Randomised Controlled Trial to determine the appropriate time to initiate peritoneal dialysis after insertion of catheter to minimise complications (Timely PD study)

Background. The most appropriate time to initiate dialysis after surgical insertion of Tenckhoff catheters is not clear in the literature. There is the possibility of peritoneal dialysis (PD) complications such as leakage and infection if dialysis is started too soon after insertion. However, much morbidity and expense could be saved by reducing dependency on haemodialysis (HD) by earlier initiation of PD post catheter insertion. Previous studies are observational and mostly compare immediate with delayed use. The primary objective is to determine the safest and shortest time interval between surgical placement of a Tenckhoff catheter and starting PD. Methods/Design. This is a randomised controlled trial of patients who will start PD after insertion of Tenckhoff catheter at Royal Brisbane and Women's Hospital (RBWH) or Rockhampton Base Hospital (RBH) who meet the inclusion criteria. Patients will be stratified by site and diabetic status. The patients will be randomised to one of three treatment groups. Group 1 will start PD one week after Tenckhoff catheter insertion, group 2 at two weeks and group 3 at four weeks. Nurses and physicians will be blinded to the randomised allocation. The primary end point is the complication rate (leaks and infection) after initiation of PD. Discussion. The study will determine the most appropriate time to initiate PD after placement of a Tenckhoff catheter

Cellular milieu in clear cell renal cell carcinoma

Clear cell renal cell carcinoma (ccRCC) is globally the most prevalent renal cancer. The cells of origin in ccRCC have been identified as proximal tubular epithelial cells (PTEC); however, the transcriptomic pathways resulting in the transition from normal to malignant PTEC state have remained unclear. Immunotherapy targeting checkpoints have revolutionized the management of ccRCC, but a sustained clinical response is achieved in only a minority of ccRCC patients. This indicates that our understanding of the mechanisms involved in the malignant transition and resistance to immune checkpoint therapy in ccRCC is unclear. This review examines recent single-cell transcriptomics studies of ccRCC to clarify the transition of PTEC in ccRCC development, and the immune cell types, states, and interactions that may limit the response to targeted immune therapy, and finally suggests stromal cells as key drivers in recurrent and locally invasive ccRCC. These and future single-cell transcriptomics studies will continue to clarify the cellular milieu in the ccRCC microenvironment, thus defining actional clinical, therapeutic, and prognostic characteristics of ccRCC

The prevalence of Fabry disease in a statewide chronic kidney disease cohort – Outcomes of the aCQuiRE (Ckd.Qld fabRy Epidemiology) study

Background: Prevalence of Fabry disease amongst Chronic Kidney Disease (CKD) patients on haemodialysis has been shown to be approximately 0.2%. Methods: We undertook a cross-sectional study employing a cascade screening strategy for Fabry Disease amongst 3000 adult, male and female patients affected by CKD stage 1-5D/T at public, specialty renal practices within participating Queensland Hospital and Health Services from October 2017 to August 2019. A multi-tiered FD screening strategy, utilising a combination of dried blood spot (DBS) enzymatic testing, and if low, then lyso-GB3 testing and DNA sequencing, was used. Results: Mean (SD) age was 64.0 (15.8) years (n = 2992), and 57.9% were male. Eight participants withrew out of the 3000 who consented. Of 2992 screened, 6 (0.20%) received a diagnosis of FD, 2902 (96.99%) did not have FD, and 84 (2.81%) received inconclusive results. Of the patients diagnosed with FD, mean age was 48.5 years; 5 were male (0.29%) and 1 was female (0.08%); 4 were on kidney replacement therapy (2 dialysis and 2 transplant); 3 were new diagnoses. Conclusions: Estimated overall FD prevalence was 0.20%. Screening of the broader CKD population may be beneficial in identifying cases of FD. Trial registration: The aCQuiRE Study has been prospectively registered with the Queensland Health Database of Research Activity (DORA, https://dora.health.qld.gov.au) as pj09946 (Registered 3rd July 2017)

Serum Creatinine and Tacrolimus Assessment With VAMS Finger-Prick Microsampling: A Diagnostic Test Study

