Drug stewardship in chronic kidney disease to achieve effective and safe medication use.

People living with chronic kidney disease (CKD) often experience multimorbidity and require polypharmacy. Kidney dysfunction can also alter the pharmacokinetics and pharmacodynamics of medications, which can modify their risks and benefits; the extent of these changes is not well understood for all situations or medications. The principle of drug stewardship is aimed at maximizing medication safety and effectiveness in a population of patients through a variety of processes including medication reconciliation, medication selection, dose adjustment, monitoring for effectiveness and safety, and discontinuation (deprescribing) when no longer necessary. This Review is aimed at serving as a resource for achieving optimal drug stewardship for patients with CKD. We describe special considerations for medication use during pregnancy and lactation, during acute illness and in patients with cancer, as well as guidance for the responsible use of over-the-counter drugs, herbal remedies, supplements and sick-day rules. We also highlight inequities in medication access worldwide and suggest policies to improve access to quality and essential medications for all persons with CKD. Further strategies to promote drug stewardship include patient education and engagement, the use of digital health tools, shared decision-making and collaboration within interdisciplinary teams. Throughout, we position the person with CKD at the centre of all drug stewardship efforts.

Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease: known knowns and known unknowns.

The Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease (CKD) updates the KDIGO 2012 guideline and has been developed with patient partners, clinicians, and researchers around the world, using robust methodology. This update, based on a substantially broader base of evidence than has previously been available, reflects an exciting time in nephrology. New therapies and strategies have been tested in large and diverse populations that help to inform care; however, this guideline is not intended for people receiving dialysis nor those who have a kidney transplant. The document is sensitive to international considerations, CKD across the lifespan, and discusses special considerations in implementation. The scope includes chapters dedicated to the evaluation and risk assessment of people with CKD, management to delay CKD progression and its complications, medication management and drug stewardship in CKD, and optimal models of CKD care. Treatment approaches and actionable guideline recommendations are based on systematic reviews of relevant studies and appraisal of the quality of the evidence and the strength of recommendations which followed the "Grading of Recommendations Assessment, Development, and Evaluation" (GRADE) approach. The limitations of the evidence are discussed. The guideline also provides practice points, which serve to direct clinical care or activities for which a systematic review was not conducted, and it includes useful infographics and describes an important research agenda for the future. It targets a broad audience of people with CKD and their healthcare, while being mindful of implications for policy and payment.

Results from a cross-specialty consensus on optimal management of patients with chronic kidney disease (CKD): from screening to complications.

BACKGROUND: Chronic kidney disease (CKD) affects around 10% of the global population and has been estimated to affect around 50% of individuals with type 2 diabetes and 50% of those with heart failure. The guideline-recommended approach is to manage with disease-modifying therapies, but real-world data suggest that prescribing rates do not reflect this in practice. OBJECTIVE: To develop a cross-specialty consensus on optimal management of the patient with CKD using a modified Delphi method. DESIGN: An international steering group of experts specialising in internal medicine, endocrinology/diabetology, nephrology and primary care medicine developed 42 statements on aspects of CKD management including identification and screening, risk factors, holistic management, guidelines, cross-specialty alignment and education. Consensus was determined by agreement using an online survey. PARTICIPANTS: The survey was distributed to cardiologists, nephrologists, endocrinologists and primary care physicians across 11 countries. MAIN OUTCOMES AND MEASURES: The threshold for consensus agreement was established a priori by the steering group at 75%. Stopping criteria were defined as a target of 25 responses from each country (N=275), and a 4-week survey period. RESULTS: 274 responses were received in December 2022, 25 responses from Argentina, Australia, Brazil, Guatemala, Mexico, Singapore, South Korea, Taiwan, Thailand, Turkey and 24 responses from Egypt. 53 responses were received from cardiologists, 52 from nephrologists, 55 from endocrinologists and 114 from primary care physicians. 37 statements attained very high agreement (≥90%) and 5 attained high agreement (≥75% and <90%). Strong alignment between roles was seen across the statements, and different levels of experience (2-5 years or 5+ years), some variation was observed between countries. CONCLUSIONS: There is a high degree of consensus regarding aspects of CKD management among healthcare professionals from 11 countries. Based on these strong levels of agreement, the steering group derived 12 key recommendations focused on diagnosis and management of CKD.

Peritoneal Dialysis-Related Peritonitis Caused by Lysinibacillus sphaericus.

Peritonitis is the major complication of peritoneal dialysis (PD) patients. Staphylococcus is the leading causative organism of PD-related peritonitis. However, there were more reports of unusual organisms causing peritonitis. Clinical features, management, and outcome of peritonitis from unusual organisms are important information. We reported herein a 72-year-old female patient who presented with fever, abdominal pain, and cloudy dialysate for 3 days. Upon admission, ceftazidime and vancomycin were given intraperitoneally. A preliminary report of blood and PD fluid culture showed the presence of Gram-positive bacilli. Her clinical status improved 48 hours after the commencement of the antibiotics. Subsequently, culture reports of blood and PD fluid showed Lysinibacillus sphaericus which was susceptible to vancomycin at a minimal inhibitory concentration of less than 0.25 µg/mL. The patient was given intraperitoneal vancomycin for a total of 14 days. Then, the PD effluent was clear, and its cell count was below 100 cells/mm3 in 3 days. The patient did not have a recurrence of peritonitis after antibiotic discontinuation. The possibility of this organism infection is environmental contamination related to the patient's gardening activities.

