Top Papers Of The Month

Top Papers in Nephrology: Research You May Have Missed in June 2021

James Matera, DO
Practicing Nephrologist, Senior Vice President for Medical Affairs, and Chief Medical Officer
CentraState Medical Center, Freehold, New Jersey

Matera J. Top papers in nephrology: research you may have missed in June 2021. Consultant360. Published online July 21, 2021.


Several interesting and timely articles have been published in the last few months which are summarized here, including research on patients with acute kidney injury and receiving dialysis, management for patients receiving maintenance hemodialysis, and adding high- vs low-dose glucocorticoids for ANCA-positive vasculitis remission.

Acute Kidney Injury Requiring Dialysis and Incident Dialysis Patient Outcomes in US Outpatient Dialysis Facilities1

This paper raises the question, “Does initiation of dialysis in patients with acute kidney injury (AKI) carry different outcomes from patients with non-AKI incident dialysis?” A study from researchers at the University of Michigan in Ann Arbor, Michigan, examined outcomes for patients who needed to start dialysis as inpatients, then required outpatient dialysis.

We know that up to 30% of patients with AKI who require hospital-based initial dialysis go on to require long-term renal replacement therapy. Little has been reviewed to compare their outcomes with those who do not present with AKI for initiation of dialysis.

Out of more than 400,000 Medicare claims for end-stage renal disease (ESRD), more than 10,000 patients had at least 1 claim for AKI, whereas more than 52,000 did not have incident AKI. Several trends were identified within the incident-AKI group:

  1. 76% were White (compared with 70% of the non-AKI group?)
  2. 82% were older than age 65 years (compared with 72% of the non-AKI group?)
  3. 92% non-Hispanic (compared with 87% of the non-AKI group?)

As far as measures of mortality, AKI-incident patients had a much higher mortality rate, which persisted throughout a 4-month follow-up period, after which time, statistical significance had regressed. Mortality risk in the AKI group was 22% higher, except when race was factored in, with Black patients showing a lower adjusted mortality rate and even persisted beyond the 4-month follow-up period. Conclusions indicate that AKI, race, age, and ethnicity were factors in outcomes.

Design and Rationale of HiLo: A Pragmatic, Randomized Trial of Phosphorous Management for Patients Receiving Maintenance Hemodialysis2

This is an interesting study that is currently enrolling patients at dialysis centers in Utah and aims to target the specific issue of hyperphosphatemia. We, as nephrologists, spend a large amount of time dealing with issues around hyperphosphatemia, including patient adherence, pill burden, and low-phosphorus diets. This study will answer the question, “Is this a beneficial thing to do?”

The researchers plan to enroll more than 4000 patients receiving hemodialysis on phosphate binders to categorize them into 2 groups: the “Hi” group aims to achieve phosphorous levels of more than 6.5 mg/dL, and the “Lo” group is striving for levels lower than 5.5 mg/dL (our traditional target). The outcomes studied will be all-cause mortality and all-cause hospitalizations.

The hypothesis is that there are no randomized clinical trials studying the benefits of phosphate-binding regimens, nor what the optimal target level should be. This leads to the question, “Is there more harm than good when trying to achieve these levels in standard practice?” These are certainly interesting questions, particularly since hyperphosphatemia in the dialysis community has extended beyond simple bone and mineral issues into the cardiovascular realm. This study plans to use innovative approaches, including broad involvement of dieticians and remote monitoring of phosphorous levels between arms.

Effect of Reduced-dose vs High-dose Glucocorticoids Added to Rituximab on Remission Induction in ANCA-Positive Vasculitis: A Randomized Controlled Trial3

We know that high-dose glucocorticoids, while proven to be very helpful, can be fraught with serious adverse events, including steroid-induced diabetes. Treatment of antineutrophil cytoplasmic antibody (ANCA)-positive vasculitis has always relied on steroids as an adjunct to other treatments like cyclophosphamide and rituximab.

The Japanese LoVAS group studied the question, “Are outcomes in this disease state affected when a lower-dose steroid regimen is used?” Patients were evenly assigned to receive either low-dose prednisolone (0.5 mg/kg/d) plus rituximab (375 mg/m2/wk, 4 doses) (n = 70) or high-dose prednisolone (1 mg/kg/d) plus rituximab (375 mg/m2/wk, 4 doses) (n = 70). The primary end point was rate of remission among the 2 groups at 6 months.

Results of this study showed that the lower-dose regimen was noninferior to the higher-dose regimen, with 71% of participants who received the lower-dose regimen achieving remission at 6 months vs 69.2% who received the higher-dose regimen. The higher-dose arm had more adverse events, as expected.

A total 18.8% of participants in the low-dose group had serious adverse events, while 36.9% in the high-dose group had serious adverse events. Some patients had more than 1 adverse event. Serious adverse events were death, disability, primary hospitalization, or prolongation of current hospitalization.

Infectious events also occurred more frequently in the high-dose group, with 7 infections in 5 participants in the low-dose group (7.2%) and infections in 13 patients in the high-dose group (20.0%). Diabetes had developed in 9 participants in the low-dose group, compared with 19 patients in high-dose group.

This study points to a potential for limiting the use of high-dose steroids without sacrificing time to remission when rituximab is used for management of newly diagnosed ANCA-positive vasculitis.


  1. Dahlerus C, Segal JH, He K, et al. Acute kidney injury requiring dialysis and incident dialysis patient outcomes in US outpatient dialysis facilities. Clin J Am Soc Nephrol. 2021;16(6):853-861.
  2. Edmonston DL, Isakova T, Dember LM, et al. Design and rationale of HiLo: a pragmatic, randomized trial of phosphate management for patients receiving maintenance hemodialysis. Am J Kidney Dis. 2021;77(6):920-930.e1.
  3. Furuta S, Nakagomi D, Kobayashi Y, et al; LoVAS Collaborators. Effect of reduced-dose vs high-dose glucocorticoids added to rituximab on remission induction in ANCA-associated vasculitis: a randomized clinical trial. JAMA. 2021;325(21):2178-2187.