The long-term effects of dapagliflozin in chronic kidney disease: a time-to-event analysis.

BACKGROUND AND HYPOTHESIS: Chronic kidney disease (CKD) presents a significant clinical and economic burden to healthcare systems worldwide, which increases considerably with progression towards kidney failure. The DAPA-CKD trial demonstrated that patients with or without type 2 diabetes (T2D) who were treated with dapagliflozin experienced slower progression of CKD versus placebo. Understanding the effect of long-term treatment with dapagliflozin on the timing of kidney failure beyond trial follow-up can assist informed decision-making by healthcare providers and patients. The study objective was therefore to extrapolate the outcome-based clinical benefits of treatment with dapagliflozin in patients with CKD via a time-to-event analysis using trial data. METHODS: Patient-level data from the DAPA-CKD trial were used to parameterise a closed cohort-level partitioned survival model that predicted time-to-event for key trial endpoints (kidney failure, all-cause mortality, sustained decline in kidney function, and hospitalisation for heart failure). Data were pooled with a subpopulation of the DECLARE-TIMI 58 trial to create a combined CKD population spanning a range of CKD stages; a parallel survival analysis was conducted in this population. RESULTS: In the DAPA-CKD and pooled CKD populations, treatment with dapagliflozin delayed time to first event for kidney failure, all-cause mortality, sustained decline in kidney function, and hospitalisation for heart failure. Attenuation of CKD progression was predicted to slow the time to kidney failure by 6.6 years (dapagliflozin: 25.2, 95%CI: 19.0-31.5; standard therapy: 18.5, 95%CI: 14.7-23.4) in the DAPA-CKD population. A similar result was observed in the pooled CKD population with an estimated delay of 6.3 years (dapagliflozin: 36.0, 95%CI: 31.9-38.3; standard therapy: 29.6, 95%CI: 25.5-34.7). CONCLUSION: Treatment with dapagliflozin over a lifetime time horizon may considerably delay the mean time to adverse clinical outcomes for patients who would go on to experience them, including those at modest risk of progression.

Periodontitis and systemic parameters in chronic kidney disease: Systematic review and meta-analysis.

OBJECTIVE: To perform a systematic review with meta-analysis to assess recent scientific evidence on the association between periodontitis and systemic parameters/conditions in individuals with chronic kidney disease (CKD). MATERIALS AND METHODS: The search for studies was performed in MedLine/PubMed, Scopus, Web of Science, and BIREME databases. Reference lists of selected articles were also searched. Studies with different epidemiological designs evaluating the influence of exposure to periodontitis on serum markers and mortality in individuals with CKD were eligible for inclusion. Three independent reviewers performed the article selection and data extraction. The assessment of methodological quality used the adapted Newcastle Ottawa Scale. Random effects meta-analysis was performed to calculate association measurements and 95% confidence intervals. RESULTS: In total, 3053 records were identified in the database search, with only 25 studies meeting the eligibility criteria and, of these, 10 studies contributed data for meta-analysis. Using a random-effects model, periodontitis was associated with hypoalbuminemia (PRunadjusted = 2.47; 95%CI:1.43-4.26), with high levels of C-reactive protein (PRunadjusted = 1.35; 95%CI%:1.12-1.64), death from cardiovascular disease (RRunadjusted = 2.29; 95%CI:1.67-3.15) and death from all causes (RRunadjusted = 1.73; 95%CI:1.32-2.27). CONCLUSIONS: The findings of this review validated a positive association between periodontitis and serum markers and mortality data in individuals with CKD.

Simultaneous Liver Kidney Transplantation in a Primary Type 2 Hyperoxaluria With Corrected TOF and Severe Cardiomyopathy: A Case Report.

Background: Primary type 2 hyperoxaluria is a very rare genetic disorder,1,2 where in the progression to renal failure was assumed to be insidious and not very common.3 PH2 is due to deficient glyoxylate reductase/hydroxypyruvate reductase (GRHPR),1,2 which was thought to have extra-hepatic production also.4 The progression to renal failure in these patient subgroups is well documented in the Literature and the role of SLK (simultaneous liver and kidney transplantation) has not been clearly established.8. Method: We present a case report of a young girl with PH2, who successfully underwent SLK, with evidence of reduction in the urine oxalate levels post SLK. Results: PH2, though a rare genetic disease, has a proven potential to progress to chronic renal failure requiring transplantation, renal transplantation alone has not shown any benefit, these patients can be offered SLK as a primary treatment option, to improve the outcomes, this needs further validation with consensus and studies.

