Ultrastructure expansion microscopy (U-ExM) of mouse and human kidneys for analysis of subcellular structures.

Ultrastructure expansion microscopy (U-ExM) involves the physical magnification of specimens embedded in hydrogels, which allows for super-resolution imaging of subcellular structures using a conventional diffraction-limited microscope. Methods for expansion microscopy exist for several organisms, organs, and cell types, and used to analyze cellular organelles and substructures in nanoscale resolution. Here, we describe a simple step-by-step U-ExM protocol for the expansion, immunostaining, imaging, and analysis of cytoskeletal and organellar structures in kidney tissue. We detail the critical modified steps to optimize isotropic kidney tissue expansion, and preservation of the renal cell structures of interest. We demonstrate the utility of the approach using several markers of renal cell types, centrioles, cilia, the extracellular matrix, and other cytoskeletal elements. Finally, we show that the approach works well on mouse and human kidney samples that were preserved using different fixation and embedding conditions. Overall, this protocol provides a simple and cost-effective approach to analyze both preclinical and clinical renal samples in high detail, using conventional lab supplies and standard widefield or confocal microscopy.

Alport syndrome and Alport kidney diseases - elucidating the disease spectrum.

PURPOSE OF REVIEW: With the latest classification, variants in three collagen IV genes, COL4A3 , COL4A4 , and COL4A5 , represent the most prevalent genetic kidney disease in humans, exhibiting diverse, complex, and inconsistent clinical manifestations. This review breaks down the disease spectrum and genotype-phenotype correlations of kidney diseases linked to genetic variants in these genes and distinguishes "classic" Alport syndrome (AS) from the less severe nonsyndromic genetically related nephropathies that we suggest be called "Alport kidney diseases". RECENT FINDINGS: Several research studies have focused on the genotype-phenotype correlation under the latest classification scheme of AS. The historic diagnoses of "benign familial hematuria" and "thin basement membrane nephropathy" linked to heterozygous variants in COL4A3 or COL4A4 are suggested to be obsolete, but instead classified as autosomal AS by recent expert consensus due to a significant risk of disease progression. SUMMARY: The concept of Alport kidney disease extends beyond classic AS. Patients carrying pathogenic variants in any one of the COL4A3/A4/A5 genes can have variable phenotypes ranging from completely normal/clinically unrecognizable, hematuria without or with proteinuria, or progression to chronic kidney disease and kidney failure, depending on sex, genotype, and interplays of other genetic as well as environmental factors.

A Case of Congenital Nephrotic Syndrome with Crescents Caused by a Novel Compound Heterozygous Pairing of NPHS1 Genetic Variants.

Congenital nephrotic syndrome is an autosomal recessive inherited disorder that manifests as steroid-resistant massive proteinuria in the first three months of life. Defects in the glomerular filtration mechanism are the primary etiology. We present a child who developed severe nephrotic syndrome at two weeks of age and eventually required a bilateral nephrectomy. Genetic testing revealed compound heterozygous variants in NPHS1 including a known pathogenic variant and a missense variant of uncertain significance. Light microscopy revealed crescent formation-an atypical finding in congenital nephrotic syndrome caused by nephrin variants-in addition to focal segmental and global glomerulosclerosis. Electron microscopy showed diffuse podocyte foot process effacement. Confocal and Airyscan immunofluorescence microcopy showed aggregation of nephrin in the podocyte cell body that is not a result of diffuse podocyte foot process effacement as seen in minimal change disease. These findings confirm the novel variant as pathogenic.

Quantitative assessment of glomerular basement membrane collagen IV α chains in paraffin sections from patients with focal segmental glomerulosclerosis and Alport gene variants.

Focal segmental glomerulosclerosis (FSGS) lesions have been linked to variants in COL4A3/A4/A5 genes, which are also mutated in Alport syndrome. Although it could be useful for diagnosis, quantitative evaluation of glomerular basement membrane (GBM) type IV collagen (colIV) networks is not widely used to assess these patients. To do so, we developed immunofluorescence imaging for collagen α5(IV) and α1/2(IV) on kidney paraffin sections with Airyscan confocal microscopy that clearly distinguishes GBM collagen α3α4α5(IV) and α1α1α2(IV) as two distinct layers, allowing quantitative assessment of both colIV networks. The ratios of collagen α5(IV):α1/2(IV) mean fluorescence intensities (α5:α1/2 intensity ratios) and thicknesses (α5:α1/2 thickness ratios) were calculated to represent the levels of collagen α3α4α5(IV) relative to α1α1α2(IV). The α5:α1/2 intensity and thickness ratios were comparable across all 11 control samples, while both ratios were significantly and markedly decreased in all patients with pathogenic or likely pathogenic Alport COL4A variants, supporting validity of this approach. Thus, with further validation of this technique, quantitative measurement of GBM colIV subtype abundance by immunofluorescence, may potentially serve to identify the subgroup of patients with FSGS lesions likely to harbor pathogenic COL4A variants who could benefit from genetic testing.

