Shorter observation times and smaller gauge needles in outpatient kidney biopsies.

Controversy exists as to the optimal observational time (OT) after outpatient percutaneous kidney biopsy. Further, there is some uncertainty about the benefit of smaller (18-gauge) vs. larger (16-gauge) biopsy needles. At our institution, we have been lowering the OT after outpatient kidney biopsies. Initially in 2015, we were monitoring for 6 hours and gradually began to decrease the OT over time. From 2020, we have adopted an OT of less than 4 hours. During this time period (in 2018), we also began using a smaller gauge needle (18 gauge). We reviewed all outpatient kidney biopsies performed by the nephrology division at our institution since 2015. There were 137 biopsies reviewed. 63 had OT of 4 - 6 hours, and 74 had OT < 4 hours. There was a total of 4 significant complications (2.9%). Two complications, symptomatic retroperitoneal bleeds, were detected in less than 3 hours. The other 2 complications were seen at 9 hours (clot retention) and 72 hours (retroperitoneal bleed after anticoagulation restarted). 63% of the biopsies were done using 18-gauge needles with 1 complication in this group vs. 3 in the 16-gauge group. All cases had adequate tissue for interpretation based on the ability to make a kidney diagnosis. The number of glomeruli obtained in the 18-gauge group was 29 ± 13 glomeruli, and in the 16-gauge group was 25 ± 10, which did not differ between groups. In summary, in an outpatient population, all significant post-biopsy complications were evident either within the first 3 hours or after 9 hours, and this suggests the feasibility of using shorter than standard OT in outpatient kidney biopsies. Furthermore, an 18-gauge needle may lower the risk of complications and obtain adequate tissue.

Point-of-care ultrasonography in nephrology comes of age.

The physical exam is changing. Many have argued that the physical exam of the 21st century should include point-of-care ultrasound (POCUS). POCUS is being taught in medical schools and has been endorsed by the major professional societies of internal medicine. In this review we describe the trend toward using POCUS in medicine and describe where the practicing nephrologist fits in. We discuss what a nephrologist's POCUS exam should entail and we give special attention to what nephrologists can gain from learning POCUS. We suggest a 'nephro-centric' approach that includes not only ultrasound of the kidney and bladder, but of the heart, lungs and vascular access. We conclude by reviewing some of the sparse data available to guide training initiatives and give suggested next steps for advancing POCUS in nephrology.

Increased Mortality Associated with Hypermagnesemia in Severe COVID-19 Illness.

Background: Although electrolyte abnormalities are common among patients with COVID-19, very little has been reported on magnesium homeostasis in these patients. Here we report the incidence of hypermagnesemia, and its association with outcomes among patients admitted with COVID-19. Methods: We retrospectively identified all patients with a positive test result for SARS-CoV-2 who were admitted to a large quaternary care center in New York City in spring 2020. Details of the patients' demographics and hospital course were obtained retrospectively from medical records. Patients were defined as having hypermagnesemia if their median magnesium over the course of their hospitalization was >2.4 mg/dl. Results: A total of 1685 patients hospitalized with COVID-19 had their magnesium levels checked during their hospitalization, and were included in the final study cohort, among whom 355 (21%) had hypermagnesemia. Patients who were hypermagnesemic had a higher incidence of shock requiring pressors (35% vs 27%, P<0.01), respiratory failure requiring mechanical ventilation (28% vs 21%, P=0.01), AKI (65% vs 50%, P<0.001), and AKI severe enough to require renal replacement therapy (18% vs 5%, P<0.001). In an adjusted multivariable model, hypermagnesemia was observed more commonly with increasing age, male sex, AKI requiring RRT, hyperkalemia, and higher CPK. Survival probability at 30 days was 34% for the patients with hypermagnesemia, compared with 65% for patients without hypermagnesemia. An adjusted multivariable time to event analysis identified an increased risk of mortality with older age, need for vasopressors, higher C-reactive protein levels, and hypermagnesemia (HR, 2.03; 95% CI, 1.63 to 2.54, P<0.001). Conclusions: In conclusion, we identified an association between hypermagnesemia among patients hospitalized with COVID-19 and increased mortality. Although the exact mechanism of this relationship remains unclear, hypermagnesemia potentially represents increased cell turnover and higher severity of illness, which is frequently associated with more severe forms of AKI.

Protocol for Local On-Site Dialysate Production for Continuous Renal Replacement Therapy during the COVID-19 Pandemic.

AKI frequently occurs in patients with COVID-19, and kidney injury severe enough to require RRT is a common complication among patients who are critically ill. During the surge of the pandemic, there was a high demand for dialysate for continuous RRT, and this increase in demand, coupled with vulnerabilities in the supply chain, necessitated alternative approaches, including internal production of dialysate. Using a standard hemodialysis machine and off-the-shelf supplies, as per Food and Drug Administration guidelines, we developed a method for on-site dialysate production that is adaptable and can be used to fill multiple bags at once. The use of a central reverse osmosis unit, dedicated hemodialysis machine, sterile bags with separate ports for fill and use, and frequent testing will ensure stability, sterility, and-therefore-safety of the produced dialysate. The dialysate made in house was tested and it showed both stability and sterility for at least 30 hours. This detailed description of our process for generating dialysate can serve as a guide for other programs experiencing similar vulnerabilities in the demand versus supply of dialysate.

