SARS-CoV-2 Vaccine Effectiveness and Breakthrough Infections Among Patients Receiving Maintenance Dialysis.

RATIONALE & OBJECTIVE: SARS-CoV-2 vaccine effectiveness and immunogenicity threshold associated with protection against COVID-19-related hospitalization or death in the dialysis population are unknown. STUDY DESIGN: Retrospective, observational study. SETTING & PARTICIPANTS: Adult patients without COVID-19 history receiving maintenance dialysis through a national dialysis provider and treated between February 1 and December 18, 2021, with follow-up through January 17, 2022. PREDICTOR: SARS-CoV-2 vaccination status. OUTCOMES: All SARS-CoV-2 infections, composite of hospitalization or death following COVID-19. ANALYTICAL APPROACH: Logistic regression was used to determine COVID-19 case rates and vaccine effectiveness. RESULTS: Of 16,213 patients receiving dialysis during the study period, 12,278 (76%) were fully vaccinated, 589 (4%) were partially vaccinated, and 3,346 (21%) were unvaccinated by the end of follow-up. Of 1,225 COVID-19 cases identified, 550 (45%) occurred in unvaccinated patients, and 891 (73%) occurred during the Delta variant-dominant period. Between the pre-Delta period and the Delta-dominant period, vaccine effectiveness rates against a severe COVID-19-related event (hospitalization or death) were 84% and 70%, respectively. In the subset of 3,202 vaccinated patients with at least one anti-spike immunoglobulin G (IgG) assessment, lower anti-spike IgG levels were associated with higher case rates per 10,000 days and higher adjusted hazard ratios for infection and COVID-19-related hospitalization or death. LIMITATIONS: Observational design, residual biases, and confounding may exist. CONCLUSIONS: Among maintenance dialysis patients, SARS-CoV-2 vaccination was associated with a lower risk of COVID-19 diagnosis and associated hospitalization or death. Among vaccinated patients, a low anti-spike IgG level is associated with worse COVID-19-related outcomes.

Comparison of Dialysis Unit and Home Blood Pressures: An Observational Cohort Study.

RATIONALE & OBJECTIVE: Prior studies of patients receiving maintenance hemodialysis have shown that, on average, blood pressure (BP) measured predialysis is higher than BP measured at home. We hypothesized that a subset of hemodialysis patients has BP that is higher when measured at home than when measured predialysis and this subgroup of patients has a higher prevalence of left ventricular hypertrophy. STUDY DESIGN: Prospective cohort. SETTING & PARTICIPANTS: 97 hypertensive hemodialysis patients enrolled in the Blood Pressure in Dialysis Study (BID), a randomized trial of comparing target predialysis BP ≤140/90 to 155-165/90 mm Hg. EXPOSURE: Differences between predialysis and next-day home systolic BP measured ≥6 times over 1 year. OUTCOME: Left ventricular mass index (LVMI) by cardiac magnetic resonance imaging. ANALYTICAL APPROACH: A hierarchical clustering analysis divided patients into 3 clusters based on the average and variability of differences in systolic predialysis and home BP. Clusters were compared with respect to clinical factors and LVMI. RESULTS: Mean differences between predialysis and home systolic BP were 19.1 (95% CI, 17.0 to 21.1) mm Hg for cluster 1 ("home lower"), 3.7 (95% CI, 1.6 to 5.8) mm Hg for cluster 2 ("home and predialysis similar"), and -9.7 (95% CI, -12.0 to -7.4) mm Hg for cluster 3 ("home higher"). Systolic BP declined during dialysis in clusters 1 and 2 but increased in cluster 3. Interdialytic weight gains did not differ. After adjusting for sex and treatment arm, LVMI was higher in cluster 3 than in clusters 1 and 2: differences in means of 10.6 ± 4.96 (SE) g/m2 (P = 0.04) and 12.0 ± 5.08 g/m2 (P = 0.02), respectively. LIMITATIONS: Limited statistical power. CONCLUSIONS: Nearly one-third of participants had home BPs higher than predialysis BPs. These patients had LVMI higher than those with similar or lower BPs at home, indicating that their BP may have been undertreated.

Comparison of Prescribed and Measured Dialysate Sodium: A Quality Improvement Project.

