COVID-19 and Kidney Disease.

COVID-19 can cause acute kidney injury and may cause or exacerbate chronic kidney diseases, including glomerular diseases. SARS-CoV-2 infection of kidney cells has been reported, but it remains unclear if viral infection of kidney cells causes disease. The most important causes of kidney injury in patients with COVID-19 include impaired renal perfusion and immune dysregulation. Chronic kidney disease, especially kidney failure with kidney replacement therapy and kidney transplant, is associated with markedly increased COVID-19 mortality. Persons with severe kidney disease have been excluded from most clinical trials of COVID-19 therapies, so therapeutic approaches must be extrapolated from studies of patients without kidney disease. Some medications used to treat COVID-19 should be avoided or used at reduced dosages in patients with severe kidney disease and in kidney transplant recipients. Additional research is needed to determine the optimal strategies to prevent and treat COVID-19 in patients with kidney disease.

Development of PD in lower-income countries: a rational solution for the management of AKI and ESKD.

It is estimated that >50% of patients with end-stage kidney disease (ESKD) in low-resource countries are unable to access dialysis. When hemodialysis is available, it often has high out-of-pocket expenditure and is seldom delivered to the standard recommended by international guidelines. Hemodialysis is a high-cost intervention with significant negative effects on environmental sustainability, especially in resource-poor countries (the ones most likely to be affected by resultant climate change). This review discusses the rationale for peritoneal dialysis (PD) as a more resource and environmentally efficient treatment with the potential to improve dialysis access, especially to vulnerable populations, including women and children, in lower-resource countries. Successful initiatives such as the Saving Young Lives program have demonstrated the benefit of PD for acute kidney injury. This can then serve as a foundation for later development of PD services for end-stage kidney disease programs in these countries. Expansion of PD programs in resource-poor countries has proven to be challenging for various reasons. It is hoped that if some of these issues can be addressed, PD will be able to permit an expansion of end-stage kidney disease care in these countries.

Changes in Cognitive Function After Kidney Transplantation: A Longitudinal Cohort Study.

RATIONALE & OBJECTIVE: Kidney disease negatively affects cognition. We assessed the effect of kidney transplantation (KT) on different cognitive domains. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: We examined pre- versus post-KT cognition in patients waitlisted for KT at an academic center. PREDICTORS: Transplant status. We measured cognitive function before KT (n=101), 3 months after KT (n=78), and 1 year after KT (n = 83). OUTCOMES: Our primary outcome was change in cognitive function before versus after KT. We used standard neuropsychological tests to assess global cognition (Mini-Mental State Exam [MMSE]), episodic/declarative memory (Logical Memory), psychomotor speed/visuospatial function (Digit Symbol Substitution Test [DSST], Trail Making Test [TMT] A), working memory/attention (Digit Span), executive function (TMT B), and semantic memory/verbal fluency/language (Category Fluency). ANALYTICAL APPROACH: Using linear mixed model analysis, we evaluated the changes in neuropsychological test scores adjusted for age, sex, race, education, and number of assessments. RESULTS: Before KT, Logical Memory I and II, DSST, MMSE, Category Fluency (animal naming), and Digit Span backward scores were low compared with normative values from the National Alzheimer's Coordinating Center data. Logical Memory I and II scores improved after KT (pre- vs post-KT, estimated group difference [d]=3.3, P<0.001 for Logical Memory I; d=4.27, P<0.001 for Logical Memory II), such that post-KT scores were similar to normative values (post-KT vs normative values, d = -0.37, P=0.06 for Logical Memory I; d = -0.89, P=0.08 for Logical Memory II). Category Fluency (animal naming; d=2.4, P<0.001) and DSST (d=3.12, P=0.01) scores also improved with KT, but post-KT DSST scores remained lower than normative values (post-KT vs normative values, d = -5.17, P<0.001). MMSE, Digit Span, and TMT A and B scores did not change after KT. LIMITATIONS: Single-center study. CONCLUSIONS: Episodic and verbal declarative memory normalize after KT. Semantic memory, verbal fluency, language, psychomotor speed, and visuospatial function show partial improvement. Cognitive impairment in kidney disease is therefore at least partly reversible with KT. PLAIN-LANGUAGE SUMMARY: Cognitive impairment in kidney disease affects self-esteem, vocational abilities, quality of life, health care costs, and mortality. It is not clear whether kidney transplantation (KT) improves cognition and whether the improvement is uniform across cognitive domains. The distinction between reversible and irreversible cognitive impairment has important implications in the clinical care of patients before and after KT. We assessed cognition before KT and 3 months and 12 months after KT and discovered that episodic and verbal declarative memory normalized with KT. Semantic memory, verbal fluency, language, psychomotor speed, and visuospatial function also improved with KT but did not reach normal levels. Cognitive impairment in kidney disease is therefore at least partly reversible.

