Pharmacogenomics of Hypertension in CKD: The CKD-PGX Study.

Background: Patients with CKD often have uncontrolled hypertension despite polypharmacy. Pharmacogenomic drug-gene interactions (DGIs) may affect the metabolism or efficacy of antihypertensive agents. We report changes in hypertension control after providing a panel of 11 pharmacogenomic predictors of antihypertensive response. Methods: A prospective cohort with CKD and hypertension was followed to assess feasibility of pharmacogenomic testing implementation, self-reported provider utilization, and BP control. The analysis population included 382 subjects with hypertension who were genotyped for cross-sectional assessment of DGIs, and 335 subjects followed for 1 year to assess systolic BP (SBP) and diastolic BP (DBP). Results: Most participants (58%) with uncontrolled hypertension had a DGI reducing the efficacy of one or more antihypertensive agents. Subjects with a DGI had 1.85-fold (95% CI, 1.2- to 2.8-fold) higher odds of uncontrolled hypertension, as compared with those without a DGI, adjusted for race, health system (safety-net hospital versus other locations), and advanced CKD (eGFR <30 ml/min). CYP2C9-reduced metabolism genotypes were associated with losartan response and uncontrolled hypertension (odds ratio [OR], 5.2; 95% CI, 1.9 to 14.7). CYP2D6-intermediate or -poor metabolizers had less frequent uncontrolled hypertension compared with normal metabolizers taking metoprolol or carvedilol (OR, 0.55; 95% CI, 0.3 to 0.95). In 335 subjects completing 1-year follow-up, SBP (-4.0 mm Hg; 95% CI, 1.6 to 6.5 mm Hg) and DBP (-3.3 mm Hg; 95% CI, 2.0 to 4.6 mm Hg) were improved. No significant difference in SBP or DBP change were found between individuals with and without a DGI. Conclusions: There is a potential role for the addition of pharmacogenomic testing to optimize antihypertensive regimens in patients with CKD.

Reconciling the Current Status of Home Hemodialysis With the 2019 Executive Order-Realistic or Obtainable?

The Advancing American Kidney Health Initiative places financial incentives largely aimed at nephrologists and dialysis providers, but including other health care providers, in an attempt to improve clinical outcomes and lower costs in the chronic kidney disease population. Both peritoneal and home hemodialysis utilization will need to be markedly increased to achieve these policy goals. This article looks at some of the concerns that may stand in the way of achieving those goals.

Perceptions of Home Dialysis Training and Experience Among US Nephrology Fellows.

RATIONALE & OBJECTIVE: Prior research suggests a lack of confidence among graduating US nephrology trainees in implementing both peritoneal dialysis (PD) and home hemodialysis (HHD). Gaps in fellowship training may represent an obstacle to achieving the Advancing American Kidney Health Initiative's goal of increasing the use of home dialysis. We sought to identify the strengths of and limitations in home dialysis training. DESIGN: A cross-sectional study surveying nephrology trainees regarding their confidence with home dialysis management and perceptions of home dialysis educational resources provided by their training program. SETTING & PARTICIPANTS: A paper survey was distributed to 110 nephrology trainees with at least 1 year of nephrology fellowship training who attended any 1 of 3 home dialysis conferences. ANALYTICAL APPROACH: Data were summarized as percentages. χ2, Fisher exact, and Kruskal-Wallis rank sum tests were used for statistical analysis. OUTCOME: Self-perception of readiness to manage PD and HHD patients. RESULTS: 76 of 110 (66%) attendees completed the survey. Most respondents were moderately confident regarding principles of PD. However, only 3% had initiated patients on "urgent-start PD" and 11% observed a PD catheter insertion. The level of confidence for HHD was low. Most trainees attended a home dialysis continuity clinic with mentorship from faculty. LIMITATIONS: A small number of participants and the inability to verify respondent-provided data for the number of PD and HHD patients seen and clinics attended. Potential lack of generalizability owing to inclusion of only trainees who attended a home dialysis conference. CONCLUSIONS: Nephrology trainees perceive low and moderate levels of preparedness for managing HHD and PD, respectively. Educational innovation and optimization of resources at both the institutional and national levels may improve confidence and promote public policy goals regarding home dialysis therapies.