Coexisting presentation of two rare genetic variants of autosomal dominant polycystic kidney disease and Alport syndrome.

Alport syndrome and autosomal dominant polycystic kidney disease are monogenic causes of chronic kidney disease and end-stage kidney failure. We present a case of a man in his 60s with progressive chronic kidney disease, bilateral sensorineural hearing loss and multiple renal cysts. Genetic analysis revealed a heterozygous variant in COL4A3 (linked to Alport syndrome) and in the GANAB gene (associated with a milder form of autosomal dominant polycystic kidney disease). Although each variant confers a mild risk of developing end-stage kidney disease, the patient presented a pronounced and accelerated progression of chronic kidney disease, which goes beyond what would be predicted by adding up their individual effects. This suggests a potential synergic effect of both variants, which warrants further investigation.

Association between non-registration of chronic kidney disease and mortality and cardiovascular outcome: a time-to-event analysis of retrospective primary care data.

OBJECTIVE: Patients with impaired kidney function and increased albuminuria are at risk of developing cardiovascular disease (CVD). Previous research has revealed that a substantial proportion of patients with chronic kidney disease (CKD) do not get a registered diagnosis in the electronic health record of the general practitioner. The aim of this study was to investigate the association between non-registration of CKD and all-cause mortality and cardiovascular outcome. DESIGN AND SETTING: A retrospective study in primary care. METHODS: The analyses were carried out in the INTEGO database, a general practice-based morbidity registration network in Flanders, Belgium. The study used INTEGO data from the year 2018 for all patients ≥18 years old, including 10 551 patients. To assess the risk of mortality and CVD, a time-to-event analysis was performed. Cox proportional hazard model was used to evaluate the association between non-registration and incidence of all-cause mortality and cardiovascular events with mortality as a competing risk. Subgroup analyses were performed for estimated glomerular filtration rate stages (3A, 3B, 4 and 5). Multiple imputation was done following the methodology of Mamouris et al. RESULTS: Mortality was higher in patients with non-registered CKD compared with patients with registered CKD (HR 1.29, 95% CI 1.19 to 1.41). Non-registration of CKD was not associated with an increased risk for the development of CVD (HR 0.92, 95% CI 0.77 to 1.11). CONCLUSION: An association between non-registration and all-cause mortality was identified, although no such association was apparent for CVD.

Mycobacterium senegalense catheter-related bloodstream infection.

Catheter-related bloodstream infection (CRBSI) is one of the common healthcare-acquired infections imposing a high burden of morbidity and mortality on the patients. Non-tuberculous mycobacterium is a rare aetiology for CRBSI and poses challenges in laboratory diagnosis and clinical management. This is a case of a woman in her early 60s with underlying end-stage renal failure, diabetes mellitus and hypertension presented with a 2-week history of high-grade fever postregular haemodialysis, vomiting, lethargy and altered mental status.Blood cultures from a permanent catheter and peripheral taken concurrently yielded Mycobacterium senegalense, identified by matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry, which established the diagnosis of CRBSI atypically presented with concurrent acute intracranial bleeding and cerebrovascular infarction at initial presentation. She was started on a combination of oral azithromycin, oral amikacin and intravenous imipenem, and the permanent catheter was removed. Despite the treatments instituted, she developed septicaemia, acute myocardial infarction and macrophage activation-like syndrome, causing the patient's death.