BACKGROUND: There is controversy regarding the optimal dialysate sodium concentration for hemodialysis patients. Dialysate sodium concentrations of 134 to 138 mEq/L may decrease interdialytic weight gain and improve hypertension control, whereas a higher dialysate sodium concentration may offer protection to patients with low serum sodium concentrations and hypotension. We conducted a quality improvement project to explore the hypothesis that prescribed and delivered dialysate sodium concentrations may differ significantly. STUDY DESIGN: Cross-sectional quality improvement project. SETTING & PARTICIPANTS: 333 hemodialysis treatments in 4 facilities operated by Dialysis Clinic, Inc. QUALITY IMPROVEMENT PLAN: Measure dialysate sodium to assess the relationships of prescribed and measured dialysate sodium concentrations. OUTCOMES: Magnitude of differences between prescribed and measured dialysate sodium concentrations. MEASUREMENTS: Dialysate sodium measured pre- and late dialysis. RESULTS: The least square mean of the difference between prescribed minus measured dialysate sodium concentration was -2.48 (95% CI, -2.87 to -2.10) mEq/L. Clinics with a greater number of different dialysate sodium prescriptions (clinic 1, n=8; clinic 2, n=7) and that mixed dialysate concentrates on site had greater differences between prescribed and measured dialysate sodium concentrations. Overall, 57% of measured dialysate sodium concentrations were within ±2 mEq/L of the prescribed dialysate sodium concentration. Differences were greater at higher prescribed dialysate sodium concentrations. LIMITATIONS: We only studied 4 facilities and dialysate delivery machines from 2 manufacturers. Because clinics using premixed dialysate used the same type of machine, we were unable to independently assess the impact of these factors. Pressures in dialysate delivery loops were not measured. CONCLUSIONS: There were significant differences between prescribed and measured dialysate sodium concentrations. This may have beneficial or deleterious effects on clinical outcomes, as well as confound results from studies assessing the relationships of dialysate sodium concentrations to outcomes. Additional studies are needed to identify factors that contribute to differences between prescribed and measured dialysate sodium concentrations. Quality assurance and performance improvement (QAPI) programs should include measurements of dialysate sodium.

Anemia management and association of race with mortality and hospitalization in a large not-for-profit dialysis organization.

BACKGROUND: The optimal hemoglobin target and possible toxicity of epoetin therapy in hemodialysis patients are controversial. Previous studies suggest that African American patients use higher doses of epoetin and have better survival compared with white hemodialysis patients. STUDY DESIGN: Retrospective longitudinal cohort. SETTING & PARTICIPANTS: Epoetin-exposed incident hemodialysis patients (N = 12,733; African Americans, n = 4,801; white, n = 7,386) treated in Dialysis Clinic Inc facilities during 2000 to 2006. PREDICTORS: Hemoglobin, epoetin, iron. OUTCOMES: Mortality, hospitalization. MEASUREMENTS: Proportional hazards models with time-varying covariates. RESULTS: Hemoglobin concentrations less than 10 g/dL in whites and less than 11 g/dL in African Americans were associated with increased mortality and hospitalization versus the referent hemoglobin level of 11 to 11.9 g/dL. Hemoglobin levels of 13 g/dL or greater in whites were associated with decreased noncardiovascular mortality. Six-month cumulative epoetin doses of 20,000 U/wk or greater were associated with increased mortality and hospitalization versus the referent group (8,000 to 12,499 U/wk). Epoetin doses less than 8,000 U/wk were associated with decreased risk. Higher epoetin doses were associated with increased mortality at hemoglobin concentrations of 10 to 12.9 g/dL and with increased hospitalization at all hemoglobin concentrations of 10 g/dL or greater. Higher epoetin doses were associated with increased mortality and hospitalization within each tertile of serum albumin concentration. These patterns did not differ by race. LIMITATIONS: Treatment-by-indication bias and unidentified confounders cannot be excluded. Small sample sizes in the highest and lowest hemoglobin strata decrease statistical power. CONCLUSIONS: Relationships between hemoglobin concentration and mortality differed between African Americans and whites. Additionally, the relationship of lower mortality with greater achieved hemoglobin concentration seen in white patients was observed for all-cause, but not cardiovascular, mortality. A higher cumulative epoetin dose was associated with worse outcomes, even in patients with albumin levels greater than 4 g/dL. There were no statistically significant interactions between race and epoetin dose. Further studies are needed to confirm and to define the mechanism of these findings.

Association between calciphylaxis and inflammation in two patients on chronic dialysis.

The pathogenesis of calciphylaxis, which has a rising incidence in the chronic dialysis population and a high mortality rate, is poorly understood. Abnormalities in the calcium-phosphorus-parathyroid axis are clinically related to calciphylaxis, but alone, they cannot explain this condition. Here, we present two patients who had chronic inflammatory conditions and hyperparathyroidism and who developed calciphylaxis. A 41-year-old white woman on hemodialysis following scleroderma, hepatitis C, liver transplant, and failed kidney transplant, developed progressive ulcerative lower extremity calciphylaxis lasting more than 3 years. She had evidence of severe hyperparathyroidism and elevated serum C-reactive protein (CRP). A 39-year-old white woman on continuous ambulatory peritoneal dialysis for 6 years for renal failure secondary to lupus nephritis, with sustained lupus activity during the dialysis period, developed rapidly progressing ulcerative calciphylaxis of the lower and upper extremities not responding to adequate treatment of hyperphosphatemia and hyperparathyroidism. Her condition culminated in death within 2 months of the appearance of the skin lesions. Her serum CRP was elevated on a sustained basis before the development of the calciphylaxis and rose to a very high level after appearance of the skin lesions. Inflammation may assist in the development of calciphylaxis through depression of serum levels of fetuin-A, an endogenous inhibitor of calcification that is also a negative acute-phase reactant. The interactions between inflammation-mediated changes in the levels of endogenous inhibitors of calcification and abnormalities in calcium-phosphorus metabolism merit intensive study in the future as potential mechanisms of calciphylaxis.

