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Having a usual source of care increases use of preventive services and is associated with improved survival in the general population. We evaluated this association in adults with chronic kidney disease (CKD).Prospective, observational cohort study.Adults with CKD enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study.Usual source of care was self-reported as: 1) clinic, 2) emergency department (ED)/urgent care, 3) other.Primary outcomes included incident end-stage kidney disease (ESKD), atherosclerotic events (myocardial infarction, stroke, or peripheral artery disease), incident heart failure, hospitalization events, and all-cause death.Multivariable regression analyses to evaluate the association between usual source of care (ED/urgent care vs clinic) and primary outcomes.Among 3,140 participants, mean age was 65 years, 44% female, 45% non-Hispanic White, 43% non-Hispanic Black, and 9% Hispanic, mean estimated glomerular filtration rate 50 mL/min/1.73 mCannot be generalized to all patients with CKD. Causal relationships cannot be established.In this large, diverse cohort of adults with moderate-to-severe CKD, those identifying ED/urgent care as usual source of care were at increased risk for death and hospitalizations. These findings highlight the need to develop strategies to improve health care access for this high-risk population.

BACKGROUND: Although Hispanics/Latinos in the United States are often considered a single ethnic group, they represent a heterogenous mixture of ancestries who can self-identify as any race defined by the U.S. Census. They have higher ESKD incidence compared with non-Hispanics, but little is known about the CKD incidence in this population. METHODS: We examined rates and risk factors of new-onset CKD using data from 8774 adults in the Hispanic Community Health Study/Study of Latinos. Incident CKD was defined as eGFR 140/90 mm Hg, higher glycated hemoglobin, lower baseline eGFR, and higher baseline urine albumin/creatinine ratio. CONCLUSIONS: CKD incidence varies by Hispanic/Latino heritage and this disparity may be in part attributed to differences in sociodemographic characteristics. Culturally tailored public heath interventions focusing on the prevention and control of risk factors might ameliorate the CKD burden in this population.

Rationale & Objective Acute kidney injury treated with kidney replacement therapy (AKI-KRT) occurs frequently in critically ill patients with COVID-19. We examined the clinical factors that determine kidney recovery in this population. Study Design Multicenter cohort study. Setting & Participants 4221 adults with COVID-19 not receiving kidney replacement therapy who were admitted to intensive care units at 68 US hospitals with COVID-19 from March 1 to June 22, 2020 (the “ICU cohort”). Among these, 876 developed AKI-KRT after admission to the ICU (the “AKI-KRT subcohort”). Exposure(s) The ICU cohort was analyzed using AKI severity as the exposure. For the AKI-KRT subcohort, exposures included demographics, comorbidities, initial mode of KRT, and markers of illness severity at the time of dialysis initiation. Outcome(s) The outcome for the ICU cohort was estimated glomerular filtration rate (GFR) at hospital discharge. A three-level outcome including death, kidney nonrecovery, and kidney recovery at discharge, was analyzed for the AKI-KRT subcohort. Analytical approach The ICU cohort was characterized using descriptive analyses. The AKI-KRT subcohort was characterized with both descriptive analyses and multinomial logistic regression to assess factors associated with kidney nonrecovery while accounting for death. Results Among a total of 4221 patients in the ICU cohort, 2361 (56%) developed AKI, including 876 (21%) who received KRT. More severe AKI was associated with higher mortality. Among survivors, more severe AKI was associated with an increased rate of kidney nonrecovery and lower kidney function at discharge. Among the 876 patients with AKI-KRT, 588 (67%) died, 95 (11%) had kidney nonrecovery, and 193 (22%) had kidney recovery by the time of discharge. The odds of kidney nonrecovery was greater for lower estimated GFR with odds ratios (ORs) of 2.09 (95% CI, 1.09-4.04), 4.27 (95% CI, 1.99-9.17), and 8.69 (95% CI, 3.07-24.55) for CKD GFR categories 3, 4, and 5, respectively, compared to estimated GFR > 60 mL/min/1.73 m2. Oliguria at the time of KRT initiation was also associated with nonrecovery (OR 2.10 [95% CI, 1.14-3.88] and 4.02 [95% CI, 1.72-9.39] for patients with 50-499 and, Critically ill patients with COVID-19 often develop acute kidney injury (AKI). This study of 4221 patients demonstrated that more severe AKI was associated with greater in-hospital mortality and poorer kidney function at hospital discharge. Among the 876 patients who required dialysis for AKI, almost two-thirds died. Among those who survived to discharge, about two-thirds recovered kidney function and were discharged without the need for dialysis. Lower baseline kidney function and reduced urine output were associated with non-recovery of kidney function. Identification of such predictors is important in assessing prognosis among these critically ill patients and has implications for clinical care of individuals critically ill with COVID-19.