Ultrastructure expansion microscopy (U-ExM) of mouse and human kidneys for analysis of subcellular structures.

Ultrastructure expansion microscopy (U-ExM) involves the physical magnification of specimens embedded in hydrogels, which allows for super-resolution imaging of subcellular structures using a conventional diffraction-limited microscope. Methods for expansion microscopy exist for several organisms, organs, and cell types, and used to analyze cellular organelles and substructures in nanoscale resolution. Here, we describe a simple step-by-step U-ExM protocol for the expansion, immunostaining, imaging, and analysis of cytoskeletal and organellar structures in kidney tissue. We detail the critical modified steps to optimize isotropic kidney tissue expansion, and preservation of the renal cell structures of interest. We demonstrate the utility of the approach using several markers of renal cell types, centrioles, cilia, the extracellular matrix, and other cytoskeletal elements. Finally, we show that the approach works well on mouse and human kidney samples that were preserved using different fixation and storage conditions. Overall, this protocol provides a simple and cost-effective approach to analyze both pre-clinical and clinical renal samples in high detail, using conventional lab supplies and standard widefield or confocal microscopy.

Serum Galactomannan: A Predictor of Poor Outcomes in Peritoneal Dialysis Patients With Fungal Peritonitis.

Introduction: The potential value of serum galactomannan index (GMI) in monitoring treatment response in patients with fungal peritonitis who are receiving peritoneal dialysis (PD) was assessed in the present study. Methods: The study included all Thailand fungal PD-related infectious complications surveillance (MycoPDICS) DATA study participants who had timely PD catheter removal and availability of both baseline and ≥2 subsequent serum GMI measurements after starting antifungal therapy (if available). Serum GMI was assessed by direct double-sandwich enzyme-linked immunosorbent assay with reference to positive and negative control samples. Comparisons of categorical variables among groups were analyzed by Fisher's exact test for categorical data and the Wilcoxon rank-sum test for continuous variables. Mortality outcomes were analyzed by survival analyses using Kaplan-Meier curves with Log-rank test. Results: Seventy-six (46%) of 166 participants from 21 PD centers between 2018 and 2022 were included. The median age was 58 (50-65) years, and a half of the patients (50%) had type II diabetes. Nineteen (25%) and 57 (75%) episodes were caused by yeast and mold, respectively. Death occurred in 11 (14%) patients at 3 months, and no differences were observed in demographics, laboratories, treatment characteristics, or in baseline serum GMI between those who died and those who survived. Serum GMI progressively declined over the follow-up period after the completion of treatment. Patients who died had significantly higher posttreatment serum GMI levels and were more likely to have positive GMI after treatment. Conclusion: Serum GMI is an excellent biomarker for risk stratification and treatment response monitoring in patients on PD with fungal peritonitis.

Effect of canagliflozin in non-diabetic obese patients with albuminuria: A randomized, double-blind, placebo-controlled trial.

BACKGROUND: Sodium-glucose co-transporter 2 inhibitor (SGLT2i) has been shown to improve renal outcomes in both diabetic and non-diabetic kidney disease. However, the effect of SGLT2i on renal outcomes in patients with non-diabetic obesity is still not established. MATERIALS AND METHODS: In this double-blind, randomized controlled trial, we assigned non-diabetic patients with body mass index (BMI) ≥ 25 kg/m2, persistent 24-hour urine albumin-creatinine ratio (UACR) ≥ 10 mg/gCr, and estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73m2, who had been treated with renin-angiotensin system blockade, to canagliflozin 100 mg daily or placebo for 24 weeks. The reduction in UACR and eGFR at 12 and 24 weeks were explored. (Thai Clinical Trials Registry 20190203003). RESULTS: Of 247 non-diabetic obese patients screened, 32 patients met inclusion criteria and underwent randomization. The median baseline of UACR was 69.1 mg/gCr. There were no statistically significant differences in albuminuria reduction between the groups at 12 weeks and 24 weeks. The estimated GFR in the canagliflozin group decreased significantly from baseline at 12 weeks (-5.39 mL/min/1.73m2; 95% CI -9.81 to -0.97; p = 0.017) but not at 24 weeks (-1.16 mL/min/1.73m2; 95% CI -5.58 to 3.26; p = 0.66), and there was no significant change from baseline in the placebo group at both 12 and 24 weeks. CONCLUSION: Canagliflozin 100 mg daily was well tolerated but did not significantly reduce UACR in non-diabetic obese patients with microalbuminuria. However, a significant temporary decline in eGFR might reflect a subtle reduction in glomerular hyperfiltration.