BK nephropathy in the native kidneys of patients with organ transplants: Clinical spectrum of BK infection.

Nephropathy secondary to BK virus, a member of the Papoviridae family of viruses, has been recognized for some time as an important cause of allograft dysfunction in renal transplant recipients. In recent times, BK nephropathy (BKN) of the native kidneys has being increasingly recognized as a cause of chronic kidney disease in patients with solid organ transplants, bone marrow transplants and in patients with other clinical entities associated with immunosuppression. In such patients renal dysfunction is often attributed to other factors including nephrotoxicity of medications used to prevent rejection of the transplanted organs. Renal biopsy is required for the diagnosis of BKN. Quantitation of the BK viral load in blood and urine are surrogate diagnostic methods. The treatment of BKN is based on reduction of the immunosuppressive medications. Several compounds have shown antiviral activity, but have not consistently shown to have beneficial effects in BKN. In addition to BKN, BK viral infection can cause severe urinary bladder cystitis, ureteritis and urinary tract obstruction as well as manifestations in other organ systems including the central nervous system, the respiratory system, the gastrointestinal system and the hematopoietic system. BK viral infection has also been implicated in tumorigenesis. The spectrum of clinical manifestations from BK infection and infection from other members of the Papoviridae family is widening. Prevention and treatment of BK infection and infections from other Papovaviruses are subjects of intense research.

Kidney disease among the Zuni Indians: the Zuni Kidney Project.

BACKGROUND: There is an epidemic of kidney disease among the Zuni Indians. In collaboration with health care providers and research institutions, the Zuni Pueblo established the Zuni Kidney Project to reduce the burden of kidney disease. METHODS: The Zuni Kidney Project conducted a population-based, cross-sectional survey to estimate the prevalence of albuminuria, hematuria, and related risk factors. Neighborhood household clusters served as the sampling frame. Participants completed a questionnaire, donated blood and urine samples, and had blood pressure, height, and weight measured. This survey provided the foundation for ongoing studies to identify genetic and environmental risk factors for disease susceptibility and progression. RESULTS: Age and gender distributions among survey participants were similar to those in the eligible Zuni population. Prevalence of incipient albuminuria (IA) (0.03< or = urine albumin:creatinine ratio, UACR <0.3) and overt albuminuria (OA) (UACR < 0.3) were higher among diabetics [IA 34.3% (28.3, 40.4%); OA 18.6% (13.7, 23.6%)] than nondiabetics [IA 11.1% (9.3, 12.8%); OA 1.7% (1.0, 2.5%)]. Nondiabetics comprised 58.6% (52.2, 65.0%) and 30.9% (19.9, 41.9%) of participants with IA and OA, respectively. The prevalence of hematuria was higher among diabetics [> or = trace 47.0% (40.7, 53.4); > or =50 red blood cell/microL 25.8% (20.3, 31.4%)] than nondiabetics [> or = trace 31.1% (28.5, 33.7%); > or =50 red blood cell/microL 16.6% (14.5, 18.7%)]. Hypertension was associated with albuminuria among diabetic and nondiabetic participants. Hypercholesterolemia was associated with albuminuria among nondiabetic participants. Diabetes and alcohol use were associated with hematuria. CONCLUSION: The high prevalences of albuminuria among nondiabetics and of hematuria among diabetics and nondiabetics are consistent with high rates of nondiabetic kidney disease among Zuni Indians with and without diabetes.

Satisfaction with Care of Patients on Hemodialysis.

