Brain perfusion single-photon emission computerized tomography/computerized tomography: Stroke-like manifestations of COVID-19 with transient antiphospholipid elevation.

COVID-19 is a viral respiratory disease associated with neurologic complications such as encephalitis or stroke in a minority of patients. The wide variety of neurologic manifestations with often unclear etiology may confound diagnosis and management. We present a young man admitted following an 8-day onset of self-resolving episodes of left hemiplegia and hemifacial droop. Diagnostic work up for seizures and stroke was largely negative. "Intra-ictal" ECD-single-photon emission computerized tomography/computerized tomography was consistent with right middle cerebral artery ischemia. Subsequent diagnostic work up revealed positive COVID-19 screening and newly-elevated antiphospholipid antibodies. Antiepileptic medications were discontinued, and the patient was successfully treated as an outpatient with corticosteroids leading to resolution of symptoms.

The association of race and COVID-19 mortality.

BACKGROUND: COVID-19 mortality disproportionately affects the Black population in the United States (US). To explore this association a cohort study was undertaken. METHODS: We assembled a cohort of 505,992 patients receiving ambulatory care at Bronx Montefiore Health System (BMHS) between 1/1/18 and 1/1/20 to evaluate the relative risk of hospitalization and death in two time-periods, the pre-COVID time-period (1/1/20-2/15/20) and COVID time-period (3/1/20-4/15/20). COVID testing, hospitalization and mortality were determined with the Black and Hispanic patient population compared separately to the White population using logistic modeling. Evaluation of the interaction of pre-COVID and COVID time periods and race, with respect to mortality was completed. FINDINGS: A total of 9,286/505,992 (1.8%) patients were hospitalized during either or both pre-COVID or COVID periods. Compared to Whites the relative risk of hospitalization of Black patients did not increase in the COVID period (p for interaction=0.12). In the pre- COVID period, compared to Whites, the odds of death for Blacks and Hispanics adjusted for comorbidity was statistically equivalent. In the COVID period compared to Whites the adjusted odds of death for Blacks was 1.6 (95% CI 1.2-2.0, p = 0.001). There was a significant increase in Black mortality risk from pre-COVID to COVID periods (p for interaction=0.02). Adjustment for relevant clinical and social indices attenuated but did not fully explain the observed difference in Black mortality. INTERPRETATION: The BMHS COVID experience demonstrates that Blacks do have a higher mortality with COVID incompletely explained by age, multiple reported comorbidities and available metrics of sociodemographic disparity. FUNDING: N/A.

AKI in Hospitalized Patients with and without COVID-19: A Comparison Study.

BACKGROUND: Reports from centers treating patients with coronavirus disease 2019 (COVID-19) have noted that such patients frequently develop AKI. However, there have been no direct comparisons of AKI in hospitalized patients with and without COVID-19 that would reveal whether there are aspects of AKI risk, course, and outcomes unique to this infection. METHODS: In a retrospective observational study, we evaluated AKI incidence, risk factors, and outcomes for 3345 adults with COVID-19 and 1265 without COVID-19 who were hospitalized in a large New York City health system and compared them with a historical cohort of 9859 individuals hospitalized a year earlier in the same health system. We also developed a model to identify predictors of stage 2 or 3 AKI in our COVID-19. RESULTS: We found higher AKI incidence among patients with COVID-19 compared with the historical cohort (56.9% versus 25.1%, respectively). Patients with AKI and COVID-19 were more likely than those without COVID-19 to require RRT and were less likely to recover kidney function. Development of AKI was significantly associated with male sex, Black race, and older age (>50 years). Male sex and age >50 years associated with the composite outcome of RRT or mortality, regardless of COVID-19 status. Factors that were predictive of stage 2 or 3 AKI included initial respiratory rate, white blood cell count, neutrophil/lymphocyte ratio, and lactate dehydrogenase level. CONCLUSIONS: Patients hospitalized with COVID-19 had a higher incidence of severe AKI compared with controls. Vital signs at admission and laboratory data may be useful for risk stratification to predict severe AKI. Although male sex, Black race, and older age associated with development of AKI, these associations were not unique to COVID-19.

Chronic Hemodialysis Patients Hospitalized with COVID-19: Short-term Outcomes in the Bronx, New York.