Apical Sparing Pattern of Longitudinal Strain and Positive Bone Scintigraphy in Metastatic Myocardial Calcification.

An apical sparing pattern of longitudinal strain and positive radionuclide bone scintigraphy are believed to be specific for the diagnosis of transthyretin cardiac amyloidosis. We report on a young woman with apical sparing of longitudinal strain and positive bone scintigraphy who was found to have metastatic myocardial calcification at autopsy. (Level of Difficulty: Intermediate.).

Choosing Home Hemodialysis: A Critical Review of Patient Outcomes.

BACKGROUND/AIM: Home hemodialysis (HHD) has been associated with improved clinical outcomes vs. in-center HD (ICHD). The prevalence of HHD in the United States is still very low at 1.8%. This critical review compares HHD and ICHD outcomes for survival, hospitalization, cardiovascular (CV), nutrition, and quality of life (QoL). METHODS: Of 545 publications identified, 44 were not selected after applying exclusion criteria. A systematic review of the identified publications was conducted to compare HHD to ICHD outcomes for survival, hospitalization, CV outcomes, nutrition, and QoL. RESULTS: Regarding mortality, 10 of 13 trials reported 13-52% reduction; three trials found no differences. According to 6 studies, blood pressure and left ventricular size measurements were generally lower in HHD patients compared to similar measurements in ICHD patients. Regarding nutritional status, conflicting results were reported (8 studies); some found improved muscle mass, total protein, and body mass index in HHD vs. ICHD patients, while others found no significant differences. There were no significant differences in the rate of hospitalization between HHD and ICHD in the 6 articles reviewed. Seven studies on QoL demonstrated positive trends in HHD vs. ICHD populations. CONCLUSIONS: Despite limitations in the current data, 66% of the publications reviewed (29/44) demonstrated improved clinical outcomes in patients who chose HHD. These include improved survival, CV, nutritional, and QoL parameters. Even though HHD may not be preferred in all patients, a review of the literature suggests that HHD should be provided as a modality choice for substantially more than the current 1.8% of HHD patients in the United States.

Symptomatic hyperammonemia after lung transplantation: lessons learnt.

Hyperammonemia, post-orthotopic lung transplantation, is a rare but mostly fatal complication. Various therapies, including those to decrease ammonia generation, increase nitrogen excretion, and several dialytic methods for removing ammonia have been tried. We describe three lung transplant recipients who developed acute hyperammonemia early after transplantation. Two of the three patients survived after a multidisciplinary approach including discontinuation of drugs, which impair urea cycle, aggressive ammonia reduction with prolonged daily intermittent hemodialysis (HD), and overnight slow low-efficiency dialysis in conjunction with early weaning of steroids and other therapeutic measures. Our experience suggests that early initiation of dialysis, high dialysis dose, increased frequency, and HD preferably to less efficient modalities increases survival in these patients.

At-home short daily hemodialysis improves the long-term health-related quality of life.

Patients with chronic kidney disease treated by in-center conventional hemodialysis (3 times per week) have significant impairments in health-related quality of life measures, which have been associated with increased morbidity and mortality. FREEDOM is an ongoing prospective cohort study measuring the potential benefits of at-home short daily (6 times per week) hemodialysis. In this interim report we examine the long-term effect of short daily hemodialysis on health-related quality of life, as measured by the SF-36 health survey. This was administered at baseline, 4 and 12 months after initiation of short daily hemodialysis to 291 participants (total cohort), of which 154 completed the 12-month follow-up (as-treated cohort). At the time of analysis, the mean age was 53 years, 66% were men, 58% had an AV fistula, 90% transitioned from in-center hemodialysis, and 45% had diabetes mellitus. In the total cohort analysis, both the physical- and mental-component summary scores improved over the 12-month period, as did all 8 individual domains of the SF-36. The as-treated cohort analysis showed similar improvements with the exception of the role-emotional domain. Significantly, in the as-treated cohort, the percentage of patients achieving a physical-component summary score at least equivalent to the general population more than doubled. Hence, at-home short daily hemodialysis is associated with long-term improvements in various physical and mental health-related quality of life measures.