BACKGROUND AND OBJECTIVES: Little is known about patients receiving dialysis who respond to satisfaction and experience of care surveys and those who do not respond, nor is much known about the corollaries of satisfaction. This study examined factors predicting response to Dialysis Clinic, Inc. (DCI)'s patient satisfaction survey and factors associated with higher satisfaction among responders. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENT: A total of 10,628 patients receiving in-center hemodialysis care at 201 DCI facilities between January 1, 2011, and December 31, 2011, aged ≥18 years, treated during the survey administration window, and at the facility for ≥3 months before survey administration. Primary outcome was response to at least one of the nine survey questions; secondary outcome was overall satisfaction with care. RESULTS: Response rate was 77.3%. In adjusted logistic regression (odds ratios with 95% confidence intervals), race other than black (white race, 1.23 [1.10 to 1.37]), missed treatments (1.16 [1.02 to 1.32]) or shortened treatments (≥5 treatments, 1.40 [1.22 to 1.60]), more hospital days (>3 days in the last 3 months, 1.89 [1.66 to 2.15]), and lower serum albumin (albumin level <3.5 g/dl, 1.4 [1.28 to 1.73]) all independently predicted nonresponse. In adjusted linear regression, the following were more satisfied with care: older patients (age ≥63 years, 1.84 [1.78 to 1.90]; age <63 years, 1.91 [1.86 to 1.97]; P<0.001), white patients (1.76 [1.71 to 1.81]) versus black patients (1.93 [1.88 to 1.99]) or those of other race (1.93 [1.83 to 2.03]) (P<0.001), patients with shorter duration of dialysis (≤2.5 years, 1.79 [1.73 to 1.84]; >2.5 years, 1.96 [1.91 to 2.02]; P<0.001), patients who had missed one or fewer treatments (1.83 [1.78 to 1.88]) versus those who had missed more than one treatment (1.92 [1.85 to 1.98]; P=0.002) and those who had shortened treatment (for one treatment or less, 1.84 [1.77 to 1.90]; for two to four treatments, 1.87 [1.81 to 1.93]; for five or more treatments, 1.92 [1.87 to 1.98]; P=0.004). CONCLUSIONS: Survey results represent healthier and more adherent patients on hemodialysis. Shorter survey administration windows were associated with higher response rates. Older, white patients with shorter dialysis vintage were more satisfied.

Genetics of kidney disease and related cardiometabolic phenotypes in Zuni Indians: the Zuni Kidney Project.

The objective of this study is to identify genetic factors associated with chronic kidney disease (CKD) and related cardiometabolic phenotypes among participants of the Genetics of Kidney Disease in Zuni Indians study. The study was conducted as a community-based participatory research project in the Zuni Indians, a small endogamous tribe in rural New Mexico. We recruited 998 members from 28 extended multigenerational families, ascertained through probands with CKD who had at least one sibling with CKD. We used the Illumina Infinium Human1M-Duo version 3.0 BeadChips to type 1.1 million single nucleotide polymorphisms (SNPs). Prevalence estimates for CKD, hyperuricemia, diabetes, and hypertension were 24%, 30%, 17% and 34%, respectively. We found a significant (p < 1.58 × 10(-7)) association for a SNP in a novel gene for serum creatinine (PTPLAD2). We replicated significant associations for genes with serum uric acid (SLC2A9), triglyceride levels (APOA1, BUD13, ZNF259), and total cholesterol (PVRL2). We found novel suggestive associations (p < 1.58 × 10(-6)) for SNPs in genes with systolic (OLFML2B), and diastolic blood pressure (NFIA). We identified a series of genes associated with CKD and related cardiometabolic phenotypes among Zuni Indians, a population with a high prevalence of kidney disease. Illuminating genetic variations that modulate the risk for these disorders may ultimately provide a basis for novel preventive strategies and therapeutic interventions.

Epidemic of diabetic and nondiabetic renal disease among the Zuni Indians: the Zuni Kidney Project.

There is an epidemic of renal disease among the Zuni Indians. The prevalence of end-stage renal disease among the Zuni Indians is 18.4-fold and 7.4-fold higher than among European Americans and American Indians/Alaskan Natives, respectively. In contrast to other American Indian tribes, nondiabetic renal disease accounts for a significant percent of the renal disease burden among the Zuni Indians. To explore this hypothesis, a community epidemiologic study of the Zuni Pueblo was conducted. A questionnaire was administered, blood and urine samples were collected, and BP, height, and weight were measured. Neighborhood household clusters were used as the sampling frame to maximize ascertainment and minimize bias. Age and gender distributions in the sample (n = 1483) were similar to those of the eligible Zuni population (n = 9228). The prevalence, age-adjusted and gender-adjusted to the Zuni population, of incipient (0.03 < or = UACR < 0.3) albuminuria (IA) (15.0% [95% confidence interval, 13.1 to 16.9%]), and overt (UACR > or = 0.3) albuminuria (OA) (4.7% [3.6 to 5.8%]) was high. The prevalence estimates for IA and OA were higher among diabetic participants (IA: 33.6% [27.6 to 39.7%]; OA: 18.7% [13.7 to 23.7%]) than nondiabetic participants (IA: 10.8% [9.0 to 12.6%]; OA: 1.8% [1.0 to 2.5%]). However, there were more nondiabetic participants; therefore, they comprised 58.0% [51.4 to 64.6%] and 30.9% [20.0 to 41.7%] of participants with IA and OA, respectively. In contrast to most other American Indian tribes, nondiabetic renal disease contributes significantly to the overall burden of renal disease among the Zuni Indians.