Outcomes of patients with Cholesterol crystal embolism treated by peritoneal dialysis: retrospective study from the RDPLF registry.

Abstract

Cholesterol crystal embolisms disease (CED) is a systemic disease characterized by tissue ischemia and microinflammation related to occlusion of arterioles by microemboli from ulcerated atheromatous plaques. The kidney is one of the most affected organs, often requiring dialysis. Our study examines the outcomes of a cohort of patients with CED treated with peritoneal dialysis (PD). As anticoagulants can favor emboli, peritoneal dialysis may theoretically have an advantage.

From the database of the French Language Peritoneal Dialysis Registry (RDPLF), between January 1, 1995, and December 31, 2021, we selected patients treated with PD for >90 days and with an age >18 years. On the basis of the variables of patient autonomy, diabetes, BMI, modified Charlson index, age, sex, pre-PD treatment, causes of death, causes of transfer to hemodialysis, and peritonitis, three types of survival were estimated (patient, technical, and composite). After adjustment by propensity scores and taking into account competitive risks, 2 groups of patients were constituted on the basis of baseline nephropathy: emboli group vs. control group.

Patient survival and strict technical survival are not associated with the type of nephropathy (CED versus others). Composite technical survival (uncensored for deaths and transfers to hemodialysis) was only associated with cholesterol emboli nephropathy in the multivariate analysis adjusted for diabetes, autonomy, and age of the patient at the start of the dialysis treatment (p=0.011; 95% CI [0.736 [0.581-0.931]]).

Our study from the RDPLF database shows no difference in technical and patient survival in a cohort of patients with CED vs. a control group. It also confirms that PD may represent an adequate choice in this pathology.

INTRODUCTION

Cholesterol emboli disease (CCE) is a systemic disease linked to diffuse atherosclerosis belonging to crystallopathies of intrinsic origin. Tissue ischemia is related to arteriolar occlusion linked to microemboli from ulcerated atheroma plaques. However, the pathophysiological mechanism also calls for the existence of micro-inflammation[1];[2];[3]. Factors favoring ulceration of atherosclerotic plaques are regularly found, but more frequently, the cause is secondary to endovascular diagnostic maneuvers[4];[5];[6]. Since the diagnosis of the disease is based solely on clinical and sometimes morpho-histological criteria, this pathology remains, perhaps, underdiagnosed, and its incidence varies according to the series in the literature[4];[5].

The kidney is among the most affected organs, and usually, depending on the mode of presentation, three types of damage are described, but all stages of chronic renal disease (CRD) remain concerned[7];[8];[9];[10];[11];[12];[13];[14]. The evolution of CCE is often pejorative, with the need for recourse to treatment by dialysis in 20-30% of patients, which is much more frequent if renal insufficiency preexists with the appearance of the disease. Mortality, which is most often of cardiovascular origin, is also high, although it seems to be reduced if the supportive treatment is intensive. The other risk factors found that can worsen the prognosis are age, diabetes, and extra-renal manifestations[4];[5];[7];[8];[9];[10];[11].

To date, there are few data in the literature concerning the management and evolution of patients with cholesterol emboli disease with renal failure on dialysis. From the data of the RDPLF (French Language Peritoneal Dialysis Registry), we were interested in the outcome of patients treated by peritoneal dialysis (PD) who had an initial diagnosis of CCE.

PATIENTS AND METHODS

This is a retrospective observational study based on the database of the RDPLF, the description and mode of operation of which are described elsewhere[15];[16].

All patients from mainland France, aged over 18, with chronic renal failure, who had been on treatment with peritoneal dialysis for at least 3 months between January 1, 1995, and December 31, 2021, were included. Patients treated with peritoneal dialysis for cardio-renal syndrome were excluded from the study.

Two groups of patients were created according to the diagnosis of the main nephropathy: those whose renal failure was consecutive to a CCE (emboli group) numbering 128, and those treated by peritoneal dialysis for another nephropathy (other group), numbering 15,180.

The variables analyzed were:

• Patient autonomy (yes/no)
• Diabetes treated (yes/no)
• Body mass index (BMI) (BMIs below 14 or above 35 were excluded from the study)
• Modified Charlson index (i.e. not taking age into account) (values less than 2 were considered unstated because they were incompatible with the diagnosis of renal insufficiency, which implies a minimum of 2)
• age (years)
• sex
• treatment before PD (untreated, hemodialysis, transplanted)
• causes of death (discontinuations of treatment for transfers to palliative care were grouped together with deaths)
• causes of hemodialysis transfers
• peritonitis (the history of at least one episode of peritonitis or not was coded in a binary way, yes/no)

Three types of PD cessation were estimated (Table I): (1) patient survival (PS): for the study of this survival, only deaths and discontinuations for palliative treatment were not censored (transfers to hemodialysis, transplants, and end of follow-up were censored); (2) strict technical survival (STS): only hemodialysis transfers were not censored (deaths, transplants, and end of follow-up were censored); and (3) composite technical survival (CTS): deaths, discontinuation for palliative care, and transfers to hemodialysis were not censored (the end of follow-up and transplantation were censored).

Table I.Description of the population before matching

Causes of PD end	PS	STS	CTS
Palliative treatment	event	competing event	event
Death	event	competing event	event
End of follow up	censor	censor	censor
Transferred to hemodialysis	competing event	event	event
Transplanted	competing event	competing event	competing event

METHODS AND STATISTICAL ANALYSIS

This was a real-life cohort study; the sample size was determined by the number of patients included in the RDPLF registry with CCE. Demographic, diagnostic, clinicopathologic, and disease-specific data were retrieved prospectively for each patient entered into the database. The missing data for the variables diabetes (n=16: 0.11%), treatment before PD (n=63 patients: 0.42%), autonomy (n=9 patients: 0.06%), and modified Charlson (n=3886 patients: 22%) were completed using the multiple imputation method using R’s “mice” package[17]. To minimize discrepancies between significantly different baseline characteristics between the two study groups, matching using a 1:1 ratio propensity score was performed. The propensity score was calculated using a logistic regression model based on the following variables: sex; diabetes; treatment before PD; autonomy; peritonitis and age of the patient at the start of peritoneal dialysis. Qualitative variables were presented as frequencies and percentages. Continuous variables were described by extreme, mean, and median values; quartiles; and standard deviations. Qualitative data comparisons were made using Chi-square or Fisher’s exact tests. Quantitative data were compared using Student’s T test or the Mann-Whitney U test. The median follow-up and its 95% CI were calculated using the Schemper method[18]. The competitive risks method was used to analyze the previously defined delays: PS, STS, and CTS between the 2 groups studied. Univariate and multivariate analyses between the groups considered were carried out using the Fine and Gray model[19]. All statistical analyses

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