May / June 2020 Abstract Roundup

ACUTE KIDNEY INJURY

AKI Outcomes Following High-Dose Chemotherapy

Clinical Genitourinary Cancer. doi.org/10.1016/j.clgc.2020.01.008

Kevin Juan Zhang, MD, and colleagues recently conducted a study to examine the risk factors and outcomes of patients who developed acute kidney injury (AKI) during high-dose chemotherapy for relapsed germ cell tumors (GCTs). All eligible patients were scheduled to receive two consecutive courses of high-dose chemotherapy (HDCT). Characteristics and outcomes of the patients with stage ≥3 AKI were compared with those in patients without stage ≥3 AKI.

The study included 462 patients; of those, 4.5% (n=21) developed stage ≥3 AKI. Of the 21 patients, 18 required hemodialysis during HDCT and six died during HDCT. Of the 15 patients who survived during HDCT, 10 experienced recovery of renal function to baseline.

AKI occurred in the first cycle of HDCT in 18 patients. Those patients were also more likely to have received HDCT in a third-line setting and/or to have Eastern Cooperative Oncology Group performance status of 1 or 2 and to have experienced gastrointestinal, hepatic, pulmonary, and infectious grade ≥3 toxicities.

At a median follow-up of 10 months after HDCT, four patients had no evidence of disease, three were alive with disease, six had died of disease, seven had died of complications from HDCT, and one had been lost to follow-up.

In conclusion, the researchers said, “Irreversible AKI during HDCT for relapsed GCT is uncommon but is associated with greater rates of infectious, gastrointestinal, hepatic, and pulmonary complications, and treatment-related deaths. These patients were also more heavily pretreated and had a lower baseline performance status, However, most surviving patients had recovered their renal function and five of the 21 were alive with no evidence of disease.”

ADPKD

Anemia as Factor for Poor Renal Prognosis

Clinical and Experimental Nephrology. doi.org/10.1007/s10157-020-01856-1

In patients with chronic kidney disease (CKD), anemia is an indicator of poor renal prognosis. However, hemoglobin (Hb) levels are typically higher in autosomal dominant kidney disease (ADPKD) compared with other kidney diseases. There are few data available on anemia as a potential prognosticator in patients with ADPKD. Yusuke Ushio, MD, and colleagues conducted a study to examine anemia as a factor for renal prognosis in ADPKD.

The analysis included 115 non-dialysis patients with ADPKD; of those 48 were men and 67 were women. The outcome of interest was a 50% reduction in the estimated glomerular filtration rate or the need for renal replacement therapy. Cox regression analysis and Kaplan-Meier analyses were used to assess the outcome.

Fifty patients reached the end point during a median follow-up of 5.5 years. At the first visit, the mean age of the patients was 49.9 years, the overall mean Hb was 12.90 g/dL, and the mean Hb in men was 13.82 g/dL and 12.25 g/dL in women. Hb levels and uric protein content were statistically significant factors for poor renal prognosis; hypertension and genetic mutations did not reach statistical significance as factors for poor renal prognosis. Statistical significance was seen in men with Hb <12 g/dL and in women with Hb <11 g/dL. There was a significant association between anemia and progression of kidney disease in patients with ADPKD.

“We found that anemia might be a factor for poor renal prognosis in ADPKD. Furthermore, a sex difference was found, wherein men with Hb <12 g/dL and women with Hb <11 g/dL were at risk of renal disease progression,” the researchers said.

ANEMIA

Novel Iron Therapies for IDA in CKD

Advances in Chronic Kidney Disease. 2019;26(4):272-291

Patients with chronic kidney disease (CKD) frequently experience iron deficiency anemia (IDA); there is an association between IDA and adverse outcomes in this patient population. Patients with IDA and CKD are commonly undertreated. Poor absorption of conventional iron agents as well as gastrointestinal side effects result in insufficient effectiveness of those agents, creating a need for novel oral iron preparations. Pablo E. Pergola, MD, and colleagues reviewed current treatment guidelines for patients with anemia and CKD. The review included clinical trial data for iron-repletion agents being used currently, as well as novel oral iron therapies in development.

Ferric citrate is a novel iron-repletion agent approved for use in patients with non–dialysis-dependent CKD and IDA; results of trials found improvements in hemoglobin levels and iron parameters, with good tolerability in that patient population. When used as a phosphate binder in patients with dialysis-dependent CKD, ferric citrate also improved hemoglobin and iron parameters; additional trials are needed to assess efficacy as an iron repletion agent.

There are other novel iron preparations in development, including ferric maltol (approved in Europe and the United States for IDA in adults) and Sucrosomial® iron that has been evaluated in IDA associated with CKD and several other clinical settings.

Pathophysiology, Diagnosis, and Treatment of Iron Deficiency in CKD

Journal of the American Society of Nephrology. doi.org/10,1681/ASN.2019020213

A majority of patients with advanced chronic kidney disease (CKD) develop anemia. Relative deficiency of erythropoietin is a major driver of anemia in CKD; however, iron deficiency is a key mechanism associated with impaired erythropoiesis in patients with reduced kidney function. Iron deficiency plays a crucial role in anemia in CKD due to absolute iron deficiency (a true paucity of iron stores) or a functional (relative) deficiency that prevents the use of available iron stores.

Both absolute and functional iron deficiency in CKD are associated with risk factors such as blood losses, impaired iron absorption, and chronic inflammation. There are limitations to the traditional biomarkers used to diagnose iron deficiency anemia (IDA) in patients with CKD, creating challenges in the detection and management of patients with CKD and IDA. Elizabeth Katherine Batchelor, MD, and colleagues reviewed the pathophysiology and available diagnostic tests for IDA in CKD and highlighted the literature that has informed current practice guidelines for the treatment of IDA in CKD.

