Associations between depressive symptoms and disease progression in older patients with chronic kidney disease: results of the EQUAL study

Background Depressive symptoms are associated with adverse clinical outcomes in patients with end-stage kidney disease; however, few small studies have examined this association in patients with earlier phases of chronic kidney disease (CKD). We studied associations between baseline depressive symptoms and clinical outcomes in older patients with advanced CKD and examined whether these associations differed depending on sex. Methods CKD patients (>= 65 years; estimated glomerular filtration rate <= 20 mL/min/1.73 m(2)) were included from a European multicentre prospective cohort between 2012 and 2019. Depressive symptoms were measured by the five-item Mental Health Inventory (cut-off <= 70; 0-100 scale). Cox proportional hazard analysis was used to study associations between depressive symptoms and time to dialysis initiation, all-cause mortality and these outcomes combined. A joint model was used to study the association between depressive symptoms and kidney function over time. Analyses were adjusted for potential baseline confounders. Results Overall kidney function decline in 1326 patients was -0.12 mL/min/1.73 m(2)/month. A total of 515 patients showed depressive symptoms. No significant association was found between depressive symptoms and kidney function over time (P = 0.08). Unlike women, men with depressive symptoms had an increased mortality rate compared with those without symptoms [adjusted hazard ratio 1.41 (95% confidence interval 1.03-1.93)]. Depressive symptoms were not significantly associated with a higher hazard of dialysis initiation, or with the combined outcome (i.e. dialysis initiation and all-cause mortality). Conclusions There was no significant association between depressive symptoms at baseline and decline in kidney function over time in older patients with advanced CKD. Depressive symptoms at baseline were associated with a higher mortality rate in men

Evolution of protein-bound uraemic solutes during predilution haemofiltration

Background: Protein-bound uraemic toxins provoke multiple biological changes involved in uraemia. Few if any dialytic strategies remove these compounds. Methods: In this post hoc analysis of remnant samples from a randomised controlled trial, we evaluate whether predilution haemofiltration ( HF) decreases the pretreatment concentration of protein-bound uraemic solutes. Patients treated with low-flux haemodialysis ( HD) were enrolled into a group continuing this strategy ( group A, n=8) over 6 months, whereas group B ( n=12) was switched to predilution online HF. Blood was sampled at baseline and after 6 months to determine total and free concentration and percentage binding of indoxyl sulfate ( IS), indole-3-acetic acid ( IAA), hippuric acid ( HA), p-cresol ( PC) and 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid ( CMPF). Results: Comparing concentrations at start versus 6 months of treatment by paired analysis, HD had no impact. In contrast, at the end of the HF period, we found a decrease in total and free PC, free IAA and total CMPF. In addition, the percentage protein binding of IAA increased significantly. However, unpaired analysis revealed no statistical difference between HD and HF, both at baseline and after 6 months of treatment for all compounds. Conclusions: Paired analysis showed a beneficial impact of predilution online HF for several protein-bound uraemic solutes. Unpaired analysis, however, showed no statistical difference

INFLUENCE OF THE PRECEDING DWELL TIME ON THE PERITONEAL EQUILIBRATION TEST WITH 3.86% GLUCOSE SOLUTION IN AUTOMATED PERITONEAL DIALYSIS

Objective: The peritoneal equilibration test (PET) using 3.86% glucose solution is preceded by a long dwell with 3.86% glucose solution. A point of concern in patients treated with automated peritoneal dialysis (APD) is the influence of the preceding short nightly dwells on the results of a standardized PET. The aim of the study was to compare net ultrafiltration, small solute transport, sodium sieving, and solute transport type between a PET preceded by a long night dwell and one preceded by short (APD) dwells. Patients and Methods: 13 stable APD patients (mean age 60 +/- 15 years; mean duration of peritoneal dialysis 31 +/- 15 months) underwent 2 PETs: 1 preceded by short nightly dwells (PET A) and 1 preceded by a long night dwell (PET B). Results: Both PETs were performed within a mean period of 8 (range 5-11) days. Mean total ultrafiltration of PET A was 626 +/- 218 mL and PET B was 644 +/- 223 mL (NS). The 4-hour results of both tests for dialysate-to-plasma (D/P) ratios of creatinine and urea, D-t/D-0 ratios of glucose, and the dip in D/P sodium (sodium sieving) were similar. Classification of transport categories was identical for 10 of 13 patients. Conclusion: In APD, the preceding dwell time of a 3.86% glucose PET does not influence fluid transport, solute transport, or transport typ