Inspiratory Muscle Training in Patients Living with Chronic Kidney Disease and Receiving Hemodialysis: Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: People living with chronic kidney disease (CKD) and receiving hemodialysis (HD) have impaired respiratory muscle strength and endurance. The objective of this study was to systematically review the effects of inspiratory muscle training (IMT) on respiratory muscle strength, functional capacity, lung function, quality of life, endothelial function, and oxidative stress in people living with CKD and receiving HD. METHODS: An electronic search was conducted from inception to June 2023. Randomized controlled trials that evaluated the effects of IMT on respiratory muscle strength, functional capacity, lung function, endothelial function, quality of life, or oxidative stress in adults living with CKD and receiving HD, compared with control, placebo IMT, or conventional physical therapy, were included. RESULTS: Eight studies were included, totaling 246 people. The meta-analysis showed that IMT increased the maximum inspiratory pressure (MIP) by 22.53 cm H2O, the maximum expiratory pressure (MEP) by 19.54 cm H2O, and the distance covered in the 6-minute walk test by 77.63 m. Changes in lung function and quality of life were not observed. It was not possible to quantitatively analyze data on endothelial function and oxidative stress. CONCLUSIONS: IMT improves MIP, MEP, and functional capacity in people living with CKD and receiving HD. IMT did not demonstrate significant results for lung function and quality of life. Effects on endothelial function and oxidative capacity remain uncertain. IMPACT: Inspiratory muscle training improves MIP, MEP, and functional capacity in people living with CKD and receiving HD, compared with conventional physical therapy or controls or placebo intervention. Increases in functional capacity in this population are extremely important because of the relationship with the survival of these people.

Causal relationship between gut microbiota and chronic renal failure: a two-sample Mendelian randomization study.

Background: Observational studies and some experimental investigations have indicated that gut microbiota are closely associated with the incidence and progression of chronic renal failure. However, the causal relationship between gut microbiota and chronic renal failure remains unclear. The present study employs a two-sample Mendelian randomization approach to infer the causal relationship between gut microbiota and chronic renal failure at the genetic level. This research aims to determine whether there is a causal effect of gut microbiota on the risk of chronic renal failure, aiming to provide new evidence to support targeted gut therapy for the treatment of chronic renal failure. Methods: Employing genome-wide association study (GWAS) data from the public MiBioGen and IEU OpenGWAS platform, a two-sample Mendelian randomization analysis was conducted. The causal relationship between gut microbiota and chronic renal failure was inferred using five different methods: Inverse Variance Weighted, MR-Egger, Weighted Median, Simple Mode, and Weighted Mode. The study incorporated sensitivity analyses that encompassed evaluations for pleiotropy and heterogeneity. Subsequently, the results of the Mendelian randomization analysis underwent a stringent correction for multiple testing, employing the False Discovery Rate method to enhance the validity of our findings. Results: According to the results from the Inverse Variance Weighted method, seven bacterial genera show a significant association with the outcome variable chronic renal failure. Of these, Ruminococcus (gauvreauii group) (OR = 0.82, 95% CI = 0.71-0.94, p = 0.004) may act as a protective factor against chronic renal failure, while the genera Escherichia-Shigella (OR = 1.22, 95% CI = 1.08-1.38, p = 0.001), Lactococcus (OR = 1.1, 95% CI = 1.02-1.19, p = 0.013), Odoribacter (OR = 1.23, 95% CI = 1.03-1.49, p = 0.026), Enterorhabdus (OR = 1.14, 95% CI = 1.00-1.29, p = 0.047), Eubacterium (eligens group) (OR = 1.18, 95% CI = 1.02-1.37, p = 0.024), and Howardella (OR = 1.18, 95% CI = 1.09-1.28, p < 0.001) may be risk factors for chronic renal failure. However, after correction for multiple comparisons using False Discovery Rate, only the associations with Escherichia-Shigella and Howardella remain significant, indicating that the other genera have suggestive associations. Sensitivity analyses did not reveal any pleiotropy or heterogeneity. Conclusion: Our two-sample Mendelian randomization study suggests that the genera Escherichia-Shigella and Howardella are risk factors for chronic renal failure, and they may serve as potential targets for future therapeutic interventions. However, the exact mechanisms of action are not yet clear, necessitating further research to elucidate their precise roles fully.

Are there lost opportunities in chronic kidney disease? A region-wide cohort study.

