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Diabetic nephropathy, also known as diabetic kidney disease (DKD), remains a challenge in clinical practice as this is the major cause of kidney failure worldwide. Clinical trials do not answer all the questions raised in clinical practice and real‐world evidence provides complementary insights from randomized controlled trials. Real‐life longitudinal data highlight the need for improved screening and management of diabetic nephropathy in primary care. Adherence to the recommended guidelines for comprehensive care appears to be suboptimal in clinical practice in patients with DKD. Barriers to the initiation of sodium‐glucose cotransporter‐2 (SGLT2) inhibitors for patients with DKD persist in clinical practice, in particular for the elderly. Attainment of blood pressure targets often remains an issue. Initiation of glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) in routine clinical practice is associated with a reduced risk of albuminuria progression and a possible beneficial effect on kidney function. Real‐world evidence confirms a beneficial effect of SGLT2 inhibitors on the decline of glomerular filtration, even in the absence of albuminuria, with a lower risk of acute kidney injury events compared to GLP‐1RA use. In addition, SGLT2 inhibitors confer a lower risk of hyperkalaemia after initiation compared with dipeptidyl peptidase‐4 inhibitors in patients with DKD. Data from a large population indicate that diuretic treatment increases the risk of a significant decline in glomerular filtration rate in the first few weeks of treatment after SGLT2 inhibitor initiation. The perspective for a global approach targeting multifaceted criteria for diabetic individuals with DKD is emerging based on real‐world evidence but there is still a long way to go to achieve this goal. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) is a major global health problem, affecting about 9.5% of the population and 850 million people worldwide. In primary care, most CKD is caused by diabetes and/or hypertension, but a substantial proportion of cases may have alternative causes. During the early stages, CKD is asymptomatic, and many people are unaware that they are living with the disease. Despite the lack of symptoms, CKD is associated with elevated risks of cardiovascular disease, progressive kidney disease, kidney failure and premature mortality. Risk reduction strategies are effective and cost‐effective but require early diagnosis through testing of the estimated glomerular filtration rate and albuminuria in high‐risk populations. Once diagnosed, the treatment of CKD centres around lifestyle interventions, blood pressure and glycaemic control, and preventative treatments for cardiovascular disease and kidney disease progression. Most patients with CKD should be managed with statins, renin‐angiotensin‐aldosterone system inhibitors and sodium‐glucose cotransporter‐2 inhibitors. Additional treatment options to reduce cardiorenal risk are available in patients with diabetes, including glucagon‐like peptide‐1 receptor agonists and non‐steroidal mineralocorticoid receptor antagonists. The Kidney Failure Risk Equation is a new tool that can support the identification of patients at high risk of progressive kidney disease and kidney failure and can be used to guide referrals to nephrology. This review summarizes the latest guidance relevant to managing adults with, or at risk of, CKD and provides practical advice for managing patients with CKD in primary care. [ABSTRACT FROM AUTHOR]

The role of aldosterone has yet to be well appreciated in chronic kidney disease (CKD). Two variables define CKD: an estimated glomerular filtration rate of <60 ml/min/1.73 m2 and a spot urine albumin‐creatinine ratio of >30 mg/g. Both are needed for an accurate diagnosis. The presence of CKD at this level is associated with an elevated risk of cardiovascular death and a greater risk of CKD progression to kidney failure and subsequent dialysis. This paper presents an overview of aldosterone's importance in CKD and its contribution to the inflammatory processes involved in CKD development. Data on outcomes, both surrogate and hard, related to outcomes on CKD progression will also be discussed in the context of mineralocorticoid blockade. Based on recent epidemiological data as well as data examining markers of diabetic kidney disease progression, it is clear that use of both renin‐angiotensin system inhibitors and aldosterone receptor antagonists have a significant role in altering the natural history of kidney disease progression itself, as well as reducing the risk of cardiovascular events that generally accompany long‐standing kidney disease. This paper will discuss these issues and the management of consequent hyperkalaemia when both steroidal and non‐steroidal mineralocorticoid receptor antagonists are used in detail. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) is a major healthcare challenge, affecting >800 million people worldwide. Implications for population health result from the strong associations of CKD with increased rates of cardiovascular disease, heart failure, progressive CKD leading to kidney failure, acute kidney injury (AKI), and mortality. In addition to a single disease perspective, CKD commonly coexists alongside other long‐term conditions, in particular type 2 diabetes and cardiovascular disease. CKD is therefore an important component of multimorbidity that influences individual management and impacts prognosis. CKD is defined by abnormalities of kidney structure or function of any cause with implications for health that are present for longer than 3 months. The diagnosis is usually made on the basis of an abnormal glomerular filtration rate (GFR < 60 mL/min/1.73 m2) and/or the presence of proteinuria (urine albumin to creatinine ratio > 30 mg/g or >3 mg/mmol). GFR is usually estimated from serum creatinine concentration using a variety of validated equations. However, serum creatinine is closely related to muscle mass and may therefore not be an accurate marker of GFR in people with high or low muscle mass (sarcopaenia). Cystatin C is an alternative endogenous marker of GFR that is increasingly being used but also has limitations. An estimate of GFR based on both creatinine and cystatin C is the most accurate. Diagnosis should be followed by classification and risk stratification to guide the development of a risk‐based, personalized care plan. Improved detection and widespread implementation of optimal CKD management has the potential to bring major benefits to population health. [ABSTRACT FROM AUTHOR]

Anti‐phospholipid syndrome (APS) nephropathy is an autoimmune disease that is sometimes accompanied by systemic lupus erythematosus (SLE). Here, we report the use of rituximab to treat a case of APS nephropathy in a SLE patient with recurrent vascular thrombosis. A 52‐year‐old woman, who had been diagnosed with SLE 11 years earlier, was referred to a nephrology clinic for evaluation of azotaemia and proteinuria. She had experienced spontaneous abortion at 35 years of age. The patient had been diagnosed with right popliteal thrombosis at 39 years of age, and with left pulmonary artery thrombosis and SLE at 41 years of age. Before admission, she was undergoing anticoagulant and immunosuppressive therapies, with follow‐up in the rheumatology clinic. At her last outpatient clinic visit before admission, she exhibited mild bilateral lower‐limb pitting oedema, impaired renal function and proteinuria. Renal biopsy revealed arteriolar wall thickening, with thrombi in the capillary lumina and marked inflammatory cell infiltration in the interstitium. The patient was treated with warfarin and high‐dose corticosteroids. Intravenous rituximab (500 mg) was also administered twice at a 4‐week interval. Her renal function did not worsen any further, and her proteinuria decreased. Here we report the successful use of rituximab to treat APS nephropathy in a patient with SLE, who had progressive renal insufficiency. [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusions To compare cardiorenal outcomes of dipeptidyl peptidase‐4 inhibitors (DPP‐4is) and sodium‐glucose co‐transporter‐2 inhibitors (SGLT‐2is) in a national diabetic kidney disease (DKD) population.A cohort study was conducted using Taiwan's National Health Insurance Research Database and Laboratory Databases. Propensity score‐matched prevalent new users of SGLT‐2is (n = 1524) and DPP‐4is (n = 6005) during 2017‐2018 were selected from adults with DKD and an estimated glomerular filtration rate (eGFR) of less than 60 mL/min/1.73m2. Composite renal outcomes included sustained eGFR decrease, renal failure and renal mortality. Composite cardiovascular (CV) outcomes included acute myocardial infarction, stroke, hospitalization for heart failure and CV death. Cox proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs).Compared with DPP‐4i users, SGLT‐2i users had a reduced risk of composite renal endpoint (HR: 0.16; CI: 0.12‐0.24), consistently for a prolonged time to 50% or higher eGFR decrease (HR 0.17; CI: 0.11‐0.27), renal failure (HR: 0.14; CI: 0.08‐0.23) and decreased renal death (HR: 0.10; CI: 0.01‐0.70). SGLT‐2i users had a better composite CV outcome than DPP‐4i users (HR: 0.74; CI: 0.64‐0.85), and lower risks of stroke (HR: 0.76; CI: 0.62‐0.92) and hospitalization for heart failure (HR: 0.68; CI: 0.55‐0.84). Findings were consistent in analyses stratified by concomitant antidiabetic agents or intervals between DKD diagnosis and study drug initiation.This study shows the superior cardiorenal benefits of SGLT‐2is compared with DPP‐4is in the DKD population, regardless of concomitant antidiabetic agents or time from DKD onset to study drug initiation. SGLT‐2is should be prioritized in adult patients with DKD. [ABSTRACT FROM AUTHOR]