Exploring hospital practice types and their impact on glomerular pathologic patterns: Insights from the largest kidney biopsy cohort in Thailand.

BACKGROUND: This study aims to investigate the influence of different kidney biopsy practices on the prevalence of glomerular pathologic patterns in the largest kidney biopsy registry in Thailand. METHODS: We conducted a retrospective review of kidney biopsy records from the period between 2000 and 2014. The records were obtained from 2 major institutions: King Chulalongkorn Memorial Hospital, a large university-based hospital, and the Kidney Center Bangkok Hospital, which provides pathology services to hospitals throughout Thailand. The study included native kidney biopsies from all provinces in Thailand, excluding paediatric patients, kidney transplant recipients, and cases of inadequate and repeated biopsies. Patient demographics, indications for biopsy, and final glomerular diagnoses were compared across different hospital practice settings: university (UVH), private (PVH) and public (PBH). RESULTS: A total of 5893 eligible native kidney biopsies were identified from a pool of 7005 biopsies conducted over a 15-year period in 25 provinces throughout Thailand. The 3 most common indications for biopsy were suspected kidney involvement in systemic lupus erythematosus (SLE) (29%), nephrotic syndrome (NS) (29%), and acute glomerulonephritis (AGN)/rapidly progressive glomerulonephritis (RPGN) (13%). The leading indication for biopsy differed across practice types, with suspected kidney involvement in SLE being the primary indication in UVH, while NS took precedence in both PBH and PVH practices. Notably, UVH performed fewer kidney biopsies for asymptomatic urinary abnormalities and diabetes-related indications compared with PVH and PBH. The leading glomerular diagnoses correlated with the biopsy indications, with lupus nephritis (LN) being the most common diagnosis in UVH and PBH practices, whiles immunoglobulin A nephropathy was the predominant diagnosis in PVH practice. CONCLUSION: Hospital practice types significantly impact the prevalence of glomerular pathologic diagnosis patterns in kidney biopsy data, highlighting the importance of considering this influence in epidemiological comparisons.

Constipation and clinical outcomes in peritoneal dialysis: Results from Thailand PDOPPS.

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.

Clinicopathological Characteristics and Impacts on Clinical Outcomes of Thrombotic Microangiopathy Lesions in Patients with Immunoglobulin A Nephropathy in Thailand.

INTRODUCTION: More reports of thrombotic microangiopathy (TMA) in immunoglobulin A (IgA) nephropathy suggest its association with poor clinical outcomes. However, the prevalence and clinical significance of TMA in IgA nephropathy have not been widely studied in different populations. METHODS: Kidney biopsies of all patients with primary IgA nephropathy from 1995 to 2015 at the King Chulalongkorn Memorial Hospital, Thailand, were retrospectively reviewed and reclassified by two pathologists following the Oxford MEST-C classification. TMA lesions were detected based solely on light microscopic findings. Associations between the presence of TMA and clinical data, other pathologic findings, and clinical outcomes were studied. RESULTS: Among 267 patients with primary IgA nephropathy, 166 had adequate clinical data and kidney tissues for the analysis. TMA was observed in 21 patients (13%) and was associated with higher mean arterial pressure (MAP), history of malignant hypertension, higher proteinuria, and lower estimated glomerular filtration rate (eGFR) at diagnosis compared to those without TMA. According to the Oxford MEST-C classification, TMA showed a significant association with severe tubular atrophy/interstitial fibrosis (T2) but not with mesangial hypercellularity (M1), endocapillary hypercellularity (E1), segmental glomerulosclerosis (S1), or crescents (C1-2). After a median follow-up of 50 months, patients with TMA had a significantly higher risk of progression to end-stage kidney disease (ESKD) (hazard ratio [HR] 5.8, 95% confidence interval [CI]: 3.1-10.9) and all-cause mortality (HR 3.4, 95% CI: 1.3-8.8). After adjusting for baseline eGFR, MAP, proteinuria, and other pathological lesions, TMA remained an independent predictor of ESKD (adjusted HR 2.4, 95% CI: 1.1-5.4). CONCLUSIONS: Kidney TMA in IgA nephropathy is associated with advanced disease stages, carries a poor prognosis, and thus should be considered in the pathological classification of IgA nephropathy.