Genetic Markers Among the Israeli Druze Minority Population With End-Stage Kidney Disease.

RATIONALE & OBJECTIVE: Genetic etiologies have been identified among approximately 10% of adults with chronic kidney disease (CKD). However, data are lacking regarding the prevalence of monogenic etiologies especially among members of minority groups. This study characterized the genetic markers among members of an Israeli minority group with end-stage kidney disease (ESKD). STUDY DESIGN: A national-multicenter cross-sectional study of Israeli Druze patients (an Arabic-speaking Near-Eastern transnational population isolate) who are receiving maintenance dialysis for ESKD. All study participants underwent exome sequencing. SETTING & PARTICIPANTS: We recruited 94 adults with ESKD, comprising 97% of the total 97 Druze individuals throughout Israel being treated with dialysis during the study period. PREDICTORS: Demographics and clinical characteristics of kidney disease. OUTCOME: Genetic markers. ANALYTICAL APPROACH: Whole-exome sequencing and the relationship of markers to clinical phenotypes. RESULTS: We identified genetic etiologies in 17 of 94 participants (18%). None had a previous molecular diagnosis. A novel, population-specific, WDR19 homozygous pathogenic variant (p.Cys293Tyr) was the most common genetic finding. Other monogenic etiologies included PKD1, PKD2, type IV collagen mutations, and monogenic forms of noncommunicable diseases. The pre-exome clinical diagnosis corresponded to the final molecular diagnosis in fewer than half of the participants. LIMITATIONS: This study was limited to Druze individuals, so its generalizability may be limited. CONCLUSIONS: Exome sequencing identified a genetic diagnosis in approximately 18% of Druze individuals with ESKD. These results support conducting genetic analyses in minority populations with high rates of CKD and for whom phenotypic disease specificity may be low. PLAIN-LANGUAGE SUMMARY: Chronic kidney disease (CKD) affects many people worldwide and has multiple genetic causes. However, there is limited information on the prevalence of genetic etiologies, especially among minority populations. Our national-multicenter study focused on Israeli Druze patients. Using exome-sequencing, we identified previously undetected genetic causes in nearly 20% of patients, including a new and population-specific WDR19 homozygous pathogenic variant. This mutation has not been previously described; it is extremely rare globally but is common among the Druze, which highlights the importance of studying minority populations with high rates of CKD. Our findings provide insights into the genetic basis of end-stage kidney disease in the Israeli Druze, expand the WDR19 phenotypic spectrum, and emphasize the potential value of genetic testing in such populations.

IgA vasculitis nephritis-outcomes in adult-onset disease.

OBJECTIVES: IgA vasculitis (IgAV) in adults has been relatively under-investigated. Since outcomes are worse in other forms of vasculitis with increasing age, we investigated the outcomes of IgAV comparing younger adults (18-34), middle aged adults (35-64) and elderly patients (≥64 years) focusing on kidney outcomes. METHODS: We identified patients with renal biopsy confirmed IgAV nephritis and collected data regarding clinical features and progression to end stage kidney disease (ESKD). The relationship between patient factors and ESKD was analysed by regression. RESULTS: We identified 202 cases, 34% aged 18-34, 43% aged 35-64 and 23% were elderly (>64 years). Median follow up was 44 months. Elderly patients were more likely to present with ESKD (23.9%) compared with middle aged (13.7%) and younger adults (2.9%)(χ2 11.6, p= 0.002). In patients with independent kidney function at biopsy, there was no difference in outcomes between age groups. Male gender, Black ethnicity, diabetes, histological evidence of chronic renal damage and eGFR < 30mls/min were risk factors for development of ESKD. In this observational study 68.3% of patients received glucocorticoids and 56.9% additional immunosuppression. CONCLUSIONS: Elderly patients with IgAV are more likely to have ESKD at presentation, but there is no difference in renal survival between age groups, among those presenting with independent renal function. Renal impairment at biopsy is an independent risk factor for subsequent development of ESKD. There is significant variability in the timing of kidney biopsy and management of these patients among specialist centres. Young adults have outcomes more in keeping with childhood IgAV.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) and clinical outcomes in dialysis patients.

BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9), a factor accelerating the degradation of LDL receptors, was associated with a gender-dependent risk for cardiovascular (CV) events in the general population and with all-cause and CV mortality in two relatively small studies in black Africans and South Korean haemodialysis patients. The effect modification by gender was untested in these studies. METHODS: The study enrolled 1188 dialysis patients from the Prospective Registry of The Working Group of Epidemiology of Dialysis Region Calabria (PROGREDIRE) cohort. PCSK9 was measured by colorimetric enzyme-linked immunosorbent assay. The primary outcomes were all-cause and CV mortality. Statistical analysis included Cox regression analysis and effect modification analysis. RESULTS: During a median 2.9-year follow-up, out of 494 deaths, 278 were CV-related. In unadjusted analyses, PCSK9 levels correlated with increased all-cause (HRfor1ln unit increase: 1.23, 95% CI 1.06-1.43, p =.008) and CV mortality (HRfor1ln unit increase: 1.26, 95% CI 1.03-1.54, p =.03). After multivariate adjustment, these associations were no longer significant (all-cause mortality, HRfor 1 ln unit increase: 1.16, 95% CI .99-1.36, p =.07; CV mortality, HRfor1ln unit increase: 1.18, 95% CI .95-1.46, p =.14). However, in fully adjusted interaction analyses, a doubling in the risk of this outcome in women was registered (Women, HRfor1ln unit increase: 1.88, 95% CI 1.27-2.78, p =.002; Men, HRfor1ln unit increase: 1.07, 95% CI .83-1.38, p =.61; p for effect modification: .02). CONCLUSIONS: PCSK9 levels are unrelated to all-cause mortality in haemodialysis patients but, like in studies of the general population, independently of other risk factors, entail a doubling in the risk of CV events in women in this population.

Effectiveness and safety of direct oral anticoagulants versus vitamin K antagonists in patients on chronic dialysis: a nationwide registry study.

BACKGROUND AND HYPOTHESIS: Clinical trials of direct oral anticoagulants (DOAC) are scarce and inconclusive in patients who are receiving dialysis, for whom DOAC are not labelled in Europe. In a French nationwide registry study of patients on chronic dialysis, we compared the effectiveness and safety of off-label DOAC use vs. approved vitamin K antagonist (VKA). METHODS: Data on patients on dialysis were extracted from the French Renal Epidemiology and Information Network (REIN) registry and merged with data from the French national healthcare system database (Système National des Données de Santé, SNDS). Patients on dialysis who had initiated treatment with an oral anticoagulant between January 1st, 2012, and December 31st, 2020, were eligible for inclusion. The primary safety outcome was the occurrence of major bleeding events and the primary effectiveness outcome was the occurrence of thrombotic events. Using propensity-score-weighted cause-specific Cox regression, we compared the safety and effectiveness outcomes for DOAC and VKA. RESULTS: 8,954 patients received an oral anticoagulant (483 DOAC and 8,471 VKA) for the first time after the initiation of dialysis. Over a median [interquartile range] follow-up period of 1.7 [0.8-3.2] years, 2,567 patients presented a first thromboembolic event and 1,254 patients had a bleeding event. After propensity score adjustment, the risk of a thromboembolic event was significantly lower in patients treated with a DOAC than in patients treated with a VKA (weighted hazard ratio (wHR) [95% confidence interval (CI)]: 0.66 [0.46; 0.94]. A non-significant trend toward a lower risk of major bleeding events was found in DOAC-treated patients, relative to VKA-treated patients (wHR [95%CI]: 0.68 [0.41; 1.12]). The results were consistent across subgroups and in sensitivity analyses. CONCLUSIONS: In a large group of dialysis patients initiating an oral anticoagulant, the off-label use of DOACs was associated with a significantly lower risk of thromboembolic events and a non-significantly lower risk of bleeding, relative to VKA use. This provides reassurance regarding the off-label use of DOACs in people on dialysis.

The direct cost of chronic kidney disease (CKD) reported in Asian countries; a systematic literature review.

BACKGROUND: The direct and indirect costs of chronic kidney disease (CKD) are substantial and increase over time. Concerns regarding our capacity to manage the financial burden that CKD) places on patients, caregivers, and society are raised by its increasing prevalence and progression. Lack of awareness of CKD's economic effects is a major reason that lawmakers and administrators pay little attention to this chronic illness. OBJECTIVE: We aimed to analyze the direct burden of CKD across Asian countries and evaluate the main cost drivers among all mentioned cost centers in previous studies. METHODOLOGY: Related works evaluating the expenditures of CKD from the perspective of the patient were interpreted by a thorough search of PUBMED and GOOGLE SCHOLAR. RESULTS: Country-wise, in Asia, the direct mean average medical costs in RRT patients were reported in 8 studies as $4574, $18668, $2901, $6848, $16669, $3489, $5945, and $6344 in Singapore, Korea, Taiwan, China, Jordan, Vietnam, Lebanon, and India respectively and the direct mean average medical costs in non-RRT patients were reported in six studies as $3412, $2241, $4534, $290 and $1500 in Singapore, Japan, China, Vietnam, and India respectively. CONCLUSION: Hemodialysis is the main cost driver having an average mean cost of $23,358 per patient per year while the average mean cost of disease management is $4977 per patient per year. More research is needed to understand the specific economic challenges disadvantaged populations face, including the impact of income, education, and access to healthcare resources on the financial burden of CKD.

