November 2017: Abstract Roundup

Chronic Kidney Disease
Direct-Acting Antiviral HCV  Treatment Safe and Effective in CKD Patients
Clinical Journal of the American Society of Nephrology. doi:10.2215/CJN.02510317

Patients with chronic kidney disease (CKD) commonly present with hepatitis C virus (HCV) infection, a complication that can lead to accelerated progression to end-stage renal disease. Sofosbuvir, a direct-acting antiviral agent, is known to be effective and safe in patients with HCV infection; however, there are few data on its safety and efficacy in patients with CKD. Meghan Sise, MD, and colleagues conducted a retrospective observational study designed to determine the safety and effectiveness of sofosbuvir in that patient population.

The study cohort included 98 patients with CKD: 42% had CKD stage 1 or 2 and 58% had CKD stage 3. Mean age of the cohort was 62 years, 78% were men, and 65% were white. Comorbidities included diabetes (49%), cirrhosis (38%), and prior solid organ transplant (33%).

Overall, sustained virologic response was 81%, and varied by regimen used and viral genotype. Average baseline estimated glomerular filtration rate (eGFR) matched, on average, eGFR during treatment; seven patients receiving sofosbuvir experienced a ≥1.5 times baseline rise in creatinine; all but one recovered.

In patients with CKD stage 3, results of regression models found that hepatitis C cure was associated with a 9.3 mL/min/1.73 m2 improvement in eGFR during the 6-month post-treatment period. There were numerous adverse events (81%), but serious adverse events (17%) and discontinuation of treatment (8%) were uncommon.

In conclusion, the researchers said, “Sofosbuvir-based direct-acting antiviral therapy is safe and effective in a cohort of patients with CKD infected with hepatitis C.”

Incidence of Community-Acquired Infections and Lower eGFR
Clinical Journal of the American Society of Nephology. 2017;12(9):1399-1408
Patients with community-based infections face adverse outcomes and increased health care costs. Hong Xu, MD, and colleagues conducted a study to test the hypothesis that with lower estimated glomerular filtration rate (eGFR) there is an increase in the incidence of community-based infections, although the pattern of site-specific infections varies. The researchers utilized data on 1,139,470 health care users in the Stockholm Creatinine Measurements Project to quantify the associations of eGFR with the risk of infections, both overall and by major types, over a 12-month period.

Throughout 1,128,313 person-years, there were 106,807 counts of infections recorded. There was an increase in the incidence rate for all infections with lower eGFR, from 74 per 1000 person-years for those with eGFR 90 to 104 mL/min/1.73 m2 to 419 per 1000 person-years for those with eGFR <30 mL/min/1.73 m2. Compared with eGFR of 90 to 104 mL/min/1.73 m2, adjusted incidence rates of community-acquired infections for eGFR of 30 to 50 mL/min/1.73 m2 were 1.08 (95% confidence interval [CI], 1.01-1.14) and 1.53 for eGFR <30 mL/min/1.73 m2 (95% CI, 1.39-1.69).

“This region-representative health care study finds an excess community-acquired infections incidence in individuals with mild to severe CKD. Lower respiratory tract infection, urinary tract infection, and sepsis are major infections in CKD,” the researchers said.

Risk of Incident Kidney Disease and Changes in Albuminuria
Clinical Journal of the American Society of Nephrology. doi:10.2215/CJN.02720317

Progression of chronic kidney disease (CKD) can be predicted using albuminuria. However, outside of clinical trials, there are few data on the associations of changes in albuminuria and the risk of kidney events. Following adjustment for confounders, researchers led by Keiichi Sumida, MD, utilized data from a nationwide cohort of 56,946 US veterans with an estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 to examine the associations of 1-year fold changes in albuminuria with subsequent incident CKD (>25% decrease in eGFR reaching <60 mL/min/1.73 m2) using Cox models. Using logistic regression, the researchers also assessed the associations between changes in albuminuria and rapid decline in eGFR (eGFR slope <–5 mL/min/1.73 m2 per year).

Mean age of the cohort was 64 years, 97% were men, and 91% had diabetes. There was a nearly linear association between 1-year fold changes in albuminuria and incident CKD. Hazard ratios, adjusted for multivariables, of incident CKD associated with more than two-fold decrease, 1.25 to two-fold decrease, 1.25 to two-fold increase, and more than two-fold increase (versus <1.25-fold decrease to <1.25-fold increase) in albuminuria were 0.82 (95% confidence interval [CI], 0.77-0.89), 0.93 (95% CI, 0.86-1.00), 1.12 (95% CI, 1.05-1.20), and 1.29 (95% CI, 1.21-1.38), respectively. There were qualitatively similar associations for rapid decline in eGFR.