OBJECTIVES: Identify the windows of opportunity for the diagnosis of chronic kidney disease (CKD) and the prevention of its adverse outcomes and quantify the potential population gains of such prevention. DESIGN AND SETTING: Observational, population-wide study of residents in the Stockholm and Skåne regions of Sweden between 1 January 2015 and 31 December 2020. PARTICIPANTS: All patients who did not yet have a diagnosis of CKD in healthcare but had CKD according to laboratory measurements of CKD biomarkers available in electronic health records. OUTCOME MEASURES: We assessed the proportions of the patient population that received a subsequent diagnosis of CKD in healthcare, that used guideline-directed pharmacological therapy (statins, renin-angiotensin aldosterone system inhibitors (RAASi) and/or sodium-glucose cotransporter-2 inhibitors (SGLT2i)) and that experienced adverse outcomes (all-cause mortality, cardiovascular mortality or major adverse cardiovascular events (MACE)). The potential to prevent adverse outcomes in CKD was assessed using simulations of guideline-directed pharmacological therapy in untreated subsets of the study population. RESULTS: We identified 99 382 patients with undiagnosed CKD during the study period. Only 33% of those received a subsequent diagnosis of CKD in healthcare after 5 years. The proportion that used statins or RAASi was of similar size to the proportion that didn't, regardless of how advanced their CKD was. The use of SGLT2i was negligible. In simulations of optimal treatment, 22% of the 21 870 deaths, 27% of the 14 310 cardiovascular deaths and 39% of the 22 224 MACE could have been avoided if every patient who did not use an indicated medication for their laboratory-confirmed CKD was treated with guideline-directed pharmacological therapy for CKD. CONCLUSIONS: While we noted underdiagnosis and undertreatment of CKD in this large contemporary population, we also identified a substantial realisable potential to improve CKD outcomes and reduce its burden by treating patients early with guideline-directed pharmacological therapy.

Global trends in chronic kidney disease-related mortality: a systematic review protocol.

INTRODUCTION: In recent decades, all-cause mortality has increased among individuals with chronic kidney disease (CKD), influenced by factors such as aetiology, standards of care and access to kidney replacement therapies (dialysis and transplantation). The recent COVID-19 pandemic also affected mortality over the past few years. Here, we outline the protocol for a systematic review to investigate global temporal trends in all-cause mortality among patients with CKD at any stage from 1990 to current. We also aim to assess temporal trends in the mortality rate associated with the COVID-19 pandemic. METHODS AND ANALYSIS: We will conduct a systematic review of studies reporting mortality for patients with CKD following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We will search electronic databases, national and multiregional kidney registries and grey literature to identify observational studies that reported on mortality associated with any cause for patients with CKD of all ages with any stage of the disease. We will collect data between April and August 2023 to include all studies published from 1990 to August 2023. There will be no language restriction, and clinical trials will be excluded. Primary outcome will be temporal trends in CKD-related mortality. Secondary outcomes include assessing mortality differences before and during the COVID-19 pandemic, exploring causes of death and examining trends across CKD stages, country classifications, income levels and demographics. ETHICS AND DISSEMINATION: A systematic review will analyse existing data from previously published studies and have no direct involvement with patient data. Thus, ethical approval is not required. Our findings will be published in an open-access peer-reviewed journal and presented at scientific conferences. PROSPERO REGISTRATION NUMBER: CRD42023416084.

Short versus long-acting erythropoiesis-stimulating agents for anemia management in Egyptian hemodialysis patients.

BACKGROUND: Chronic kidney disease (CKD) often results in renal anemia, impacting the well-being of patients and causing various negative consequences. Erythropoiesis-stimulating agents (ESAs) offer promising solutions for managing anemia in CKD. This study aimed to evaluate and compare the effectiveness, safety profile, and cost-effectiveness of short-acting (Eprex®) and long-acting (Aranesp®) ESAs. METHOD: This comparative prospective cohort cost-effectiveness study was carried out over 6 months among adult Egyptian hemodialysis patients of either gender. Participants were categorized into two groups based on the type of ESA administered: the Eprex group, receiving epoetin alfa, and the Aranesp group, receiving darbepoetin alfa. These two treatment groups' efficacy, safety, and cost were analyzed and compared. RESULTS: Of 127 hemodialysis patients, 60 (47.2%) received Eprex, while 67 (52.8%) were treated with Aranesp. Target hemoglobin (Hb) was achieved by 50.6% of patients in the Eprex group versus 63.4% in the Aranesp group, with a significant difference (P < 0.001). Both treatment groups exhibited a similar safety profile, while Aranesp® was considered the cost-saving protocol. CONCLUSION: In hemodialysis Egyptian patients, Aranesp with extended dosing intervals proved to be more effective in achieving target Hb with comparable adverse effect profiles, a substantial cost-saving strategy, and offered time-saving advantages for medical staff workload compared to Eprex. TRIAL REGISTRATION: The Clinicaltrial.gov registration ID is NCT05699109 (26/01/2023).