Evaluating the safety of bariatric surgery as a bridge to kidney transplant: a retrospective cohort study.

BACKGROUND: Bariatric surgery has been proven safe in end-stage kidney disease (ESKD); however, few studies have evaluated whether a history of bariatric surgery impacts transplant-specific outcomes. We hypothesize that a history of bariatric surgery at the time of transplant does not adversely impact transplant-specific outcomes. METHODS: The IBM MarketScan Commercial Claims and Encounters database was queried for patients with a history of kidney transplant between 2000 and 2021. Patients were stratified into three groups based on bariatric surgery status and body mass index (BMI) at the time of transplant: patients with obesity (O), patients without obesity (NO), and patients with a history of bariatric surgery (BS). Inverse probability of treatment weighting was used to control for confounding. Adjusted hazard ratios (aHRs) describing the risk of transplant-specific and postoperative outcomes were estimated using weighted Kaplan-Meier curves. Primary outcomes included 30-day and 1-year risk of transplant-specific outcomes. Secondary outcomes included 30-day and 1-year postoperative complications and 30-day and 1-year risk of wound-related complications. RESULTS: We identified 14,806 patients; 128 in the BS group, 1572 in the O group, and 13,106 in the NO group. There was no difference in 30-day or 1-year risk of transplant-specific complications between the BS and NO group or the O and NO group. Patients with obesity (O) were more likely to experience wound infection (aHR 1.49, 95% CI 1.12-1.99), wound dehiscence (aHR 2.2, 95% CI 1.5-3.2), and minor reoperation (aHR 1.52, 95% CI 1.23-1.89) at 1 year. BS patients had increased risk of wound infection at 1 year (aHR 2.79, 95% CI 1.26-6.16), but were without increase in risk of minor or major reoperation. CONCLUSION: A history of bariatric surgery does not adversely affect transplant-specific outcomes after kidney transplant. Bariatric surgery can be safely utilized to improve the transplant candidacy of patients with obesity with CKD and ESKD.

Improved Clinical Outcomes Associated with Hungry Bone Syndrome Following Parathyroidectomy in Dialysis Patients.

OBJECTIVE: Hungry bone syndrome (HBS) is a common complication after parathyroidectomy in dialysis patients with severe secondary hyperparathyroidism. The rapid decline in parathyroid hormone (PTH) levels diminishes bone resorption and accelerates bone formation. This causes a significant influx of calcium and phosphate into the bone, resulting in severe and prolonged hypocalcemia. While previous studies have established risk factors for HBS, the outcomes beyond the reduced recurrence rate of hyperparathyroidism have been largely unexplored. METHODS: This single-center retrospective study analyzed 322 cases in 314 dialysis patients who underwent parathyroidectomy between 2012 and 2022. The study examined baseline factors associated with HBS, adverse events, and clinical outcomes, including changes in blood pressure and hematologic and nutritional parameters over 3-12 months of follow-up, stratified by HBS status. RESULTS: Total parathyroidectomy was performed in 28 cases (8.7%), total parathyroidectomy with implantation in 98 cases (30.4%), and subtotal parathyroidectomy in 196 cases (60.9%). HBS occurred in 207 cases (64%). Independent predictors of HBS included male sex, lower serum calcium levels, higher PTH levels, and lack of active vitamin D treatment at baseline. Patients with HBS had longer hospital stays but did not experience an increase in other adverse events. Following parathyroidectomy, the HBS group showed a greater reduction in blood pressure and more significant increases in hemoglobin, total lymphocyte count, and serum creatinine. This group also saw a more substantial decrease in the proportions of patients with hemoglobin <11 g/dL and serum creatinine/body surface area <380 µmol/L/m2. Although the HBS group showed a more significant decline in PTH levels from baseline, similar proportions achieved the target PTH level by the end of the study. Serum calcium levels remained substantially lower in the HBS group throughout the follow-up, while serum phosphate and PTH levels were comparable. CONCLUSION: HBS was associated with more pronounced improvements in blood pressure, anemia, and nutritional parameters. The presence of HBS could indicate greater achievement in controlling hyperparathyroidism following parathyroidectomy.

Association between TMSE/MoCA and MIS/NAF in ESKD patients undergoing hemodialysis: a cross-sectional study.

