Burden of CKD-Associated Pruritus and Adverse Clinical Outcomes in Patients Receiving Dialysis: The Stockholm CREAtinine Measurements (SCREAM) Project.

RATIONALE & OBJECTIVE: Pruritus is a common but not well-characterized complaint of patients receiving maintenance dialysis. This study sought to quantify the burden of pruritus and its associated adverse health outcomes in this population. STUDY DESIGN: Observational study. SETTING & PARTICIPANTS: All patients receiving maintenance dialysis in Stockholm, Sweden, during 2005-2021. EXPOSURE: Clinically recognized pruritus, defined using ICD-10 codes or the prescription for anti-pruritus treatments (including UV-therapy). OUTCOMES: All-cause mortality, severe infection-related hospitalizations (composite of endocarditis, peritoneal dialysis-related peritonitis, hemodialysis/peritoneal dialysis-related catheter infection, sepsis due to Staphylococcus Spp., or skin infection) and incident diagnoses of anxiety/depression and sleep disorders. ANALYTICAL APPROACH: Multivariable logistic regression and cause-specific hazards models to analyze factors associated with prevalent and new-onset pruritus, respectively. Multivariable cause-specific hazards models with time-varying exposure to explore the association of prevalent and new-onset pruritus with adverse health outcomes. RESULTS: Among 3281 dialysis patients (median age 64 years, 66% men, 69% on hemodialysis,77% incident dialysis patients), 456 (14%) had pruritus at enrollment. During a median follow-up of 3.3 [IQR: 1.3-9.2] years, 539 (19%) additional patients developed pruritus. Older age, female sex, a lower serum albumin level, and higher C-reactive protein, serum calcium and phosphorus levels were independently associated with pruritus. Compared to patients without pruritus, patients with pruritus were at a higher risk of suffering sleep disorders (adjusted HR: 1.96 [95%CI 1.60-2.39]), developing anxiety/depression (aHR: 1.56 [1.23-1.98]), and being hospitalized for severe infections (aHR: 1.36 [1.18-1.57]), the latter attributed to higher risk of sepsis and peritoneal dialysis-related peritonitis. There was no detectable association between developing pruritus and all-cause mortality. LIMITATIONS: Potential misclassification bias if pruritus is not clinically recognized; lack of information on pruritus intensity/severity; use of diagnostic codes for exposure and outcome diagnoses. CONCLUSION: At least one-third of patients experience pruritus during their first years on dialysis, and pruritus was consistently associated with adverse health outcomes.

Heart failure: the grim reaper of the cardio-renal-metabolic triad.

AIMS: Current understanding of the prognosis for patients with chronic kidney disease (CKD) and overlapping cardio-renal-metabolic components, specifically heart failure (HF) and diabetes mellitus (DM), remains limited. While previous studies have explored the interactions between CKD, HF, and DM, they have predominantly focused on cohorts of HF or DM patients. This study aims to fill this gap by investigating the long-term outcomes and treatment patterns in a cohort of CKD patients, particularly those with coexisting HF and DM. METHODS AND RESULTS: We analysed data from the Swedish national CKD patient cohort, the Swedish Renal Registry, with a follow-up period extending up to 10 years. The study examined the risks of all-cause mortality, major adverse cardiovascular events (MACE)-defined as a composite of non-fatal myocardial infarction, hospitalization for congestive HF, non-fatal stroke, or cardiovascular death-and the initiation of kidney replacement therapy (KRT). Analyses were conducted using Cox proportional hazards and competing risk models. Among the 27 647 patients, 48% had CKD alone, 12% had CKD with HF, 27% had CKD with DM, and 13% had CKD with both HF and DM. After 5 years, mortality rates were 23% for patients with CKD, 30% for those with CKD/DM, 54% for CKD/HF, and 55% for CKD/HF/DM. The 10 year absolute risk of MACE was 28% for CKD alone, 35% for CKD/DM, 67% for CKD/HF, and 73% for CKD/HF/DM. The adjusted hazard ratio (HR) for mortality was approximately three times higher in patients with any HF combination, with HRs of 2.57 [95% confidence interval (CI) 2.43-2.71] for CKD/HF and 3.22 (95% CI 3.05-3.39) for CKD/HF/DM, compared with CKD alone. The impact of HF on MACE prognosis was even more pronounced, with adjusted sub-hazard ratios (SHRs) of 3.33 (95% CI 3.14-3.53) for CKD/HF and 4.26 (95% CI 4.04-4.50) for CKD/HF/DM. Additionally, CKD patients diagnosed with HF were less likely to commence KRT, and the risk of death prior to KRT initiation was roughly twice as high for these groups, with SHRs of 2.05 (95% CI 1.93-2.18) for CKD + HF and 2.43 (95% CI 2.29-2.58) for CKD + HF + DM. CONCLUSIONS: In a cohort of CKD patients, having HF contributes substantially to increased mortality and the risk of MACE, and these patients are less likely to start KRT. These findings highlight the urgent need for targeted therapeutic strategies and management plans for CKD patients, particularly those with concurrent HF, to enhance patient prognosis.