Melittin induces autophagy to alleviate chronic renal failure in 5/6-nephrectomized rats and angiotensin II-induced damage in podocytes.

BACKGROUND/OBJECTIVES: Chronic renal failure (CRF) is a complex pathological condition that lacks a cure. Certain Chinese medicines, such as melittin, a major component in bee venom, have shown efficacy in treating CRF patients. On the other hand, the mechanisms underlying the therapeutic effects of melittin are unclear. MATERIALS/METHODS: A 5/6 nephrectomy model (5/6 Nx) of renal failure was established on rats for in vivo assays, and mouse podocyte clone 5 (MPC5) mouse podocyte cells were treated with angiotensin II (AngII) to establish an in vitro podocyte damage model. The 24-h urine protein, serum creatinine, and blood urea nitrogen levels were evaluated after one, 2, and 4 weeks. Hematoxylin and eosin staining, Masson staining, and periodic acid-Schiff staining were used to examine the pathological changes in kidney tissues. A cell counting kit 8 assay was used to assess the cell viability. Reverse transcription polymerase chain reaction and Western blot were used to assess the mRNA and protein levels in the cells, respectively. RESULTS: In the rat 5/6 Nx, melittin reduced the 24-h urinary protein excretion and the serum creatinine and blood urea nitrogen levels. Furthermore, the renal pathology was improved in the melittin-treated 5/6 Nx rats. Melittin promoted podocin, nephrin, Beclin 1, and the LC3II/LC3I ratio and inhibited phosphorylated mammalian target of rapamycin (mTOR)/mTOR in 5/6 Nx-induced rats and AngII-induced MPC5 mouse podocyte cells. Moreover, inhibiting autophagy with 3-MA weakened the effects of melittin on podocin, nephrin, and the LC3II/LC3I ratio in podocytes. CONCLUSION: Melittin may offer protection against kidney injury, probably by regulating podocyte autophagy. These results provide the theoretical basis for applying melittin in CRF therapy.

Omentin reduces venous neointimal hyperplasia in arteriovenous fistula through hypoxia-inducible factor-1 alpha inhibition.

Arteriovenous fistula (AVF) failure often involves venous neointimal hyperplasia (VNH) driven by elevated hypoxia-inducible factor-1 alpha (HIF-1α) in the venous wall. Omentin, known for its anti-inflammatory and anti-hyperplasia properties, has an uncertain role in early AVF failure. This study investigates omentin's impact on VNH using a chronic renal failure (CRF) rabbit model. The CRF rabbit model of AVF received omentin-expressing adenoviral vector or control ß-gal vector to assess omentin's effects on VNH. Human vascular smooth muscle cells (HVSMCs), stimulated with tumor necrosis factor-α (TNF-α), were exposed to recombinant human omentin (Rh-OMT) to study its influence on cell proliferation and migration. The AMP-activated protein kinase (AMPK) inhibitor compound C and the mammalian target of rapamycin (mTOR) activator MHY1485 were employed to explore omentin's mechanisms in VNH reduction through HIF-1α inhibition. Omentin treatment reduced VNH in CRF rabbits, concomitant with HIF-1α down-regulation and the suppression of downstream factors, including vascular endothelial growth factor and matrix metalloproteinases. Rh-OMT inhibited TNF-α-induced HVSMC proliferation and migration by modulating both cell cycle and cell adhesion proteins. Additionally, omentin reduced HIF-1α expression through the AMPK/mTOR pathway activation. Notably, the blockade of AMPK/mTOR signaling reversed omentin-mediated inhibition of VNH, cell proliferation, and migration, both in vivo and in vitro. In conclusion, omentin mitigates VNH post-AVF creation by restraining HIF-1α via AMPK/mTOR signaling. Strategies boosting circulating omentin levels may offer promise in averting AVF failure.

The Effect of Hope Therapy on the Management of Hemodialysis Outcomes: A Review Article.