BACKGROUND: Both cognitive impairment and malnutrition are common in hemodialysis (HD) patients and are associated with increased hospitalization rates, infection, poor clinical outcomes, and mortality. The study investigated the association between cognitive and nutrition status among end-stage kidney disease (ESKD) patients undergoing hemodialysis. METHODS: In this cross-sectional study, we enrolled 115 patients with ESKD who underwent regular hemodialysis (HD). Data collection included the use of screening tools for mild cognitive impairment (MCI), specifically Thai Mental State Examination (TMSE) and Montreal Cognitive Assessment (MoCA). In addition, we collected data using nutritional screening tools including Malnutrition Inflammation Score (MIS) and Nutrition Alert Form (NAF). Our primary outcome was to demonstrate whether there was a relationship between TMSE/MoCA and MIS/NAF scores in this population. Secondary outcomes were a prevalence of MCI and malnutrition status in ESKD patients, an association between TMSE and MoCA with other surrogate nutritional markers, and factors affecting MCI in such patients. RESULTS: A total of 109 patients undergoing HD completed our protocol. Their mean age was 63.42 (± 15.82) years, and 51.38% were male. Mean TMSE and MoCA were 23.98 (± 5.06) points and 18.3 (± 6.40) points, respectively. The prevalence of TMSE ≤ 23 and MoCA ≤ 24 were 39.45% and 83.49%, respectively. TMSE had a statistically significant negative correlation with MIS (R2 = 0.16, p < 0.001) and NAF. MoCA also negatively correlated with MIS and NAF. The age, total educational year, the status of whether having a caregiver, serum albumin, serum phosphorus level, handgrip strength, and lean mass tissue were correlated with TMSE. CONCLUSION: Nutritional parameters, including MIS score, NAF score, serum albumin, lean tissue mass, and lean tissue index, significantly correlate with TMSE and MoCA.

Renin-Angiotensin-Aldosterone System: From History to Practice of a Secular Topic.

Renin-angiotensin-aldosterone system (RAAS) inhibitors are standard care in patients with hypertension, heart failure or chronic kidney disease (CKD). Although we have studied the RAAS for decades, there are still circumstances that remain unclear. In this review, we describe the evolution of the RAAS and pose the question of whether this survival trait is still necessary to humankind in the present age. We elucidate the benefits on cardiovascular health and kidney disease of RAAS inhibition and present promising novel medications. Furthermore, we address why more studies are needed to establish a new standard of care away from generally prescribing ACEi or ARB toward an improved approach to combine drugs tailored to the needs of individual patients.

Prevalence of Cognitive Impairment and Relationships with Other Factors in Patients with End Stage Kidney Disease Receiving Hemodialysis.

Despite recommendations, cognitive screening in patients with end stage kidney disease (ESKD) rarely happens, leading to underestimates of cognitive impairment (CI) prevalence and missed opportunities for intervention. We aimed to describe CI prevalence and associated factors in 100 patients receiving in-center hemodialysis aged 50 years and older. Cognitive function was measured using the Montreal Cognitive Assessment (MoCA). Descriptive analysis techniques characterized the sample and estimated mean scores. Non-parametric and parametric tests explored relationships among MoCA scores and other patient factors. Of the 100 patients, 32% had normal cognitive function, 56% mild CI, and 12% moderate CI. Age, income, and education level significantly corelated with cognitive function in our sample. Identifying clinical factors and appropriate follow up for abnormal screening are crucial next steps in managing cognitive impairment in patients with ESKD receiving in-center hemodialysis.

Effect of Adopting the New Race-Free 2021 Chronic Kidney Disease Epidemiology Collaboration Estimated Glomerular Filtration Rate Creatinine Equation on Racial Differences in Kidney Disease Progression Among People With Human Immunodeficiency Virus: An Observational Study.

BACKGROUND: The impact of adopting a race-free estimated glomerular filtration rate (eGFR) creatinine (eGFRcr) equation on racial differences in chronic kidney disease (CKD) progression among people with human immunodeficiency virus (PWH) is unknown. METHODS: We defined eGFR stages using the original race-adjusted Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) eGFRcr equation and the new race-free CKD-EPI eGFRcr equation. We then estimated 5-year probabilities of transitioning from baseline kidney function to more advanced eGFR stages and examined the association of race (black vs white) with rates of CKD progression using Markov models. RESULTS: With the race-adjusted eGFRcr equation, black participants (n = 31 298) had a lower risk of progressing from eGFR stage 1 to 2 (hazard ratio [HR], 0.77; 95% confidence interval [CI], .73-.82), an equal risk of progressing from stage 2 to 3 (1.00; .92-.07) and a 3-fold risk of progressing from stage 3 to 4 or 5 (3.06; 2.60-3.62), compared with white participants (n = 27 542). When we used the race-free eGFRcr equation, 16% of black participants were reclassified into a more severe eGFR stage at baseline. The reclassified black individuals had a higher prevalence of CKD risk factors than black PWH who were not reclassified. With the race-free eGFRcr equation, black participants had a higher risk of disease progression across all eGFR stages than white participants. CONCLUSIONS: The original eGFRcr equation systematically masked a subgroup of black PWH who are at high-risk of CKD progression. The new race-free eGFRcr equation unmasks these individuals and may allow for earlier detection and management of CKD.