Intractable ascites in a female receiving hemodialysis.

We report a case of a 60-year-old female who presented with intractable ascites 2 months after switching from peritoneal dialysis (PD) to hemodialysis (HD) due to an episode of refractory culture-negative peritonitis (CNP). Abdominal paracentesis yielded inflammatory ascites, which later grew Cladosporium cladosporioides, establishing the diagnosis of fungal peritonitis. She was successfully treated with a 4-week course of oral voriconazole. Cladosporium spp. are common fungi in the environment but rarely cause PD-associated peritonitis and can be challenging to diagnose with conventional microbiologic evaluation. In summary, PD-associated peritonitis can worsen after a patient switches to HD. Therefore, it is essential to maintain a high level of suspicion for such complications related to their previous dialysis modality to arrive at an accurate diagnosis.

A Case of Extranodal NK/T-cell Lymphoma Infiltrating Kidneys, Presenting With Hematuria and Proteinuria With False-Positive Serum Anti-proteinase 3, and Mimicking Granulomatosis With Polyangiitis.

We report a case of misdiagnosed extranodal NK/T-cell lymphoma, nasal type, mimicking granulomatosis with polyangiitis (GPA). A 30-year-old male presented with chronic non-resolving right paranasal sinusitis for two years accompanied by multiple generalized cutaneous nodules, and subnephrotic-range proteinuria. Biopsies from skin lesions and paranasal sinuses demonstrated leukocytoclastic vasculitis and necrotizing granulomatous inflammation, respectively. Serum proteinase 3 (PR3)-antineutrophilic cytoplasmic antibody (ANCA) was positive, suggesting the diagnosis of GPA based on the 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology Classification Criteria for GPA. A kidney biopsy was not pursued due to the cause of glomerulonephritis (GN) being clinically evident, per the KDIGO 2021 GN Clinical Practice Guidelines. Immunosuppression was administered, which led to a transient improvement in clinical symptoms. However, subsequent kidney biopsy and other organ biopsies with cytogenic and molecular tests eventually confirmed extranodal NK/T-cell lymphoma infiltrating kidneys, skin, and paranasal sinuses. Physicians should always consider the possibility of hematologic malignancy in young adults presenting with multiple-organ involvement with vasculitic lesions or pauci-immune crescentic GN, albeit positive ANCA serologies. Kidney biopsy with cytogenic support should be performed to exclude threatening diseases, especially in atypical cases such as in young patients despite a context of compatible manifestations with other syndromes.

Oral Health-Related Quality of Life, A Proxy of Poor Outcomes in Patients on Peritoneal Dialysis.

Introduction: We sought to evaluate the associations of poor oral health hygiene with clinical outcomes in patients receiving peritoneal dialysis (PD). Methods: As part of the multinational Peritoneal Dialysis Outcomes and Practice Patterns Study (PDOPPS), PD patients from 22 participating PD centers throughout Thailand were enrolled from May 2016 to December 2019. The data were obtained from questionnaires that formed part of the PDOPPS. Oral health-related quality of life (HRQoL) used in this study was the short form of the oral health impact profile (oral health impact profile [OHIP]-14, including 7 facets and 14 items). Patient outcomes were assessed by Kaplan-Meier analysis. Cox proportional hazards model regression was used to estimate associations between oral HRQoL and clinical outcomes. Results: Of 5090 PD participants, 675 were randomly selected, provided informed consent, and completely responded to the OHIP-14 questionnaire. The median follow-up time of the study was 3.5 (interquartile range = 2.7-5.1 months) years. Poor oral health was associated with lower educational levels, diabetes, older age, marriage, and worse nutritional indicators (including lower time-averaged serum albumin and phosphate concentrations). After adjusting for age, sex, comorbidities, serum albumin, shared frailty by study sites, and PD vintage, poor oral health was associated with increased risks of peritonitis (adjusted hazard ratio [HR] = 1.45, 95% confidence interval [CI]: 1.06-2.00) and all-cause mortality (adjusted HR = 1.55, 95% CI: 1.04-2.32) but not hemodialysis (HD) transfer (adjusted HR = 1.89, 95% CI: 0.87-4.10) compared to participants with good oral health. Conclusion: Poor oral health status was present in one-fourth of PD patients and was independently associated with a higher risk of peritonitis and death.

