Knowledge of natural stone promoters in the urine was previously limited, but is essential to develop new targets for better management of calcium oxalate (CaOx) kidney stones. This work, therefore, unveils such information in the urine of CaOx stone formers (patients with stones). Urinary proteins were fractionated by DEAE/GigaQ anion-exchange chromatography, and individual fractions were subjected to multiple crystal assays. The fractions with the summed crystal-promoting score ≥ 3 were subjected to proteomic analysis using nanoLC-ESI-Qq-TOF tandem mass spectrometry (MS/MS). Almost all of the chromatographic fractions (SFQ1-SFQ9) showed promoting effects on CaOx crystallization, growth, aggregation and crystal-cell adhesion. Among them, SFQ2, SFQ8 and SFQ9 provided the greatest summed crystal-promoting score, implicating their roles in stone promotion. MS/MS successfully identified 12, 38 and 6 proteins in fractions SFQ2, SFQ8 and SFQ9, respectively. Among all proteins identified, CD44 antigen, galectin-3-binding protein, kallikrein-1, and protein AMBP were found in more than one fraction, suggesting that they might serve as candidates for the stone promoters. These findings narrow the gap to better understand the pathogenesis and offer opportunities to define new therapeutic targets for better management of CaOx kidney stones.

Introduction Various urinary parameters are used for determining kidney stone risk. However, almost all of the widely used lithogenic indices rely on urinary concentrations of small molecules/ions and pH. Objective To address whether urinary macromolecules (especially oxidatively modified proteins) also play a critical role in determining the stone risk. Methods Complexed urinary proteins (proteome) were purified from healthy individuals and calcium oxalate (CaOx) stone formers and performed various crystal assays and quantitative proteomics to compare them. Bioinformatic analyses were performed to gain additional insights, and the obtained data were verified by ELISA. Results While the normal urinary proteome inhibited CaOx stone-forming mechanisms (i.e., crystallization, growth and aggregation), the stone formers’ urinary proteome promoted all these CaOx crystal parameters. Descriptive proteomics by nanoLC-ESI-LTQ-Orbitrap-MS/MS analysis identified 203 and 381 proteins in the urine of healthy individuals and stone formers, respectively. Analyses of physicochemical properties revealed only molecular mass and isoelectric point that slightly increased in the stone formers’ urine, whereas instability index, grand average of hydrophathicity (GRAVY) and amino acid composition were comparable. Interestingly, proportion of oxidatively modified proteins (particularly those with methionine oxidation, methionine dioxidation and cysteine trioxidation) markedly increased (∼2.5-fold) in the stone formers’ urine. Quantitative proteomics revealed 89 increased and 56 decreased proteins in the stone formers’ urine. The oxidized proteins had a greater proportion (>3-fold) in the increased proteins (77 %) compared with the decreased ones (23 %), whereas the non-oxidized proteins showed comparable proportions (54 % and 46 %, respectively). Functional enrichment analyses revealed a correlation between the increased proteins and oxidative stress biological processes and molecular functions. Finally, ELISA confirmed the significantly increased levels of oxidized proteins in the stone formers’ urine compared with that of healthy individuals. Conclusion These data implicate that oxidatively modified proteome serves as a key pathogenic factor or risk for CaOx kidney stone formation.

Background A single dose of intraperitoneal (IP) meropenem is recommended for peritoneal-dialysis (PD)-related peritonitis stemming from extended-spectrum β-lactamase-producing organisms. However, data on IP meropenem is limited. Methods This prospective, descriptive study was conducted to examine plasma and dialysate meropenem levels during continuous IP meropenem administration in five patients with PD-related peritonitis. All patients received an IP meropenem loading dose of 500 mg, followed by IP meropenem at 125 mg/L, with four exchanges daily. The plasma and dialysate meropenem concentrations were measured at specified intervals for a 24-hour period utilizing a high-performance, liquid chromatography method. Results Five patients with PD related peritonitis were studied. The mean-maximum dialysate and plasma meropenem levels were 158.1 mg/L (standard deviation [SD] ± 62.9) and 29.4 mg/L (SD ± 15.9), respectively. The mean dialysate meropenem level was at its minimum of 32.6 mg/L (SD ± 19.1) at 24 hours. Throughout the period, the dialysate meropenem levels exceeded the minimal inhibitory concentration of the pathogenic resistance organism (> 8 mg/L). Four patients responded to the treatment, whereas one developed treatment failure from fungal peritonitis. Conclusion An IP meropenem loading of 500 mg, followed by 125 mg/L every 6 hours, provided an adequate dialysate meropenem concentration and is an effective treatment for PD related peritonitis. Trial registration Thai Clinical Trials Registry (TCTR20191121002) with date of first registration at 21/11/2019 (retrospectively registered).