Psoriasis is an immune‐mediated chronic inflammatory skin disease and chronic kidney disease is one of the common comorbidities of psoriasis. Ixekizumab, a humanized IgG4 monoclonal antibody, has been approved for the treatment of moderate‐to‐severe plaque psoriasis in recent years. However, ixekizumab has not been studied in a population of patients with renal insufficiency. We report two cases of plaque psoriasis patients with renal dysfunction successfully treated with ixekizumab without dose reduction，which experience no side effects and does not cause further kidney injury. [ABSTRACT FROM AUTHOR]

Immunoglobulin A (IgA) nephropathy is the most common primary glomerulonephritis worldwide and thought to be a benign disease. Recent literature review would suggest otherwise, with outcomes remaining generally poor. Few patients do not progress to kidney failure in their lifetime even in population groups previously thought to be low risk. The previously established treatment approach predominantly focuses on supportive care through renin–angiotensin–aldosterone system inhibition and steroid‐based immunosuppression in selected cases. However, recent advances in the understanding of the pathogenic mechanisms underlying this disease process have allowed for the development of new target therapies. This brief review provides an overview of improved understanding of IgA nephropathy and novel therapeutic strategies. [ABSTRACT FROM AUTHOR]

Aims Materials and Methods Results Conclusions Chronic kidney disease (CKD) and obesity are major global health challenges, eventually leading to kidney replacement therapy (KRT), but body mass index (BMI) thresholds hinder kidney transplantation. Glucagon‐like peptide‐1 receptor agonists induce weight loss, thereby offering attractive treatment options; however, their safety and efficacy have not been systematically investigated in patients undergoing dialysis.We conducted a prospective 12‐week, open‐label trial with 13 patients who had a BMI ≥ 30.00 kg/m2, were undergoing dialysis (12 haemodialysis and 1 peritoneal dialysis) and had not been listed for transplantation due to their weight. Semaglutide was administered once weekly subcutaneously, and the dose was increased from 0.25 mg to 0.5 mg and then to 1 mg. Study endpoints included change in body weight and BMI (primary – statistically evaluated by repeated measures analysis of variance [ANOVA]), side effects, adverse events, blood parameters and patient‐reported outcomes (secondary).At baseline, the mean age ± standard deviation of patients was 64.0 ± 6.4 years, the mean weight was 113.9 ± 16.6 kg, and the mean BMI was 37.3 ± 3.9 kg/m2. At week 12, average weight reduction under semaglutide treatment was 4.6 ± 2.4 kg and ranged from 2.0 to 9.7 kg (p < 0.001 for weight and BMI reduction across the study period). One patient discontinued treatment due to nausea/vomiting, two patients died of unrelated causes and six patients reported side effects. Approximately 9 months after the treatment started, three patients were able to seriously reconsider being listed for transplantation.Semaglutide treatment resulted in significant reduction in weight and BMI in patients with obesity undergoing dialysis, while maintaining an acceptable side effect profile comparable to that of the non‐dialysis population. [ABSTRACT FROM AUTHOR]

Aim Method Results Conclusion Optimal care for patients with kidney failure reduces the risks of adverse health outcomes, including cardiovascular events and death. We evaluated data from the third iteration of the International Society of Nephrology Global Kidney Health Atlas (ISN‐GKHA) to assess the capacity for quality service delivery for kidney failure care across countries and regions.We explored the quality of kidney failure care delivery and the monitoring of quality indicators from data provided by an international survey of stakeholders from countries affiliated with the ISN from July to September 2022.One hundred and sixty seven countries participated in the survey, representing about 97.4% of the world's population. In countries where haemodialysis (HD) was available, 81% (n = 134) provided standard HD sessions (three times weekly for 3–4 h per session) to patients. Among countries with peritoneal dialysis (PD) services, 61% (n = 101) were able to provide standard PD care (3–4 exchanges per day). In high‐income countries, 98% (n = 62) reported that >75% of centers regularly monitored dialysis water quality for bacteria compared to 28% (n = 5) of low‐income countries (LICs). Capacity to monitor the administration of immunosuppression drugs was generally available in 21% (n = 4) of LICs, compared to 90% (n = 57) of high‐income countries. There was significant variability between and within regions and country income groups in reporting the quality of services utilized for kidney replacement therapies.Quality assurance standards on diagnostic and treatment tools were variable and particularly infrequent in LICs. Standardization of delivered care is essential for improving outcomes for people with kidney failure. [ABSTRACT FROM AUTHOR]

Introduction: This multi‐centre retrospective cohort study aimed to determine whether the cause of an undiagnosed pleural effusion differed depending on if a patient presented as an outpatient or inpatient. Methods: A total of 1080 adult patients (556 inpatients and 524 outpatients) presenting primarily with an undiagnosed pleural effusion from 1 January 2021 to 31 December 2022 from four UK hospitals were included. Results: We found malignant effusions were more common in outpatients compared to inpatients (48.3% vs. 36.0% p < 0.0001). Infection was common in inpatients but uncommon in outpatients (36.2% vs. 5.0% p < 0.0001). Other causes in all patients included heart and/or renal failure (13.1%) and non‐specific pleuritis (5.6%). No diagnosis was possible in 11.8% of patients referred. Conclusion: Investigative pathways should vary depending on whether patients present as an inpatient or outpatient. [ABSTRACT FROM AUTHOR]

Background: To investigate the efficacy of bilirubin reduction by hemoadsorption with CytoSorb® in patients with acute‐on‐chronic liver failure (ACLF) receiving continuous renal replacement therapy (CRRT). Methods: A prospective, randomized, single‐center, open‐label, controlled pilot trial. Patients with ACLF, acute kidney injury, and serum bilirubin ≥5 mg/dL were assigned 1:1:1 to one of three study groups (CRRT with or without hemoadsorption, no CRRT). In the hemoadsorption group, the CytoSorb adsorber was incorporated into the CRRT system, replaced after 12, 24, and 48 h, and removed after 72 h. The primary endpoint was the serum bilirubin level after 72 h. Results: CYTOHEP was terminated early due to difficulties in recruiting patients and ethical concerns. Three of 9 patients (33%) were treated in each group. Comparing the three groups, mean bilirubin levels after 72 h were lower by −8.0 mg/dL in the "CRRT with hemoadsorption" group compared to "CRRT without hemoadsorption" (95% CI, −21.3 to 5.3 mg/dL; p = 0.17). The corresponding mean difference between "CRRT without hemoadsorption" and "no CRRT" was −1.4 mg/dL (95% CI, −14.2 to 11.5 mg/dL; p = 0.78). Comparing "CRRT with hemoadsorption" and "no CRRT," it was −9.4 mg/dL (95% CI, −20.8 to 2.1 mg/dL; p = 0.0854). Only 1/9 patients (11%, "no CRRT" group) survived day 30 after study inclusion but died on day 89. IL‐6, liver function parameters, and clinical scores were similar between the study groups. Conclusions: CYTOHEP failed to demonstrate that extracorporeal hemoadsorption combined with CRRT can reduce serum bilirubin in ACLF patients with acute kidney failure. [ABSTRACT FROM AUTHOR]

Research has evidenced that purpose in life helps to minimise the strains of providing informal care to a significant other, but little is known about whether this psychological resource influences the paths from stressors to the health outcomes of family caregiving and through which mechanisms it can exert this protective effect. This study aimed to explore the moderating role of purpose in life on the (mediated through adaptive coping) relationship between caregiver burden and psychological distress in haemodialysis caregivers. A cross‐sectional study was conducted with a convenience sample of family caregivers (n = 173; M = 55.9, SD = 15.6 years old) of adults undergoing haemodialysis. A moderated‐mediation model was computed to explore the interaction effects of purpose in life on the path between burden and distress, having adaptive coping behaviours as parallel mediators. Results showed that purpose in life had a buffering effect on the mediated (through acceptance coping) relationship between burden and distress (index of partial moderated‐mediation: bsimple = −0.029, 95% bootstrap confidence interval (CI) [‐0.070, −0.002]), and that this conditional effect was lowest at high levels of the moderator (at +1SD: bsimple = 0.038, SE = 0.026, 95% bootstrap CI [0.001, 0.098]). Use of emotional support (F(1,159) = 4.395, p = 0.038) and positive reframing (F(1,159) = 5.648, p = 0.019) also mediated this path. This study expands knowledge about the modifiable internal resources through which purpose in life can help promote psychosocial adjustment to the haemodialysis caregiving process. Mental health promotion initiatives aimed at this population need to consider combining different intervention approaches to foster purpose in life and train adaptive (and flexible) coping skills. [ABSTRACT FROM AUTHOR]

