Performance and Interpretation of Sonography in the Practice of Nephrology: Core Curriculum 2024.

Ultrasonography is increasingly being performed by clinicians at the point of care, and nephrologists are no exception. This Core Curriculum illustrates how ultrasonography can be incorporated into clinical decision making across the spectrum of kidney disease to optimize the care nephrologists provide to patients. Sonography is valuable in outpatient and inpatient settings for the diagnosis and management of acute and chronic kidney disease, evaluation of cystic disease, urinary obstruction, pain, hematuria, proteinuria, assessment of volume status, and in providing guidance for kidney biopsy. As kidney disease advances, ultrasound is useful in the placement and maintenance of temporary and permanent access for dialysis. After kidney transplantation, ultrasonography is critical for evaluation of allograft dysfunction and for biopsies. Sonography skills expedite patient care and enhance the practice of nephrology and are relatively easily acquired with training. It is our hope that this curriculum will encourage nephrologists to learn and apply this valuable skill.

Metabolic alkalosis in hemodialysis patients.

BACKGROUND: Hemodialysis solutions typically contain a high alkali concentration designed to counter interdialytic acidosis, but this could result in persistent alkalosis in some patients. The prevalence and significance of persistent alkalosis were therefore examined at four outpatient centers over a 10-year period. METHODS: Alkalosis was defined as a pre-dialysis serum [HCO3 ] ≥ 26 meq/L in >6 months of a 12-month period and was persistent if present in a majority of months thereafter. Control patients had a serum [HCO3 ] of 19-23 meq/L > 6 of every 12 months. Standard, citrate-containing dialysate was used in all patients without adjustment of bicarbonate concentration. RESULTS: 444 of 1271 patients had alkalosis that persisted in 73. Compared to control patients, persistently alkalotic patients were older, but gender, race, starting weight, comorbidities, and mortality did not differ. Dialysis dose was 7% greater, protein catabolic rate was 11% lower, and interdialytic weight gain was 29% lower, all p < 0.001. Persistently alkalotic patients had double the incidence of cardiac arrhythmias (p = 0.07) and a 20% greater intradialytic blood pressure decrease (p < 0.001). CONCLUSIONS: Alkalosis is common in hemodialysis patients and can be persistent, likely due to decreased protein catabolic rate and increased dialysis dose, and may have detrimental cardiovascular effects.

Point-of-Care Ultrasound Training during Nephrology Fellowship: A National Survey of Fellows and Program Directors.

BACKGROUND AND OBJECTIVES: Point-of-care ultrasound (POCUS)-performed by a clinician during a patient encounter and used in patient assessment and care planning-has many potential applications in nephrology. Yet, US nephrologists have been slow to adopt POCUS, which may affect the training of nephrology fellows. This study sought to identify the current state of POCUS training and implementation in nephrology fellowships. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Concise survey instruments measuring attitudes toward POCUS, its current use, fellow competence, and POCUS curricula were disseminated to (1) 912 US nephrology fellows taking the 2021 Nephrology In-Training Examination and (2) 229 nephrology training program directors and associate program directors. Fisher exact, chi-squared, and Wilcoxon rank sum tests were used to compare the frequencies of responses and the average responses between fellows and training program directors/associate program directors when possible. RESULTS: Fellow and training program directors/associate program directors response rates were 69% and 37%, respectively. Only 38% of fellows (240 respondents) reported receiving POCUS education during their fellowship, and just 33% of those who did receive POCUS training reported feeling competent to use POCUS independently. Similarly, just 23% of training program directors/associate program directors indicated that they had a POCUS curriculum in place, although 74% of training program directors and associate program directors indicated that a program was in development or that there was interest in creating a POCUS curriculum. Most fellow and faculty respondents rated commonly covered POCUS topics-including dialysis access imaging and kidney biopsy-as "important" or "very important," with the greatest interest in diagnostic kidney ultrasound. Guided scanning with an instructor was the highest-rated teaching strategy. The most frequently reported barrier to POCUS program development was the lack of available instructors. CONCLUSIONS: Despite high trainee and faculty interest in POCUS, the majority of current nephrology fellows are not receiving POCUS training. Hands-on training guided by an instructor is highly valued, yet availability of adequately trained instructors remains a barrier to program development. PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2022_09_21_CJN01850222.mp3.