Rationale & Objective Recent studies suggest that periodontal disease may be associated with incident chronic kidney disease (CKD). However, studies have focused on older populations, and US Hispanics/Latinos were not well represented. Study Design Observational cohort. Setting & Participants We analyzed data from the Hispanic Community Health Study/Study of Latinos who completed a baseline visit with a periodontal examination and a follow-up visit, and did not have CKD at baseline. Predictors Predictors included ≥30% of sites with clinical attachment loss ≥3 mm, ≥30% of sites with probing depth ≥4 mm, percentage of sites with bleeding on probing, and absence of functional dentition (, Graphical abstract

Rationale & Objective Underlying kidney disease is an emerging risk factor for more severe COVID-19 illness. We examined the clinical courses of critically ill COVID-19 patients with and without pre-existing kidney disease and investigated the association between degree of underlying kidney disease and in-hospital outcomes. Study Design Retrospective cohort study Settings & Participants 4,264 critically ill COVID-19 patients (143 dialysis patients, 521 chronic kidney disease [CKD] patients, and 3,600 patients without CKD) admitted to ICUs at 68 hospitals in the United States. Predictor(s) Presence (versus absence) of pre-existing kidney disease Outcome(s) In-hospital mortality (primary); respiratory failure, shock, ventricular arrhythmia/ cardiac arrest, thromboembolic event, major bleed, and acute liver injury (secondary) Analytical Approach We used standardized differences to compare patient characteristics (values >0.10 indicate a meaningful difference between groups) and multivariable adjusted Fine and Gray survival models to examine outcome associations. Results Dialysis patients had a shorter time from symptom onset to ICU admission compared to other groups (median [quartile 1-quartile 3] days: 4 [2-9] for dialysis patients; 7 [3-10] for CKD patients; 7 [4-10] for patients without pre-existing kidney disease). More dialysis patients (25%) reported altered mental status than those with CKD (20%, standardized difference = 0.12) and no kidney disease (12%, standardized difference = 0.36). Half of dialysis and CKD patients died within 28-days of ICU admission versus 35% of patients without pre-existing kidney disease. Compared to patients without pre-existing kidney disease, dialysis patients had a higher risk of 28-day in-hospital death (adjusted HR 1.41; 95% CI 1.09, 1.81), while patients with CKD had an intermediate risk (adjusted HR 1.25; 95% CI 1.08, 1.44). Limitations Potential residual confounding Conclusions Findings highlight the high mortality of individuals with underlying kidney disease and severe COVID-19, underscoring the importance of identifying safe and effective COVID-19 therapies for this vulnerable population., Individuals with underlying kidney disease may be particularly vulnerable to severe COVID-19 illness, marked by multi-system organ failure, thrombosis, and a heightened inflammatory response. Among 4,264 critically ill adults with COVID-19 admitted to 68 intensive care units across the U.S., we found that both chronic kidney disease and dialysis patients had a ∼50% 28-day in-hospital mortality rate. Patients with underlying kidney disease had higher in-hospital mortality than patients without kidney disease, with patients on maintenance dialysis having the highest risk. As evidenced by differences in symptoms and clinical trajectories, patients with pre-existing kidney disease may have unique susceptibility to COVID-19-related complications which warrants additional study and special consideration in the pursuit and development of targeted therapies.

BackgroundResidual kidney function (RKF) is thought to exert beneficial effects through clearance of uremic toxins. However, the level of native kidney function where clearance becomes negligible is not known.MethodsWe aimed to assess whether levels of nonurea solutes differed among patients with ‘clinically negligible’ RKF compared with those with no RKF. The hemodialysis study excluded patients with urinary urea clearance >1.5 mL/min, below which RKF was considered to be ‘clinically negligible’. We measured eight nonurea solutes from 1280 patients participating in this study and calculated the relative difference in solute levels among patients with and without RKF based on measured urinary urea clearance.ResultsThe mean age of the participants was 57 years and 57% were female. At baseline, 34% of the included participants had clinically negligible RKF (mean 0.7 ± 0.4 mL/min) and 66% had no RKF. Seven of the eight nonurea solute levels measured were significantly lower in patients with RKF than in those without RKF, ranging from −24% [95% confidence interval (CI) −31 to −16] for hippurate, −7% (−14 to −1) for trimethylamine-N-oxide and −4% (−6 to −1) for asymmetric dimethylarginine. The effect of RKF on plasma levels was comparable or more pronounced than that achieved with a 31% higher dialysis dose (spKt/Vurea 1.7 versus 1.3). Preserved RKF at 1-year follow-up was associated with a lower risk of cardiac death and first cardiovascular event.ConclusionsEven at very low levels, RKF is not ‘negligible’, as it continues to provide nonurea solute clearance. Management of patients with RKF should consider these differences.