An ex vivo culture model of kidney podocyte injury reveals mechanosensitive, synaptopodin-templating, sarcomere-like structures.

Chronic kidney diseases are widespread and incurable. The biophysical mechanisms underlying them are unclear, in part because material systems for reconstituting the microenvironment of relevant kidney cells are limited. A critical question is how kidney podocytes (glomerular epithelial cells) regenerate foot processes of the filtration apparatus following injury. Recently identified sarcomere-like structures (SLSs) with periodically spaced myosin IIA and synaptopodin appear in injured podocytes in vivo. We hypothesized that SLSs template synaptopodin in the initial stages of recovery in response to microenvironmental stimuli and tested this hypothesis by developing an ex vivo culture system that allows control of the podocyte microenvironment. Results supported our hypothesis. SLSs in podocytes that migrated from isolated kidney glomeruli presented periodic synaptopodin-positive clusters that nucleated peripheral, foot process-like extensions. SLSs were mechanoresponsive to actomyosin inhibitors and substrate stiffness. Results suggest SLSs as mechanobiological mediators of podocyte recovery and as potential targets for therapeutic intervention.

Urinary red blood cell-derived microparticles and phosphatidylserine-exposing red blood cells in glomerular and non-glomerular hematuria patients.

BACKGROUND: Distinguishing glomerular hematuria (GH) from non-glomerular hematuria (NGH) is important for treating the cause of hematuria. We aimed to determine red blood cell-derived microparticles (RMPs) and phosphatidylserine (PS)-exposing red blood cells (RBCs) and evaluate their use for diagnosing GH and NGH patients. METHODS: All patients received a physical assessment and urological examination. Dysmorphic RBCs (dRBCs) and acanthocytes were examined using a light microscope. The urinary RMPs and PS-exposing RBCs were determined using flow cytometry. RESULTS: The ratio of RMPs to RBCs was higher in GH patients (n = 29) than in NGH patients (n = 29) (1.06 vs. 0.18). The value of the sum of the PS-exposing RBCs plus RMPs divided by the number of RBCs was higher in GH patients than in NGH patients (48.3% vs. 19.4%). The percentage of RBCs was higher in GH patients than in NGH patients (54.5% vs. 21.8%). Similarly, both the percentages of acanthocytes and of non-acanthocytes were higher in GH patients than in NGH patients (29% vs. 7.7% and 25.4% vs. 14.2%, respectively). The ROC-AUC of the number of PS-exposing RBCs plus RMPs divided by the number of RBCs was 0.9 (95% CI, 0.82-0.97), and the RMPs:RBCs ratio was 0.88 (95% CI, 0.79-0.98). The ROC-AUCs of the dRBCs and acanthocytes were 0.85 (95% CI, 0.78-0.95) and 0.88 (95% CI, 0.8-0.97), respectively. CONCLUSIONS: Patients with GH have higher numbers of urinary RMPs and PS-exposing RBCs. These parameters have the potential to be predictive tools for classifying GH in the future.

Predictors and outcomes of peritoneal dialysis-related infections due to filamentous molds (MycoPDICS).

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.

Efficacy of Potassium Supplementation in Hypokalemic Patients Receiving Peritoneal Dialysis: A Randomized Controlled Trial.