Handgrip strength and mortality in a cohort of kidney failure patients: Comparative analysis of different normalization methods.

OBJECTIVES: Reduced handgrip strength (HGS) is associated with adverse clinical outcomes. We analyzed and compared associations of HGS with mortality risk in dialysis patients, using different normalization methods of HGS. METHODS: HGS and clinical and laboratory parameters were measured in a cohort of 446 incident dialysis patients (median age 56 y, 62% men). The area under the receiver operating characteristic curve (AUROC) was used to compare different normalization methods of HGS as predictors of mortality: absolute HGS in kilograms; HGS normalized to height, weight, or body mass index; and HGS of a reference population of sex-matched controls (percentage of the mean HGS value [HGS%]). Multivariate linear regression analysis was used to assess HGS predictors. Competing risk regression analysis was used to evaluate 5-year all-cause mortality risk. Differences in survival time between HGS% tertiles were quantitated by analyzing the restricted mean survival time. RESULTS: The AUROC for HGS% was higher than the AUROCs for absolute or normalized HGS values. Compared with the high HGS% tertile, low HGS% (subdistribution hazard ratio [sHR] = 2.36; 95% CI, 1.19-3.70) and middle HGS% (sHR = 1.79; 95% CI, 1.12-2.74) tertiles were independently associated with higher all-cause mortality and those with high HGS% tertile survived on average 7.95 mo (95% CI, 3.61-12.28) and 18.99 mo (95% CI, 14.42-23.57) longer compared with middle and low HGS% tertile, respectively. CONCLUSIONS: HGS% was a strong predictor of all-cause mortality risk in incident dialysis patients and a better discriminator of survival than absolute HGS or HGS normalized to body size dimensions.

Levels of Cell-Free DNA in Kidney Failure Patients before and after Renal Transplantation.

Circulating cell-free DNA (cfDNA) has diverse applications in oncological, prenatal, toxicological, cardiovascular, and autoimmune diseases, diagnostics, and organ transplantation. In particular, mitochondrial cfDNA (mt-cfDNA) is associated with inflammation and linked to early vascular ageing (EVA) in end-stage kidney failure (ESKF), which could be a noninvasive marker for graft rejection and organ damage. Plasma samples from 44 ESKF patients, of whom half (n = 22) underwent either conservative therapy (non-HD) or hemodialysis (HD) before kidney transplantation (KT). These samples were analyzed at baseline and two years after KT. cfDNA was extracted from plasma and quantified using the fluorometric method. qPCR was used to quantify and differentiate the fractions of mt-cfDNA and nuclear cfDNA (nc-cfDNA). mt-cfDNA levels in KT patients decreased significantly from baseline to two years post-KT (p < 0.0268), while levels of total cfDNA and nc-cfDNA did not differ. Depending on therapy modality (HD vs. non-HD) before KT, total cfDNA levels were higher in HD patients at both baseline (p = 0.0133) and two years post-KT (p = 0.0421), while nc-cfDNA levels were higher in HD only at baseline (p = 0.0079). Males showed a nonsignificant trend of higher cfDNA levels. Patients with assessed vascular fibrosis (p = 0.0068), either alone or in combination with calcification plus fibrosis, showed reduced mt-cfDNA post-KT (p = 0.0195). Changes in mt-cfDNA levels suggests the impact of KT on the inflammatory state of ESKF, as evidenced via its correlation with high sensitivity C-reactive protein after KT. Further studies are warranted to assess if cfDNA could serve as a noninvasive method for monitoring the response to organ transplantation and even for amelioration of EVA status per se.