BACKGROUND: Pregnancy in women with ESKD undergoing dialysis is uncommon due to impaired fertility. Data on pregnancy in women on dialysis in the United States is scarce. METHODS: We evaluated a retrospective cohort of 47,555 women aged 15–44 years on dialysis between January 1, 2005 and December 31, 2013 using data from the United States Renal Data System with Medicare as primary payer. We calculated pregnancy rates and identified factors associated with pregnancy. RESULTS: In 47,555 women on dialysis, 2352 pregnancies were identified. Pregnancy rate was 17.8 per thousand person years (PTPY) with the highest rate in women aged 20–24 (40.9 PTPY). In the adjusted time-to-event analysis, a higher likelihood of pregnancy was seen in Native American (HR, 1.77; 95% CI, 1.33 to 2.36), Hispanic (HR, 1.51; 95% CI, 1.32 to 1.73), and black (HR, 1.33; 95% CI, 1.18 to 1.49) women than in white women. A higher rate of pregnancy was seen in women with ESKD due to malignancy (HR, 1.64; 95% CI, 1.27 to 2.12), GN (HR, 1.38; 95% CI, 1.21 to 1.58), hypertension (HR, 1.32; 95% CI, 1.16 to 1.51), and secondary GN/vasculitis (HR, 1.18; 95% CI, 1.02 to 1.37) than ESKD due to diabetes. A lower likelihood of pregnancy was seen among women on peritoneal dialysis than on hemodialysis (HR, 0.47; 95% CI, 0.41 to 0.55). CONCLUSIONS: The pregnancy rate is higher in women on dialysis than previous reports indicate. A higher likelihood of pregnancy was associated with race/ethnicity, ESKD cause, and dialysis modality.

Rationale & Objective Cardiovascular events are less common in women than men in general populations; however, studies in chronic kidney disease (CKD) are less conclusive. We evaluated sex-related differences in cardiovascular events and death in adults with CKD. Study Design Prospective cohort study. Setting & Participants 1,778 women and 2,161 men enrolled in the Chronic Renal Insufficiency Cohort (CRIC). Exposure Sex (women vs men). Outcome Atherosclerotic composite outcome (myocardial infarction, stroke, or peripheral artery disease), incident heart failure, cardiovascular death, and all-cause death. Analytical Approach Cox proportional hazards regression. Results During a median follow-up period of 9.6 years, we observed 698 atherosclerotic events (women, 264; men, 434), 762 heart failure events (women, 331; men, 431), 435 cardiovascular deaths (women, 163; men, 274), and 1,158 deaths from any cause (women, 449; men, 709). In analyses adjusted for sociodemographic, clinical, and metabolic parameters, women had a lower risk of atherosclerotic events (HR, 0.71 [95% CI, 0.57-0.88]), heart failure (HR, 0.76 [95% CI, 0.62-0.93]), cardiovascular death (HR, 0.55 [95% CI, 0.42-0.72]), and death from any cause (HR, 0.58 [95% CI, 0.49-0.69]) compared with men. These associations remained statistically significant after adjusting for cardiac and inflammation biomarkers. Limitations Assessment of sex hormones, which may play a role in cardiovascular risk, was not included. Conclusions In a large, diverse cohort of adults with CKD, compared with men, women had lower risks of cardiovascular events, cardiovascular mortality, and mortality from any cause. These differences were not explained by measured cardiovascular risk factors.

