SLED, for up to 10 sessions. The recruitment rate and other feasibility outcomes were determined. Secondary exploratory outcomes included ultrafiltration volumes and metrics of hemodynamic instability. RESULTS: Sixty patients (271 SLED sessions) were recruited over 10 months. Age and severity of illness were similar between study groups. Most had septic shock and required vasopressor support at baseline. Protocol adherence occurred for 244 sessions (90%); no patients were lost to follow-up; no study-related adverse events were observed; open label albumin use was 9% and 15% in the albumin and saline arms, respectively. Ultrafiltration volumes were not significantly different. Compared to the saline group, the albumin group experienced less hemodynamic instability across all definitions assessed including a smaller absolute decrease in systolic blood pressure (mean difference 10.0 mmHg, 95% confidence interval 5.2-14.8); however, there were significant baseline differences in the groups with respect to vasopressor use prior to SLED sessions (80% vs 61% for albumin and saline groups, respectively). CONCLUSIONS: The efficacy of using hyperoncotic albumin to prevent hemodynamic instability in critically ill patients receiving SLED remains unclear. A larger trial to evaluate its impact in this setting, including evaluating clinically relevant outcomes, is feasible. Trial registration ClinicalTrials.gov (NCT03665311); First Posted: Sept 11th, 2018. https://clinicaltrials.gov/ct2/show/NCT03665311?term=NCT03665311&draw=2&rank=1.

Acute kidney injury in renal transplant recipients undergoing cardiac surgery.

BACKGROUND: Acute kidney injury (AKI) is a key risk factor for chronic kidney disease in the general population, but has not been investigated in detail among renal transplant recipients (RTRs). We investigated the incidence, severity and risk factors for AKI following cardiac surgery among RTRs compared with non-RTRs with otherwise similar clinical characteristics. METHODS: We conducted a retrospective cohort study of RTRs (n = 83) and non-RTRs (n = 83) who underwent cardiac surgery at two major academic medical centers. Non-RTRs were matched 1:1 to RTRs by age, preoperative (preop) estimated glomerular filtration rate and type of cardiac surgery. We defined AKI according to Kidney Disease: Improving Global Outcomes criteria. RESULTS: RTRs had a higher rate of AKI following cardiac surgery compared with non-RTRs [46% versus 28%; adjusted odds ratio 2.77 (95% confidence interval 1.36-5.64)]. Among RTRs, deceased donor (DD) versus living donor (LD) status, as well as higher versus lower preop calcineurin inhibitor (CNI) trough levels, were associated with higher rates of AKI (57% versus 33% among DD-RTRs versus LD-RTRs; P = 0.047; 73% versus 36% among RTRs with higher versus lower CNI trough levels, P = 0.02). The combination of both risk factors (DD status and higher CNI trough level) had an additive effect (88% AKI incidence among patients with both risk factors versus 25% incidence among RTRs with neither risk factor, P = 0.004). CONCLUSIONS: RTRs have a higher risk of AKI following cardiac surgery compared with non-RTRs with otherwise similar characteristics. Among RTRs, DD-RTRs and those with higher preop CNI trough levels are at the highest risk.

Acquired 5-oxoproline acidemia successfully treated with N-acetylcysteine.

Acquired 5-oxoprolinemia is increasingly recognized as a cause of anion gap metabolic acidosis. It predominantly occurs in chronically ill, malnourished women with impaired renal function and chronic acetaminophen ingestion. Depletion of glutathione and cysteine stores leads to elevated 5-oxoproline levels. N-acetylcysteine, given its effect in repleting glutathione and cysteine stores, has been proposed as a potential treatment for 5-oxoprolinemia, though reports of its successful use are lacking. We present a case of 5-oxoproline metabolic acidosis that persisted despite discontinuation of acetaminophen. However, the acidosis rapidly resolved with N-acetylcysteine administration.

Lanthanum deposition from oral lanthanum carbonate in the upper gastrointestinal tract.