RATIONALE & OBJECTIVE: Hypokalemia is a common electrolyte abnormality in patients on peritoneal dialysis (PD) and has been associated with increased risks of peritonitis and death. Whether correction of hypokalemia improves these outcomes is unknown. STUDY DESIGN: Multicenter, open-label, prospective, randomized controlled trial. SETTING & PARTICIPANTS: Adult (aged ≥18 years) PD patients with hypokalemia (defined as at least 3 values or an average value <3.5 mEq/L in the past 6 months). Randomization was stratified according to center and residual urine output (≤100 or >100 mL/day). INTERVENTIONS: Random assignment to either protocol-based potassium supplementation (titratable dose of oral potassium chloride to maintain serum potassium of 4-5 mEq/L) or conventional potassium supplementation (reactive supplementation when serum potassium is <3.5 mEq/L) over 52 weeks. Treatment groups were compared using intention-to-treat analyses implemented using Cox proportional hazards regression. OUTCOME: The primary outcome was time from randomization to first peritonitis episode (any organism). Secondary outcomes were all-cause mortality, cardiovascular mortality, hospitalization, and conversion to hemodialysis. RESULTS: A total of 167 patients with time-averaged serum potassium concentrations of 3.33 ± 0.28 mEq/L were enrolled from 6 PD centers: 85 were assigned to receive protocol-based treatment, and 82 were assigned to conventional treatment. The median follow-up time was 401 (IQR, 315-417) days. During the study period, serum potassium levels in the protocol-based treatment group increased to 4.36 ± 0.70 mEq/L compared with 3.57 ± 0.65 mEq/L in the group treated conventionally (mean difference, 0.66 [95% CI, 0.53-0.79] mEq/L; P < 0.001). The median time to first peritonitis episode was significantly longer in the protocol-based group (223 [IQR, 147-247] vs 133 [IQR, 41-197] days, P = 0.03). Compared with conventional treatment, the protocol-based group had a significantly lower hazard of peritonitis (HR, 0.47 [95% CI, 0.24-0.93]) but did not differ significantly with respect to any of the secondary outcomes. Asymptomatic hyperkalemia (>6 mEq/L) without characteristic electrocardiographic changes occurred in 3 patients (4%) in the protocol-based treatment group. LIMITATIONS: Not double-masked. CONCLUSIONS: Compared with reactive potassium supplementation when the serum potassium level falls below 3.5 mEq/L, protocol-based oral potassium treatment to maintain a serum potassium concentration in the range of 4-5 mEq/L may reduce the risk of peritonitis in patients receiving PD who have hypokalemia. TRIAL REGISTRATION: Registered at the Thai Clinical Trials Registry with study number TCTR20190725004.

Spiritual well-being and its relationship with patient characteristics and other patient-reported outcomes in peritoneal dialysis patients: Findings from the PDOPPS.

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.

Assisted peritoneal dialysis performed by caregivers and its association with patient outcomes.

BACKGROUND: Although caregivers allow peritoneal dialysis (PD) patients with disabilities the opportunity to perform PD, it is crucial to clarify the safety and effectiveness of assisted PD performed by caregivers compared to self-PD. METHODS: PD patients from 22 PD centres in Thailand were prospectively followed in the Peritoneal Dialysis Outcomes and Practice Patterns Study during 2016-2017. Patients receiving assisted PD performed by caregivers were matched 1:1 with self-PD patients using propensity scores calculated by logistic regression. The associations between assisted PD and risk of mortality, peritonitis and permanent transfer to haemodialysis (HD) were assessed by multivariable competing risk regression. RESULTS: Of 778 eligible patients, 447 (57%) required assisted PD performed by caregivers. Most of the caregivers were family members (98%), while the rest were non-family paid caregivers (2%). Patient factors associated with assisted PD were older age, female gender, lower educational level, cardiovascular comorbidities, diabetes, automated PD modality, poorer functional status and lower blood chemistries (albumin, creatinine, sodium, potassium and phosphate). After 1:1 matching, the baseline characteristics were adequately matched, and 269 patients in each group were analysed. Compared with self-PD, assisted PD was significantly associated with an increased risk of all-cause mortality (adjusted sub-hazard ratio: 2.15, 95% confidence interval: 1.24-3.74). There were no differences in the occurrences of peritonitis and permanent HD transfer between the groups. CONCLUSIONS: Assisted PD was required by more than half of Thai PD patients and was independently associated with a higher mortality risk. This may reflect causal effect or confounding by indication.

Barriers to and constraints of acute peritoneal dialysis in acute kidney injury: A nationwide survey.

This national survey of barriers to and constraints of acute peritoneal dialysis (aPD) in acute kidney injury (AKI) was performed by distributing an online questionnaire to all medical directors of public dialysis units registered with the Nephrology Society of Thailand during September-November 2019. One hundred and thirteen adult facilities responded to the survey covering 75 from 76 provinces (99%) of Thailand. aPD was performed in 66 centres (58%). In facilities where aPD practice was available, the utilization rate was relatively low (<10 cases/year) and limited to specific conditions, including HIV seropositive patients, previous receiving dialysis education and plan and difficult vascular access creation. Only 9% of facilities performed aPD routinely, but interestingly all such units permitted bedside catheter insertion by the nephrologists or internists. The major constraints placed on aPD practice were PD catheter insertion competency, timely catheter insertion support and the medical supporting team's knowledge/competency deficits. aPD for AKI is underutilized in Thailand and limited by the inability to undertake timely PD catheter insertion and knowledge and competency deficits.