ABSTRACT Wolf isotopic response (WIR) is a phenomenon in which a second, unrelated skin disease arises at the same site as a previously healed dermatosis. WIR most commonly occurs in healed herpes zoster but has also been described in other conditions, such as herpes simplex virus, varicella‐zoster virus, and skin tumors. Acquired perforating dermatosis (APD) is characterized by transepidermal elimination of collagen bundles that lead to the development of ulcerative papules, which are often associated with systemic conditions such as diabetes or renal failure. This report documents a rare occurrence of APD after WIR and reviews related published works. [ABSTRACT FROM AUTHOR]

Aims: To provide an overview of the primary outcomes and key clinical implications of the CANVAS Program and CREDENCE trial, which were event‐driven, double‐blind randomized controlled trials that established the efficacy and safety of canagliflozin in those with type 2 diabetes (T2D) and high cardiovascular risk (CV) or albuminuric chronic kidney disease (CKD). Methods and Results: The CANVAS programme (CANVAS and CANVAS‐R trials) randomized 10 142 people with T2D and high CV risk to canagliflozin or placebo and followed them for a median of 126 weeks. The primary efficacy outcome was met, with canagliflozin treatment associated with a 14% reduction in major adverse CV events (hazard ratio [HR] 0.86, 95% confidence interval [CI] 0.75 to 0.97; p < 0.001) as compared to placebo. The CREDENCE trial randomized 4401 individuals with T2D and albuminuric CKD to canagliflozin or placebo and followed them for 109 weeks. The CREDENCE trial also met its primary endpoint; canagliflozin treatment was associated with a 30% reduction in the composite of kidney failure, sustained doubling of serum creatinine level, or death from kidney or CV causes (HR 0.70, 95% CI 0.59 to 0.82; p < 0.001). Substantial reductions in hospitalization for heart failure (CANVAS: HR 0.67, 95% CI 0.52 to 0.87; CREDENCE: HR 0.61, 95% CI 0.47 to 0.80) and other key CV and kidney outcomes were also identified. Relative clinical benefits were consistent across subgroups defined by baseline age, sex, kidney function and history of CV disease but absolute benefits were greatest in those at highest baseline risk. Total serious adverse events were less common with canagliflozin treatment. Concerns about amputation and fracture risk observed in the CANVAS Program were not seen in CREDENCE and appear to have been spurious chance findings. Conclusion: Canagliflozin reduced important CV, kidney and mortality outcomes in those with T2D and high CV risk or CKD across diverse patient groups, with a good safety profile. Taken together with the other sodium‐glucose cotransporter‐2 inhibitor CV and renal outcomes trials, these landmark findings have changed the treatment landscape for patients worldwide. [ABSTRACT FROM AUTHOR]

Depletion of veins for dialysis access is a challenging life threatening situation for patients in need of haemodialysis. The utilisation of intracardiac catheter is a rare procedure with scarce reported experience. We describe the case of a 68‐year‐old male that contributes to the limited knowledge of performing a life‐saving intracardiac catheter placement for emergency haemodialysis in a patient without immediate alternative renal replacement therapy available. We also retrospectively analyse the experience reported so far and summarise complications and outcomes. In our case, the patient was able to pursue haemodialysis after intracardiac catheter placement without any complications. Two weeks later, the patient successfully received a kidney transplant from a deceased donor and has a serum creatinine of 1.7 mg/dL after 2 years of follow‐up. There are only four reported cases of kidney transplantation after the procedure, including our own. Intracardiac catheter is an emerging option that could be considered in certain patients as the last resort. Further investigation with regards to patient candidacy and procedure security are necessary. [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusion Determining specific causes of allograft failure allows a focus on understanding and treating these conditions. Previous studies highlight chronic antibody‐mediated rejection as a leading cause of late allograft failure. We sought to define causes of allograft failure in a large cohort of kidney transplant recipients across multiple centres in Australia and New Zealand, including cases previously attributed to chronic allograft nephropathy (CAN).All death‐censored allograft failures at 9 participating centres between 1 January 2014 to 31 December 2018 were included. Available clinical and biopsy data were reviewed and the “most likely” cause assigned.There were 642 death‐censored allograft failures in the study period. Of these, 495 (77.1%) had an informative biopsy performed a median of 13.4 months (IQR 2.5–39.1 months) prior to allograft failure. Rejection of any type was the leading cause of allograft failure (47.5%), comprised chiefly of chronic antibody‐mediated rejection (37.4%) and chronic T‐cell mediated rejection (6.4%). Other leading causes were undifferentiated interstitial fibrosis and tubular atrophy (10.8%), late medical and surgical complications (8.1%) and recurrent or de novo glomerulonephritis (7.0%). Polyoma viral nephropathy and calcineurin inhibitor toxicity each contributed to <2%. Causes of allograft failure previously attributed to CAN (n = 419, 65.3%) had a similar distribution to the overall cohort, with 43.9% attributed to chronic antibody‐mediated rejection.To prolong allograft survival, improved strategies are needed to curtail alloimmune responses. Greater understanding of the causes of undifferentiated interstitial fibrosis and tubular atrophy and potential treatments would also be of considerable benefit. [ABSTRACT FROM AUTHOR]

Background Aims Materials and Methods Results Conclusions Current understanding of clinical practice and care for maternal kidney disease in pregnancy in Australia is hampered by limitations in available renal‐specific datasets.To capture the epidemiology, management, and outcomes of women with significant kidney disease in pregnancy and demonstrate feasibility of a national cohort study approach.An Australian prospective study (2017–2018) using a new kidney disease‐specific survey within the Australasian Maternity Outcomes Surveillance System (AMOSS). Women who gave birth with acute kidney injury (AKI), advanced chronic kidney disease (CKD), dialysis dependence or a kidney transplant were included. Demographic data, renal and obstetric management, and perinatal outcomes were collected.Among 58 case notifications from 12 hospitals in five states, we included 23 cases with kidney transplant (n = 12), pre‐existing CKD (n = 8), newly diagnosed CKD (n = 2) and dialysis (n = 1). No cases of AKI were reported. Reporting rates were better in states with study investigators and, overall, cases were likely under‐reported. Nearly 35% of women had a non‐delivery‐related antenatal admission. Nephrology involvement was 78.3% during pregnancy and 91% post‐partum. Adverse events were increased, including pre‐eclampsia (21.7%), and preterm birth (60.9%). Women had high rates of aspirin (82.6%) and antihypertensive (73.9%) use, indwelling catheter for labour/delivery (65.2%), caesarean delivery (60.9%), and blood transfusion (21.7%).This first‐ever Australian prospective study of significant kidney diseases in pregnancy provided novel insights into renal‐specific clinical patterns and practices. However, under‐reporting was likely. Future studies need to overcome the challenges of case identification and data collection burden. [ABSTRACT FROM AUTHOR]

Alport syndrome (AS) is one of the most common inherited kidney disorders, involving pathogenic variants of COL4A3, COL4A4 and COL4A5 genes that lead to disruption of the normal structure of collagen IV protein through improper chain or heterotrimer folding or degradation of heterotrimer components. Lipoprotein glomerulopathy (LPG) is an autosomal dominant disease involving APOE gene mutations disturbing lipoprotein metabolism. We report the first case with both AS and LPG in an 11‐year‐old girl. The patient presented with blepharedema, and decreased vision. Laboratory examinations showed hematemesis, proteinuria, hypoproteinemia, hyperlipidemia and progressive renal failure. Renal biopsy showed the changes of LPG and AS. Whole‐exome sequencing (WES) identified two pathogenic variants, c.127C > T in exon 3 of APOE gene, and c.930 + 1G > A in exon 15 of COL4A4 gene. We emphasize the importance of early completion of renal biopsy and WES for early diagnosis of LPG and AS. [ABSTRACT FROM AUTHOR]