AIMS: Lanthanum carbonate is used as an alternative to calcium-based phosphate binders to manage hyperphosphataemia in patients with renal failure. The deposition of lanthanum within gastroduodenal mucosa of patients treated with the medication has been described, but given the relative novelty of this entity, the histiocytic deposits in the gastroduodenal mucosa can be confused with a variety of other processes, including infections and other drug-induced forms of injury. METHODS AND RESULTS: We describe five cases of lanthanum phosphate deposition in upper gastrointestinal (GI) tract biopsies. Three cases were confirmed with scanning electron microscopy and energy dispersive X-ray analysis, including one unique patient, status post-renal transplant for polycystic kidney disease, who had last taken lanthanum 7 years prior to biopsy. CONCLUSION: Lanthanum deposition in the upper GI tract is a mimic of other drug-related forms of GI injury, including iron pill-related gastropathy. The key to making this diagnosis is a thorough drug history and awareness of the histological features.

Hydroxyurea for Treatment of Nephrotic Syndrome Associated With Polycythemia Vera.

Myeloproliferative disorders are a rare cause of focal segmental glomerulosclerosis (FSGS), although the mechanism is unclear. Hydroxyurea is commonly used in these disorders for its cytoreductive properties; however, the effect of this treatment on proteinuria or kidney function remains unclear in cases of myeloproliferative disorder-associated FSGS. We describe the clinical course of a patient with polycythemia vera and nephrotic-range proteinuria, demonstrated to have FSGS on biopsy. The patient had a distant history of granulomatosis with polyangiitis (Wegener's), for which he routinely had his kidney function and proteinuria measured, allowing for early detection of nephrotic syndrome soon after being diagnosed with polycythemia vera. Treatment with hydroxyurea resulted in rapid improvement in proteinuria that correlated with a decrease in hematocrit. This response was replicated 2 additional times when the patient was taken off and then restarted on hydroxyurea therapy. He now maintains a steady dose of hydroxyurea with favorable kidney measures (proteinuria with <1g/d of protein excretion and serum creatinine of 1.27mg/dL [corresponding to estimated glomerular filtration rate of 56mL/min/1.73 m(2)]). This case suggests that early screening and treatment for myeloproliferative disorder-associated FSGS may lead to improved long-standing kidney function.

Large-volume barium aspiration.

We present a case of large-volume barium aspiration in a 56-year-old woman with stage IV tongue squamous cell carcinoma and longstanding dysphagia. The patient rapidly developed hypoxemic respiratory failure from the resultant chemical pneumonitis. However, her respiratory status improved with supportive care alone in 48 hours. Barium aspiration is rare and often produces dramatic radiographic findings, but is generally associated with a favorable prognosis.

Vascular endothelial growth factor-a and islet vascularization are necessary in developing, but not adult, pancreatic islets.

Pancreatic islets are highly vascularized mini-organs, and vascular endothelial growth factor (VEGF)-A is a critical factor in the development of islet vascularization. To investigate the role of VEGF-A and endothelial cells (ECs) in adult islets, we used complementary genetic approaches to temporally inactivate VEGF-A in developing mouse pancreatic and islet progenitor cells or in adult ß-cells. Inactivation of VEGF-A early in development dramatically reduced pancreatic and islet vascularization, leading to reduced ß-cell proliferation in both developing and adult islets and, ultimately, reduced ß-cell mass and impaired glucose clearance. When VEGF-A was inactivated in adult ß-cells, islet vascularization was reduced twofold. Surprisingly, even after 3 months of reduced islet vascularization, islet architecture and ß-cell gene expression, mass, and function were preserved with only a minimal abnormality in glucose clearance. These data show that normal pancreatic VEGF-A expression is critical for the recruitment of ECs and the subsequent stimulation of endocrine cell proliferation during islet development. In contrast, although VEGF-A is required for maintaining the specialized vasculature observed in normal adult islets, adult ß-cells can adapt and survive long-term reductions in islet vascularity. These results indicate that VEGF-A and islet vascularization have a lesser role in adult islet function and ß-cell mass.