Effects of frequent hemodialysis on measures of CKD mineral and bone disorder.

More frequent hemodialysis sessions and longer session lengths may offer improved phosphorus control. We analyzed data from the Frequent Hemodialysis Network Daily and Nocturnal Trials to examine the effects of treatment assignment on predialysis serum phosphorus and on prescribed dose of phosphorus binder, expressed relative to calcium carbonate on a weight basis. In the Daily Trial, with prescribed session lengths of 1.5-2.75 hours six times per week, assignment to frequent hemodialysis associated with both a 0.46 mg/dl decrease (95% confidence interval [95% CI], 0.13-0.78 mg/dl) in mean serum phosphorus and a 1.35 g/d reduction (95% CI, 0.20-2.50 g/d) in equivalent phosphorus binder dose at month 12 compared with assignment to conventional hemodialysis. In the Nocturnal Trial, with prescribed session lengths of 6-8 hours six times per week, assignment to frequent hemodialysis associated with a 1.24 mg/dl decrease (95% CI, 0.68-1.79 mg/dl) in mean serum phosphorus compared with assignment to conventional hemodialysis. Among patients assigned to the group receiving six sessions per week, 73% did not require phosphorus binders at month 12 compared with only 8% of patients assigned to sessions three times per week (P<0.001). At month 12, 42% of patients on nocturnal hemodialysis required the addition of phosphorus into the dialysate to prevent hypophosphatemia. Frequent hemodialysis did not have major effects on calcium or parathyroid hormone concentrations in either trial. In conclusion, frequent hemodialysis facilitates control of hyperphosphatemia and extended session lengths could allow more liberal diets and freedom from phosphorus binders.

Impact of short daily hemodialysis on restless legs symptoms and sleep disturbances.

BACKGROUND AND OBJECTIVES: Restless legs syndrome (RLS) and sleep disturbances are common among in-center hemodialysis patients and are associated with increased morbidity/mortality. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The FREEDOM study is an ongoing prospective cohort study investigating the benefits of home short daily hemodialysis (SDHD) (6 times/week). In this interim report, we examine the long-term effect of SDHD on the prevalence and severity of RLS, as measured by the International Restless Legs Syndrome (IRLS) Study Group rating scale, and sleep disturbances, as measured by the Medical Outcomes Study sleep survey. RESULTS: 235 participants were included in this report (intention-to-treat cohort), of which 127 completed the 12-month follow-up (per-protocol cohort). Mean age was 52 years, 55% had an arteriovenous fistula, and 40% suffered from RLS. In the per-protocol analysis, among patients with RLS, the mean IRLS score improved significantly at month 12, after adjustment for use of RLS-related medications (18 versus 11). Among patients with moderate-to-severe RLS (IRLS score ≥15), there was an even greater improvement in the IRLS score (23 versus 13). The intention-to-treat analysis yielded similar results. Over 12 months, there was decline in the percentage of patients reporting RLS (35% versus 26%) and those reporting moderate-to-severe RLS (59% versus 43%). There was a similar and sustained 12-month improvement in several scales of the sleep survey, after adjustment for presence of RLS and use of anxiolytics and hypnotics. CONCLUSIONS: Home SDHD is associated with long-term improvement in the prevalence and severity of RLS and sleep disturbances.

Thymoglobulin induction dosing strategies in a low-risk kidney transplant population: three or four days?