Widely regarded as safe and effective, proton pump inhibitors (PPIs) are among the most commonly used medications in the world today. However, a spate of observational studies suggest an association between PPI use and adverse events, including infection, bone fracture, and dementia. This review details evidence linking the use of PPI therapy to the development of kidney disease, including early case reports of acute interstitial nephritis and subsequent large observational studies of acute kidney injury (AKI), chronic kidney disease (CKD), and end-stage renal disease (ESRD). The majority of studies showed higher risk of kidney outcomes among persons prescribed PPI medications, with effect sizes that were slightly higher for AKI (∼2-3-fold) compared to CKD and ESRD (1.2-1.8-fold). Although observational pharmaco-epidemiology studies are limited by the possibility of residual confounding and confounding by indication, many of the described studies conducted rigorous sensitivity analyses aimed at minimizing these biases, including new-user design, comparison to similar agents (e.g., histamine2 receptor antagonists), and evaluation for a dose-response, with robust results. Given the widespread use of PPIs, even a small effect on kidney outcomes could result in large public health burden. Timely cessation of PPI therapy when there is no clear indication for use might reduce the population burden of kidney disease.

The association of residual kidney function (RKF) with improved outcomes in peritoneal dialysis and hemodialysis patients is now widely recognized. RKF provides substantial volume and solute clearance even after dialysis initiation. In particular, RKF provides clearance of non-urea solutes, many of which are potential uremic toxins and not effectively removed by conventional hemodialysis. The presence of RKF provides a distinct advantage to incident dialysis patients and is an opportunity for nephrologists to individualize dialysis treatments tailored to their patients' unique solute, volume, and quality of life needs. The benefits of RKF present the opportunity to personalize the management of uremia

Maintenance hemodialysis is typically prescribed thrice weekly irrespective of a patient's residual kidney function (RKF). We hypothesized that a less frequent schedule at hemodialysis therapy initiation is associated with greater preservation of RKF without compromising survival among patients with substantial RKF.A longitudinal cohort.23,645 patients who initiated maintenance hemodialysis therapy in a large dialysis organization in the United States (January 2007 to December 2010), had available RKF data during the first 91 days (or quarter) of dialysis, and survived the first year.Incremental (routine twice weekly for6 continuous weeks during the first 91 days upon transition to dialysis) versus conventional (thrice weekly) hemodialysis regimens during the same time.Changes in renal urea clearance and urine volume during 1 year after the first quarter and survival after the first year.Among 23,645 included patients, 51% had substantial renal urea clearance (≥3.0mL/min/1.73m(2)) at baseline. Compared with 8,068 patients with conventional hemodialysis regimens matched based on baseline renal urea clearance, urine volume, age, sex, diabetes, and central venous catheter use, 351 patients with incremental regimens exhibited 16% (95% CI, 5%-28%) and 15% (95% CI, 2%-30%) more preserved renal urea clearance and urine volume at the second quarter, respectively, which persisted across the following quarters. Incremental regimens showed higher mortality risk in patients with inadequate baseline renal urea clearance (≤3.0mL/min/1.73m(2); HR, 1.61; 95% CI, 1.07-2.44), but not in those with higher baseline renal urea clearance (HR, 0.99; 95% CI, 0.76-1.28). Results were similar in a subgroup defined by baseline urine volume of 600mL/d.Potential selection bias and wide CIs.Among incident hemodialysis patients with substantial RKF, incremental hemodialysis may be a safe treatment regimen and is associated with greater preservation of RKF, whereas higher mortality is observed after the first year of dialysis in those with the lowest RKF. Clinical trials are needed to examine the safety and effectiveness of twice-weekly hemodialysis.

Background Patients starting dialysis often have substantial residual kidney function. Incremental hemodialysis provides a hemodialysis prescription that supplements patients’ residual kidney function while maintaining total (residual + dialysis) urea clearance (standard Kt/Vurea) targets. We describe our experience with incremental hemodialysis in patients using NxStage System One for home hemodialysis. Case presentation From 2011 to 2015, we initiated 5 incident hemodialysis patients on an incremental home hemodialysis regimen. The biochemical parameters of all patients remained stable on the incremental hemodialysis regimen and they consistently achieved standard Kt/Vurea targets. Of the two patients with follow-up >6 months, residual kidney function was preserved for ≥2 years. Importantly, the patients were able to transition to home hemodialysis without automatically requiring 5 sessions per week at the outset and gradually increased the number of treatments and/or dialysate volume as the residual kidney function declined. Conclusions An incremental home hemodialysis regimen can be safely prescribed and may improve acceptability of home hemodialysis. Reducing hemodialysis frequency by even one treatment per week can reduce the number of fistula or graft cannulations or catheter connections by >100 per year, an important consideration for patient well-being, access longevity, and access-related infections. The incremental hemodialysis approach, supported by national guidelines, can be considered for all home hemodialysis patients with residual kidney function.