Incremental peritoneal dialysis is a safe and feasible prescription in incident patients with preserved residual kidney function.

BACKGROUND: Incremental peritoneal dialysis (PD) is recommended as a component of high-quality care by the international society for PD; however, its feasibility and clinical outcomes have not been widely reported. The aim of this study is to describe our experience with incremental PD. METHODS: This was a retrospective cohort study of incident PD patients at Eastern Health between 2015 and 2019. Patients who stopped PD within 30 days were excluded. Incremental PD was defined in CAPD as using <8 L/day of exchange volume and in automated PD as dialysing without a last fill. Dialysis modality accorded with patient and physician preferences. RESULTS: The 96 patients were included in this study; 54 with incremental PD. Compared to full-dose PD, incremental PD patients were more likely to be female, had less comorbid diabetes (28% vs. 52%) and higher residual kidney function (RKF) (Kt/V 2.0 ± 0.7 vs. 1.4 ± 0.7). Age, BMI and starting eGFR did not differ between groups. Incremental PD exposed patients to lower exchange volumes (4.4 ± 2.1 vs. 8.5 ± 1.1 L/day), glucose load (46 ± 41 g/day vs. 119 ± 46) and was associated with a longer peritonitis-free survival. PD technique survival, rates of peritonitis or hospitalization were comparable between groups. Predictors for longer incremental PD use included older age and higher starting eGFR. CONCLUSIONS: Incremental PD is a feasible, goal-directed initial prescription in patients with RKF with comparable peritonitis rates and technique survival. Validation of this prescription in prospective studies is warranted.

A controlled study of the effects of ferric carboxymaltose on bone and haematinic biomarkers in chronic kidney disease and pregnancy.

Background: Intravenous (IV) iron can modulate fibroblast growth factor 23 (FGF23) concentrations and cause transient but significant hypophosphataemia. However, it is unknown what other markers might be involved, especially in different patient groups. This study aimed to determine changes in bone and haematinic biomarkers following IV ferric carboxymaltose (FCM) and to identify risk factors for hypophosphataemia in pregnant subjects and those with chronic kidney disease (CKD). Methods: Changes in bone [serum FGF23, fractional excretion of phosphate urinary fractional excretion of phosphate (FEPi), serum phosphate and serum vitamin D derivatives] and haematinic [plasma hepcidin, serum ferritin and transferrin saturation (TSAT)] biomarkers after 1 g of IV FCM were followed in iron-deficient pregnant and CKD patients and compared with controls (estimated glomerular filtration rate > 60 mL/min/1.73 m2). Data were collected at baseline and up to 42 days after infusion. Risk factors for post-FCM hypophosphataemia were also assessed. Results: Sixty-five subjects completed the study (control, n = 20; pregnant, n = 20; CKD, n = 25). A uniform but variable increase across groups was seen in intact FGF23 (peak Day 2), whereas c-terminal FGF23 varied markedly. Trough serum phosphate timed with the peak FEPi at Day 7, recovering by Day 21 in the pregnant group and Day 42 in other groups. Independent predictors of a low phosphate nadir included baseline phosphate, FEPi and weight-adjusted FCM dose. All groups showed an early and marked increase in plasma hepcidin (peak Day 2), serum ferritin and TSAT (peak Day 7 for both). Conclusions: Changes in bone and haematinic biomarkers differ between patient groups following IV FCM. For patients with lower serum phosphate concentrations, limiting the dose and measuring levels 7 days after administration may mitigate clinically significant hypophosphataemia.

Long-term graft survival in patients with chronic antibody-mediated rejection with persistent peritubular capillaritis treated with intravenous immunoglobulin and rituximab.

Chronic antibody-mediated rejection (cAMR) is the major cause of premature renal allograft loss and is resistant to therapy with 12-month graft failure of up to 50% reported. We examined the duration of graft survival and associates of graft failure in patients with donor-specific antibody-positive cAMR and treatment-resistant peritubular capillaritis between June 2007 and October 2010. Those with advanced interstitial fibrosis (n=5) were excluded. Included patients (n=24) received treatment with high-dose intravenous immunoglobulin and fixed-dose rituximab (500 mg). Compared with previous reports, the study group experienced prolonged graft survival (median 82.1 months). Graft loss was predicted by eGFR and degree of proteinuria at diagnosis but not by donor-specific HLA antibody class or intensity, nor individual or summed Banff scores. Allograft biopsies were further examined for infiltrating leukocyte subtypes and location with high numbers of glomerular leukocytes, particularly macrophages, independently associated with an increased risk of graft failure. This study suggests that patients with cAMR and persistent microcirculatory inflammation, excluding those with advanced histological damage, can expect prolonged graft survival when treated with IVIg and rituximab. Trial level evidence is required to validate this observation. Further examination of the role of macrophages in cAMR is warranted.

Myeloid mineralocorticoid receptor activation contributes to progressive kidney disease.