Given the lack of cost-effectiveness information, continuous ambulatory peritoneal dialysis (CAPD) with icodextrin (CAPD+ICO) has not yet been included in the Universal Health Coverage (UHC) scheme. This study aimed to evaluate the cost-utility of dialysis treatments for end-stage renal disease (ESRD) patients with fluid and sodium overload, comparing CAPD+ICO and automated peritoneal dialysis (APD) against glucose-based CAPD. A Markov model was applied to evaluate lifetime costs and health outcomes from a societal perspective. Data, including transitional probabilities, direct medical and non-medical costs, and utilities, were collected from randomized controlled trials conducted across 16 hospitals in various regions of Thailand. Compared to glucose-based CAPD, the incremental cost-effectiveness ratio (ICER) for CAPD+ICO was 908,440 THB (26,082 USD) per quality-adjusted life year (QALY) gained, while APD was dominated, incurring higher costs and yielding fewer QALYs. The results indicated that glucose-based CAPD had a 90% probability of being the most cost-effective option from a societal perspective, based on Thailand’s willingness-to-pay (WTP) threshold of 160,000 THB (4,603 USD) per QALY gained. Therefore, CAPD+ICO is not considered a good value for money, requiring an additional annual budget of approximately 58 million THB (2 million USD). These findings provide important economic evaluation evidence to support policy decision-making alongside clinical effectiveness and equity considerations in guiding future UHC benefit package decisions for dialysis modalities among ESRD patients with fluid and sodium overload in Thailand.

Urinary proteins have crucial roles in modulating kidney stone formation. While stone-inhibiting urinary proteins are well characterized, stone-promoting urinary proteins are insufficiently explored. This knowledge gap limits our ability to fully comprehend the pathogenic mechanisms underlying nephrolithiasis and hampers the development of targeted therapeutic/preventive interventions. Therefore, we systematically identified stone-promoting proteins from the urine of 30 calcium oxalate (CaOx) nephrolithiatic patients (stone formers). Urinary proteins were fractionated by anion exchange and size-exclusion chromatography. A total of 15 protein fractions (SF1-SF15) were tested for their modulating activities on CaOx crystals by various assays compared with the control. The fractions with net CaOx-promoting activities were then identified by nanoLC-ESI-Qq-TOF MS/MS. From 15 fractions, 9 had net CaOx-promoting activities in all crystal assays. Among 3-99 proteins identified from these fractions, alpha-1acid glycoprotein 2, alpha-1-antitrypsin, apolipoprotein D, CD44 antigen, endosialin, fibrinogen alpha chain, interleukin-18-binding protein, kallikrein-1, retinol-binding protein 4, and titin have been found to increase in the urine of stone formers compared with controls, reinforcing their potential roles as CaOx stone promoters. This study offers the largest collection of CaOx stone-promoting proteins that will shed light on pathogenic mechanisms of nephrolithiasis and may allow further development of new drug targets to treat/prevent nephrolithiasis.