Background: Patients with ESKD who are on chronic hemodialysis have a high burden of comorbidities that may place them at increased risk for adverse outcomes when hospitalized with COVID-19. However, data in this unique patient population are limited. The aim of our study is to describe the clinical characteristics and short-term outcomes in patients on chronic hemodialysis who require hospitalization for COVID-19. Methods: We performed a retrospective study of 114 patients on chronic hemodialysis who were hospitalized with COVID-19 at two major hospitals in the Bronx from March 9 to April 8, 2020 during the surge of SARS-CoV-2 infections in New York City. Patients were followed during their hospitalization through April 22, 2020. Comparisons in clinical characteristics and laboratory data were made between those who survived and those who experienced in-hospital death; short-term outcomes were reported. Results: Median age was 64.5 years, 61% were men, and 89% were black or Hispanic. A total of 102 (90%) patients had hypertension, 76 (67%) had diabetes mellitus, 63 (55%) had cardiovascular disease, and 30% were nursing-home residents. Intensive care unit (ICU) admission was required in 13% of patients, and 17% required mechanical ventilation. In-hospital death occurred in 28% of the cohort, 87% of those requiring ICU, and nearly 100% of those requiring mechanical ventilation. A large number of in-hospital cardiac arrests were observed. Initial procalcitonin, ferritin, lactate dehydrogenase, C-reactive protein, and lymphocyte percentage were associated with in-hospital death. Conclusions: Short-term mortality in patients on chronic hemodialysis who were hospitalized with COVID-19 was high. Outcomes in those requiring ICU and mechanical ventilation were poor, underscoring the importance of end-of-life discussions in patients with ESKD who are hospitalized with severe COVID-19 and the need for heightened awareness of acute cardiac events in the setting of COVID-19. Elevated inflammatory markers were associated with in-hospital death in patients with ESKD who were hospitalized with COVID-19.

Safety and Efficacy of Treatment of Hepatitis C in Kidney Transplant Recipients With Directly Acting Antiviral Agents.

BACKGROUND: With the development of all oral, interferon-free directly acting antiviral (DAA) medications, treatment of hepatitis C virus (HCV) infection in renal transplant recipients is possible, but limited data exists on its safety and efficacy. METHODS: We performed a retrospective cohort analysis of patients transplanted at our center with HCV who have been started on DAAs. Primary endpoints included sustained virologic response as defined as negative viral load at 12 weeks postcompletion of therapy and allograft function. RESULTS: A total of 31 patients met inclusion criteria. The most commonly used regimen was sofosbuvir and ledipasvir (n = 21). Of the treated patients, 100% had undetectable viral load at the completion of therapy. Of the 31 patients treated, 30 (97%) achieved sustained virologic response. Both graft and patient survivals at most recent follow-up was 100%. There was no significant change in glomerular filtration rate (GFR) before or after therapy (64.2 ± 16.5 mL/min per body surface area before vs. 58.9 ± 17.5 mL/min per body surface area after therapy; P = 0.22); however, 3 patients now have GFR less than 20. A total of 6 (19.3%) of 31 patients had worsening proteinuria during or shortly after therapy. Patients with more than 500 mg/g of proteinuria at the start of treatment were significantly more likely to develop worsening proteinuria than those with less than 500 mg/g of proteinuria at the start of therapy (P < 0.001). Retrospective review of 20 untreated HCV patients did not demonstrate worsening allograft function and proteinuria during a median follow-up time of 1386 days (range, 332-6254). CONCLUSIONS: Our preliminary data demonstrate that DAAs can be used safely and effectively in patients after kidney transplantation. Patients with proteinuria or lower GFR should be monitored more closely.

CKD-Mineral Bone Disorder in Stage 4 and 5 CKD: What We Know Today?