Advances in immunosuppressive therapy and postoperative management have greatly improved the graft and patient survival rates after kidney transplantation; however, the incidence of post‐transplant malignant tumors is increasing. Post‐renal transplantation malignant tumors are associated with renal failure, immunosuppression, and viral infections. Moreover, the risk of developing cancer is higher in kidney transplant recipients than in the general population, and the tendency to develop cancer is affected by the background and environment of each patient. Recently, cancer after kidney transplantation has become the leading cause of death in Japan. Owing to the aggressive nature and poor prognosis of genitourinary malignancies, it is crucial to understand their epidemiology, risk factors, and best practices in kidney transplant recipients. This review has a special emphasis on the epidemiology, risk factors, and treatment protocols of genitourinary malignancies in kidney transplant recipients to enhance our understanding of the appropriate management strategies. Optimal immunosuppressive therapy and cancer management for these patients remain controversial, but adherence to the general guidelines is recommended. [ABSTRACT FROM AUTHOR]

Background Study Design and Methods Results Conclusions Low titer group O whole blood (LTOWB) is commonly used for severe bleeding in trauma patients. LTOWB may also benefit young children requiring cardiac surgery with cardiopulmonary bypass (CPB) at risk of severe bleeding.In this retrospective study, children <2 years old who underwent cardiac surgery with CPB were included. Comparisons were performed between those receiving component therapy (CT) versus those receiving LTOWB plus CT (LTOWB+CT). Outcomes included drainage tube (DT) output and total transfusion volumes. Optimization‐based weighting was used for adjusted analyses between groups.There were 117 patients transfused with only CT and 127 patients transfused with LTOWB+CT. In the LTOWB+CT group, 66 were Group non‐O and 61 were Group O. Total transfusion volumes given from the start of the operation until the first 24 h in the cardiac intensive care unit was a median (IQR) 41 (10, 93) mL/kg in the CT group and 48 (28, 77) mL/kg in the LTOWB+CT group, (p = .28). Median (IQR) DT output was 22 (15–32) in CT versus 22 (16–28) in LTOWB+CT groups, (p = .27). There were no differences in death, renal failure and a composite of death and renal failure between the two groups, but there were statistically fewer re‐explorations for bleeding in the LTOWB+CT group (p < .001).The use of LTOWB appears to be safe in <2 years old undergoing cardiac surgery and may reduce re‐explorations for severe bleeding. Large trials are needed to determine the efficacy and safety of LTOWB in this population with severe bleeding. [ABSTRACT FROM AUTHOR]

Aims Methods Results Conclusion Across its operational span of more than 25 years, the observational, nationwide, multicentre Finnish Diabetic Nephropathy (FinnDiane) Study has aimed to unravel mechanisms underlying diabetic kidney disease, with a special focus on its metabolic risk factors. We sought to compile key findings relating to this topic and to offer a current perspective on the natural course of diabetic kidney disease among individuals with type 1 diabetes.In this narrative review, articles relevant to the subject published by the FinnDiane Study were identified and summarized together with work published by others, when relevant.The FinnDiane Study has underscored the significance of dysglycaemia and insulin resistance, increased visceral fat mass, hypertension and dyslipidaemia—particularly high triglycerides and remnant cholesterol—as risk factors for diabetic kidney disease. Factors like abdominal obesity seem to influence the early stages of the disease, while the presence of the metabolic syndrome becomes implicated at later stages. Epidemiological reports have revealed that after an initial decline, the cumulative incidence of albuminuria plateaued post‐1980s, with the progression rate to kidney failure remaining high. Fortunately, 23% of the FinnDiane cohort regressed to less advanced stages of albuminuria, improving their overall prognosis.A substantial burden of albuminuria associated with type 1 diabetes persists, and therefore, novel kidney‐protecting therapies are highly awaited. In addition, given that metabolic factors influence the progression of diabetic kidney disease both in its early and advanced stages, emphasis should be placed on ensuring that their treatment targets are met. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions BK polyomavirus‐associated nephropathy (BKPyVAN) is an important cause of allograft dysfunction and failure in kidney transplant recipients (KTRs) and there are no proven effective treatments. Case reports and in vitro data support the potential activity of cidofovir against BK polyomavirus (BKPyV).We report the results of a phase I/II, double‐blind, placebo‐controlled randomized dose‐escalation trial of cidofovir in KTRs with biopsy‐confirmed BKPyVAN and estimated glomerular filtration rate ≥30 mL/min. Intravenous cidofovir (0.25 mg/kg/dose or 0.5 mg/kg/dose) or placebo was administered on days 0, 7, 21, and 35, with final follow‐up through day 49.The trial was prematurely discontinued due to slow accrual after 22 KTRs had completed the study. Cidofovir was safe and tolerated at the doses and duration studied. The proportion of subjects with any adverse event (AE) was similar between groups (9/14 [64%] in the combined cidofovir dose groups and 6/8 [75%] in the placebo group); 84% of AEs were mild. BKPyV DNAemia reduction by day 49 was similar between groups (>1 log10 reduction in (2/9 [22.2%] of 0.25 mg/kg group, 1/5 [20%] of 0.5 mg/kg group, and 2/8 [25%] of placebo group).These preliminary results indicate that low‐dose cidofovir was safe and tolerated but had no significant BKPyV‐specific antiviral effect in KTRs with BKPyVAN. [ABSTRACT FROM AUTHOR]

Summary: Idiopathic hypereosinophilic syndrome (iHES) is a condition wherein persistent hypereosinophilia associated with end‐organ damage occurs without any known causes. Due to the rarity of the disease, insufficient knowledge has been accumulated. We therefore conducted a retrospective, multicentre, nationwide survey on iHES in Japan. A total of 57 patients were identified. For 43 patients who received any treatment, all cases were first treated with corticosteroids. An eosinophil percentage of less than 30% in the bone marrow and the absence of oedema were identified as factors associated with steroid dependency. The 5‐year overall survival was 88.2%, and five patients died during follow‐up; factors associated with worse overall survival were age >50, haemoglobin <12 g/dL, activated partial thromboplastin time >34 s, the presence of dyspnoea, the presence of thrombotic tendency and the presence of renal failure. Given the rarity of fatalities in our cohort, time‐to‐next‐treatment (TTNT) was further analysed; the presence of renal failure, splenomegaly and lung abnormalities were associated with worse TTNT. Our nationwide study not only demonstrated clinical characteristics and the outcome of patients with iHES but also for the first time revealed clinical factors associated with steroid dependency and duration of first‐line corticosteroid efficacy. [ABSTRACT FROM AUTHOR]

HLA donor specific antibodies (DSA) are implicated in antibody‐mediated rejection (AMR), graft dysfunction and failure in kidney transplant (KT) recipients. Non‐HLA antibodies including angiotensin II type 1 receptor (AT1R) may also play a role in AMR, impact graft function and survival. Data is limited in paediatric KT cohorts. We aimed to assess the prevalence and effect of pre‐transplant AT1R antibodies on rejection, graft function and survival in paediatric KT recipients. This was a retrospective cohort study conducted across two paediatric centres including KT recipients with a pre‐transplant AT1R antibody level. Outcomes included rejection, de novo DSA formation, graft function, failure, proteinuria and hypertension. Of 71 individuals, 72% recorded a positive pre‐transplant AT1R Ab level (≥17 U/mL). Over a median follow‐up of 4.7 years, AT1R Ab positivity demonstrated a trend towards increased risk of rejection however was not statistically significant (HR 3.45, 95% CI 0.97–12.35, p‐value 0.06). Sensitivity analysis with AT1R Ab levels of ≥25 U/mL (HR 2.05 95% CI 0.78–5.39, p‐value 0.14) and ≥40 U/mL (HR 1.32, CI 95% 0.55–3.17, p‐value 0.53) validated this. De novo DSA formation occurred more frequently with AT1R Ab positivity (41% vs. 20%, p‐value 0.9). AT1R Ab was not associated with hypertension, proteinuria, graft failure or dysfunction. In conclusion, this cohort study demonstrated a high prevalence of pre‐transplant AT1R Ab positivity (72%). AT1R Ab positivity demonstrated a trend towards increased risk of rejection and de novo DSA formation however did not meet statistical significance. There was no association between AT1R Ab and hypertension, proteinuria, graft failure or dysfunction. [ABSTRACT FROM AUTHOR]