SCU-Net: A deep learning method for segmentation and quantification of breast arterial calcifications on mammograms.

PURPOSE: Measurements of breast arterial calcifications (BAC) can offer a personalized, non-invasive approach to risk-stratify women for cardiovascular diseases such as heart attack and stroke. We aim to detect and segment breast arterial calcifications in mammograms accurately and suggest novel measurements to quantify detected BAC for future clinical applications. METHODS: To separate BAC in mammograms, we propose a lightweight fine vessel segmentation method Simple Context U-Net (SCU-Net). Due to the large image size of mammograms, we adopt a patch-based way to train SCU-Net and obtain the final whole-image-size results by stitching patchwise results together. To further quantify calcifications, we test five quantitative metrics to inspect the progression of BAC for subjects: sum of mask probability metric ( P M ), sum of mask area metric ( A M ), sum of mask intensity metric ( S I M ), sum of mask area with threshold intensity metric T A M X , and sum of mask intensity with threshold X metric T S I M X . Finally, we demonstrate the ability of the metrics to longitudinally measure calcifications in a group of 26 subjects and evaluate our quantification metrics compared with calcified voxels and calcium mass on breast CT for 10 subjects. RESULTS: Our segmentation results are compared with state-of-the-art network architectures based on recall, precision, accuracy, F1 score/Dice score, and Jaccard index evaluation metrics and achieve corresponding values of 0.789, 0.708, 0.997, 0.729, and 0.581 for whole-image-size results. The quantification results all show >95% correlation between quantification measures on predicted masks of SCU-Net as compared to the groundtruth and measurement of calcification on breast CT. For the calcification quantification measurement, our calcification volume (voxels) results yield R2 -correlation values of 0.834, 0.843, 0.832, 0.798, and 0.800 for the P M , A M , S I M , T A M 100 , T S I M 100 metrics, respectively; our calcium mass results yield comparable R2 -correlation values of 0.866, 0.873, 0.840, 0.774, and 0.798 for the same metrics. CONCLUSIONS: Simple Context U-Net is a simple method to accurately segment arterial calcification retrospectively on routine mammograms. Quantification of the calcifications based on this segmentation in the retrospective cohort study has sufficient sensitivity to detect the normal progression over time and should be useful for future research and clinical applications.

Vascular Calcification Slows But Does Not Regress After Kidney Transplantation.

INTRODUCTION: Medial arterial calcification is a common and progressive lesion in end-stage renal disease that is associated with poor cardiovascular outcomes. Whether this lesion can be arrested or reversed is unknown, and was examined retrospectively by measuring progression of breast arterial calcification before and after kidney transplantation. METHODS: Arterial calcification was measured on serial mammograms from patients with previous kidney transplantation and compared to measurements performed before transplantation or in patients on the active waitlist. Serum creatinine >2.0 mg/dl after transplantation or warfarin use were exclusions. RESULTS: Median (interquartile range) progression of arterial calcification was 12.9 mm/breast per year (5.9 to 32.6) in 34 patients before or awaiting transplantation compared to just 1.2 mm/breast per year (-0.54 to 5.1) in 34 patients after transplantation (P < 0.001). Slowing of progression was also seen in longitudinal analyses of patients with mammograms performed both before and after transplantation. Duration of end-stage renal disease before transplantation but not age, diabetes, baseline calcification, or serum chemistries correlated with progression after transplantation. Significant regression was not observed in any patient. CONCLUSION: In this first quantitative study of the effect of kidney transplantation, medial arterial calcification appeared to slow to rates seen in patients with normal renal function, indicating that the effect of renal failure may be completely abrogated. Overall, however, there was no significant regression, suggesting that calcification is irreversible and emphasizing the importance of prevention. Duration of pretransplant end-stage renal disease but not baseline calcification was a determinant of progression, consistent with cumulative, permanent changes to arteries that promote calcification.