Patients with CKD stages 4 and 5 experience biochemical derangements associated with CKD-mineral bone disorder. Some of the key abnormalities are hyperparathyroidism, hyperphosphatemia, hypocalcemia, and metabolic acidosis. We review the available treatments for these conditions and the evidence behind the treatments. We conclude that there is greater evidence for treating hyperphosphatemia than hyperparathyroidism. Treatment of metabolic acidosis in small clinical trials appears to be safe. We caution the reader about side effects associated with some of these treatments that differ in patients with CKD Stages 4 and 5 compared with patients on dialysis. The use of cinacalcet has been associated with hyperphosphatemia in patients with functioning kidneys. Activated vitamin D therapy has been associated with elevated creatinine levels, which may or may not be a reflection of true decrement in kidney function. Finally, the use of non-calcium-containing phosphate binders may be associated with improved clinical outcomes in patients; however, many more clinical trials are needed in this important area of medicine.

Cocaine and kidney injury: a kaleidoscope of pathology.

Cocaine is abused worldwide as a recreational drug. It is a potent activator of the sympathetic nervous system leading to intense vasoconstriction, endothelial dysfunction, oxidative stress, platelet activation and decrease in prostaglandins E2 and prostacyclin. Cocaine can lead to widespread systemic adverse effects such as stroke, myocardial infarction, arterial dissection, vascular thrombosis and rhabdomyolysis. In human and rat kidneys, cocaine has been associated with glomerular, tubular, vascular and interstitial injury. It is not uncommon to diagnose cocaine-related acute kidney injury (AKI), malignant hypertension and chronic kidney disease. Cocaine abuse can lead to AKI by rhabdomyolysis, vasculitis, infarction, thrombotic microangiopathy and malignant hypertension. It is reported that 50-60% of people who use both cocaine and heroin are at increased risk of HIV, hepatitis and additional risk factors that can cause kidney diseases. While acute interstitial nephritis (AIN) is a known cause of AKI, an association of AIN with cocaine is unusual and seldom reported. We describe a patient with diabetes mellitus, hypertension and chronic hepatitis C, who presented with AKI. Urine toxicology was positive for cocaine and a kidney biopsy was consistent with AIN. Illicit drugs such as cocaine or contaminants may have caused AIN in this case and should be considered in the differential diagnosis of causes of AKI in a patient with substance abuse. We review the many ways that cocaine adversely impacts on kidney function.

Effect of risedronate on bone in renal transplant recipients.

Bisphosphonates may prevent or treat the bone loss promoted by the immunosuppressive regimens used in renal transplantation. Risedronate is a commonly used third-generation amino-bisphosphonate, but little is known about its effects on the bone health of renal transplant recipients. We randomly assigned 42 new living-donor kidney recipients to either 35 mg of risedronate weekly or placebo for 12 months. We obtained bone biopsies at the time of renal transplant and after 12 months of protocol treatment. Treatment with risedronate did not affect bone mineral density (BMD) in the overall cohort. In subgroup analyses, it tended to preserve BMD in female participants but did not significantly affect the BMD of male participants. Risedronate did associate with increased osteoid volume and trabecular thickness in male participants, however. There was no evidence for the development of adynamic bone disease. In summary, further study is needed before the use of prophylactic bisphosphonates to attenuate bone loss can be recommended in renal transplant recipients.

Angiotensin converting enzyme inhibitor use soon after renal transplantation: a randomized, double-blinded placebo-controlled safety study.

Activation of the renin-angiotensin system (RAS) followed by increased inflammatory cytokines may be important in the pathogenesis of chronic allograft dysfunction. As many renal transplant recipients show chronic changes on biopsy within the first year, early RAS blockade with angiotensin converting enzyme inhibitor (ACEI) could be beneficial. However, it remains unclear that early ACEI use is safe. We conducted a prospective, randomized, placebo-controlled trial to assess the safety of enalapril 5 mg during the early post-transplant period. Subjects took the study medication for six months. Primary endpoints were serum potassium (K) >5.9 mEq/L and 30% increase in baseline creatinine. A total of 53 subjects were randomized, and of them, 27 received the study drug. Twenty-nine subjects, 14 ACEI and 15 controls, completed the six-month protocol without reaching an endpoint. Patients on ACEI had higher K and higher BUN at six months. Serum creatinine, hematocrit, and urinary protein were not different. There was no difference in urinary TGF-ß1. Twenty-four subjects reached study endpoints. When the common clinical endpoints of elevated creatinine and hyperkalemia were combined, ACEI group had significantly increased endpoints vs. control (10/13, 77% vs. 5/11, 45%, p < 0.05). We conclude that ACEI use in the early post-transplant period can be safe but patients must be carefully selected and monitored for elevations in serum creatinine and potassium. Whether early ACEI is beneficial in preserving allograft function requires further study.