High rate of renal recovery in survivors of COVID-19 associated acute renal failure requiring renal replacement therapy.

INTRODUCTION: A large proportion of patients with COVID-19 develop acute kidney injury (AKI). While the most severe of these cases require renal replacement therapy (RRT), little is known about their clinical course. METHODS: We describe the clinical characteristics of COVID-19 patients in the ICU with AKI requiring RRT at an academic medical center in New York City and followed patients for outcomes of death and renal recovery using time-to-event analyses. RESULTS: Our cohort of 115 patients represented 23% of all ICU admissions at our center, with a peak prevalence of 29%. Patients were followed for a median of 29 days (2542 total patient-RRT-days; median 54 days for survivors). Mechanical ventilation and vasopressor use were common (99% and 84%, respectively), and the median Sequential Organ Function Assessment (SOFA) score was 14. By the end of follow-up 51% died, 41% recovered kidney function (84% of survivors), and 8% still needed RRT (survival probability at 60 days: 0.46 [95% CI: 0.36-0.56])). In an adjusted Cox model, coronary artery disease and chronic obstructive pulmonary disease were associated with increased mortality (HRs: 3.99 [95% CI 1.46-10.90] and 3.10 [95% CI 1.25-7.66]) as were angiotensin-converting-enzyme inhibitors (HR 2.33 [95% CI 1.21-4.47]) and a SOFA score >15 (HR 3.46 [95% CI 1.65-7.25). CONCLUSIONS AND RELEVANCE: Our analysis demonstrates the high prevalence of AKI requiring RRT among critically ill patients with COVID-19 and is associated with a high mortality, however, the rate of renal recovery is high among survivors and should inform shared-decision making.

Use of lung ultrasonography to determine the accuracy of clinically estimated dry weight in chronic hemodialysis patients.

PURPOSE: The use of lung ultrasound (LUS) to identify extravascular lung water has received increasing acceptance. Sonographic B-lines, discrete vertical lines that originate from the pleura, represent pulmonary edema and are correlated with the accumulation of fluid. The goal of this study was to evaluate the utility of LUS to determine the accuracy of prescribed dry weight (DW) in chronic hemodialysis (HD) patients and to ascertain the adequacy of fluid removal. METHODS: LUS was scheduled to be performed pre- and post-HD in 20 patients. The HD prescription and DW challenge were done independent of the results of the LUS. The presence of B-lines was tabulated and compared to the intradialytic ultrafiltration parameters. RESULTS: Of the 20 patients, 3 did not exhibit B-lines at the first dialysis session. In regard to the other 17 patients, B-lines disappeared in 7 patients at the end of the HD session (mean B-lines 4.2-0). One patient was 0.3 kg away from the prescribed dry weight, but the 6 patients were a mean of 1.7 kg below DW. Of the remaining 10 patients, eight decreased but did not eliminate the B-lines (mean B-lines 15.5-3.8) and were a mean of 3.8 kg below DW post-HD. Two patients who exhibited more cardiac insufficiency than initially recognized could not reach DW or eliminate the B-lines. Eight patients who had residual B-lines at the end of the first HD session had their DW re-estimated and had a second session. Two were able to eliminate the B-lines (mean 2.5-0) and reached a mean of 1.2 kg below DW. Six did not eliminate the B-lines (mean 11.5-4.2) but were able to reach a mean of 0.6 kg below DW. Correlation analysis showed a statistically significant correlation (P < 0.05) between the intradialytic percent change in B-lines and the percent change in total body weight (r = 0.40) and ultrafiltration rate (r = 0.33). Seven of 10 patients with clear chest X-rays pre-HD exhibited B-lines. CONCLUSIONS: This study supports the hypothesis that reduction in B-lines during HD can provide accurate information regarding changes in pulmonary fluid content. Further, LUS is a valuable diagnostic tool for recognizing both the adequacy of fluid removal and the occurrence of error in the estimation of dry weight by usual clinical parameters.

Dystonia-Causing Mutations as a Contribution to the Etiology of Spasmodic Dysphonia.