Background: Thrombotic microangiopathy (TMA) is a rare complication after lung transplantation (LT) that has seldom been characterized in detail. Recent evidence has linked TMA other than primary atypical hemolytic uremic syndrome (aHUS) with hyperactivation of the complement alternative pathway. The focus of this investigation was to analyze the treatment response with eculizumab in TMA after LT. Methods: Case series where we have studied 11 patients with TMA after LT from 2 Spanish tertiary healthcare centers. Clinical data and response rates to eculizumab are provided. Results: The main indication for lung transplant was chronic obstructive pulmonary disease (COPD) (36%) and most cases (82%) received bilateral LT. The median time to TMA diagnosis was 11.6 months (4.7–28.9) and the TMA trigger in the majority of cases (73%) was immunosuppressive drugs. Platelet and hemoglobin nadir were 58 × 103/µL (24–108) and 7.7 g/dL (7.1–7.9), respectively. All cases presented acute kidney injury (AKI) with a median creatinine of 4 mg/dL (3.2–4.8) and 54.5% required acute dialysis. Eculizumab was started after a median time of 8 days (6–14) with a median duration of 3 weeks (2–8). Complete TMA response was observed in 7 (63.6%) cases and hematologic response in 10 (90.9%). The time to hematologic and renal response was 23 days (13–29) and 28 days (14–46), respectively. Conclusions: TMA after LT is infrequent but potentially devastating. Our findings suggest that short cycles of eculizumab may be effective for severe TMA after LT. [ABSTRACT FROM AUTHOR]

Diabetic nephropathy is a serious metabolic disease that is usually caused by diabetes mellitus and ends in chronic kidney disease and renal failure. Many drugs used to treat diabetic nephropathy have limitations and side effects. There is an urgent need to find safe and effective new drugs for the treatment of diabetic nephropathy. The polysaccharides from natural sources, including plants, fungi, and algae, have good protective effects on diabetic nephropathy without side effects. In this paper, the natural sources, chemical composition, and structural characteristics of polysaccharides are reviewed. In addition, the study summarizes the different mechanisms that polysaccharides improve diabetic nephropathy, such as antioxidative stress, regulation of inflammation, inhibition of apoptosis, and renal fibrosis. This review provides theoretical support for the protective effect of polysaccharides and reveals potential therapeutic methods for diabetic nephropathy. [ABSTRACT FROM AUTHOR]

Adrenalectomy is the gold standard for canine adrenal tumours, but not always recommended due to patient age, underlying conditions and perioperative mortality. Ethanol ablation is an alternative in human medicine for poor surgical candidates. A 13‐year‐old neutered female toy‐poodle with hypercortisolism presented with severe haematuria. Ultrasonography revealed left adrenal and right kidney tumours. Due to high surgical risk, simultaneous laparotomic right nephroureterectomy and ethanol ablation of the left adrenal tumour were performed. Post‐ethanol injection complications included transient hypertension and arrhythmia, which resolved spontaneously. The adrenal tumour size decreased within 2.5 months, and cortisol levels normalised within 8 days, remaining stable for 12 months. No hypercortisolism signs were observed without trilostane until death from renal insufficiency. Autopsy showed that the ablated left adrenal gland was an adrenocortical tumour and had shrunk. Ethanol ablation may be a feasible alternative to adrenalectomy for high‐risk canine patients. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to examine the clinical and pathological characteristics as well as the prognosis of immunoglobulin A nephropathy (IgAN) accompanied by renal thrombotic microangiopathy (rTMA) in paediatric patients. Methods: After balancing epidemiological characteristics and pathological types between groups, 427 patients (rTMA group: 23, non‐rTMA group: 46) were included. The clinical and pathological features, prognosis and clinical risk factors of the two groups were analysed. Results: IgAN‐rTMA children showed more severe clinical and pathological manifestations. The findings from the logistic regression analysis indicated that hypercellularity 1 (E1) (HR: 0.805, 95% CI: 0.763 ~ 1.452, P =.016), endocapillary proliferation (HR: 1.214, 95% CI: 0.093 ~ 4.815, P =.025) and C3 staining (HR: 7.554, 95% CI: 2.563 ~ 15.729, P =.037) were the risk factors for rTMA in children with IgAN. The renal survival in rTMA group was lower than non‐rTMA group (χ2 = 18.467, P =.000). Cox regression analysis showed that E1 (HR: 7.441, 95% CI: 1.095 ~ 10.768, P =.037), C3 disposition (HR: 3.414, 95% CI: 0.834 ~ 11.578, P =.027) and rTMA (HR: 8.918, 95% CI: 1.032 ~ 16.754, P =.041) were identified as independent risk factors for the development of end‐stage renal disease (ESRD). Conclusion: The presence of rTMA had a significant impact on the severity and prognosis of IgAN. And rTMA has been identified as an independent risk factor for the development of renal failure in children diagnosed with IgAN. [ABSTRACT FROM AUTHOR]

Primary coenzyme Q10 deficiency‐1, caused by COQ2 disease‐causing variants, is an autosomal recessive disorder, and genetic testing is the gold standard for diagnosing this condition. A Chinese boy with steroid‐resistant nephrotic syndrome, focal segmental glomerulosclerosis, and progressive kidney insufficiency was included in the study. Electron microscopy revealed the glomerular basement membrane with irregular thickness and lamellation with diffuse effacement of foot processes in the podocytes, and swollen mitochondria with abnormal cristae in the podocytes. Coenzyme Q10 supplementation started about 3 weeks after the onset of mild kidney dysfunction did not improve the proband's kidney outcome. Proband‐only whole‐exome sequencing and Sanger sequencing revealed two heteroallelic COQ2 variants: a maternally inherited novel variant c.1013G > A[p.(Gly338Glu)] in exon 6 and a variant of unknown origin c.1159C > T[p.(Arg387*)] in exon 7. Subsequent long‐read sequencing demonstrated these two variants were located on different alleles. Our report extends the phenotypic and genotypic spectrum of COQ2 glomerulopathy. [ABSTRACT FROM AUTHOR]

Objective: The 'Connected We St@nd' is an online self‐management intervention programme for people receiving in‐centre haemodialysis and family caregivers that combines an educational and psychosocial support component. This study aimed to evaluate its feasibility and acceptability before proceeding to a large‐scale trial. Design: This was a pre‐post single‐arm feasibility pilot study conducted with adults undergoing in‐centre haemodialysis and family caregivers. Methods: Feasibility was based on eligibility, consent, retention, completion and intervention adherence rates, while acceptability was assessed in post‐intervention focus group interviews. Results: Twenty‐six people (16 adults on haemodialysis and 10 family caregivers) recruited through social networks completed the intervention. Consent, retention and completion rates were excellent (>90%) and eligibility (77.5%) and intervention adherence were satisfactory (69% for the psychosocial support sessions). Qualitative findings revealed that participants shared positive feelings regarding their participation in the programme. The valuable interactions with group peers and health psychologists during the support sessions, the perception of the adequacy and coherence of the programme's contents and materials and the participants' confidence in using the platform developed to deliver the intervention were some of the aspects highlighted as facilitators of intervention acceptability. Additionally, people on haemodialysis and caregivers reported that participation in the programme brought several educational and emotional benefits (e.g., additional disease‐related knowledge, improved communication and coping skills, greater confidence in managing dialysis complications or caregiving demands) that helped increase their self‐management skills and psychosocial adjustment to the demands of kidney failure and renal therapies. Conclusions: The results suggested that the 'Connected We St@nd' programme is likely to be feasible and acceptable for adults on haemodialysis and family caregivers, thus representing a promising resource for the future of interdisciplinary renal rehabilitation. Suggestions were made to fine‐tune the intervention design to proceed with a large‐scale trial. [ABSTRACT FROM AUTHOR]

Background: Children and young people affected by kidney failure experience complexities in their care. Little is known about the unique needs of this young patient population group living with a long‐term condition. Objective: A meta‐aggregation of all qualitative studies was conducted to identify experiences of supportive care among children and young people living with kidney failure. Methods: A systematic review of qualitative studies was conducted following the Joanna Briggs Institute meta‐aggregation method. This review has been reported according to the PRISMA statement guidelines. Six electronic databases (CINAHL, Cochrane Library, MEDLINE, Proquest, PsycINFO, and Scopus) were comprehensively searched by an expert systematic review librarian using keywords and subject headings, from inception to September 2022. All studies were accessed using a predetermined inclusion and exclusion criteria. Methodological quality assessment and data extraction performed. Qualitative findings accompanied by illustrative quotes from included studies were extracted and grouped into categories which created the overall synthesised findings. Results: A total of 34 studies were included in this review representing a total of 613 children and young people affected by kidney failure. There was a total of 190 findings which created 13 categories representing experiences of supportive care. The meta‐aggregation developed five synthesised findings namely: 'physical needs', 'information and technology', 'treatment and healthcare', 'social needs' and 'psychological impacts'. Conclusion: This systematic review identified that children and young people affected by kidney failure can experience a range of unmet supportive care needs in routine clinical services. Kidney failure impacted children and young people's self‐identify, social and peer networks, introduced daily practical needs because of inherent physical and psychological burden due to the failure and associated treatments. Despite improvements in the medical management of kidney failure in children and young people, further attention is needed to optimise supported self‐management in this young patient group. [ABSTRACT FROM AUTHOR]