The article addresses the potential risks of a more liberal approach to iron supplementation and the potential risks and benefits of intravenous versus oral iron supplementation in this patient population.

CHRONIC KIDNEY DISEASE

Cardiovascular Diagnosis & Therapy  2020;10(1):24-30

Racial Differences in Progression of Aortic Stenosis in CKD

In patients with  advanced chronic kidney disease (CKD) and European ancestry, there is a high prevalence of aortic stenosis. There are few data available on a comparison of progression of aortic stenosis in white and black patients in an advanced CKD population.

Aamir Husain, MD, and colleagues conducted a study to compare the progression of aortic stenosis between white and black patients in a CKD-specific population and determine whether the genetic link between white adults and aortic progression prevails in a CKD population. The cohort included 1283 patients with CKD stage 4-5 who were referred to the University of North Carolina Cardiorenal Clinic for preoperative kidney transplant evaluation.

Of the 1283 patients, 140 (34% white; 66% black) developed or had baseline aortic stenosis. Initially, 81% had no aortic stenosis, 13% had mild, and 6% had moderate aortic stenosis. White patients were more likely to be male and less likely to be on hemodialysis compared with black patients. There were no differences in severity of aortic stenosis or age at baseline.

In white versus black patients, mean gradient increased at 1.90 (95% confidence interval [CI], 0.79 to 3.01) mmHg per year versus 1.46 (95% CI, 0.79 to 2.14) mmHg per year (P=.20); aortic valve area decreased at -0.10 (95% CI, -0.15 to -0.05) m² per year versus –0.08 (95% CI, -0.11 to -0.05) m² per year (P=.13); and transvalvular velocity increased at 0.11 (95% CI, 0.04 to 0.18) meters per second (m/s) per year versus 0.07 (95% CI, 0.03 to 0.11) m/s per year (P=.09).

In conclusion, the researchers said, “Compared to black patients, white patients in an advanced CKD cohort may have exhibited more rapid progression of aortic stenosis. Ours is the first study to analyze racial differences in such a population. A study with a larger sample size is needed to confirm our findings.”

DIABETES

Current Diabetes Reviews. doi:10.2174/1573399816666200211120402

Nutritional Needs in Patients with Diabetes and CKD

Up to 40% of patients with diabetes are diagnosed with chronic kidney disease (CKD) as a direct result of diabetes-related complications. Due to the need for disease-specific diets for patients with diabetes, management of patients with diabetes and CKD presents challenges; there are also increased risks for malnutrition in this patient population.

Researchers led by Nourhan Khaled Hassan, MD, recently conducted a systematic review to examine nutritional requirements for patients with type 2 diabetes and chronic renal failure. The researchers screened 85 articles; of those, 22 were analyzed and included as per the study criteria. The data search included PubMed using medical subject headings terms, and a literature review through the Cochrane library and the British Medical Journal.

The review highlighted nutrients and minerals needed to be maintained within a specified range defined by a patient’s needs and conditions. Dietary restrictions to prevent disease progression were also necessary. Patients receiving hemodialysis required vigorous monitoring of blood glucose levels as well as strict management of dietary intake. Risk-to-benefit ratios were utilized to determine optimal protein intake in patients on hemodialysis.

“Dietary requirements should be individualized based on the patient’s disease severity and progression. Assessment of the patient’s previous and current diet, as well as matching it with their dietary requirements and preferences is crucial,” the researchers said.

HYPERKALEMIA

Economic Impact of Hyperkalemia in a Managed Care Population

American Health & Drug Benefits. 2019.12(7):352-361

Hyperkalemia, serum potassium level >5 mEq/L, can lead to life-threatening arrhythmias and sudden cardiac death. The complexity of care is significantly increased in patients with coexisting cardiac and renal disease (cardiorenal syndrome). There are few data available of the economic impact of hyperkalemia in patients with cardiorenal syndrome in patients in the Medicaid managed care population.

Nihar R. Desai, MD, MPH, and colleagues conducted a retrospective cohort study using real-world data to calculate the economic impact of hyperkalemia in patients with cardiorenal syndrome in a Medicaid managed care population in the United States.

The data were from a proprietary Medicaid managed care database from a southern state. The total study cohort included 3563 patients: 973 patients with hyperkalemia and 2590 without hyperkalemia (controls). Patients and controls were matched based on age, comorbidities, and Medicaid eligibility status between 2013 and 2016.

For the patients with hyperkalemia, mean healthcare costs (medical and pharmacy per member per year [PMPY]) were higher than for patients in the control cohort: $56,002 versus $23,653, respectively. The cost differences were driven by medical costs accrued in the hyperkalemia and in the control cohorts: $49,648 and $18,399 PMPY, respectively. Inpatient costs ($33,116 vs $10,629 PMPY for the hyperkalemia cohort vs the controls, respectively) and dialysis costs ($2716 vs $810 PMPY, respectively) were two of the largest drivers of the variance in medical costs. Both cohorts had revenue deficits to the health plan, but the hyperkalemia cohort had double the medical loss ratio compared with controls.

In conclusion, the researchers said, “The findings from this Medicaid managed care population suggest that hyperkalemia increased healthcare utilization and costs, which were primarily driven by the costs associated with inpatient care and dialysis. Our findings demonstrate that the Medicaid beneficiaries who have cardiorenal comorbidities accrue high costs to the Medicaid health plan, and these costs are even higher if a hyperkalemia diagnosis is present. The very high medical loss ratio for the hyperkalemia cohort in our analysis indicates that enhanced monitoring and management of patients with hyperkalemia should be considered.”