The optimal dose and duration of rabbit antithymocyte globulin (rATG) induction has not been defined. Methods. We compared the safety and efficacy of 2 dosing strategies, rATG 1.5 mg/kg for 4 days (n = 59) versus 2 mg/kg for 3 days (n = 59), in a retrospective, cohort study. Results. Two-year rejection-free survival was 95% in each group (P = .983). Renal function and infection rates were similar. The incidence of leucopenia was similar, although the 2 mg/kg group was more likely to be thrombocytopenic on day 2 (4% versus 28%, P = .04). Length of stay tended to be longer for the 1.5 mg/kg group (6.0 ± 3.7 versus 5.1 ± 1.9 days P = .104). A cost savings of $920 per patient for rATG were seen in the 2 mg/kg group (P = .122). Conclusions. Shorter, more intense dosing of rATG is safe and effective. The 3-day dose strategy resulted in a clinically shorter length of stay and may result in cost savings.

Effect of daily hemodialysis on depressive symptoms and postdialysis recovery time: interim report from the FREEDOM (Following Rehabilitation, Economics and Everyday-Dialysis Outcome Measurements) Study.

BACKGROUND: Clinical depression and postdialysis fatigue are important concerns for patients with kidney failure and can have a negative impact on quality of life and survival. STUDY DESIGN: The FREEDOM (Following Rehabilitation, Economics and Everyday-Dialysis Outcome Measurements) Study is an ongoing prospective cohort study investigating the clinical and economic benefits of daily (6 times per week) hemodialysis (HD). In this interim report, as part of an a priori planned analysis, we examine the long-term impact of daily HD on depressive symptoms, measured using the Beck Depression Inventory (BDI) survey, and postdialysis recovery time, measured using a previously validated questionnaire. SETTING & PARTICIPANTS: Adult patients initiating daily HD with a planned 12-month follow-up. OUTCOMES & MEASUREMENTS: The BDI survey and postdialysis recovery time question were administered at baseline, and changes were assessed at months 4 and 12. RESULTS: 239 participants were enrolled (intention-to-treat cohort) and 128 completed the study (per-protocol cohort). Mean age was 52 years, 64% were men, 55% had an arteriovenous fistula, and 90% transitioned from in-center HD therapy. In the per-protocol cohort, there was a significant decrease in mean BDI score over 12 months (11.2 [95% CI, 9.6-12.9] vs 7.8 [95% CI, 6.5-9.1]; P<0.001). For robustness, the intention-to-treat analysis was performed, yielding similar results. The percentage of patients with depressive symptoms (BDI score>10) significantly decreased during 12 months (41% vs 27%; P=0.03). Similarly, in the per-protocol cohort, there was a significant decrease in postdialysis recovery time over 12 months (476 [95% CI, 359-594] vs 63 minutes [95% CI, 32-95]; P<0.001). The intention-to-treat analysis yielded similar results. The percentage of patients experiencing prolonged postdialysis recovery time (>or=60 minutes) also significantly decreased (81% vs 35%; P=0.001). LIMITATIONS: Observational study with lack of control arm. CONCLUSIONS: Daily HD is associated with long-term improvement in depressive symptoms and postdialysis recovery time.

Serum sickness after treatment with rabbit antithymocyte globulin in kidney transplant recipients with previous rabbit exposure.

Serum sickness after rabbit antithymocyte globulin administration has a reported incidence of 7% to 27% in kidney transplant recipients. We describe 4 patients with previous exposure to rabbits who developed serum sickness after primary rabbit antithymocyte globulin induction. All patients presented with jaw pain. Three of 4 patients treated with plasmapheresis and steroids had prompt recovery, and 1 patient treated with steroids had slower recovery. We performed a telephone interview of 214 patients who contemporaneously underwent transplantation between November 2006 and July 2008 regarding rabbit exposure. More than half the patients had some type of previous rabbit exposure. There was a suggestion that patients with serum sickness were exposed more frequently to rabbits than those without. Jaw pain appears to be a hallmark symptom, and treatment with plasmapheresis and steroids relieves symptoms more rapidly than steroids alone.

Survival and hospitalization among patients using nocturnal and short daily compared to conventional hemodialysis: a USRDS study.