Role of Anemia in Dementia Risk Among Veterans With Incident CKD.

RATIONALE & OBJECTIVE: Although some evidence exists of increased dementia risk from anemia, it is unclear whether this association persists among adults with CKD. Anemia may be a key marker for dementia among adults with CKD, so we evaluated whether anemia is associated with an increased risk of dementia among adults with CKD. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: The study included 620,095 veterans aged≥45 years with incident stage 3 CKD (estimated glomerular filtration rate [eGFR]<60mL/min/1.73m2) between January 2005 and December 2016 in the US Veterans Health Administration system and followed through December 31, 2018, for incident dementia, kidney failure, or death. EXPOSURE: Anemia was assessed based on the average of hemoglobin levels (g/L) during the 2 years before the date of incident CKD and categorized as normal, mild, or moderate/severe anemia (≥12.0, 11.0-11.9,<11.0g/dL, respectively, for women, and≥13.0, 11.0-12.9,<11.0g/dL for men). OUTCOME: Dementia and the composite outcome of kidney failure or death. ANALYTICAL APPROACH: Adjusted cause-specific hazard ratios were estimated for each outcome. RESULTS: At the time of incident CKD, the mean age of the participants was 72 years, 97% were male, and their mean eGFR was 51mL/min per 1.73m2. Over a median 4.1 years of follow-up, 92,306 veterans (15%) developed dementia before kidney failure or death. Compared with the veterans with CKD without anemia, the multivariable-adjusted models showed a 16% (95% CI, 14%-17%) significantly higher risk of dementia for those with mild anemia and a 27% (95% CI, 23%-31%) higher risk with moderate/severe anemia. Combined risk of kidney failure or death was higher at 39% (95% CI, 37%-40%) and 115% (95% CI, 112%-119%) for mild and moderate/severe anemia, respectively, compared with no anemia. LIMITATIONS: Residual confounding from the observational study design. Findings may not be generalizable to the broader US population. CONCLUSIONS: Anemia was significantly associated with an increased risk of dementia among veterans with incident CKD, underscoring the role of anemia as a predictor of dementia risk. PLAIN-LANGUAGE SUMMARY: Adults with chronic kidney disease (CKD) often have anemia. Prior studies among adults in the general population suggest anemia is a risk factor for dementia, though it is unclear whether this association persists among adults with CKD. In this large study of veterans in the United States, we studied the association between anemia and the risk of 2 important outcomes in this population: (1) dementia and (2) kidney failure or death. We found that anemia was associated with a greater risk of dementia as well as risk of kidney failure or death. The study findings therefore emphasize the role of anemia as a key predictor of dementia risk among adults with CKD.

Engineering Equity Into the Promise of Xenotransplantation.

Two of the greatest challenges facing kidney transplantation are the lack of donated organs and inequities in who receives a transplant. Xenotransplantation holds promise as a treatment approach that could solve the supply problem. Major advances in gene-editing procedures have enabled several companies to raise genetically engineered pigs for organ donation. These porcine organs lack antigens and have other modifications that should reduce the probability of immunological rejection when transplanted into humans. The US Food and Drug Administration and transplantation leaders are starting to chart a path to test xenotransplants in clinical trials and later integrate them into routine clinical care. Here we provide a framework that industry, regulatory authorities, payers, transplantation professionals, and patient groups can implement to promote equity during every stage in this process. We also call for immediate action. Companies developing xenotransplant technology should assemble patient advocacy boards to bring the concerns of individuals with end-stage kidney disease to the forefront. For trials, xenotransplantation companies should partner with transplant programs with substantial patient populations of racial and ethnic minority groups and that have reciprocal relationships with those communities. Those companies and transplant programs should reach out now to those communities to inform them about xenotransplantation and try to address their concerns. These actions have the potential to make these communities full partners in the promise of xenotransplantation.

Plasma Soluble Tumor Necrosis Factor Receptor Concentrations and Clinical Events After Hospitalization: Findings From the ASSESS-AKI and ARID Studies.