Diabetic kidney disease (DKD) is the most common cause of kidney failure, characterized by chronic inflammation and fibrosis. The complement system is increasingly implicated in the development and progression of diabetic nephropathy. The important complement anaphylatoxins C3a and C5a are key mediators of the innate immune system, which regulates cellular inflammation, oxidative stress, mitochondrial homeostasis and tissue fibrosis. This review summarizes the involvement of anaphylatoxins in the pathogenesis of diabetic kidney disease, highlights their important roles in the pathophysiologic changes of glomerulopathy, tubulointerstitial damage and immune cell infiltration, and discusses the modulatory effects of new anti‐diabetic drugs acting on the complement system. Based on available clinical data and findings from the preclinical studies of complement blockade, anaphylatoxin‐targeted therapeutics may become a promising approach for patients with DKD in the future. [ABSTRACT FROM AUTHOR]

Aims Methods Results Conclusions Mitiperstat is a novel, highly potent myeloperoxidase inhibitor being evaluated in patients with cardio‐metabolic disease (phase 2). These patients often have impaired renal function, which may affect mitiperstat pharmacokinetics. This study assessed mitiperstat pharmacokinetics, safety and tolerability in participants with severe renal impairment and normal renal function, to inform inclusion of participants with estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2 in phase 3.Participants with severe renal impairment (eGFR ≥15 and <30 mL/min/1.73 m2) who were not on dialysis (n = 10) and group‐matched controls (eGFR ≥90 mL/min/1.73 m2; n = 10) received a single mitiperstat 2.5 mg oral tablet. Blood samples were collected at intervals for 2 weeks and urine samples for 24 h post‐dose.Total apparent mitiperstat clearance was 10.83 L/h in the severe renal impairment cohort and 25.62 L/h in the control cohort. The area under the plasma concentration–time curve was 2.37‐fold higher (90% confidence interval [CI]: 1.79, 3.12) in the severe renal impairment cohort than in the control cohort, with longer elimination half‐life and similar maximum concentration. Non‐renal clearance was similar between the cohorts.Mitiperstat apparent clearance was approximately twofold lower in individuals with severe renal impairment than in those with normal renal function. Lower clearance was driven by reduced renal clearance; non‐renal clearance was similar. Mitiperstat was generally well tolerated by participants with severe renal impairment and normal renal function. These findings, together with efficacy and safety/tolerability data from phase 2b, will guide the dosing regimen for phase 3. [ABSTRACT FROM AUTHOR]

Aim: To validate the Klinrisk machine learning model for prediction of chronic kidney disease (CKD) progression in patients with type 2 diabetes in the pooled CANVAS/CREDENCE trials. Materials and Methods: We externally validated the Klinrisk model for prediction of CKD progression, defined as 40% or higher decline in estimated glomerular filtration rate (eGFR) or kidney failure. Model performance was assessed for prediction up to 3 years with the area under the receiver operating characteristic curve (AUC), Brier scores and calibration plots of observed and predicted risks. We compared performance of the model with standard of care using eGFR (G1‐G4) and urine albumin‐creatinine ratio (A1‐A3) Kidney Disease Improving Global Outcomes (KDIGO) heatmap categories. Results: The Klinrisk model achieved an AUC of 0.81 (95% confidence interval [CI] 0.78‐0.83) at 1 year, and 0.88 (95% CI 0.86‐0.89) at 3 years. The Brier scores were 0.020 (0.018‐0.022) and 0.056 (0.052‐0.059) at 1 and 3 years, respectively. Compared with the KDIGO heatmap, the Klinrisk model had improved performance at every interval (P <.01). Conclusions: The Klinrisk machine learning model, using routinely collected laboratory data, was highly accurate in its prediction of CKD progression in the CANVAS/CREDENCE trials. Integration of the model in electronic medical records or laboratory information systems can facilitate risk‐based care. [ABSTRACT FROM AUTHOR]

Angiotensin II receptor blockers (ARBs) are contraindicated during pregnancy because of fetal toxicity. All previous reports on adverse fetal outcomes involved women who continued to take low‐dose ARBs for hypertension and were unaware of the adverse effects. Herein, we report the case of a 23‐year‐old pregnant woman in her third trimester who experienced an ARB overdose after an argument with her partner. Pregnancy was complicated by transient oligohydramnios, and fetal magnetic resonance imaging suggested renal failure. Despite these concerns, the newborn had no morphological abnormalities or abnormal neurological findings. Renal impairment improved over time, and the infant grew well. A single overdose of ARBs in the third trimester can lead to fetal renal failure, similar to long‐term low‐dose ARB administration; however, favorable outcomes are possible. An overdose of ARBs may transiently cause renal failure, which may improve. The study findings may inform counseling for women who are unexpectedly exposed to an overdose of ARBs. [ABSTRACT FROM AUTHOR]

Introduction: People living with HIV (PLWH) have higher rates of non‐infectious comorbid diseases (NCDs) than individuals without HIV. We characterized the risk of NCDs among PLWH with undetectable viral load and persistent low‐level viraemia (pLLV) in the African Cohort Study (AFRICOS). We secondarily quantified the role of immune activation in the association between LLV and NCDs. Methods: AFRICOS enrols participants in 12 clinics in Uganda, Kenya, Tanzania and Nigeria. Participants on antiretroviral therapy ≥ 6 months without an NCD at enrolment were included. PLLV was defined as at least two consecutive visits with a detectable viral load <1000 copies/ml. We examined elevated blood pressure, hypercholesterolemia, hyperglycaemia, renal insufficiency and a composite variable of any NCD. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazard modelling. Among a subset of participants with biomarker data, we assessed the interaction between viral load and 13 biomarkers in the association with any NCD. Results: From 23 January 2013 to 1 December 2022, 1755 participants met the inclusion criteria for these analyses. At the first eligible visit, the majority of participants had an undetectable viral load (n = 1375, 78.35%). Participants with pLLV had an increased rate of developing any NCD (aHR: 1.22, 95% CI: 1.02−1.47) compared to participants with an undetectable viral load. There was a statistically significant interaction between LLV and TNF‐α, CCL2/MCP‐1 and TNF‐RII in the association with any NCD. Conclusions: PLLV was significantly associated with NCDs and immune inflammation in this population. Aggressive management of LLV may positively impact NCDs in PLWH. [ABSTRACT FROM AUTHOR]

Background: Acute kidney injury (AKI) is a common complication of pediatric heart transplant, with a subset of patients developing severe AKI requiring dialysis (AKI‐D). We aimed to identify the epidemiology, risk factors, and outcomes of postoperative AKI‐D in pediatric heart transplant recipients. Methods: We retrospectively identified all pediatric first‐time, single‐organ heart transplants at our institution from 2014 to 2022. Postoperative AKI was defined as AKI within 2 weeks of transplant. Unadjusted and adjusted logistic regression were used to identify characteristics associated with AKI‐D, and unadjusted time‐to‐event analyses were used to determine the association between AKI‐D and survival free of kidney failure. Results: Among 177 patients included, 116 (66%) developed postoperative AKI of any stage, including 13 (7%) who developed AKI‐D with median time from transplant to dialysis initiation of 6 days (IQR 3–13). In adjusted models, increased cardiopulmonary bypass time (OR 1.19, 95% CI 1.04–1.37, per 15 min increase in bypass time) and higher weight at transplant were associated with higher odds of AKI‐D, whereas patient demographics and pretransplant kidney function were not associated with AKI‐D. AKI‐D was associated with greater mortality during initial hospitalization (46% vs. 1%, p < 0.001) and a lower rate of survival free of kidney failure. Conclusions: The incidence of AKI‐D after pediatric heart transplant was 7%, with extended cardiopulmonary bypass time associated with postoperative AKI‐D even in adjusted models. Further research is needed to improve the prediction and management of AKI‐D in this population. [ABSTRACT FROM AUTHOR]