Clinical and experimental studies have shown that mineralocorticoid receptor (MR) antagonists substantially reduce kidney injury. However, the specific cellular targets and mechanisms by which MR antagonists protect against kidney injury must be identified. We used conditional gene deletion of MR signaling in myeloid cells (MR(flox/flox) LysM(Cre) mice; MyMRKO) or podocytes (MR(flox/flox) Pod(Cre) mice; PodMRKO) to establish the role of MR in these cell types in the development of mouse GN. Accelerated anti-glomerular basement membrane GN was examined in groups of mice: MyMRKO, PodMRKO, wild-type (WT) littermates, and WT mice receiving eplerenone (100 mg/kg twice a day; EPL-treated). At day 15 of disease, WT mice had glomerular crescents (37%±5%), severe proteinuria, and a 6-fold increase in serum cystatin-C. MyMRKO, PodMRKO, and EPL-treated mice with GN displayed proteinuria similar to that in these disease controls. However, MyMRKO and EPL-treated groups had a 35% reduction in serum cystatin-C levels and reduced crescent numbers compared with WT mice, whereas PodMRKO mice were not protected. The protection observed in MyMRKO mice appeared to result predominantly from reduced recruitment of macrophages and neutrophils into the inflamed kidney. Suppression of kidney leukocyte accumulation in MyMRKO mice correlated with reductions in gene expression of proinflammatory molecules (TNF-α, inducible nitric oxide synthase, chemokine (C-C motif) ligand 2, matrix metalloproteinase-12), tubular damage, and renal fibrosis and was similar in EPL-treated mice. In conclusion, MR signaling in myeloid cells, but not podocytes, contributes to the progression of renal injury in mouse GN, and myeloid deficiency of MR provides protection similar to eplerenone in this disease.

Multicentre registry analysis of incremental peritoneal dialysis incidence and associations with patient outcomes.

BACKGROUND: Incremental peritoneal dialysis (PD) is increasingly advocated to reduce treatment burden and costs, with potential to better preserve residual kidney function. Global prevalence of incremental PD use is unknown and use in Australia and New Zealand has not been reported. METHODS: Binational registry analysis including incident adult PD patients in Australia and New Zealand (2007-2017), examining incidence of and outcomes associated with incremental PD (first recorded PD exchange volume <42 L/week (incremental) vs. ≥42 L/week (standard)). RESULTS: Incremental PD use significantly increased from 2.7% of all incident PD in 2007 to 11.1% in 2017 (mean increase 0.84%/year). Duration of incremental PD use was 1 year or less in 67% of cases. Male sex, Aboriginal and Torres Strait Islander (ATSI) or Maori ethnicities, age 45-59 years, medical comorbidities or treatment at a centre with low use of automated PD or icodextrin was associated with lower incidence of incremental PD use. Low body mass index and higher estimated glomerular filtration rate was associated with higher incidence. After accounting for patient and centre variables, commencing PD with an incremental prescription was associated with reduced peritonitis risk (adjusted hazard ratio 0.73, 95% confidence interval (CI) 0.61-0.86).When kidney transplantation and death were considered as competing risks, the association between incremental PD and peritonitis was not significant (sub-hazard ratio [SHR] 0.91, 95%CI 0.71-1.17, p = 0.5), however cumulative incidence of 30-day transfer to haemodialysis was lower in those receiving incremental PD (SHR 0.73, 95%CI 0.56-0.94, p = 0.01). There was no association between incremental PD and death. CONCLUSIONS: Incremental PD use is increasing in Australia and New Zealand and is not associated with patient harm.

Incremental Versus Standard (Full-Dose) Peritoneal Dialysis.

Incremental peritoneal dialysis (PD), defined as less than "standard dose" PD prescription, has a number of possible benefits, including better preservation of residual kidney function (RKF), reduced risk of peritonitis, lower peritoneal glucose exposure, lesser environmental impact, and reduced costs. Patients commencing PD are often new to kidney replacement therapy and possess substantial RKF, which may allow safe delivery of an incremental prescription, often in the form of lower frequency or duration of PD. This has the potential to help improve quality of life (QOL) and life participation through reducing time requirements and burden of treatment. Alternatively, incremental PD could potentially contribute to reduced small solute clearance, fluid overload, or patient reluctance to increase dialysis prescription when later needed. This review discusses the definition, rationale, uptake, potential advantages and disadvantages, and clinical trial evidence pertaining to the use of incremental PD.

Non-Touch Aseptic Technique Maintains Sterility of Antibiotic-Admixed Peritoneal Dialysis Fluid.

There is a paucity of data on the sterility of peritoneal dialysis fluid (PDF) after drug admixture. International Society for Peritoneal Dialysis (ISPD) guidelines suggest using sterile technique when admixing antibiotics; however, the degree of sterility remains unclear. This issue is most pertinent when preparing take-home PDF for outpatient treatment of peritonitis. This study compares the sterility of PDF admixed with antibiotics using a non-touch aseptic technique (NTAT) versus sterile technique.Groups of 8 PDF mixtures (1.5% Dianeal or Icodextrin [Baxter International Inc., Spring Grove, IL, USA]) were admixed with 1 g/L ceftazidime and vancomycin, or 20 mL saline, either by a pharmacist using sterile technique in a sterile suite, or a nurse in a clinical room using NTAT. Dianeal inoculated with 1 × 106 colony-forming units (CFU)/L of coagulase-negative Staphylococcus (CNS), with and without antibiotics, served as positive controls. Admixed PDFs were left at room temperature for 72 hours, then cultured using the BacT/ALERT system. A positive culture by day 5 constituted a contamination. Differences in proportion of contamination between groups were assessed using the Chi-squared test.Eighty PDF bags underwent microbiological testing. Sterility was maintained in all bags, independent of technique (NTAT versus sterile technique), type of PDF (Dianeal versus Icodextrin), or whether antibiotics were admixed. Of the positive controls, CNS-inoculated PDFs without antibiotics were all culture positive; however, when inoculated into antibiotic-admixed PDFs, only S. haemolyticus remained culture-positive (p < 0.0001).In conclusion, PDF sterility can be maintained using NTAT for up to 3 days at room temperature. Currently, there is insufficient evidence to adopt sterile technique in sterile suites when admixing take-home PDF.