RATIONALE & OBJECTIVE: The role of plasma soluble tumor necrosis factor receptor 1 (sTNFR1) and sTNFR2 in the prognosis of clinical events after hospitalization with or without acute kidney injury (AKI) is unknown. STUDY DESIGN: Prospective cohort. SETTING & PARTICIPANTS: Hospital survivors from the ASSESS-AKI (Assessment, Serial Evaluation, and Subsequent Sequelae of Acute Kidney Injury) and ARID (AKI Risk in Derby) studies with and without AKI during the index hospitalization who had baseline serum samples for biomarker measurements. PREDICTORS: We measured sTNFR1 and sTNFR2 from plasma samples obtained 3 months after discharge. OUTCOMES: The associations of biomarkers with longitudinal kidney disease incidence and progression, heart failure, and death were evaluated. ANALYTICAL APPROACH: Cox proportional hazard models. RESULTS: Among 1,474 participants with plasma biomarker measurements, 19% had kidney disease progression, 14% had later heart failure, and 21% died during a median follow-up of 4.4 years. For the kidney outcome, the adjusted HRs (AHRs) per doubling in concentration were 2.9 (95% CI, 2.2-3.9) for sTNFR1 and 1.9 (95% CI, 1.5-2.5) for sTNFR2. AKI during the index hospitalization did not modify the association between biomarkers and kidney events. For heart failure, the AHRs per doubling in concentration were 1.9 (95% CI, 1.4-2.5) for sTNFR1 and 1.5 (95% CI, 1.2-2.0) for sTNFR2. For mortality, the AHRs were 3.3 (95% CI, 2.5-4.3) for sTNFR1 and 2.5 (95% CI, 2.0-3.1) for sTNFR2. The findings in ARID were qualitatively similar in terms of the magnitude of association between biomarkers and outcomes. LIMITATIONS: Different biomarker platforms and AKI definitions; limited generalizability to other ethnic groups. CONCLUSIONS: Plasma sTNFR1 and sTNFR2 measured 3 months after hospital discharge were independently associated with clinical events regardless of AKI status during the index admission. sTNFR1 and sTNFR2 may assist with the risk stratification of patients during follow-up.

Dipping Status, Ambulatory Blood Pressure Control, Cardiovascular Disease, and Kidney Disease Progression: A Multicenter Cohort Study of CKD.

RATIONALE & OBJECTIVE: Ambulatory blood pressure (BP) monitoring allows concurrent evaluation of BP control and nocturnal BP dipping status, both related to adverse outcomes. However, few studies have assessed the prognostic role of combining information on dipping status and achieved ambulatory BP in patients with chronic kidney disease (CKD). STUDY DESIGN: Prospective observational cohort study. SETTING & PARTICIPANTS: 906 patients with hypertension and CKD attending 1 of 3 Italian nephrology clinics. EXPOSURE: Four groups were defined by simultaneously classifying systolic ambulatory BP levels as being at goal (daytime SBP <135 and nighttime SBP <120 mm Hg) or above goal, and the presence or absence of nocturnal dipping (nighttime to daytime SBP ratio of <0.9 versus ≥0.9). OUTCOME: The composite of time to initiation of maintenance dialysis or estimated glomerular filtration rate (eGFR) decline ≥50%, and the composite of fatal and nonfatal cardiovascular events. ANALYTICAL APPROACH: Multivariable Cox proportional hazards models were used to estimate risks of kidney disease progression and cardiovascular disease in the 4 exposure groups where nocturnal dipping with systolic ambulatory BP at goal was the reference group. RESULTS: The mean patient age was 63.8 years, 61% were male, and 26.4% had diabetes; eGFR was 41.1 ± 20.8 mL/min/1.73 m2. The dipping prevalence in each of the 4 groups was as follows: nocturnal dipping with ambulatory BP at goal, 18.6%; no nocturnal dipping with ambulatory BP at goal, 20.5%; nocturnal dipping with ambulatory BP above goal, 11.8%; and no nocturnal dipping with ambulatory BP above goal, 49.1%. Among patients with ambulatory BP above goal, the risk of cardiovascular events was greater in the absence (HR, 2.79 [95% CI, 1.64-4.75]) and presence (HR, 2.05 [95% CI, 1.10-3.84]) of nocturnal dipping. The same held true for risk of kidney disease progression (HRs of 2.40 [95% CI, 1.58-3.65] and 2.11 [95% CI, 1.28-3.48] in the absence and presence of nocturnal dipping, respectively). Patients at the ambulatory BP goal but who did not experience nocturnal dipping had an increased risk of the cardiovascular end point (HR, 2.06 [95% CI, 1.15-3.68]) and the kidney disease progression outcome (HR, 1.82 [95% CI, 1.17-2.82]). LIMITATIONS: Lack of a diverse cohort (all those enrolled were White). Residual uncontrolled confounding. CONCLUSIONS: Systolic ambulatory BP above goal or the absence of nocturnal dipping, regardless of ambulatory BP, is associated with higher risks of cardiovascular disease and kidney disease progression among patients with CKD. PLAIN-LANGUAGE SUMMARY: Among patients with chronic kidney disease (CKD), ambulatory blood pressure (BP) monitoring improves the identification of individuals at high risk of clinical disease outcomes. Those with uncontrolled ambulatory BP are known to have a higher risk of developing cardiovascular disease and kidney disease progression, particularly when their ambulatory BP does not decline by at least 10% at night. Whether this is also true for patients with presence of optimal ambulatory BP levels but a BP pattern of no nighttime decline is largely unknown. We measured ambulatory BP in 900 Italian patients with CKD and followed them for several years. We found that, independent of ambulatory BP level, the absence of nighttime reductions in BP was associated with worsening of CKD and more frequent cardiovascular events. The absence of nighttime declines in BP is an independent risk factor for adverse events among patients with CKD. Future studies are needed to examine whether treating the absence of nighttime declines in BP improves clinical outcomes.