Cerebral blood flow regulation in end-stage kidney disease.

Patients with chronic kidney disease (CKD) and end-stage kidney disease (ESKD) experience an increased risk of cerebrovascular disease and cognitive dysfunction. Hemodialysis (HD), a major modality of renal replacement therapy in ESKD, can cause rapid changes in blood pressure, osmolality, and acid-base balance that collectively present a unique stress to the cerebral vasculature. This review presents an update regarding cerebral blood flow (CBF) regulation in CKD and ESKD and how the maintenance of cerebral oxygenation may be compromised during HD. Patients with ESKD exhibit decreased cerebral oxygen delivery due to anemia, despite cerebral hyperperfusion at rest. Cerebral oxygenation further declines during HD due to reductions in CBF, and this may induce cerebral ischemia or "stunning." Intradialytic reductions in CBF are driven by decreases in cerebral perfusion pressure that may be partially opposed by bicarbonate shifts during dialysis. Intradialytic reductions in CBF have been related to several variables that are routinely measured in clinical practice including ultrafiltration rate and blood pressure. However, the role of compensatory cerebrovascular regulatory mechanisms during HD remains relatively unexplored. In particular, cerebral autoregulation can oppose reductions in CBF driven by reductions in systemic blood pressure, while cerebrovascular reactivity to CO2 may attenuate intradialytic reductions in CBF through promoting cerebral vasodilation. However, whether these mechanisms are effective in ESKD and during HD remain relatively unexplored. Important areas for future work include investigating potential alterations in cerebrovascular regulation in CKD and ESKD and how key regulatory mechanisms are engaged and integrated during HD to modulate intradialytic declines in CBF.

Warfarin Accelerates Medial Arterial Calcification in Humans.

OBJECTIVE: Warfarin is associated with medial arterial calcification in humans, but the magnitude and specificity of this effect and the role of other risk factors are unknown. Using serial mammograms, progression of arterial calcification was compared in women receiving no anticoagulants, warfarin, or other anticoagulants, and before, during, and after warfarin use. Approach and Results: Warfarin users with mammograms were identified by computerized searches of medical records that included renal function and diabetes mellitus. Lengths of calcified arterial segments were measured, with progression expressed as millimeters per breast per year and presented as medians and interquartile range (IQR). In women with normal renal function (estimated glomerular filtration rate >60 mL/minute per 1.73 m2), progression was 3.9-fold greater in warfarin users: 9.9 (3.8-16) versus 2.5 (0.7-6.7) in controls, P=0.0003, but not increased in users of other anticoagulants. In longitudinal analyses, progression increased from 2.1 (IQR, 0.3-3.9) to 13.8 (IQR, 7.8-38.7; P=0.011) after starting warfarin (n=11) and decreased from 8.8 (IQR, 1.1-10) to 1.9 (IQR, -10 to 6.7; P=0.024) after discontinuation of warfarin (n=13). Progression of calcification was similar in warfarin users with chronic kidney disease (7.3 [IQR, 3.6-17], n=29) but markedly accelerated in warfarin users with end-stage renal disease (47 [IQR, 31-183], n=11; P=0.0002). Progression was similar in diabetic and nondiabetic warfarin users (10.1 [IQR, 3.8-24] versus 7.8 [IQR, 3.6-15]) and did not correlate with age (r=0.09) or duration of warfarin therapy (r=0.12). CONCLUSIONS: Warfarin significantly accelerates medial arterial calcification in humans. This effect is markedly augmented in end-stage renal disease.

Progression of Medial Arterial Calcification in CKD.