In conclusion, the researchers said, “Relative changes in albuminuria over a 1-year interval were linearly associated with subsequent risk of kidney outcomes. Additional studies are warranted to elucidate the underlying mechanisms of the observed associations and test whether active interventions to lower elevated albuminuria can improve kidney outcomes.”

END-STAGE RENAL DISEASE
Facility Stays Following Dialysis Initiation
Journal of General Internal Medicine. doi:10.1007/s11606-017-4151-6

Maria E. Montez-Rath, MD, and colleagues recently conducted an observational study designed to assess hospital and nursing facility stays in the years before and after initiation of dialysis during the transition from pre-dialysis kidney disease to dialysis-dependent end-stage renal disease. The researchers also sought to develop a novel method for visualizing the data.

The study utilized data from the US Renal Data System on patients who initiated dialysis from October 2011 to October 2012. Eligible patients were ≥67 years of age and had Medicare Parts A and B for 1-year prior to dialysis initiation. The primary measures of interest were the proportion of patients with ≥1 facility day, and, among those, the mean number of days and mean proportion of time spent in a facility during the first year after dialysis initiation. The researchers created heat maps to visually represent the data.

The cohort included 28,049 patients. Of those, 60% initiated dialysis in the hospital. Patients with at least 1 facility day spent 37 to 42 days in a facility in the pre-dialysis year and 59 to 67 days in the year after initiation of dialysis. Variations in duration of facility stay occurred by age: patients 67 to 70 years of age spent 60 days (25.8% of the first year after dialysis initiation) in a facility; those >80 years of age spent 67 days (36.8% of the first year after dialysis initiation in a facility).

Patterns of facility stays varied depending on the presence or absence of certain comorbidities. Patients with dementia spent ~50% of the first year following initiation of dialysis in a facility, regardless of age.

“Older patients, particularly octogenarians and patients with dementia and other comorbidities, spend a large proportion of time in a facility during the first year after dialysis initiation. Our heat maps provide a novel and concise visual representation of a large amount of quantitative data regarding expected outcomes after initiation of dialysis,” the researchers said.

Hospitalization Rates Higher in Women than Men on Maintenance Hemodialysis
Journal of the American Society of Nephrology. 2017;28(9):2721-2728

Among patients with end-stage renal disease undergoing maintenance hemodialysis, hospitalization is a major source of morbidity, and a significant contributor to health care costs.
Scott V. Adams, MD, and colleagues conducted an analysis to identify subgroups at the highest risk of hospitalization. The analyses were stratified by sex, age, and race, adjusting for demographic and clinical characteristics. Outcomes of interest were hospitalization rates and 30-day readmissions.

The study cohort included 111,653 patients with 333,756 hospitalizations; the patients were undergoing maintenance hemodialysis at facilities operated by a large dialysis organization in the United States from 2007 to 2011.

The overall hospital rate was 1.85 hospitalizations per person-years. The rate was higher among women compared with men: 2.08 versus 1.68 hospitalizations per year, respectively; P<.001. In addition, age group-specific hospitalizations were consistently higher for women than for men of the same age; the difference was greatest in younger age groups: women 18 to 34 years of age and ≥75 years of age had 54% and 14% higher hospitalization rates, respectively, compared with men of respective ages.

The risk for 30-day readmission was also substantially higher for women than for men; the greatest differences between women and men occurred at younger ages. Albumin level was significantly higher in women than in men, and stratification by serum albumin level attenuated sex differences in the age group-specific hospitalization and 30-day readmission rates.

In conclusion, the researchers said, “These findings suggest that women undergoing maintenance hemodialysis have substantially higher risks for hospitalization and 30-day readmission than men. In this cohort, the sex differences were greatest in the younger age groups and were attenuated by accounting for differences in health status reflected by serum albumin level.”

Polycystic Kidney Disease
Patients with No Apparent Family History of Polycystic Kidney Disease
Journal of the American Society of Nephrology. 2017;28(9):2768-2776

Ten percent to 25% of patients with autosomal dominant polycystic kidney disease (ADPKD) have no positive family history of ADPKD, posing a diagnostic challenge for clinicians. Ioan-Andrei Iliuta, MD, and colleagues utilized data from the Toronto Genetic Epidemiology Study of Polycystic Kidney Disease to review all patients with and without an apparent family history, examined their parental medical records, and performed renal imaging in all available patients of unknown disease status. Patients in the Toronto study underwent renal function testing, abdominal imaging, and comprehensive PKD1 and PKD2 mutation screening.