OBJECTIVE: Spasmodic dysphonia is a focal dystonia of the larynx with heterogeneous manifestations and association with familial risk factors. There are scarce data to allow precise understanding of etiology and pathophysiology. Screening for dystonia-causing genetic mutations has the potential to allow accurate diagnosis, inform about genotype-phenotype correlations, and allow a better understanding of mechanisms of disease. STUDY DESIGN: Cross-sectional study. SETTING: Tertiary academic medical center. SUBJECTS AND METHODS: We enrolled patients presenting with spasmodic dysphonia to the voice clinic of our academic medical center. Data included demographics, clinical features, family history, and treatments administered. The following genes with disease-causing mutations previously associated with spasmodic dysphonia were screened: TOR1A (DYT1), TUBB4 (DYT4), and THAP1 (DYT6). RESULTS: Eighty-six patients were recruited, comprising 77% females and 23% males. A definite family history of neurologic disorder was present in 15% (13 of 86). Average age (± standard deviation) of symptom onset was 42.1 ± 15.7 years. Most (99%; 85 of 86) were treated with botulinum toxin, and 12% (11 of 86) received oral medications. Genetic screening was negative in all patients for the GAG deletion in TOR1A (DYT1) and in the 5 exons currently associated with disease-causing mutations in TUBB4 (DYT4). Two patients tested positive for novel/rare variants in THAP1 (DYT6). CONCLUSION: Genetic screening targeted at currently known disease-causing mutations in TOR1A, THAP1, and TUBB4 appears to have low diagnostic yield in sporadic spasmodic dysphonia. In our cohort, only 2 patients tested positive for novel/rare variants in THAP1. Clinicians should make use of genetic testing judiciously and in cost-effective ways.

Clinical advantages of quantitative electroencephalogram (QEEG)-electrical neuroimaging application in general neurology practice.

QEEG-electrical neuroimaging has been underutilized in general neurology practice for uncertain reasons. Recent advances in computer technology have made this electrophysiological testing relatively inexpensive. Therefore, this study was conducted to evaluate the clinical usefulness of QEEG/electrical neuroimaging in neurological practice. Over the period of approximately 6 months, 100 consecutive QEEG recordings were analyzed for potential clinical benefits. The patients who completed QEEG were divided into 5 groups based on their initial clinical presentation. The main groups included patients with seizures, headaches, post-concussion syndrome, cognitive problems, and behavioral dysfunctions. Subsequently, cases were reviewed and a decision was made as to whether QEEG analysis contributed to the diagnosis and/or furthered patient's treatment. Selected and representative cases from each group are presented in more detail, including electrical neuroimaging with additional low-resolution electromagnetic tomography analysis or using computerized cognitive testing. Statistical analysis showed that QEEG analysis contributed to 95% of neurological cases, which indicates great potential for wider application of this modality in general neurology. Many patients also began neurotherapy, depending on the patient's desire to be involved in this treatment modality.

Identification of 2-oxo-N-(phenylmethyl)-4-imidazolidinecarboxamide antagonists of the P2X(7) receptor.

A backup molecule to compound 2 was sought by targeting the most likely metabolically vulnerable site in this molecule. Compound 18 was subsequently identified as a potent P2X(7) antagonist with very low in vivo clearance and high oral bioavailability in all species examined. Some evidence to support the role of P2X(7) in the etiology of pain is also presented.

Discovery and structure-activity relationships of a series of pyroglutamic acid amide antagonists of the P2X7 receptor.

A computational lead-hopping exercise identified compound 4 as a structurally distinct P2X(7) receptor antagonist. Structure-activity relationships (SAR) of a series of pyroglutamic acid amide analogues of 4 were investigated and compound 31 was identified as a potent P2X(7) antagonist with excellent in vivo activity in animal models of pain, and a profile suitable for progression to clinical studies.

Structure-activity relationships and in vivo activity of (1H-pyrazol-4-yl)acetamide antagonists of the P2X(7) receptor.

Structure-activity relationships (SAR) of analogues of lead compound 1 were investigated and compound 16 was selected for further study in animal models of pain. Compound 16 was shown to be a potent antihyperalgesic agent in both the rat acute complete Freund's adjuvant (CFA) model of inflammatory pain [Iadarola, M. J.; Douglass, J.; Civelli, O.; Naranjo, J. R. rain Res.1988, 455, 205] and the knee joint model of chronic inflammatory pain [Wilson, A. W.; Medhurst, S. J.; Dixon, C. I.; Bontoft, N. C.; Winyard, L. A.; Brackenborough, K. T.; De Alba, J.; Clarke, C. J.; Gunthorpe, M. J.; Hicks, G. A.; Bountra, C.; McQueen, D. S.; Chessell, I. P. Eur. J. Pain2006, 10, 537].

Synthesis and structure-activity relationships of a series of (1H-pyrazol-4-yl)acetamide antagonists of the P2X7 receptor.

High-throughput screening identified compound 1 as a potent P2X(7) receptor antagonist suitable for lead optimisation. Structure-activity relationships (SAR) of a series of (1H-pyrazol-4-yl)acetamides were investigated and compound 32 was identified as a potent P2X(7) antagonist with enhanced potency and favourable physicochemical and pharmacokinetic properties.

2-Amino-5-aryl-pyridines as selective CB2 agonists: synthesis and investigation of structure-activity relationships.

2-Amino-5-aryl-pyridines, exemplified by compound 1, had been identified as a synthetically tractable series of CB(2) agonists from a high-throughput screen of the GlaxoSmithKline compound collection. Described herein are the results of an investigation of the structure-activity relationships (SAR) which led to the identification a number of potent and selective agonists.