Rationale & Objective: Kidney transplant recipients require frequent venipunctures. Microsampling methods that use a finger-prick draw of capillary blood, like volumetric absorptive microsamplers (VAMS), have the potential to reduce the pain, inconvenience, and volume of blood loss associated with venipuncture. This study aimed to provide diagnostic accuracy using VAMS for measurement of tacrolimus and creatinine compared to gold standard venous blood in adult kidney transplant recipients. Study Design: Diagnostic test study. Prospective blood samples for measurement of tacrolimus and creatinine were collected using Mitra VAMS and venipuncture immediately before and 2 hours after tacrolimus dosing. Setting & Participants: A convenience sample of 40 adult kidney transplant participants in the outpatient setting. Tests Compared: Method comparison was assessed by Passing-Bablok regression and Bland-Altman analysis. The predictive performance of VAMS measurement compared to venipuncture was also assessed through estimation of the median prediction error and median absolute percentage prediction error. Results: A total of 74 tacrolimus samples and 70 creatinine samples were analyzed from 40 participants. Passing-Bablok regression showed a systematic difference between VAMS and venipuncture when measuring tacrolimus and creatinine with a slope of 1.08 (95% CI, 1.03-1.13) and a slope of 0.65 (95% CI, 0.6-0.7), respectively. These values were then corrected for the systematic difference. When used for Bland-Altman analysis, corrected values of tacrolimus and creatinine showed a bias of -0.1 μg/L and 0.04 mg/dL, respectively. Tacrolimus (corrected) and creatinine (corrected) microsampling values when compared to corresponding venipuncture values met median prediction error and median absolute percentage prediction error predefined acceptability limits of <15%. Limitations: This study was conducted in a controlled environment using a trained nurse to collect VAMS samples. Conclusions: In this study, VAMS was used to reliably measured tacrolimus and creatinine. This represents a clear opportunity for more frequent and less invasive sampling for patients

Future phosphorus: advancing new 2D phosphorus allotropes and growing a sustainable bioeconomy

With more than 40 countries currently proposing to boost their national bioeconomies, there is no better time for a clarion call for a “new” bioeconomy, which, at its core, tackles the current disparities and inequalities in phosphorus (P) availability. Existing biofuel production systems have widened P inequalities and contributed to a linear P economy, impairing water quality and accelerating dependence on P fertilizers manufactured from finite nonrenewable phosphate rock reserves. Here, we explore how the emerging bioeconomy in novel, value-added, bio-based products offers opportunities to rethink our stewardship of P. Development of integrated value chains of new bio-based products offers opportunities for codevelopment of “P refineries” to recover P fertilizer products from organic wastes. Advances in material sciences are exploiting unique semiconductor and opto-electrical properties of new “two-dimensional” (2D) P allotropes (2D black phosphorus and blue phosphorus). These novel P materials offer the tantalizing prospect of step-change innovations in renewable energy production and storage, in biomedical applications, and in biomimetic processes, including artificial photosynthesis. They also offer a possible antidote to the P paradox that our agricultural production systems have engineered us into, as well as the potential to expand the future role of P in securing sustainability across both agroecological and technological domains of the bioeconomy. However, a myriad of social, technological, and commercialization hurdles remains to be crossed before such an advanced circular P bioeconomy can be realized. The emerging bioeconomy is just one piece of a much larger puzzle of how to achieve more sustainable and circular horizons in our future use of P

Assessment of arterial stiffness, oxidative stress and inflammation in acute kidney injury

Background: It is well know that arterial stiffness, oxidative stress and inflammation are features of chronic kidney disease. The arterial changes have a multitude of potential interconnected causes including endothelial dysfunction, oxidative stress, inflammation, atherosclerosis and vascular calcification. There is evidence that arterial stiffness becomes progressively worse as CKD progresses. The contribution of the biochemical changes of uremic toxicity to arterial stiffness is less clear. The aim of this study is to elucidate the vascular changes in acute kidney injury. We hypothesise that arterial stiffness will be increased during acute kidney injury and this will return to normal after kidney function recovers

Randomised Controlled Trial to determine the appropriate time to initiate peritoneal dialysis after insertion of catheter to minimise complications (Timely PD study)

