A population-based study on the incidence and aetiology of infectious complications in peritoneal dialysis in South Sweden.

BACKGROUND: Peritonitis is a major cause of morbidity in peritoneal dialysis (PD) and an independent risk factor for elevated all-cause mortality. The aims of this study were to report the incidence, trend, aetiology, and antimicrobial susceptibility of PD-associated peritonitis and catheter-related infections in South Sweden between 2011-2020. METHODS: This population-based observational cohort study included all patients with PD between the years 2011-2020 in the county of Skåne. Data was accessed through the Swedish Renal Registry and the Department of Clinical Microbiology in Lund. Definitions issued by the International Society for Peritoneal Dialysis were implemented to assess PD-associated infections. RESULTS: Medical records of 675 paediatric and adult PD patients were eligible for inclusion. Of those, 208 (31%) were female and the median age was 67 years (range 0-91). The overall rate of PD-peritonitis was 0.38 episodes per year at risk. Out of 484 episodes of peritonitis, 61% (n = 295) were caused by Gram-positive bacteria. There were 289 occurrences of exit site infections, of which most (n = 152, 53%) were Gram-positive. Tunnel infections occurred in 16 episodes and were caused by S. aureus or P. aeruginosa. Among all isolates, 37 were of MRSE, four of ESBL-producing E. coli, and one of MRSA. CONCLUSION: The crude rate of PD-peritonitis was stable during the study period. Gram-positive bacteria dominated the microbial aetiology, and antibiotic resistance was limited. It is important to monitor the aetiology, incidence, and resistance rates in PD-associated infections, to base empirical antibiotic regimens and facilitate prevention.

Effects of Steady Glucose Concentration Peritoneal Dialysis on Ultrafiltration Volume and Sodium Removal: A Pilot Crossover Trial.

BACKGROUND: Volume overload is common in patients treated with peritoneal dialysis (PD) and is associated with poor clinical outcome. Steady concentration PD is where a continuous glucose infusion maintains the intraperitoneal glucose concentration and as a result provides continuous ultrafiltration throughout the dwell. The primary objective of this study was to investigate the ultrafiltration rate and glucose ultrafiltration efficiency for steady concentration PD in comparison with a standard continuous ambulatory PD (CAPD) dwell, using the novel Carry Life UF device. METHODS: Eight stable patients treated with PD (six fast and two fast average transporters) were investigated four times: a standard 4-hour CAPD dwell with 2 L of 2.5% dextrose solution as control and three 5-hour steady concentration PD treatments (glucose dose 11, 14, 20 g/h, initial fill 1.5 L of 1.5% dextrose solution). All investigations were preceded by an overnight 2 L 7.5% icodextrin dwell. RESULTS: Intraperitoneal glucose concentration increased during the first 1-2 hours of the steady concentration PD treatments and remained stable thereafter. Ultrafiltration rates were significantly higher with steady concentration PD treatments (124±49, 146±63, and 168±78 mL/h with 11, 14, and 20 g/h, respectively, versus 40±60 mL/h with the control dwell). Sodium removal and glucose ultrafiltration efficiency (ultrafiltration volume/gram glucose uptake) were significantly higher with steady concentration PD treatments versus the control dwell, where the 11 g/h glucose dose was most efficient. CONCLUSIONS: Steady concentration PD performed with the Carry Life UF device resulted in higher ultrafiltration rates, more efficient use of glucose (increased ultrafiltration volume/gram glucose absorbed), and greater sodium removal compared with a standard 2.5% dextrose CAPD dwell. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: A Performance Analysis of the Peritoneal Ultrafiltration (PUF) Achieved With the Carry Life ® UF, NCT03724682 .

Dual SGLT1/SGLT2 inhibitor phlorizin reduces glucose transport in experimental peritoneal dialysis.

INTRODUCTION: Glucose absorption during peritoneal dialysis (PD) is commonly assumed to occur via paracellular pathways. We recently showed that SGLT2 inhibition did not reduce glucose absorption in experimental PD, but the potential role of glucose transport into cells is still unclear. Here we sought to elucidate the effects of phlorizin, a non-selective competitive inhibitor of sodium glucose co-transporters 1 and 2 (SGLT1 and SGLT2), in an experimental rat model of PD. METHODS: A 120-min PD dwell was performed in 12 anesthetised Sprague-Dawley rats using 1.5% glucose fluid with a fill volume of 20 mL with (n = 6) or without (n = 6) intraperitoneal phlorizin (50 mg/L). Several parameters for peritoneal water and solute transport were monitored during the treatment. RESULTS: Phlorizin markedly increased the urinary excretion of glucose, lowered plasma glucose and increased plasma creatinine after PD. Median glucose diffusion capacity at 60 min was significantly lower (p < 0.05) being 196 µL/min (IQR 178-213) for phlorizin-treated animals compared to 238 µL/min (IQR 233-268) in controls. Median fractional dialysate glucose concentration at 60 min (D/D 0) was significantly higher (p < 0.05) in phlorizin-treated animals being 0.65 (IQR 0.63-0.67) compared to 0.61 (IQR 0.60-0.62) in controls. At 120 min, there was no difference in solute or water transport across the peritoneal membrane. CONCLUSION: Our findings indicate that a part of glucose absorption during the initial part of the dwell occurs via transport into peritoneal cells.