Serum alkaline phosphatase and phosphate and risk of mortality and hospitalization.

BACKGROUND AND OBJECTIVES: Elevated alkaline phosphatase (AlkPhos) and phosphate levels are associated with cardiovascular morbidity and mortality in patients receiving dialysis. A retrospective cohort study was conducted to test these associations in outpatients with an estimated GFR > or =60 ml/min/1.73 m(2). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Patients with serum AlkPhos and phosphate levels measured between 2000 and 2002 (n = 10,743) at Montefiore Medical Center (MMC) clinics were followed through September 11, 2008 (median 6.8 years). Mortality data were obtained via Social Security Administration records (n = 949 deaths). Hospitalization data were obtained from MMC records. RESULTS: The mean age was 51 years, 64% were women, 22% were white, 26% were non-Hispanic black, 16% were Hispanic, 13% had a diagnosis of hypertension, 9% had diabetes mellitus, and 8% had cardiovascular disease at baseline. AlkPhos and phosphate were independently associated with mortality and cardiovascular-related hospitalization after multivariable adjustment. Comparing patients in the highest (> or =104 U/L) versus lowest quartile of AlkPhos (< or =66 U/L), the adjusted hazard ratio (HR) for mortality was 1.65 (P trend across quartiles <0.001). For the highest compared with the lowest quartile of serum phosphate (> or =3.8 mg/dl versus < or =3.0 mg/dl), the adjusted HR for mortality was 1.29 (P trend across quartiles = 0.008). High AlkPhos but not phosphate levels were also associated with all-cause, infection-related, and fracture-related hospitalization. CONCLUSIONS: Higher levels of serum AlkPhos and phosphate were associated with increased mortality and cardiovascular-related hospitalization in an inner-city clinic population. Further studies are needed to elucidate mechanisms underlying these associations.

Treating the renal patient who has a fracture: opinion vs evidence.

The patient with chronic renal disease who has a fracture remains a unique management challenge. Opinions on treatment abound, but without adequate evidence to back them up.

Analyses of age, gender and other risk factors of erythropoietin resistance in pediatric and adult dialysis cohorts.

Previous studies often report lower responses to erythropoietin (EPO) therapy in pediatric patients on chronic dialysis than those of adults. Because of the greater capacity for hematopoiesis in the younger population, these studies may be confounded by poorly identified variables. Thus, we made parallel studies of pediatric and adult cohorts to explore the relationship between age, gender and other risk factors with EPO resistance. Thirty pediatric subjects (aged 8-20 years) and 66 adult subjects (aged 22-85 years) on chronic hemodialysis and EPO were enrolled. After stratification by 50th percentile of EPO response, the best predictive model was identified by backward elimination of the risk factors with the least contribution to the regression. Relationship between age, gender and EPO resistance was examined by analysis of covariance (ANCOVA). The most predictive model of EPO response for the pediatric cohort had, as the major variables, urea clearance x dialysis duration/total body water (Kt/V), urea reduction ratio (URR), intact parathyroid hormone (iPTH), blood loss, normalized protein catabolic rates (nPCR) and indices of malnutrition and inflammation, whereas adults had iron and folate deficiencies as the dominant variables. Although EPO resistance was more common in female subjects than in male subjects, relationship with neither age nor gender was significant. Furthermore, the prescription of a larger (initiating) EPO dose by pediatric physicians compared with adult nephrologists confounded the interaction between age and EPO resistance. In summary EPO resistance in the pediatric dialysis cohort was predicted by nutritional deficits, inflammation, poor dialysis, and hyperparathyroidism, while iron and folate deficits were the major determinants in adults. Although confounded by the pattern of EPO prescription, neither age nor gender was predictive of EPO resistance in the two study groups.

The effect of sirolimus on sex hormone levels of male renal transplant recipients.