Of 210 affected probands, reclassification of 209 revealed 72.2% (n=151/209) had a positive family history, 15.3% (n=32/209) had de novo disease, 10.5% (n=22/209) had indeterminate family history, and 1.9% (n=4/209) had positive family history in retrospect. Among the patients with de novo cases, the researchers found two families with germline mosaicism and one family with somatic mosaicism. Analysis of renal imaging demonstrated that 16.3% (34/209) of patients had typical PKD, most of which followed one of three patterns: (1) asymmetric or focal PKD with positive family history and an identified PKD1 or PKD2 mutation (n=15/34); (2) asymmetric and de novo PKD with proven or suspected somatic mosaicism (n=7/34); or (3) focal PKD without any identifiable PKD1 or PKD2 mutation.

The researchers summarized their findings by saying, “PKD without an apparent family history may be due to de novo disease, missing parental missing medical records, germline or somatic mosaicism, or mild disease from hypomorphic PKD1 and PKD2 mutations. Furthermore, mutations of a newly identified gene for ADPKD, GANAB, and somatic mosaicism need to be considered in the mutation-negative patients with focal disease.”

Transplantation
Treating HCV Following Combined Liver-Kidney Transplantation
American Journal of Transplantation. doi:10.1111/ajt.14490

Patients undergoing combined liver-kidney transplantation are at risk of hepatitis C
virus (HCV) infection. Sébastien Dharancy, MD, and colleagues conducted a study to examine the efficacy and safety of second generation direct-acting antivirals in a population of patients with combined liver-kidney transplantation. The cohort was drawn from the ANRS CO23 CUPILT study, a prospective cohort that included transplant recipients with recurrent
HCV who were treated with direct-acting antivirals.

The current study focused on recipients with at least one NS5B inhibitor (sofosbuvir) in their antiviral regimen an average of 90 months following the combined transplant (n=23). Of the 23 participants, 96% achieved a sustained virologic response at week 12, and 39% experienced at least one serious adverse event. None of the patients experienced acute rejection during therapy and there were no deaths reported.

There was a decline in glomerular filtration rate (GFR) from baseline to the end of therapy; however, there was no indication that the decline in GFR persisted over time or that it was directly related to treatment with direct-acting antivirals.

The researchers concluded by saying, “The direct-acting antiviral-based regimen is well tolerated with excellent results in terms of efficacy. It will become the gold standard for the treatment of recurrent HCV following liver-kidney transplantation.”

Health-Related Quality of Life among Frail Transplant Recipients
Transplantation. doi:10.1097/TP.0000000000001943

Following kidney transplantation, there is, on average, improvement in patients’ health-related quality of life (HRQOL). The degree of change depends on the ability of the patient to withstand the stress of dialysis versus the ability to tolerate the intense physiologic changes associated with kidney transplantation. Frail recipients of kidney transplantation may be particularly vulnerable to the stresses associated with transplant, affecting change in HRQOL.

Mara A. McAdams-DeMarco, MS, PhD, et al. conducted a study among a multicenter prospective cohort of 443 kidney transplant recipients (May 20-14-May 2017). Using Kidney Disease Quality of Life criteria, the researchers aimed to assess the frailty and physical, mental, and kidney-disease specific HRQOL in the cohort. Using adjusted mixed-effects linear regression models, the researchers also sought to quantify the 3-month rate of change in HRQOL following transplantation by frailty status.

At the time of transplantation, mean HRQOL scores were 43.3 for physical, 52.8 for mental, and 72.6 for kidney-disease specific HRQOL. Scores among frail recipients were worse for physical (P<.001) and kidney-disease specific (P=.001) HRQOL compared with nonfrail recipients, but similar for the mental component of HRQOL. Following transplantation, rates of improvement in physical and kidney-disease specific HRQOL were significantly greater among frail recipients compared with nonfrail recipients; there was no difference in improvement in mental HRQOL scores.
“Despite decreased physiologic reserve, frail recipients experience improvement in post-kidney transplantation physical and kidney-disease specific HRQOL better than nonfrail recipients,” the researchers concluded.