Hemodialysis can have specific adverse effects, so it's critical to minimize them by employing non-pharmacological techniques. This review's primary goal was to assess how hope therapy affected the treatment of hemodialysis patients. This review was conducted by analyzing the results of previous studies published between 1996 and 2023. We chose sixteen studies in consideration of the inclusion and exclusion criteria and by employing Medical Subject Headings (MeSH) terms to the literature discussed in international databases. The findings of the current study revealed that hope therapy can significantly reduce anxiety, stress, and depression and also considerably increase happiness, quality of life, and adherence to treatment in hemodialysis patients. In addition, effective interventions for improving hope in hemodialysis patients included spiritual counseling, spiritual therapy, stress management training, intervention based on disease perception, positive thinking training, and other similar methods. Based on the findings, we concluded that the caregivers of hemodialysis patients and their families must use other non-pharmacological methods, especially hope therapy, to reduce the adverse outcomes of hemodialysis.

Protective effect of cilostazol on vascular injury in rats with acute ischemic stroke complicated with chronic renal failure.

Chronic renal failure (CRF) resulting in vascular calcification, which does damage to blood vessels and endothelium, is an independent risk factor for stroke. It has been reported that cilostazol has a protective effect on the focal cerebral ischemic infarct. However, its impact on vascular injury in CRF combined stroke and its molecular protection mechanism have not been investigated. In this study, we carried out the effect of cilostazol on CRF combined stroke rats, and the results confirmed that it improved the neurobehavior, renal function as well as pathologic changes in both the kidney and brain. In addition, the inflammation and oxidative stress factors in the kidney and brain were suppressed. Moreover, the rates of brain edema and infarction were decreased. The injured brain-blood barrier (BBB) was recovered with less Evans blue extravasation and more expressions of zonula occludens-1(ZO-1) and occludin. More cerebral blood flow (CBF) in the ipsilateral hemisphere and more expression of CD31 and vascular endothelial growth factor (VEGF) in brain and kidney were found in the cilostazol group. Furthermore, cell apoptosis and cell autophagy became less, on the contrary, proteins of vascular endothelial growth factor receptor 2 (VEGFR2) after the cilostazol treatment were increased. More importantly, this protective effect is related to the pathway of Janus Kinase (JAK)/signal transducer and activator of transcription 3 (STAT3), mammalian target of rapamycin (mTOR), and the hypoxia inducible factor-1α (HIF-1α). In conclusion, our results confirmed that cilostazol exerted a protective effect on the brain and kidney function, specifically in vascular injury, oxidative stress, cell apoptosis, cell autophagy, and inflammation response in CRF combined with stroke rats which were related to the upregulation of JAK/STAT3/mTOR signal pathway. Supplementary Information: The online version contains supplementary material available at 10.1007/s43188-023-00217-w.

Deep learning algorithms for predicting renal replacement therapy initiation in CKD patients: a retrospective cohort study.

BACKGROUND: Chronic kidney disease (CKD) requires accurate prediction of renal replacement therapy (RRT) initiation risk. This study developed deep learning algorithms (DLAs) to predict RRT risk in CKD patients by incorporating medical history and prescriptions in addition to biochemical investigations. METHODS: A multi-centre retrospective cohort study was conducted in three major hospitals in Hong Kong. CKD patients with an eGFR < 30ml/min/1.73m2 were included. DLAs of various structures were created and trained using patient data. Using a test set, the DLAs' predictive performance was compared to Kidney Failure Risk Equation (KFRE). RESULTS: DLAs outperformed KFRE in predicting RRT initiation risk (CNN + LSTM + ANN layers ROC-AUC = 0.90; CNN ROC-AUC = 0.91; 4-variable KFRE: ROC-AUC = 0.84; 8-variable KFRE: ROC-AUC = 0.84). DLAs accurately predicted uncoded renal transplants and patients requiring dialysis after 5 years, demonstrating their ability to capture non-linear relationships. CONCLUSIONS: DLAs provide accurate predictions of RRT risk in CKD patients, surpassing traditional methods like KFRE. Incorporating medical history and prescriptions improves prediction performance. While our findings suggest that DLAs hold promise for improving patient care and resource allocation in CKD management, further prospective observational studies and randomized controlled trials are necessary to fully understand their impact, particularly regarding DLA interpretability, bias minimization, and overfitting reduction. Overall, our research underscores the emerging role of DLAs as potentially valuable tools in advancing the management of CKD and predicting RRT initiation risk.

Significance of genetic analysis in adult patients with inherited chronic kidney disease.