We estimated the survival and hospitalization among frequent hemodialysis users in comparison to those patients undergoing thrice-weekly conventional hemodialysis. All patients had similar characteristics and medical histories. In this cohort study of frequent hemodialysis users and propensity score-matched controls, the collaborating clinicians identified 94 patients who used nocturnal hermodialysis (NHD) and 43 patients who used short-duration daily hemodialysis (SDHD) for a minimum of 60 days. Ten propensity score-matched control patients for each NHD and SDHD patient were identified from the United States Renal Data System database. Primary outcomes were risk for all-cause mortality and risk for the composite outcome of mortality or major morbid event (acute myocardial infarction or stroke) estimated using Cox proportional hazards models. Risks for all-cause, cardiovascular-related, infection-related, and vascular access-related hospital admissions were also studied. Nocturnal hemodialysis was associated with significant reductions in mortality risk and risk for mortality or major morbid event when compared to conventional hemodialysis. There was a reduced but non-significant risk of death for patients using SDHD compared to controls. All-cause and specific hospitalizations did not differ significantly between NHD and SDHD patients and their matched control cohorts. Our study suggests that NHD may improve patient survival.

Scope and design of the Following Rehabilitation, Economics and Everyday-Dialysis Outcome Measurements (FREEDOM) Study.

BACKGROUND: Conventional thrice-weekly hemodialysis (HD) has limited the ability to generate further improvements in patient quality of life, morbidity, and mortality. Daily HD (DHD) offers the promise of providing clinical and economic benefits. The objectives of the Following Rehabilitation, Economics and Everyday-Dialysis Outcome Measurements Study are to evaluate outcomes of DHD (6 times/wk) with the NxStage System One (NxStage Medical Inc, Lawrence, MA) device. DESIGN: Cohort study with matched control group. SETTING & PARTICIPANTS: The DHD group will include up to 500 participants at 70 clinical sites, enrolling for 3 years with a minimum of 1-year follow-up. Study candidates include adult patients (age >or= 18 years) with end-stage renal disease who are considered suitable candidates for DHD with the NxStage System One device by the treating physician and who have Medicare as their primary insurance payer. The control group will consist of a matched thrice-weekly in-center HD cohort derived from the US Renal Data System database using a 10:1 ratio, totaling 5,000 patients. PREDICTOR: Treatment with DHD and "standard of care" thrice-weekly HD. OUTCOMES & MEASUREMENTS: The primary intent-to-treat analysis compares hospitalization days/patient-year between the DHD and thrice-weekly HD groups. Other outcomes recorded in both groups include non-treatment-related medical expenditures. In addition, in the DHD cohort, changes in quality-of-life measures (baseline, 4 and 12 months, and every 6 months thereafter); urea kinetics; parameters related to anemia, bone and mineral metabolism, and nutrition; vascular access interventions; and use of medications will be examined. CONCLUSIONS: This study has the potential to elucidate the health and economic benefits of DHD and complement results of current clinical trials.

Planning for renal replacement therapy in the patient with obesity.

The last stages of chronic kidney disease (CKD) are known for anorexia, weight loss, nausea, and muscle wasting, yet obesity and morbid obesity are now frequently encountered at the initiation of dialysis or referral for kidney transplantation. This development is a relatively new phenomenon, and few evidence-based practices are available to guide the clinician. Recommendations are mostly based on extrapolation from the general population, personal experience, institutional protocols, or anecdotal reports in the literature. This article will briefly review the issues that surround planning for renal replacement therapy in the obese CKD patient.

Chronic kidney disease in solid-organ transplantation.

As the long-term survival of nonrenal solid-organ transplant recipients continues to improve, more complications related to transplantation occur. Among the most serious is chronic kidney disease (CKD). Although CKD was previously thought to only clinically affect a minority of this population, closer measurements of kidney function and monitoring of CKD complications now show that CKD will affect a significant number, if not a majority, of transplant recipients-particularly the long-term survivors who often have excellent function of their primary allograft. This article will review the incidence, risk factors, treatment, and outcomes of patients who develop CKD after heart, liver, and lung transplantation.