Background: Antibody‐mediated rejection is one of the most significant risk factors for allograft dysfunction and failure in children and adolescents with kidney transplants, yet optimal treatment remains unidentified. To date, there are mixed findings regarding the use of Bortezomib, a plasma cell apoptosis inducer, as an adjunct therapy in the treatment of antibody‐mediated rejection. Methods: In a retrospective single center study, we reviewed the efficacy and tolerability of bortezomib as adjunct therapy for treatment‐refractory antibody‐mediated rejection. Results: Six patients with a median age of 14.6 years (range 6.9–20.1 years) received bortezomib at a mean of 71 months (range 15–83 months) post‐kidney transplant. Four patients experienced decline in estimated glomerular filtration rate (eGFR) from 4% to 42%. One patient started bortezomib while on hemodialysis and did not recover graft function, and another patient progressed to hemodialysis 6 months after receiving bortezomib. Although DSA did not completely resolve, there was a statistically significant decline in DSA MFI pre and 12‐months post‐BZ (p =.012, paired t‐test) for the subjects who were not on dialysis at the time of bortezomib. Chronic Allograft Damage Index (CADI) score of ≥3 was seen in all six subjects at their biopsy prior to therapy. No adverse effects were reported. Conclusions: Bortezomib was well tolerated and resulted in improvements in MFI of DSA among four pediatric subjects without allograft failure, although no effects were observed on eGFR trajectory. Further studies are needed to clarify whether earlier intervention with bortezomib could prevent renal failure progression. [ABSTRACT FROM AUTHOR]

Gout affects 15%–30% of individuals with advanced kidney disease. Allopurinol which is rapidly and extensively metabolised to an active metabolite, oxypurinol, is the most commonly prescribed urate‐lowering therapy. Oxypurinol is almost entirely eliminated by the kidneys (>95%) and has an elimination half‐life of 18–30 h in those with normal kidney function. However, oxypurinol pharmacokinetics are poorly understood in individuals with kidney failure on peritoneal dialysis. This study characterised the elimination of oxypurinol and urate in people with gout receiving peritoneal dialysis. Oxypurinol steady‐state oral clearance (CL/F), elimination half‐life as well as kidney (CLk) and peritoneal (CLpd) clearances for oxypurinol and urate were calculated from the plasma, urine and dialysate concentration data for each individual. Our results demonstrate that oxypurinol and urate are removed by peritoneal dialysis, accounting for more than 50% of oxypurinol and urate clearances. An allopurinol dose about 50%–60% lower than the usual dose used for a patient with normal kidney function will provide adequate urate‐lowering therapy. [ABSTRACT FROM AUTHOR]

Aim: Ankylosing spondylitis (AS) predominantly affects the spine and sacroiliac joints, with rare renal involvement. We investigated the incidence rate and risk factors for chronic kidney disease (CKD) in patients with AS and its relationship with long‐term nonsteroidal anti‐inflammatory drug (NSAID) use. Methods: We retrospectively analyzed data of patients diagnosed with AS from the Korean National Health Insurance service. The 3‐month, 6‐month, and 1‐year Assessment of SpondyloArthritis International Society (ASAS) NSAID Intake Scores were categorized into four groups, as follows: =0, >0 and ≤33.3, 33.3–66.6, and >66.6. Results: Of the 12 000 patients with AS, 150 were identified with CKD, and the incidence rate was 4.64 per 10 000 patient‐years. Factors significantly associated with CKD included age ≥60 years, Charlson Comorbidity Index, hypertension, and diabetes mellitus. In the nested case–control analysis, among the ASAS NSAIDs Intake Scores for 0–365 days from diagnosis, the ≥66.6 group had a significantly lower odds ratio than those of the =0 group. Conclusion: The present study established the incidence rate of CKD in Korean patients with AS. Though older age and comorbidities were found to be associated with a higher CKD risk, long‐term NSAID use was associated with a lower risk. Therefore, the optimal use of NSAIDs in inflammatory diseases requires extensive research. [ABSTRACT FROM AUTHOR]

Key Clinical Message: In recent years, it is necessary to Redo‐TAVR for the patients with bioprosthetic valve degeneration. This case report described a unique instance to successfully Redo‐TAVR a patient with bioprosthetic valve degeneration, in addition, with left cerebral infarction and renal insufficiency. Over time, more and more patients have bioprosthetic valve degeneration either used in SAVR or TAVR. In order to solve the produced problems due to the degenerated bioprosthetic valve, Redo‐TAVR was increasingly popular due to its safe and efficiency especially for the high risk and complicated symptoms patients. In this case, the patient with left cerebral infarction and renal insufficiency has exhibited severe regurgitation and obvious neoplasm around the previous replaced aortic valve. For the patient with complicated symptoms, we did not image for this patient and only used CT to determine the position and angle for the Redo‐TAVR on the base of metal stent for the previous replaced aortic valve. During the Redo‐TAVR process, for fear of the obvious neoplasm slipping from the previous replaced aortic valve to embolism of important organs, before carrying out the Redo‐TAVR, cerebral protection device, temporary pacemaker, and coronary artery protection device were utilized in order to avoid the damage for the important organs from the obvious neoplasm slipping from the previous replaced aortic valve. The surgery was successful and the patient recovered well. The patient's symptoms of chest tightness and suffocation have been greatly reduced. [ABSTRACT FROM AUTHOR]

Aims: The postvoid residual (PVR) volume of urine in the bladder is widely used in clinical practice as a guide to initiate treatment, including clean‐intermittent self‐catheterization (CISC). It is often believed that an elevated PVR causes complications such as recurrent urinary tract infections (UTI) and renal failure. However, evidence for this is limited and identifying alternative measures to guide treatment decisions may optimize patient care. At the International Consultation on Incontinence Research Society (ICI‐RS) meeting in 2023 a Think Tank addressed the question of whether we can define the optimal PVR at which CISC should be recommended, and whether there are other measures that could guide a CISC protocol. Methods: The Think Tank conducted a literature review and expert consensus meeting focusing on current limitations in defining and measuring PVR, and highlighting other measures that may optimize selection for, and persistence with, CISC. Results: There is no consensus on the threshold value of PVR that is considered "elevated" or "significant." There is a lack of standardization on terminology, and the normal range of PVR in different populations of different ages remains to be well‐studied. The measurement of PVR is influenced by several factors, including intraindividual variation, timing and method of measurement. Furthermore, the evidence linking an elevated PVR with complications such as UTI and renal failure is mixed. Other measures, such as bladder voiding efficiency or urodynamic parameters, may be better at predicting such complications, and therefore may be more relevant at guiding a CISC protocol. Conclusions: There is a lack of high quality evidence to support PVR as a predictor for complications of UTI or renal failure. Threshold values for normal PVR in different populations are unknow, and so threshold values for "elevated" or "significant" PVR cannot be determined. Other factors, such as urodynamic findings, may be better at predicting complications and therefore guiding management decisions, and this remains to be studied. Areas for further research are proposed. [ABSTRACT FROM AUTHOR]

