Faculty Bibliography

BACKGROUND:Elevated parathyroid hormone (PTH) levels have been reported as a potential risk factor for cognitive impairment. Compared to the general population, older adults with end-stage renal disease (ESRD) who are frequently affected by secondary hyperparathyroidism (SHPT) are at increased risk of developing dementia. The main objective of our study was to evaluate if the risk of dementia in older (age ≥ 65) ESRD patients differed if they were treated for SHPT. METHODS:Using the United States Renal Data System (USRDS) and Medicare claims, we identified 189 433 older adults without a diagnosis of dementia, who initiated dialysis between 2006-2016. SHPT treatment was defined as use of vitamin D analogs, phosphate binders, calcimimetics, or parathyroidectomy. We quantified the association between treated SHPT and incident dementia during dialysis using a multivariable Cox proportional hazards model with inverse probability weighting, considering SHPT treatment as a time varying exposure. RESULTS:Of 189 433 older ESRD adults, 92% had a claims diagnosis of SHPT, and 123 388 (65%) were treated for SHPT. The rate of incident dementia was 6 cases per 100 person-years among SHPT treated patients compared to 11 cases per 100 person-years among untreated patients. Compared to untreated SHPT patients, the risk of dementia was 42% lower (aHR = 0.58, 95% CI: 0.56-0.59) among SHPT treated patients. The magnitude of the beneficial effect of SHPT treatment differed by sex (pinteraction = 0.02) and race (pinteraction ≤ 0.01) with females (aHR = 0.56, 95% CI: 0.54-0.58) and those of Asian (aHR = 0.51, 95% CI: 0.46-0.57) or Black race (aHR = 0.51, 95% CI: 0.48-0.53) having greatest reduction in dementia risk. CONCLUSION/CONCLUSIONS:Receiving treatment for SHPT was associated with a lower risk of incident dementia among older patients with ESRD. This work provides additional support for treatment of SHPT in older ESRD patients.

Heterologous vaccination ("mixing platforms") for the third (D3) dose of SARS-CoV-2 vaccine is a potential strategy to improve antibody responses in solid organ transplant recipients (SOTRs), but data are mixed regarding potential differential immunogenicity. We assessed for differences in immunogenicity and tolerability of homologous (BNT162b2 or mRNA-1273; D3-mRNA) versus heterologous (Ad.26.COV2.S; D3-JJ) D3 among 377 SARS-CoV-2-infection naïve SOTRs who remained seronegative after two mRNA vaccines. We measured anti-spike titers and used weighted Poisson regression to evaluate seroconversion and development of high-titers, comparing D3-JJ to D3-mRNA, at 1-, 3-, and 6 month post-D3. 1-month post-D3, seroconversion (63% vs. 52%, p = .3) and development of high-titers (29% vs. 25%, p = .7) were comparable between D3-JJ and D3-mRNA recipients. 3 month post-D3, D3-JJ recipients were 1.4-fold more likely to seroconvert (80% vs. 57%, weighted incidence-rate-ratio: wIRR = _1.10 1.40_1.77 , p = .006) but not more likely to develop high-titers (27% vs. 22%, wIRR = _0.44 0.92_1.93 , p = .8). 6 month post-D3, D3-JJ recipients were 1.41-fold more likely to seroconvert (88% vs. 59%, wIRR = _1.04 1.41_1.93 , p = .029) and 2.63-fold more likely to develop high-titers (59% vs. 21%, wIRR = _1.38 2.63_5.00 , p = .003). There was no differential signal in alloimmune events or reactogenicity between platforms. SOTRs without antibody response after two mRNA vaccines may derive benefit from heterologous Ad.26.COV2.S D3.

Estimating the total coronavirus disease 2019 (COVID-19) mortality burden of solid organ transplant recipients (SOTRs), both directly through COVID-19 infection and indirectly through other impacts on the healthcare system and society, is critical for understanding the disease's impact on the SOTR population. Using SRTR data, we modeled expected mortality risk per month pre-COVID (January 2015-February 2020) for kidney/liver/heart/lung SOTRs, and compared monthly COVID-era deaths (March 2020-March 2021) to expected rates, overall and among subgroups. Deaths above expected rates were designated "excess deaths." Between March 2020 and March 2021, there were 3739/827/265/252 excess deaths among kidney/liver/heart/lung SOTRs, respectively, representing a 41.2%/27.4%/18.5%/15.0% increase above expected deaths. 93.0% of excess deaths occurred in patients age≥50. The observed:expected ratio was highest among Hispanic SOTRs (1.82) and lowest among White SOTRs (1.20); 56.0% of excess deaths occurred among Black or Hispanic SOTRs. 64.7% of excess deaths occurred among patients who had survived ≥5 years post-transplant. Excess deaths peaked in January 2021; geographic distribution of excess deaths broadly mirrored COVID-19 incidence. COVID-19 likely caused over 5000 excess deaths among SOTRs in the US in a 13-month period, representing 1 in 75 SOTRs and a substantial proportion of all deaths among SOTRs during this time. SOTRs will remain at elevated mortality risk until the COVID-19 pandemic can be controlled.