18 Renal & Urology News
SPRING 2022
www.renalandurologynews.com
Early Dialysis Initiation Associated With Lower Risks for Death, MACE Recent finding from an observational study contrasts with previous research
Allopurinol May Improve KT Outcomes URATE-LOWERING treatment with
EARLY INITIATION of dialysis may modestly reduce the risks for death and major adverse cardiovascular events (MACE), an observational study finds. But the tradeoff may be in quality of life. Among 10,290 patients with advanced chronic kidney disease (median age 73 years; 36% women) in the National Swedish Renal Registry, 3822 started
Lowest death risk observed when dialysis started at an eGFR of 15-16. dialysis, 4160 died, and 2446 had a MACE (a composite of cardiovascular death, nonfatal myocardial infarction, or non-fatal stroke). Investigators examined dialysis initiation in this cohort at estimated glomerular filtration rates (eGFR; in mL/min/1.73 m2) from 4 to 19 in increments of 1.
Mortality displayed a U-shaped curve with eGFR, with the lowest death risk at eGFR 15-16. Compared with dialysis initiation at eGFR 6-7, initiation at eGFR 15-16 was significantly associated with a 5.1% lower absolute risk for death within 5 years, Edouard L. Fu, MD, PhD, of Leiden University Medical Center, Leiden, The Netherlands, and colleagues reported in BMJ. “This 5.1% absolute risk difference corresponded to a mean postponement of death of 1.6 months over five years of follow-up,” Dr Fu’s team wrote. “However, dialysis would need to be started four years earlier.” For most patients, this purported survival benefit would not outweigh the burden of more years spent on dialysis, according to the investigators. The lowest absolute risk for MACE was 3.3% when dialysis was initiated at an eGFR of 13-14, using an eGFR of 6-7 as a reference. The investigators adjusted analyses for multiple relevant factors, such as laboratory values and comorbidities. However,
the study lacked information on nutritional status or muscle mass, uremic symptoms, volume status, and quality of life or physical activity. The team also noted that optimal eGFR to start dialysis may differ between hemodialysis and peritoneal dialysis; up to 39% of patients in Sweden start with peritoneal dialysis. “Our results further suggest that in the absence of symptoms or strong indications, initiation of dialysis may be postponed until lower eGFR values are reached (intent to defer), without a large increase in mortality or cardiovascular events,” according to Dr Fu’s team. The new findings differ from those of some previous reports, including one in Hemodialysis International in 2021. That report, which provides details of a study involving 676,196 adult patients initiating hemodialysis between 2006 and 2014, found that patients who started hemodialysis early (eGFR 13 or higher) had a significant 93% increased risk for all-cause mortality compared with those who started late (eGFR less than 8.7). ■
allopurinol may help maintain graft function in kidney transplant (KT) recipients with elevated serum uric acid levels, a new study suggests. In the ADOPTR (Allopurinol Drug use on GFR and Proteinuria in Renal Transplantation Recipients) study, researchers randomly assigned 124 KT recipients to receive allopurinol (300 mg once daily) or matched placebo. Mean serum uric acid levels significantly decreased from 6.98 mg/dL at baseline to 6.00 mg/dL at 24 weeks in the allopurinol group, but did not change significantly in the placebo group, Özlem Usalan, MD, and colleagues from Gaziantep University School of Medicine, Gaziantep, Turkey, reported in Transplant Immunology. In the allopurinol group, mean estimated glomerular filtration rate (eGFR; according to the Modification of Diet in Renal Disease study equation) significantly increased from 68.05 to 71.97 mL/
Poor Nutrition at Dialysis Start Ups Mortality Odds PATIENTS WITH POOR or declining nutritional status during dialysis initiation are at higher risk for death for up to 5 years afterward, according to investigators. “This calls for special attention to be paid to diet and adequate treatment of comorbidities as patients approach dialysis, in order to optimize survival after dialysis start,” Sara Blumberg Benyamini, PhD, of Wolfson Medical Center in Holon, Israel, and colleagues reported in the Journal of Renal Nutrition. They also observed, “Our study also suggests the importance of improving the nutritional status during the first months in dialysis. Dietary intervention at this time, during the first 3 months on dialysis, might improve survival during the 3 years following RRT commencement.” The investigators calculated an Integrative Clinical Nutrition Dialysis Score (ICNDS) for 297 patients at dialysis initiation and 1, 2, and 3 months later. For each patient, they ranked 7 parameters — serum albumin, creatinine, and urea, cholesterol, dialysis
adequacy, C-reactive protein (CRP), and post-dialysis weight change — on a scale from 1 (abnormal) to 5 (meets guideline recommendations) and tallied the score. Weight change and albumin levels each accounted for 25% of the ICNDS, and the remaining 5 parameters each made up 10%. A low
Findings suggest special attention be paid to diet as patients approach dialysis. ICNDS was less than 75 and a high ICNDS 75 or more. Patients with a low vs high ICNDS at baseline had 2.5- and 1.5-fold increased odds of all-cause death at 1 and 5 years, respectively. Deterioration of nutritional status within the first 3 months of dialysis (indicated by a negative vs positive ICNDS slope) was significantly associated with 1.7-fold increased odds of mortality within 3 years — even
among those with favorable nutritional status at baseline. Patients with a low ICNDS at dialysis initiation were significantly older and had a higher prevalence of diabetes, cardiovascular disease, and malignancy. They also had higher CRP levels. According to the investigators, protein-energy wasting and inflammation, together known as malnutritioninflammation complex syndrome, likely explains the differences between the low and high ICNDS groups. “We suggest a multidisciplinary approach that includes attention to diet and provision of adequate treatment for comorbidities in the period before initiation of dialysis, with the aim of increasing the ICNDS during the transition to [RRT],” Dr Benyamini’s team wrote. “This then might improve survival odds after dialysis initiation.” The authors acknowledged a number of study limitations. For example, it had a relatively small sample size and was conducted at a single dialysis center, “thereby limiting the possibility of generalizing these findings.” ■
min/1.73 m2 and mean urinary albumin to creatinine ratio (UACR) significantly decreased from 325.14 to 319.29 mg/g. No meaningful kidney function changes occurred in the placebo group. C-reactive protein levels increased significantly over 24 weeks in the placebo group but not the allopurinol group. “Our results seem to support the view that lowering circulating urate levels plays a role in improving kidney function in kidney transplant recipients,” Dr Usalan’s team concluded. They acknowledged that elevated uric acid levels may reflect metabolic acidosis or other conditions, and not just hyperuricemia. Routine prophylaxis of asymptomatic hyperuricemia is not recommended in current guidelines. Previous studies have yielded conflicting results on the use of allopurinol in patients at various stages of chronic kidney disease. Limitations of the study include its small sample size and short duration of follow-up, the investigators noted. ■
