Day 1

Pathophysiology of secondary hyperparathyroidism (secondary to CKD)

 

Calcium and phosphorous homeostasis is tightly regulated between bone, the kidney, and the parathyroid gland. Key modulators of calcium and phosphorous include FGF-23, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, and parathyroid hormone. FGF-23 is released from bone due to increasing serum phosphorus levels and acts in the kidney to increase phosphorous excretion and decrease 1 alpha hydroxylation of 25-hydroxyvitamin D. FGF-23, along with serum phosphorous, also decreases parathyroid hormone secretion, to maintain calcium and phosphorous balance.

Renal hyperparathyroidism (rHPT) is a common complication of CKD characterized by derangements in the homeostasis of calcium, phosphorus, and vitamin D.3 rHPT is classically broken into 2 types on the basis of the patient’s serum calcium level. SHPT secondary to renal disease is an overproduction of PTH that is caused by many changes occurring in bone and mineral metabolism as a result of decreased kidney function. The first changes that occur with declining kidney function involve the deficiency of activated vitamin D and an increase in phosphorus secretion by the remaining functional nephrons. These two changes cause an increase in PTH synthesis and secretion.

An increase in PTH levels usually develops when the GFR is less than 60 mL/min/1.73 m^2. In CKD, stages 3-5 (eGFR < 59 mL/min), FGF-23 levels increase, initially leading to phosphaturia and decreased parathyroid hormone excretion. Abnormalities in serum levels of phosphorus and calcium can occur later in the course of CKD (GFR lower than 40). Initially, elevated PTH increases renal phosphorus excretion. However, as GFR decreases further, serum phosphorus levels increase and induce hypocalcemia by binding bioavailabile calcium as CaHPO4 (dicalcium phosphate), which leads to even more PTH production. CKD also decreases the activity of 1-a-hydroxylase, thereby decreasing 1,25 OH vitamin D. This inhibits the gastrointestinal absorption of calcium and directly stimulates the parathyroid glands. 

In CKD, chronic stimulation of the parathyroid gland triggers polyclonal hyperplasia. As it continues, the paraphyroids develop monoclonal nodules, which demonstrate increased resistance to vitamin D and calcimimetic medications. This may be the etiology of the loss of negative feedback that’s seen in tertiary HPT.

Sources

https://spectrum.diabetesjournals.org/content/21/1/19

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4991918/pdf/permj20_3p0078.pdf

Day 2

Types of Testing for COVID-19

NAAT (RT-PCR) – to diagnose current infection

• The diagnosis of COVID-19 is made by detection of SARS-CoV-2 RNA by nucleic acid application tests, primarily reverse transcriptase polymerase chain reaction. Different assays amplify and detect different regions of the SARS-CoV-2 genome. Common gene targets include nucleocapsid (N), envelope (E), spike (S), and RNA-dependent RNA polymerase (RdRp), as well as regions in the first open reading frame
• Test results range from 15 minutes to several hours and require different specimen types
• The turnaround time for clinicians to relieve a result also depends on how the lab performs the test
• The IDSA suggests nasopharyngeal, mid-turbinate, or nasal specimens rather than an oropharyngeal specimen (or saliva) because of limited data suggesting lower sensitivity with oropharyngeal specimens and lack of data on accuracy of saliva specimens
• Lower respiratory tract specimens are also an option for testing; the IDSA suggests reserving these for hospitalized patients who have an initial negative test on an upper respiratory tract specimen but for whom suspicion for lower respiratory tract SARS-CoV-2 infection remains
  • sputum should be collected from patients with productive cough, and tracheal aspirate or bronchoalveolar lavage should be collected from patients who are intubated
  • Lower respiratory tract specimens may have higher viral loads and be more likely to yield positive tests than upper respiratory tract specimens
• Interpretation — A positive test for SARS-CoV-2 generally confirms the diagnosis of COVID-19. However, false-negative tests from upper respiratory specimens have been well documented. If initial testing is negative but the suspicion for COVID-19 remains and determining the presence of infection is important for management or infection control, we suggest repeating the test. Repeat testing is performed 24 to 48 hours after the initial test. In such cases, the WHO and IDSA recommend testing a lower respiratory tract specimen if the patient has evidence of lower respiratory tract illness
• The accuracy and predictive values of SARS-CoV-2 tests have not been systematically evaluated, and the sensitivity of testing likely depends on the precise RT-PCR assay, the type of specimen obtained, the quality of the specimen, and duration of illness at the time of testing.
• Roche cobas® and Abbott RealTime SARS-CoV-2 assays – 4-8 hours to complete 
• Abbott ID NOW™ COVID-19 and the Cepheid Xpert® Xpress SARS-CoV-2 assays can generate results in less than one hour.
• Rapid vs. standard RNA testing
  • The sensitivity and specificity of the rapid isothermal EUA compared to standard laboratory-based assays ranged between 75-94% and 99-100%, respectively

• Molecular tests typically involve inserting a 6-inch long swab into the back of the nasal passage through one nostril and rotating the swab several times for 15 seconds – results can range from 5-45 min in rapid testing
• Saliva tests – 24-48 hours 
• the first at-home collection molecular test, called Pixel by LabCorp, on April 20. The test kits contain supplies to collect samples, including a nasal swab which you send back to the lab for testing. Unlike other swab-based tests, Pixel uses swabs that only need to go as far as the nostril, instead of deeper into the nasal passage. A study led by the UnitedHealth Group suggests that results from self-collected testing are similar in accuracy to provider-collected testing – 1 to 2 days 

Antibody testing 

• antibody or serology testing  is used to detect an immune response in the patient
• Antibody tests include both traditional enzyme immunoassays and rapid lateral flow immunoassays.5 There are not yet any published data on whether samples drawn from a vein result in better sensitivity or specificity than fingerstick specimens
• There are different isotypes of antibodies, including IgM, IgA, and IgG. Among these, IgG is the best marker to indicate exposure to SARS-CoV-2. The presence of IgG indicates that the patient has been infected with the virus and has mounted an immune response against it
• Most patients have detectable IgG antibodies by day 14 following symptom onset, and the likelihood of detection increases over time. In studies, antibody tests that detected both IgG and IgM were positive in 90% of symptomatic individuals by days 11-24.

IgG by ELISA 

• NY DOH approved 
• 0.7 Index or less    Negative
• 0.8-1.0 Index    Indeterminate
• 1.1 Index or greater    Positive
• 87-93% sensitivity nad 95-100% specificity 

 

R0 (r naught, also referred to as the reproduction number, is a mathematical term that indicated how contagious an infectious disease is)

• calculated by the infectious period, contact rate, and mode of transmission 
• It tells the average number of people who will contract the disease from an already infected person – it applied to populations who were not infected or vaccinated 
• If R0 less than 1 – each existing infection causes less than 1 new infection – disease will die out 
• R0 is 1 – existing infection causes 1 new infection – disease stays alive but wont cause an outbreak 
• R0 is greater than 1 – disease transmits between people and causes an outbreak 
• For COVID-19, the R0 has a median of 5.7 – meaning one person with COVID can transmit the virus to 5 or 6 people – researchers believe that 82% of the population need to become immune to stop the transmission (through herd immunity or vaccination)

 

Sources

https://www.uptodate.com/contents/coronavirus-disease-2019-covid-19-epidemiology-virology-clinical-features-diagnosis-and-prevention#H3536220593

 

https://www.idsociety.org/practice-guideline/covid-19-guideline-diagnostics/

 

https://www.healthline.com/health/r-nought-reproduction-number#conditions-it-measures