Metabolic acidosis‐induced kidney injury (MAKI) is asymptomatic and lack of clinical biomarkers in early stage, but rapidly progresses to severe renal fibrosis and ultimately results in end‐stage kidney failure. Therefore, developing rapid and noninvasive strategies direct responsive to renal tubular acidic microenvironment rather than delayed biomarkers are essential for timely renoprotective interventions. Herein, we develop pH‐responsive luminescent gold nanoparticles (p‐AuNPs) in the second near‐infrared emission co‐coated with 2,3‐dimethylaleic anhydride conjugated β‐mercaptoethylamine and cationic 2‐diethylaminoethanethiol hydrochloride, which showed sensitive pH‐induced charge reversal and intrarenal self‐assembly for highly sensitive and long‐time (~24 h) imaging of different stages of MAKI. By integrating advantages of pH‐induced intrarenal self‐assembly and enhanced interactions between pH‐triggered positively charged p‐AuNPs and renal tubular cells, the early‐ and late‐stage MAKI could be differentiated rapidly within 10 min post‐injection (p.i.) with contrast index (CI) of 3.5 and 4.3, respectively. The corresponding maximum CI could reach 5.1 and 9.2 at 12 h p.i. respectively. Furthermore, p‐AuNPs were demonstrated to effectively real‐time monitor progressive recovery of kidney injury in MAKI mice after therapy, and also exhibit outstanding capabilities for drug screening. This pH‐responsive strategy showed great promise for feedback on kidney dysfunction progression, opening new possibilities for early‐stage diagnosis of pH‐related diseases. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) is one of the most serious non‐communicable diseases affecting the population. In the early‐stages patients have no obvious symptoms, until it becomes life‐threatening leading end‐stage kidney failure. Therefore, it is important to early diagnose CKD to allow therapeutic interventions and progression monitoring. Here, a point‐of‐care (POC) sensing platform is reported for the simultaneous detection of three CKD biomarkers, namely creatinine, urea, and human serum albumin (HSA), using reduced graphene oxide/polydopamine‐molecularly imprinted polymer (rGO/PDA‐MIP) fabricated with novel surface‐molecularly imprinting technology. A multi‐channel electrochemical POC readout system with differential pulse voltammetry (DPV) function is developed, allowing the simultaneous detection of the three biomarkers, in combination with the surface‐MIP electrodes. This sensing platform achieves the record low limit‐of‐detection (LoD) at a femtomolar level for all three analytes, with wide detection ranges covering their physiological concentrations. Clinical validation is performed by measuring these analytes in serum and urine from healthy controls and patients with CKD. The average recovery rate is 81.8–119.1% compared to the results obtained from the hospital, while this platform is more cost‐effective, user‐friendly, and requires less sample‐to‐result time, showing the potential to be deployed in resource‐limited settings for the early diagnosis and tracking progression of CKD. [ABSTRACT FROM AUTHOR]

Randomized controlled trials (RCTs) show a reduction in acute kidney injury, renal impairment and acute renal failure after initiation of a sodium glucose cotransporter‐2 inhibitor. Observational literature on the association is conflicting, but important to understand for populations with a higher risk of medication‐related adverse renal events. We aimed to systematically review the literature to summarize the association between sodium glucose cotransporter‐2 inhibitor use and acute kidney injury, renal impairment and acute renal failure in three at‐risk groups: older people aged >65 years, people with heart failure and people with reduced renal function. A systematic search of Embase (1974 until 23 February 2024) and PubMed (1946 until 23 February 2024) was performed. RCTs were included if they reported numbers of acute kidney injury or acute renal failure in people using sodium glucose cotransporter‐2 inhibitors compared to other diabetic therapies. Studies needed to report results by level of renal function, heart failure status or age. Of 922 results, eight studies were included. The absolute risk of acute kidney injury or acute renal failure was higher in people >65 years compared to those <65 years, higher in people with heart failure (vs without) and higher in people with reduced kidney function (vs preserved kidney function), but insufficient evidence to determine if the relative effect of sodium glucose cotransporter‐2 inhibitors on this risk was similar for each group. At‐risk cohorts are associated with a higher incidence of acute kidney problems in users of sodium glucose cotransporter‐2 inhibitors. [ABSTRACT FROM AUTHOR]

Introduction: Broad national or international programs contribute to mitigating the expected longer waiting list (WL) time for sensitized patients but with minor benefits for highly sensitized subjects. Therefore, strategies to prevent high sensitization are urgently required. In this study, we investigated the risk of developing highly sensitized patients with different immunosuppressive (IS) handling after kidney allograft failure (KAF). Methods: Data from 185 patients with KAF, retransplanted/relisted from 2010 to 2020 in two regions of Italy that share the same regional WL, were analyzed. Patients were categorized according to IS management at 12 months after KAF as follows: patients maintaining IS with calcineurin inhibitors (CNI) (late withdrawal group [LWG], n = 58) and those who withdrew all IS therapy or were on steroids only (early withdrawal group [EWG], n = 127). Results: Patients in the LWG showed lower panel reactive antibodies (PRA) at 12 (29.0% vs. 85.5%, p < 0.001) and 24 months (61.0% vs. 91.0%, p = 0.001), reduced risk of high sensitization (PRA ≥90%) at 12 (9.4% vs. 40.7%, p < 0.001, OR = 0.15) and 24 months (25.6% vs. 57.3%, p = 0.001, OR = 0.26) and almost no very high sensitization (PRA ≥ 98%) at 12 months (1.9% vs. 18.6%, p = 0.003, OR = 0.08) after KAF. In the LWG subgroup analysis, patients who maintained IS for up to 24 months after KAF did not show very high sensitization. The LWG showed shorter active WL times (406 vs. 813 days, p = 0.001) without an increased risk of complications. Conclusions: CNI maintenance for at least 12 months after KAF could be a useful approach to prevent high sensitization and reduce WL times in patients who are offered retransplantation, without a higher burden of complications. [ABSTRACT FROM AUTHOR]

Excessive dietary phosphorus is a concern among patients with kidney failure undergoing dialysis treatment because it may contribute to hyperparathyroidism and hyperphosphatemia. A long‐standing but untested component of the low‐phosphorus diet is the promotion of refined grains over whole grains. This paper reviews the scientific premise for restricting whole grains in the dialysis population and estimates phosphorus exposure from grain products based on three grain intake patterns modeled from reported intakes in the general US population, adjusting for the presence of phosphorus additives and phosphorus bioavailability: (1) standard grain intake, (2) 100% refined grain intake, and (3) mixed (50/50 whole and refined grain) intake. Although estimated phosphorus exposure from grains was higher with the mixed grain pattern (231 mg/day) compared to the 100% refined grain pattern (127 mg/day), the amount of additional phosphorus from grains was relatively low. Given the lack of strong evidence for restricting whole grains in people with CKD, as well as the potential health benefits of whole grains, clinical trials are warranted to address the efficacy and health impact of this practice. [ABSTRACT FROM AUTHOR]

Cultural safety is increasingly recognised as imperative to delivering accessible and acceptable healthcare for First Nations Peoples within Australia and in similar colonised countries. A literature review undertaken to inform the inaugural Caring for Australians with Renal Insufficiency (CARI) guidelines for clinically and culturally safe kidney care for Aboriginal and Torres Strait Islander peoples revealed a timeline of the emergence of culturally safe kidney care in Australia. Thirty years ago, kidney care literature was purely biomedically focused, with culture, family and community viewed as potential barriers to patient 'compliance' with treatment. The importance of culturally informed care was increasingly recognised in the mid‐1990s, with cultural safety within kidney care specifically cited from 2014 onwards. The emergence timeline is discussed in this paper in relation to the five principles of cultural safety developed by Māori nurse Irihapeti Ramsden in Aotearoa/New Zealand. These principles are critical reflection, communication, minimising power differences, decolonisation and ensuring one does not demean or disempower. For the kidney care workforce, culturally safe care requires ongoing critical reflection, deep active listening skills, decolonising approaches and the eradication of institutional racism. Cultural safety is the key to truly working in partnership, increasing Indigenous Governance, respectful collaboration and redesigning kidney care. [ABSTRACT FROM AUTHOR]

Introduction: Many individuals start dialysis in an acute setting with suboptimal pre‐dialysis education. These individuals are often treated with central venous catheter insertion and initiation of in‐center hemodialysis and only a minority will transfer to a home‐based therapy. The dialysis start unit is a program performing in‐center hemodialysis in a separate space while providing support and education on chronic kidney disease and treatment options in the initial weeks of kidney replacement therapy. We aimed to assess the uptake of home dialysis therapies between 2013 and 2021 among patients who started acute inpatient hemodialysis at University Health Network, Toronto and underwent dialysis at the dialysis start unit. Methods: This is a retrospective observational cohort study based on prospectively collected data. Patients' demographics were obtained from electronic charts. In the dialysis start unit, all patients received dialysis modality education by a nurse educator, dedicated home dialysis nurses, and the allied health care team. Findings: During 2013–2021, 122 patients were dialyzed in the dialysis start unit and included in the study. Among those patients, 68 patients ultimately chose home dialysis (57 peritoneal dialysis and 11 home hemodialysis). Fifty‐four patients continued in‐center hemodialysis. Patients adopting home dialysis were less likely to have diabetes and hypertension as the etiology of kidney failure and more likely to have glomerulonephritis or vasculitis. Discussion: Dialysis modality education is implementable in advanced chronic kidney disease. Individualized education and care after unplanned start dialysis can potentially enhance home dialysis choice and utilization. [ABSTRACT FROM AUTHOR]