Association of osteopontin with kidney function and kidney failure in chronic kidney disease patients: the GCKD study.

BACKGROUND: Osteopontin (OPN), synthesized in the thick ascending limb of Henle's loop and in the distal tubule, is involved in the pathogenesis of kidney fibrosis, a hallmark of kidney failure (KF). In a cohort of chronic kidney disease (CKD) patients, we evaluated OPN's association with kidney markers and KF. METHODS: OPN was measured from baseline serum samples of German Chronic Kidney Disease study participants. Cross-sectional regression models for estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (UACR) as well as Cox regression models for all-cause mortality and KF were evaluated to estimate the OPN effect. Additionally, the predictive ability of OPN and time-dependent population-attributable fraction were evaluated. RESULTS: Over a median follow-up of 6.5 years, 471 KF events and 629 deaths occurred among 4950 CKD patients. One-unit higher log(OPN) was associated with 5.5 mL/min/1.73 m2 lower eGFR [95% confidence interval (95% CI) -6.4 to -4.6] and 1% change in OPN with 0.7% higher UACR (estimated effect 0.7, 95% CI 0.6-0.8). Moreover, higher OPN levels were associated with a higher risk of KF [hazard ratio (HR) 1.4, 95% CI 1.2-1.7] and all-cause mortality (HR 1.5, 95% CI 1.3-1.8). After 6 years, 31% of the KF events could be attributed to higher OPN levels (95% CI 3%-56%). CONCLUSIONS: In this study, higher OPN levels were associated with kidney function markers worsening and a higher risk for adverse outcomes. A larger proportion of KF could be attributed to higher OPN levels, warranting further research on OPN with regards to its role in CKD progression and possible treatment options.

Insomnia in patients on incident maintenance dialysis and the risk of major acute cardio-cerebrovascular events and all-cause mortality.

BACKGROUND AND HYPOTHESIS: Insomnia is a known risk factor for cardio-cerebrovascular disease in the general population; however, its effect on cardio-cerebrovascular outcomes in end-stage kidney disease patients is unclear. Therefore, this study aimed to investigate the association between cardio-cerebrovascular outcomes and insomnia in patients who initiated maintenance dialysis. METHODS: This study used nationwide Korean health insurance claims data to analyze 79 420 patients who initiated maintenance dialysis from January 2009 to December 2017. Insomnia was defined using claim codes and sleep medication prescription data. Patients were categorized according to the presence of insomnia before and after dialysis initiation: a) no insomnia, b) insomnia before dialysis only (improved insomnia), c) insomnia after dialysis only (developed insomnia), and d) insomnia in both periods (persistent insomnia). The primary and secondary outcomes were major adverse cardiac and cerebrovascular events (MACCE) and all-cause mortality, respectively. The outcome risks were estimated by Cox regression models with inverse probability of treatment weighting. RESULTS: The mean age was 61.4 ± 13.4 years, and 39.7% were women. During the transition period from pre-dialysis to maintenance dialysis, 13.2% experienced insomnia. The insomnia groups showed significantly higher risks for MACCE (weighted hazard ratios [95% confidence intervals]: developed insomnia, 1.26 [1.25-1.28]; improved insomnia, 1.31 [1.29-1.33]; persistent insomnia, 1.39 [1.37-1.41]) and higher all-cause mortality risks than the no insomnia group. The insomnia related cardio-cerebrovascular disease risk elevation was more prominent in younger and male patients. CONCLUSIONS: Insomnia may increase cardio-cerebrovascular disease and all-cause mortality risk among end-stage kidney disease patients who initiate maintenance dialysis.