Phloretin Improves Ultrafiltration and Reduces Glucose Absorption during Peritoneal Dialysis in Rats.

BACKGROUND: Harmful glucose exposure and absorption remain major limitations of peritoneal dialysis (PD). We previously showed that inhibition of sodium glucose cotransporter 2 did not affect glucose transport during PD in rats. However, more recently, we found that phlorizin, a dual blocker of sodium glucose cotransporters 1 and 2, reduces glucose diffusion in PD. Therefore, either inhibiting sodium glucose cotransporter 1 or blocking facilitative glucose channels by phlorizin metabolite phloretin would reduce glucose transport in PD. METHODS: We tested a selective blocker of sodium glucose cotransporter 1, mizagliflozin, as well as phloretin, a nonselective blocker of facilitative glucose channels, in an anesthetized Sprague-Dawley rat model of PD. RESULTS: Intraperitoneal phloretin treatment reduced glucose absorption by >30% and resulted in a >50% higher ultrafiltration rate compared with control animals. Sodium removal and sodium clearances were similarly improved, whereas the amount of ultrafiltration per millimole of sodium removed did not differ. Mizagliflozin did not influence glucose transport or osmotic water transport. CONCLUSIONS: Taken together, our results and previous results indicate that blockers of facilitative glucose channels may be a promising target for reducing glucose absorption and improving ultrafiltration efficiency in PD.

SGLT2 inhibition does not reduce glucose absorption during experimental peritoneal dialysis.

INTRODUCTION: Unwanted glucose absorption during peritoneal dialysis (PD) remains a clinical challenge, especially in diabetic patients. Recent experimental data indicated that inhibitors of the sodium and glucose co-transporter (SGLT)-2 could act to reduce glucose uptake during PD, which raises the question of whether glucose absorption may also occur via intracellular or trans-cellular pathways. METHODS: We performed PD in anesthetized Sprague-Dawley rats using a fill volume of 20 mL with either 1.5% glucose fluid or 4.25% glucose fluid for 120 min dwell time to evaluate the effects of SGLT2 inhibition by empagliflozin on peritoneal water and solute transport. To assess the diffusion capacity of glucose, we developed a modified equation to measure small solute diffusion capacity, taking convective- and free water transport into account. RESULTS: SGLT2 inhibition markedly increased the urinary excretion of glucose and lowered plasma glucose after PD compared to sham groups. Glucose absorption for 1.5% glucose was 165 mg 95% CI (145-178) in sham animals and 157 mg 95% CI (137-172) for empagliflozin-treated animals. For 4.25% glucose, absorption of glucose was 474 mg 95% CI (425-494) and 472 mg 95% CI (420-506) for sham and empagliflozin groups, respectively. No significant changes in the transport of sodium or water across the peritoneal barrier could be detected. CONCLUSION: We could not confirm recent findings that SGLT2 inhibition reduced glucose absorption and increased osmotic water transport during experimental PD.

Novel Method for Osmotic Conductance to Glucose in Peritoneal Dialysis.

INTRODUCTION: The osmotic conductance to glucose (OCG) is a crucial determinant of ultrafiltration (UF) in peritoneal dialysis (PD) patients and can be used to monitor membrane integrity in patients on long-term PD. It has been proposed that OCG can be assessed based on drained volumes in 2 consecutive 1-hour glucose dwells, usually 1.5% and 4.25% glucose, in a so-called double mini-peritoneal equilibration test (dm-PET). However, recent data indicated that the dm-PET provides a poor estimate of OCG unless the residual volume (RV) is taken into account. We introduce an easy, robust, and accurate method to measure OCG and compare it with conventional methods. METHODS: In a prospective cohort of 21 PD patients, a modified version of the dm-PET was performed, along with the determination of RV before, between, and after dwells. Based on computer simulations derived from the 3-pore model (TPM) for membrane permeability, we developed and validated a novel single-dwell method to estimate OCG. We next validated the equation in an independent cohort consisting of 32 PD patients. RESULTS: Single-dwell OCG correlated more closely with actual UF (r = 0.94 vs. r = 0.07 for conventional dm-PET), sodium sieving, and free water transport (FWT) compared with other methods. These findings were replicated in the validation cohort in which OCG calculated using the single-dwell method closely correlated with parameters of osmotic water transport, even when RV was not taken into account, using only drained volumes. CONCLUSION: We propose a novel, easy, and robust single-dwell method to determine OCG in individual patients and to monitor membrane integrity over time on PD.