Peritonitis is a common cause of morbidity and mortality in patients undergoing peritoneal dialysis (PD). Early diagnosis of PDRP can reduce mortality and improve PD outcomes. H-NGAL, produced by activated neutrophils, is present in the peritoneal dialysis effluent (PDE) of PDRP patients and may serve as a reliable marker for peritonitis. This study aims to determine the lowest neutrophil count detectable by the H-NGAL point-of-care test (POCT) and to evaluate the influence of time, temperature, and other factors on its performance. Eighteen patients diagnosed with PDRP (according to the International Society for Peritoneal Dialysis [ISPD] guidelines) were enrolled in the study. Age, sex, diabetes status, peritoneal dialysis (PD) modality, symptoms-to-hospital arrival time (SH), symptoms-to-laboratory arrival time (SL), and symptoms-to-treatment time (ST) were recorded. Peritoneal dialysis effluent (PDE) samples were analyzed for white cell count (WCC), differentiation, and culture. The H-NGAL point-of-care test (POCT) was performed on PDE samples collected from home and hospital settings upon patient arrival. Hospital-collected PDE samples were serially diluted to approximate WCC concentrations of 200, 100, 50, 25, 12, 6, and 3 cells/μL and tested using the H-NGAL POCT at baseline (Time 0, T0) under room temperature (RT, 22.0–24.9°C) conditions. The last two positive tubes and the first two negative tubes were incubated at RT, 35°C, 40°C, and 45°C for 1 hour (T1), 2 hours (T2), and 12 hours (T12). The minimum white cell and neutrophil counts required to yield a positive H-NGAL POCT result (MWCP and MNCP, respectively) at T0 under RT conditions were set as reference values. The correlation and differences between MNCPs at different time points and temperatures and the above clinical factors were analyzed and compared to the MNCP at T0 under RT conditions. The median (Q25, Q75) white cell count and percentage of neutrophils in the PDE samples were 1,269 (592, 4,604) cells/μL and 90% (91%, 97%), respectively. All undiluted PDE samples (from home and hospital settings) tested positive using the H-NGAL POCT. The median (Q25, Q75, range) MWCP, consisting of 100% neutrophils and representing the MNCP, was 9 (5, 19; 3–22) cells/μL at T0 under RT conditions. The MNCP decreased after 12 hours, with a statistically significant reduction (P = 0.021 and P = 0.028, respectively) at T2 and T12 when incubated at 45°C, compared to the MNCP at T0 under RT conditions (Table 1). No statistically significant associations were found between MNCP and age, diabetes status, WCC, bacterial type causing peritonitis, ST, SH, SL time, or PD modality. The H-NGAL POCT is a highly sensitive diagnostic tool capable of detecting PDRP at very low neutrophil counts. Its sensitivity is influenced by incubation time and temperature.

The small solute clearances in peritoneal dialysis (PD) depend on dwell time and daily dialysate volume. The objective of our study was to identify the optimal dwell time that reflects the dialysate flow rate producing maximal small solute clearances and solute removal rates in peritoneal dialysis.

Kidney stone disease (KSD) is a prevalent and complex condition, with an incidence of 85 cases per 100,000 individuals in Thailand. Notably, over 40

Background. The effectiveness of tixagevimab-cilgavimab as pre-exposure prophylaxis (PrEP) against breakthrough coronavirus disease 2019 (COVID-19) in dialysis patients remains uncertain due to limited data. Methods. In this multicenter prospective study, we enrolled vaccinated dialysis patients and divided them into two groups: a tixagevimab-cilgavimab group ( received a 150 mg/150 mg intramuscular dose of tixagevimab-cilgavimab) and a control group ( age-matched patients not receiving tixagevimab-cilgavimab). The primary outcome was the breakthrough COVID-19 rate at 6 months, whereas secondary outcomes included COVID-19-related hospitalization, intensive care unit admission, endotracheal intubation and mortality. The safety of tixagevimab-cilgavimab was assessed. Results. Two hundred participants were enrolled, with equal numbers in each group ( n = 100 each) . Baseline characteristics were comparable between groups, except for a higher number of COVID-19 vaccine doses in the tixagevimab-cilgavimab group [median (IQR) 4 ( 3-5) vs. 3 ( 3-4) ; P = .01]. At 6 months, the breakthrough COVID-19 rates were comparable between the tixagevimab-cilgavimab ( 17%) and control ( 15%) groups ( P = .66) . However, the median (IQR) time to diagnosis of breakthrough infections tended to be longer in the tixagevimab-cilgavimab group [4.49 ( 2.81-4.98) vs 1.96 ( 1.65-2.91) months; P = .08]. Tixagevimab-cilgavimab significantly reduced COVID-19-related hospitalization rates ( 5.9% vs 40.0%; P = .02) among participants with breakthrough infections. All tixagevimab-cilgavimab-related adverse events were mild. Conclusion. The use of tixagevimab-cilgavimab as PrEP in vaccinated dialysis patients during the Omicron surge did not prevent breakthrough infections but significantly reduced COVID-19-related hospitalizations. Further research should prioritize alternative strategies.