BACKGROUND: It is unclear whether sirolimus, a newer immunosuppressive agent, widely used in renal transplantation, affects male sex hormone levels or sexual function. METHODS: Sex hormone profiles in male renal transplant recipients were obtained and compared between a sirolimus-treated group and a group not on sirolimus in a cross-sectional study. Both groups also completed a sexual dysfunction questionnaire. RESULTS: Sixty-six subjects were evaluated, 32 in the sirolimus group and 34 in the control group. Total testosterone level was significantly lower in the sirolimus group than the control group (393.3 +/- 188 vs. 537.4 +/-232 pg/mL; p = 0.08) while follicle stimulating hormone and luteinizing hormone levels were significantly higher in the sirolimus group (12.8 +/- 14 vs. 6.0 +/- 5, p = 0.013; 10.9 +/- 14 vs. 4.7 +/- 4, p = 0.018, respectively). There was a significant negative correlation between 24-h sirolimus trough and total testosterone levels (p < 0.03). By multiple regression analysis, use of sirolimus was independently associated with decreased total testosterone level. There was no significant difference in subjective sexual dysfunction as assessed by questionnaire scores between the two groups. There was no correlation between questionnaire scores and total testosterone level. CONCLUSION: Sirolimus is associated with decreased total testosterone levels in male renal transplant recipients. It is unclear whether sirolimus may affect other aspects of sexual function.

Pamidronate used to attenuate post-renal transplant bone loss is not associated with renal dysfunction.

BACKGROUND: Pamidronate is a second-generation bisphosphonate that has been used to attenuate post-renal transplant bone loss, but its effect on the function of the renal allograft is unclear. Therefore, we evaluated the long-term renal function in 57 subjects who had participated in a prospective, randomized clinical trial using pamidronate to attenuate bone loss in the renal transplant recipient. METHODS: Thirty subjects (PAM) received intravenous pamidronate, 60 mg at baseline post-transplant and 30 mg in months 1, 2, 3 and 6 post-transplant, while 27 subjects (CON) did not receive pamidronate. We followed renal function, need for renal replacement therapy following transplant rejection, and mortality for 3 years following the start of the original study. RESULTS: PAM did not have increased incidence of renal dysfunction or mortality compared with CON at any time point during the 3 years of follow-up. The incidence of proteinuria was also not different between the two groups. CONCLUSIONS: The prophylactic use of pamidronate in the above doses to attenuate bone loss in renal transplant recipients is not associated with higher incidence of renal dysfunction or mortality in a 3 year follow-up study. These findings may support the use of bisphosphonates in the treatment of early renal transplant-related bone loss.

Prevention of bone loss in renal transplant recipients: a prospective, randomized trial of intravenous pamidronate.

Renal transplant recipients are at risk of developing bone abnormalities that result in bone loss and bone fractures. These are related to underlying renal osteodystrophy, hypophosphatemia, and immunosuppressive treatment regimen. Although bisphosphonates are useful in ameliorating bone mineral loss after transplantation, it is not known whether their use in renal transplant patients leads to excessive suppression of bone turnover and increased incidence of adynamic bone disease. A randomized, prospective, controlled, clinical trial was conducted using the bisphosphonate pamidronate intravenously in patients with new renal transplants. Treatment subjects (PAM) received pamidronate with vitamin D and calcium at baseline and at months 1, 2, 3, and 6. Control (CON) subjects received vitamin D and calcium only. During months 6 to 12, the subjects were observed without pamidronate treatment. Biochemical parameters of bone turnover were obtained monthly and, bone mineral density (BMD) was obtained at baseline and months 6 and 12. Bone biopsies for mineralized bone histology were obtained at baseline and at 6 mo in a subgroup of subjects who underwent scheduled living donor transplantation. PAM preserved bone mass at 6 and 12 mo as measured by bone densitometry and histomorphometry. CON had decreased vertebral BMD at 6 and 12 mo (4.8 +/- 0.08 and 6.1 +/- 0.09%, respectively). Biochemical parameters of bone turnover were similar in both groups at 6 and 12 mo. Bone histology revealed low turnover bone disease in 50% of the patients at baseline. At 6 mo, all of PAM had adynamic bone disease, whereas 50% of CON continued to have or developed decreased bone turnover. Pamidronate preserved vertebral BMD during treatment and 6 mo after cessation of treatment. Pamidronate treatment was associated with development of adynamic bone histology. Whether an improved BMD with adynamic bone histology is useful in maintaining long-term bone health in renal transplant recipients requires further study.