Genetic focal segmental glomerulosclerosis (FSGS) is an important but underestimated cause of inherited proteinuric chronic kidney disease (CKD) in adults. We discuss a case of familial CKD due to inverted formin 2 (INF2) gene mutation, where three siblings had disparate phenotypic presentations ranging from CKD with subnephrotic proteinuria to nephrotic-range proteinuria with collapsing FSGS on kidney biopsy over a period of 8 years. The youngest sibling was the index case. The family agreed to undergo genetic testing only after two more siblings were diagnosed with kidney disease. This case highlights how clinical heterogeneity, absence of family history in the index case, initial lack of specific biopsy-proven diagnosis and reluctance to undergo genetic testing can delay the diagnosis of genetic kidney disease in adults.

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.

Correlation between urine anion gap and urine ammonia-creatinine ratio in healthy cats and cats with kidney disease.

BACKGROUND: Ammonium excretion decreases as kidney function decreases in several species, including cats, and may have predictive or prognostic value in patients with chronic kidney disease (CKD). Urine ammonia measurement is not readily available in clinical practice, and urine anion gap (UAG) has been proposed as a surrogate test. OBJECTIVES: Evaluate the correlation between urine ammonia-to-creatinine ratio (UACR) and UAG in healthy cats and those with CKD and determine if a significant difference exists between UAG of healthy cats and cats with CKD. ANIMALS: Urine samples collected from healthy client-owned cats (n = 59) and those with stable CKD (n = 17). METHODS: Urine electrolyte concentrations were measured using a commercial chemistry analyzer and UAG was calculated as ([sodium] + [potassium]) - [chloride]. Urine ammonia and creatinine concentrations had been measured previously using commercially available enzymatic assays and used to calculate UACR. Spearman's rank correlation coefficient between UAG and UACR was calculated for both groups. The UAG values of healthy cats and cats with CKD were assessed using the Mann-Whitney test (P < .05). RESULTS: The UAG was inversely correlated with UACR in healthy cats (P < .002, r0 = -0.40) but not in cats with CKD (P = .55; r0 = -0.15). A significant difference was found between UAG in healthy cats and those with CKD (P < .001). CONCLUSIONS AND CLINICAL IMPORTANCE: The UAG calculation cannot be used as a substitute for UACR in cats. The clinical relevance of UAG differences between healthy cats and those with CKD remains unknown.

Randomised, blinded, cross-over evaluation of the palatability of and preference for different potassium binders in participants with chronic hyperkalaemia in the USA, Canada and Europe: the APPETIZE study.

OBJECTIVES: Traditional potassium (K+) binders for treating hyperkalaemia are unpalatable and poorly tolerated. Newer K+ binders are reportedly better tolerated; however, no published data describe their palatability, a determinant of long-term adherence. This study evaluated the palatability of and preference for three K+ binders: sodium and calcium polystyrene sulfonate (S/CPS), sodium zirconium cyclosilicate (SZC) and calcium patiromer sorbitex (patiromer). DESIGN: Phase 4, randomised, participant-blinded, cross-over study. Participants were randomised to one of six taste sequences and, using a 'sip and spit' approach, tasted each K+ binder before completing a survey. SETTING: 17 centres across the USA, Canada and European Union. PARTICIPANTS: 144 participants with chronic kidney disease, hyperkalaemia and no recent use of K+ binders. MAIN OUTCOME MEASURES: For the primary (USA) and key secondary (Canada and European Union) endpoints, participants rated palatability attributes (taste, texture, smell and mouthfeel) and willingness to take each K+ binder on a scale of 0-10 (rational evaluation). Feelings about each attribute, and the idea of taking the product once daily, were evaluated using a non-verbal, visual measure of emotional response. Finally, participants ranked the K+ binders according to palatability. RESULTS: In each region, SZC and patiromer outperformed S/CPS on overall palatability (a composite of taste, texture, smell and mouthfeel), based on rational evaluation and emotional response. Taking the product once daily was more appealing for SZC and patiromer, creating greater receptivity than the idea of taking S/CPS. The emotional response to mouthfeel had the strongest influence on feelings about taking each product. In each region, a numerically greater proportion of participants ranked SZC as the most preferred K+ binder versus patiromer or S/CPS. CONCLUSIONS: Preference for more palatable K+ binders such as SZC and patiromer may provide an opportunity to improve adherence to long-term treatment of hyperkalaemia. TRIAL REGISTRATION NUMBER: NCT04566653.