Daniel M. Keller, PhD

June 22, 2012

June 22, 2012 (Paris, France) — In an Austrian study of patients receiving peritoneal dialysis, researchers found that oral active vitamin D was associated with a lower risk forperitonitis and all-cause mortality.

Presenting study results here at the XLIX European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Congress, lead investigator Julia Kerschbaum, MD, from the Nephrology and Hypertension Division in the Department of Internal Medicine IV at the Medical University Innsbruck, Austria, said that peritonitis can lead to hospitalization, catheter loss, dialysis failure, and mortality. However, she noted that the incidence rates of peritonitis in the literature, especially in Austria, are scant, and the published risk factors for peritonitis are inconsistent.

The investigators therefore undertook a retrospective study spanning the 10-year period from 2000 to 2009. They examined the records of 720 patients from 7 centers, which was 44.3% of the peritoneal dialysis population treated in Austria during that time, representing 1703 patient-years. The researchers collected data on demographics, comorbidities, laboratory parameters, and the use of concomitant medications.

Vitamin D Appears Protective

"The median peritonitis incidence rate was 0.34 episodes per patient-year, which is in the range recommended [by the International Society for Peritoneal Dialysis]," Dr. Kerschbaum told meeting delegates.

In a univariate analysis of risk factors for peritonitis, those that were significant were a serum albumin level less than 3500 mg/dL, older age, peripheral artery disease (PAD), and diabetes. In addition, other underlying renal disease such as interstitial nephritis or other unknown renal diseases also contributed to the risk forperitonitis.

"Significant protective factors were hemoglobin levels above 12 g/dL and the treatment with oral active vitamin D," Dr. Kerschbaum reported. A Kaplan-Meier analysis showed that patients receiving oral active vitamin D had significantly better outcomes in terms of avoiding peritonitis over time compared with patients who were not taking it (P < .001).

A multivariate analysis incorporating all significant factors from the univariate analysis showed that oral active vitamin D reduced the risk of developing peritonitis by 57% (hazard ratio [HR], 0.43; 95% confidence interval [CI], 0.28 - 0.64). The multivariate analysis adjusted for serum albumin level, hemoglobin, age, renal disease, PAD, diabetes, dialysis center, and year of treatment initiation.

A renal diagnosis of "other," for example, interstitial nephritis or unknown type, was associated with a 65% increased risk forperitonitis (HR, 1.65; 95% CI, 1.08 - 2.53). A serum albumin less than 3500 mg/dL raised the risk by 49% (HR, 1.49; 95% CI, 1.04 - 2.15).

Vitamin D Associated With Lower Risk for All-Cause Death

A univariate analysis revealed that age, underlying renal disease, albumin levels less than 3500 mg/dL, diabetes, cardiomyopathy, previous myocardial infarction, and cerebrovascular disease raised the risk fordeath from any cause.

Significant protective factors against all-cause mortality were serum calcium levels greater than 2.37 mmol/L (9.48 mg/dL), female sex, treatment with oral active vitamin D, and treatment with a non–calcium based phosphate binder.

In a multivariate analysis, cardiomyopathy tripled the risk forall-cause death (HR, 3.01; 95% CI, 1.62 - 5.59), age added 6% risk for each advancing year (HR, 1.06; 95% CI, 1.03 - 1.09), and a low albumin level almost doubled the risk (HR, 1.89; 95% CI, 1.13 - 3.17).

In contrast, "oral active vitamin D was associated with a 54% decreased risk for all-cause death" (HR, 0.46; 95% CI, 0.27 - 0.81; P < .001), Dr. Kerschbaum reported.

In response to a request from an audience member to speculate on why vitamin D appeared protective against peritonitis and all-cause death, Dr. Kerschbaum said that vitamin D may be acting as an immunomodulator and as an anti-inflammatory agent. She also said that the researchers compared patients taking vitamin D with those who were not, and they did not find any underlying differences or factors that would account for taking the vitamin or not, so as far as the researchers could tell, vitamin D was the independent factor associated with the risk forperitonitis and all-cause death.

Speaking with Medscape Medical News, Raymond Vanholder, MD, chief of the nephrology department at the University Hospital in Ghent, Belgium, and president of the ERA-EDTA, who did not participate in the study, agreed with the idea of vitamin D exerting multiple effects, including a positive effect on the immune system.

"The easiest way to explain it is to say that vitamin D is pleiotropic and it gives better protection against infection," he said. However, "it may somehow be the other way around that if they have infection of their peritoneal dialysate...that due to these infections they are inflammatory.... So there are many ways to explain it to my opinion."

Moreover, he emphasized that the main cause of peritonitis probably lies in the "hook-ups" for peritoneal dialysis. "I think the problem is more in 'connectology' than in the patient itself for [peritoneal dialysis]," he said. "That means making the connection, etc, causes a lot of infection, but the 'connectology' has been improved dramatically."

The biggest problem in studying the effects of vitamin D, he said, is that it is "too cheap...so there is no company interested in this kind of study. But this should be stimulated by authorities, I think. It's a cheap drug, and probably it is a very valuable one."

The study did not receive commercial support. Dr. Kerschbaum has disclosed no relevant financial relationships. Dr. Vanholder has received unrestricted research grants from Fresenius Medical Care and Baxter.

XLIX European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Congress: Abstract SAO031. Presented May 26, 2012.