BACKGROUND:Patient-reported outcome measures (PROMs) are widely recognized as valuable predictors of clinical outcomes in peritoneal dialysis (PD). Our study aimed to explore the connections between patient-reported constipation and clinical outcomes.METHODS:We assessed constipation in patients across 22 facilities participating in the Thailand Peritoneal Dialysis Outcomes and Practice Patterns Study (PDOPPS) from 2014 to 2017. Constipation diagnosis utilized objective assessment tools such as the Bristol stool form scale (BSFS) and a self-reported questionnaire known as the constipation severity score (CSS). The BSFS is a 7-level scale that visually inspects feces based on texture and morphology, while the CSS measures constipation duration and severity using a 5-point Likert scale for various factors. We employed Cox proportional hazards model regression to determine the associations between constipation and clinical outcomes, including mortality, hemodialysis (HD) transfer and peritonitis.RESULTS:Among 975 randomly selected PD patients from 22 facilities, 845 provided written informed consent, and 729 completed CSS questionnaire. Constipation was prevalent in the PD population (13%), particularly among older patients, those who were caregiver dependent, had diabetes and poorer nutritional status (indicated by lower time-averaged serum albumin, potassium, creatinine and phosphate concentrations). Twenty-seven percent of which experiencing symptoms of constipation for over a year. Notably, self-reported constipation at baseline was significantly associated with a shorter time to first peritonitis and higher rates of peritonitis and death. However, no significant association was found between constipation and HD transfer after adjusting for various factors, including age, gender, PD vintage, comorbidities, shared frailty by study sites and serum albumin.CONCLUSION:Patient-reported constipation independently correlated with increased risks of peritonitis and all-cause mortality, though no such correlation was observed with HD transfer. These findings underscore the need for further investigation to identify effective interventions for constipation in PD patients.

AimTo assess whether the peritoneal dialysis (PD) centres included in the Peritoneal Dialysis Outcomes and Practise Patterns Study (PDOPPS) in Thailand are representative of other PD centres in the country, based on 8 key performance indicators (KPIs 1-8). MethodsA retrospective analysis was conducted comparing PD-related clinical outcomes between PD centres included in the PDOPPS (the PDOPPS group) and those not included (the non-PDOPPS group) from January 2018 to December 2019. Logistic regression analysis was used to identify predictors associated with achieving the target KPIs. ResultsOf 181 PD centres, 22 (12%) were included in the PDOPPS. PD centres in the PDOPPS group were larger and tended to serve more PD patients than those in the non-PDOPPS group. However, the process and outcome KPIs (KPIs 1-8) were comparable between the 2 groups. Large hospitals (& GE;120 beds), providing care to & GE;100 PD cases and having experience for >10 years were independent predictors of achieving the peritonitis rate target of <0.5 episodes/year. Most PD centres in Thailand showed weaknesses in off-target haemoglobin levels and culture-negative peritonitis rate. ConclusionsThe PD centres included in Thai PDOPPS were found to be representative of other PD centres in Thailand in terms of clinical outcomes. Thus, Thai PDOPPS findings may apply to the broader PD population in Thailand.

Distal renal tubular acidosis (dRTA), a disease characterized by the failure of the distal nephron to secrete acid into the urine, can be caused by mutations in SLC4A1 gene encoding erythroid and kidney anion exchanger 1 (AE1). Here, an induced pluripotent stem cell (iPSC) line was generated from a patient with dRTA and hemolytic anemia carrying compound heterozygous SLC4A1 mutations containing c.1199_1225del (p.Ala400_Ala408del), resulting in Southeast Asian ovalocytosis (SAO), and c.1331C>A (p.Thr444Asn). Peripheral blood mononuclear cells (PBMCs) were reprogrammed using Sendai viral reprogramming. The established iPSC line, MUSIi019-A, exhibited pluripotent property and retained the same mutations observed in the patients.