Correlation of the Dietary Protein Intake between Those Estimated from a Short Protein Food-Recall Questionnaire and from 24-Hour Urinary Urea-Nitrogen Excretion in Stages 3-4 Chronic Kidney Disease Patients.

Introduction: High protein intake may accelerate progression of chronic kidney disease (CKD). Estimation of dietary protein intake (DPI) is indispensable for management of CKD, but to achieve optimum DPI is quite challenging in routine clinical practice. We recently studied a beneficial effect of utilizing integrated care on the management of CKD at the rural community level. In that study, we created a short protein food-recall questionnaire (S-PFRQ) as a working tool to estimate DPI of the CKD patients during home visit by community health personnel. Herein, we reported the initial evaluation of the reliability of S-PFRQ from our previous study. Objective: We compared the amount of DPI obtained from S-PFRQ with that obtained from protein-equivalent of total nitrogen appearance (PNA). Methods: In the previous ESCORT-2 study, 914 patients with CKD stage 3 or 4, who were living in the rural area of Thailand, were prospectively followed while receiving integrated care for 36 consecutive months. During home visits by community nurses from subdistrict health centers, dietary food recall was made, recorded in S-PFRQ, and DPI was obtained. Among these, sixty patients were randomly selected, and 24-h urine was collected for urinary urea-N and estimation of PNA. A correlation was made between DPI obtained from S-PFRQ and PNA. Results: The DPIs derived from S-PFRQ and PNA were 28.8 ± 14.8 and 39.26 ± 17.79 g/day, respectively. The mean difference and 95% CI between the 2 methods was -10.43 (-7.1 to -13.8) g/day, respectively (P < 0.001). Interclass correlation between these 2 methods was 0.24, P = 0.007. The difference between the 2 methods remained constant across different amounts of DPI. Conclusion: The DPI estimated from S-PFRQ significantly correlated to that from PNA. However, the S-PFRQ method yielded a DPI value which was about 10 g of protein or 25% less than the PNA method. Despite this amount of difference, this S-PFRQ is user-friendly and could be used during field work as an easy and simple tool for DPI estimation in resource-limiting condition.

Effectiveness of integrated care on delaying chronic kidney disease progression in rural communities of Thailand (ESCORT-2) trials.

AIM: We conducted a prospective cohort study to evaluate the effectiveness of an integrated care model on delaying chronic kidney disease (CKD) progression in routine clinical practice in rural primary care setting. METHODS: After enrolment, patients with stages 3 to 4 CKD patients from five district hospitals in a northern province of Thailand (400 km from Bangkok) received integrated care comprising hospital multidisciplinary care and home visits by community care teams. Clinical characteristics and biochemical data were collected at baseline and every 3-month interval thereafter for 36 months. The primary outcome was the rate of estimated glomerular filtration rate (eGFR) decline. RESULTS: Nine hundred and fourteen stage -3 and - 4 CKD patients were enrolled. The mean age of our cohort was 62 years. Diabetic kidney disease (DKD) was the main cause of CKD (53%) whereas hypertension was the most common co-morbidity (92%). The mean rate of eGFR decline was -0.92 mL/min/1.73 m2 /year. The rate of eGFR decline among patients with DKD was about three times faster than patients without DKD. Patients with higher blood pressure, metabolic acidosis, proteinuria or anaemia had a faster rate of eGFR decline. CONCLUSION: This integrated care model at the community level was effective in delaying CKD progression in routine clinical practice situation.

Altering host resistance to infections through microbial transplantation.

Host resistance to bacterial infections is thought to be dictated by host genetic factors. Infections by the natural murine enteric pathogen Citrobacter rodentium (used as a model of human enteropathogenic and enterohaemorrhagic E. coli infections) vary between mice strains, from mild self-resolving colonization in NIH Swiss mice to lethality in C3H/HeJ mice. However, no clear genetic component had been shown to be responsible for the differences observed with C. rodentium infections. Because the intestinal microbiota is important in regulating resistance to infection, and microbial composition is dependent on host genotype, it was tested whether variations in microbial composition between mouse strains contributed to differences in "host" susceptibility by transferring the microbiota of resistant mice to lethally susceptible mice prior to infection. Successful transfer of the microbiota from resistant to susceptible mice resulted in delayed pathogen colonization and mortality. Delayed mortality was associated with increased IL-22 mediated innate defense including antimicrobial peptides Reg3γ and Reg3ß, and immunono-neutralization of IL-22 abrogated the beneficial effect of microbiota transfer. Conversely, depletion of the native microbiota in resistant mice by antibiotics and transfer of the susceptible mouse microbiota resulted in reduced innate defenses and greater pathology upon infection. This work demonstrates the importance of the microbiota and how it regulates mucosal immunity, providing an important factor in susceptibility to enteric infection. Transfer of resistance through microbial transplantation (bacteriotherapy) provides additional mechanisms to alter "host" resistance, and a novel means to alter enteric infection and to study host-pathogen interactions.