INTRODUCTION: Medial arterial calcification is common in chronic kidney disease (CKD) and portends poor clinical outcomes, but its progression relative to the severity of CKD and the role of other risk factors is unknown because of the lack of reliable quantification. METHODS: Calcification of breast arteries detected by mammography, which is exclusively medial and correlates with medial calcification in peripheral arteries and with cardiovascular outcomes, was used to measure the progression of medial arterial calcification in women with CKD and end-stage renal disease (ESRD). Measurements showed intra- and interobserver correlations of 0.98, an interstudy variability of 8% to 11%, and a correlation with computed tomographic measurements of 0.92. RESULTS: Progression of calcification was measured in 60 control subjects (estimated glomerular filtration rate (eGFR) ≥ 90 ml/min per 1.73 m2) and 137 subjects with CKD (eGFR < 90 ml/min per 1.73 m2). Progression in control subjects was linear over time and independent of age. The rate of progression was increased in CKD but only at eGFR < 40 ml/min per 1.73 m2 (median, 8.1 vs. 3.9 mm/breast/yr in controls; P = 0.006). Progression accelerated markedly in subjects with ESRD (median, 20 mm/breast/yr; n = 36), but did not differ from controls after kidney transplantation (n = 25). Diabetes significantly augmented progression in subjects with CKD and ESRD but not in controls. CONCLUSION: Mammography is a convenient and reliable method to measure the progression of medial arterial calcification. Progression does not increase until advanced stages of CKD, accelerates markedly in ESRD, and returns to control rates after kidney transplantation. Diabetes significantly increases progression in CKD and ESRD.

Questionable specificity of histologic findings in calcific uremic arteriolopathy.

A variety of criteria exist for histopathologic diagnosis of calciphylaxis, also known as calcific uremic arteriolopathy but data on their specificity are limited. To assess this, histologic findings of 38 skin biopsies performed for a suspicion of calcific uremic arteriolopathy were compared with histologic findings in skin obtained from healthy margins of 43 amputations in patients with end-stage renal disease (ESRD) without evidence of calcific uremic arteriolopathy. Abnormalities in small arteries or arterioles were present in 35% of amputation specimens and 55% of skin biopsies, and among these only thrombosis but not calcification was significantly more prevalent in skin biopsies. The prevalence of extravascular calcification did not differ. Vascular lesions were more common in skin biopsies from patients with high clinical suspicion of calcific uremic arteriolopathy (81%), significantly driven by increases in both calcification and thrombosis, compared to amputations (35%). The combination of medial calcification and thrombosis was six-fold more prevalent in high-suspicion skin biopsies than in amputation specimens. The location of affected vessels did not differ. In two autopsy cases, some but not all findings of involved skin were also present in uninvolved skin. Thus, histopathologic findings historically associated with calcific uremic arteriolopathy can also occur in viable tissue from unaffected patients with ESRD, calling into question the specificity of individual histologic findings for calcific uremic arteriolopathy. However, the combination of medial calcification and thrombosis was rare in unaffected patients and may provide a higher degree of specificity.

Pyrophosphate deficiency in vascular calcification.

Pathologic cardiovascular calcification is associated with a number of conditions and is a common complication of chronic kidney disease. Because ambient calcium and phosphate levels together with properties of the vascular matrix favor calcification even under normal conditions, endogenous inhibitors such as pyrophosphate play a key role in prevention. Genetic diseases and animal models have elucidated the metabolism of extracellular pyrophosphate and demonstrated the importance of pyrophosphate deficiency in vascular calcification. Therapies based on pyrophosphate metabolism have been effective in animal models, including renal failure, and hold promise as future therapies to prevent vascular calcification.

Point-of-care ultrasound in the practice of nephrology.

Sonography is increasingly being performed by clinicians and has applications throughout the spectrum of nephrology, including acute and chronic renal failure, urinary obstruction, cystic disease, pain, hematuria, transplantation, kidney biopsy, temporary and permanent vascular access, and assessment of fluid status. The skill is relatively easily acquired, expedites patient care, and enhances the practice of nephrology. However, the lack of exposure in most training programs remains a major obstacle.

Understanding the pathogenesis of vascular calcification: timing is everything.

A number of histologic changes are associated with the medial arterial calcification that occurs in chronic kidney disease, leading to several different hypotheses concerning the underlying mechanism. Careful timing of these changes in relation to the onset of the calcification, as reported in this issue of the journal, can shed light on which changes are pathogenic as opposed to secondary in reaction to the calcification.