Introduction: Mortality following hemodialysis initiation may influence the decision to initiate hemodialysis in elderly patients. Our objective is to demonstrate mortality following hemodialysis initiation in elderly patients (≥70 years) and to derive a prediction risk score based on clinical and laboratory indicators to determine risk of all-cause mortality in patients aged ≥80 years. Methods: We identified elderly patients (≥70 years) who initiated maintenance hemodialysis between January 2005 and December 2016 using data from the Thai Renal Replacement Therapy (TRT) registry. The mortality rate was determined based on age categories. A predictive risk score for all-cause mortality was created for 4,451 patients aged ≥80 years by using demographics, laboratory values, and interview-based parameters. Using a flexible parametric survival analysis, we predicted mortality 3 months, 6 months, 1 year, 5 years, and 10 years after hemodialysis initiation. Results: 17,354 patients (≥70 years) were included, mean age 76.9 ± 5.1 years, 46.5% male, and 6,309 (36.4%) died. Patients aged <80 years had a median survival time of 110.6 months. A 9-point risk score was developed to predict mortality in patients aged ≥80 years: age >85 years, male, body mass index <18.5 kg/m2, hemoglobin <10.0 g/dL, albumin <3.5 g/dL, substantial assistance required in daily living (1 point each), and Karnofsky Performance Status (KPS) score <50 (3 points). C-statistic of 0.797 indicated high model discrimination. Internal validation demonstrated good agreement between observed and anticipated mortalities. Conclusions: Hemodialysis is appropriate for patients aged 70–80 years. A risk score for mortality in patients aged ≥80 years has been developed. The score is based on seven readily obtainable and evaluable clinical characteristics.

Introduction We sought to evaluate the predictors and outcomes of mold peritonitis in patients with peritoneal dialysis (PD). Methods This cohort study included PD patients from the MycoPDICS database who had fungal peritonitis between July 2015-June 2020. Patient outcomes were analyzed by Kaplan Meier curves and the Log-rank test. Multivariable Cox proportional hazards model regression was used to estimating associations between fungal types and patients’ outcomes. Results The study included 304 fungal peritonitis episodes (yeasts n = 129, hyaline molds n = 122, non-hyaline molds n = 44, and mixed fungi n = 9) in 303 patients. Fungal infections were common during the wet season (p <0.001). Mold peritonitis was significantly more frequent in patients with higher hemoglobin levels, presentations with catheter problems, and positive galactomannan (a fungal cell wall component) tests. Patient survival rates were lowest for non-hyaline mold peritonitis. A higher hazard of death was significantly associated with leaving the catheter in-situ (adjusted hazard ratio [HR] = 6.15, 95%confidence interval [CI]: 2.86–13.23) or delaying catheter removal after the diagnosis of fungal peritonitis (HR = 1.56, 95%CI: 1.00–2.44), as well as not receiving antifungal treatment (HR = 2.23, 95%CI: 1.25–4.01) or receiving it for less than 2 weeks (HR = 2.13, 95%CI: 1.33–3.43). Each additional day of antifungal therapy beyond the minimum 14-day duration was associated with a 2% lower risk of death (HR = 0.98, 95%CI: 0.95–0.999). Conclusion Non-hyaline-mold peritonitis had worse survival. Longer duration and higher daily dosage of antifungal treatment were associated with better survival. Deviations from the 2016 ISPD Peritonitis Guideline recommendations concerning treatment duration and catheter removal timing were independently associated with higher mortality.

Background Spiritual well-being (SWB), an individual's understanding of the meaning and purpose of life, may help patients with chronic or terminal illnesses cope with their diseases. This study aimed to assess SWB in patients on peritoneal dialysis (PD), as well as its relationship with patient characteristics and patient-reported outcomes (PRO). Methods The data were obtained from questionnaires that formed part of the PD Outcomes and Practice Patterns Study (PDOPPS). Measures used in this study were SWB scores derived from the WHO quality of life, spirituality, religiousness and personal beliefs (WHOQOL-SRPB) tool including 32 items from eight facets; physical (PCS) and mental component summary (MCS) scores of the 12-Item Short-Form Health Survey (SF-12), Center of Epidemiologic Studies Depression Scale-10 (CES-D-10) scores, burden of kidney disease scores and functional status scores. Results Overall, 529 out of 848 participants (62%) completely responded to the questionnaires and were included in the analysis. Over two-thirds of PD patients (70%) had moderate or higher SWB scores. The SWB scores were significantly lower in patients with age >65 years and unemployed status. SWB scores positively correlated with higher PCS, MCS, burden of kidney disease scores and functional status scores, while negatively correlated with depression scores by CES-D-10 scale. Patients who reported significant depressive symptoms (CES-D-10 score >= 10) had significantly lower SWB scores. Conclusion Better SWB was significantly associated with better health-related QOL (HRQOL) and the absence of depressive symptoms. SWB may be an essential consideration in the delivery of high-quality PD.