Synthetic ACTH in High Risk Patients with Idiopathic Membranous Nephropathy: A Prospective, Open Label Cohort Study

<div><p>New therapeutic agents are warranted in idiopathic membranous nephropathy. Synthetic ACTH may be advantageous with reported remission rates up to 85% and few side effects. We conducted a prospective open label cohort study from 2008 till 2010 (<a href="https://clinicaltrials.gov/ct2/show/NCT00694863" target="_blank">NCT00694863</a>). We prospectively selected patients with idiopathic membranous nephropathy and high risk for progression (defined as βeta-2-microglobulin (β2m) excretion of >500 ng/min). For comparison, we selected matched historical controls treated with cyclophosphamide. The prospectively selected patients received intramuscular injections of synthetic ACTH during 9 months (maximal dose 1 mg twice a week). The primary endpoints concerned the feasibility and incidence of remissions as a primary event. Secondary endpoints included side effects of treatment and the incidence of remissions and relapses at long-term follow-up. Twenty patients (15 men) were included (age 54±14 years, serum creatinine 104 μmol/l [IQR 90–113], urine protein:creatinine ratio 8.7 g/10 mmol creatinine [IQR 4.3–11.1]). Seventeen patients (85%) completed treatment. 97% of injections were administered correctly. Cumulative remission rate was 55% (complete remission in 4 patients, partial remission 7 patients). In a group of historical controls treated with cyclophosphamide and steroids, 19 of 20 patients (95%) developed a remission (complete remission in 13 patients, partial remission in 6 patients) (p<0.01). The main limitation of our study is its small size and the use of a historical control group. We show that treatment with intramuscular injections of synthetic ACTH is feasible. Our data suggest that synthetic ACTH is less effective than cyclophosphamide in inducing a remission in high risk patients with idiopathic membranous nephropathy. The use of synthetic ACTH was also associated with many adverse events. Therefore, we advise against synthetic ACTH as standard treatment in membranous nephropathy.</p><p>Trial Registration</p><p>ClinicalTrials.gov <a href="https://clinicaltrials.gov/ct2/show/NCT00694863" target="_blank">NCT00694863</a></p></div

Flowchart of treatment and events during follow-up in the ACTH group.

<p>Legend: ACTH = synthetic ACTH, CR = complete remission, PR = partial remission, PNS = persisting nephrotic syndrome, RF = renal failure, 2^nd treatment = alternative immunosuppressive treatment</p

Kaplan-Meier plot for cumulative incidence of remission.

<p>Legend: Number of patients at risk for a remission at each time point are given below the figure. Log-rank test p = 0.005. ACTH = synthetic ACTH, CP = cyclophosphamide.</p

Adverse events with ACTH treatment.

<p>AE = adverse events, SAE = serious adverse events.</p><p>Adverse events with ACTH treatment.</p

Kaplan-Meier plot for relapse free survival.

<p>Legend: Number of patients at each time point are given below the figure. Log-rank test p = 0.020. ACTH = ACTH, CP = cyclophosphamide.</p

Baseline characteristics.

<p>Values are expressed as number (percent), means ± SD and median [interquartile ranges]. ACTH = synthetic ACTH, eGFR = estimated glomerular filtration rate (by MDRD 4 equation), PCR = protein:creatinine ratio, β2m excretion = urinary beta2-microglobulin excretion, α1m excretion = urinary alfa1-microglobulin excretion, min = minute, T0 = start of ACTH treatment.</p><p>* The interval between the end of previous treatment and start of the current treatment was respectively 20, 38, 80 and 162 months in the ACTH group.</p><p>** In the CP treated group this interval was 27 months in one patient and 257 months in the other patient.</p><p>Baseline characteristics.</p