Background. The most appropriate time to initiate dialysis after surgical insertion of Tenckhoff catheters is not clear in the literature. There is the possibility of peritoneal dialysis (PD) complications such as leakage and infection if dialysis is started too soon after insertion. However, much morbidity and expense could be saved by reducing dependency on haemodialysis (HD) by earlier initiation of PD post catheter insertion. Previous studies are observational and mostly compare immediate with delayed use. The primary objective is to determine the safest and shortest time interval between surgical placement of a Tenckhoff catheter and starting PD. Methods/Design. This is a randomised controlled trial of patients who will start PD after insertion of Tenckhoff catheter at Royal Brisbane and Women's Hospital (RBWH) or Rockhampton Base Hospital (RBH) who meet the inclusion criteria. Patients will be stratified by site and diabetic status. The patients will be randomised to one of three treatment groups. Group 1 will start PD one week after Tenckhoff catheter insertion, group 2 at two weeks and group 3 at four weeks. Nurses and physicians will be blinded to the randomised allocation. The primary end point is the complication rate (leaks and infection) after initiation of PD. Discussion. The study will determine the most appropriate time to initiate PD after placement of a Tenckhoff catheter

Spatially Resolved Transcriptomes of Mammalian Kidneys Illustrate the Molecular Complexity and Interactions of Functional Nephron Segments

Available transcriptomes of the mammalian kidney provide limited information on the spatial interplay between different functional nephron structures due to the required dissociation of tissue with traditional transcriptome-based methodologies. A deeper understanding of the complexity of functional nephron structures requires a non-dissociative transcriptomics approach, such as spatial transcriptomics sequencing (ST-seq). We hypothesize that the application of ST-seq in normal mammalian kidneys will give transcriptomic insights within and across species of physiology at the functional structure level and cellular communication at the cell level. Here, we applied ST-seq in six mice and four human kidneys that were histologically absent of any overt pathology. We defined the location of specific nephron structures in the captured ST-seq datasets using three lines of evidence: pathologist's annotation, marker gene expression, and integration with public single-cell and/or single-nucleus RNA-sequencing datasets. We compared the mouse and human cortical kidney regions. In the human ST-seq datasets, we further investigated the cellular communication within glomeruli and regions of proximal tubules–peritubular capillaries by screening for co-expression of ligand–receptor gene pairs. Gene expression signatures of distinct nephron structures and microvascular regions were spatially resolved within the mouse and human ST-seq datasets. We identified 7,370 differentially expressed genes (padj < 0.05) distinguishing species, suggesting changes in energy production and metabolism in mouse cortical regions relative to human kidneys. Hundreds of potential ligand–receptor interactions were identified within glomeruli and regions of proximal tubules–peritubular capillaries, including known and novel interactions relevant to kidney physiology. Our application of ST-seq to normal human and murine kidneys confirms current knowledge and localization of transcripts within the kidney. Furthermore, the generated ST-seq datasets provide a valuable resource for the kidney community that can be used to inform future research into this complex organ

Chronic kidney disease in public renal practices in Queensland, Australia, 2011–2018

Aim: To describe adults with (non-dialysis) chronic kidney disease (CKD) in nine public renal practice sites in the Australian state of Queensland. Methods: 7,060 persons were recruited to a CKD Registry in May 2011 and until start of kidney replacement therapy (KRT), death without KRT or June 2018, for a median period of 3.4 years. Results: The cohort comprised 7,060 persons, 52% males, with a median age of 68 yr; 85% had CKD stages 3A to 5, 45.4% were diabetic, 24.6% had diabetic nephropathy, and 51.7% were obese. Younger persons mostly had glomerulonephritis or genetic renal disease, while older persons mostly had diabetic nephropathy, renovascular disease and multiple diagnoses. Proportions of specific renal diagnoses varied >2-fold across sites. Over the first year, eGFR fell in 24% but was stable or improved in 76%. Over follow up, 10% started KRT, at a median age of 62 yr, most with CKD stages 4 and 5 at consent, while 18.8% died without KRT, at a median age of 80 yr. Indigenous people were younger at consent and more often had diabetes and diabetic kidney disease and had higher incidence rates of KRT. Conclusion: The spectrum of characteristics in CKD patients in renal practices is much broader than represented by the minority who ultimately start KRT. Variation in CKD by causes, age, site and Indigenous status, the prevalence of obesity, relative stability of kidney function in many persons over the short term, and differences between those who KRT and die without KRT are all important to explore