Effects of rare kidney diseases on kidney failure: a longitudinal analysis of the UK National Registry of Rare Kidney Diseases (RaDaR) cohort.

BACKGROUND: Individuals with rare kidney diseases account for 5-10% of people with chronic kidney disease, but constitute more than 25% of patients receiving kidney replacement therapy. The National Registry of Rare Kidney Diseases (RaDaR) gathers longitudinal data from patients with these conditions, which we used to study disease progression and outcomes of death and kidney failure. METHODS: People aged 0-96 years living with 28 types of rare kidney diseases were recruited from 108 UK renal care facilities. The primary outcomes were cumulative incidence of mortality and kidney failure in individuals with rare kidney diseases, which were calculated and compared with that of unselected patients with chronic kidney disease. Cumulative incidence and Kaplan-Meier survival estimates were calculated for the following outcomes: median age at kidney failure; median age at death; time from start of dialysis to death; and time from diagnosis to estimated glomerular filtration rate (eGFR) thresholds, allowing calculation of time from last eGFR of 75 mL/min per 1·73 m2 or more to first eGFR of less than 30 mL/min per 1·73 m2 (the therapeutic trial window). FINDINGS: Between Jan 18, 2010, and July 25, 2022, 27 285 participants were recruited to RaDaR. Median follow-up time from diagnosis was 9·6 years (IQR 5·9-16·7). RaDaR participants had significantly higher 5-year cumulative incidence of kidney failure than 2·81 million UK patients with all-cause chronic kidney disease (28% vs 1%; p<0·0001), but better survival rates (standardised mortality ratio 0·42 [95% CI 0·32-0·52]; p<0·0001). Median age at kidney failure, median age at death, time from start of dialysis to death, time from diagnosis to eGFR thresholds, and therapeutic trial window all varied substantially between rare diseases. INTERPRETATION: Patients with rare kidney diseases differ from the general population of individuals with chronic kidney disease: they have higher 5-year rates of kidney failure but higher survival than other patients with chronic kidney disease stages 3-5, and so are over-represented in the cohort of patients requiring kidney replacement therapy. Addressing unmet therapeutic need for patients with rare kidney diseases could have a large beneficial effect on long-term kidney replacement therapy demand. FUNDING: RaDaR is funded by the Medical Research Council, Kidney Research UK, Kidney Care UK, and the Polycystic Kidney Disease Charity.

Chronic kidney disease: detect, diagnose, disclose-a UK primary care perspective of barriers and enablers to effective kidney care.

Chronic kidney disease (CKD) is a global public health problem with major human and economic consequences. Despite advances in clinical guidelines, classification systems and evidence-based treatments, CKD remains underdiagnosed and undertreated and is predicted to be the fifth leading cause of death globally by 2040. This review aims to identify barriers and enablers to the effective detection, diagnosis, disclosure and management of CKD since the introduction of the Kidney Disease Outcomes Quality Initiative (KDOQI) classification in 2002, advocating for a renewed approach in response to updated Kidney Disease: Improving Global Outcomes (KDIGO) 2024 clinical guidelines. The last two decades of improvements in CKD care in the UK are underpinned by international adoption of the KDIGO classification system, mixed adoption of evidence-based treatments and research informed clinical guidelines and policy. Interpretation of evidence within clinical and academic communities has stimulated significant debate of how best to implement such evidence which has frequently fuelled and frustratingly forestalled progress in CKD care. Key enablers of effective CKD care include clinical classification systems (KDIGO), evidence-based treatments, electronic health record tools, financially incentivised care, medical education and policy changes. Barriers to effective CKD care are extensive; key barriers include clinician concerns regarding overdiagnosis, a lack of financially incentivised care in primary care, complex clinical guidelines, managing CKD in the context of multimorbidity, bureaucratic burden in primary care, underutilisation of sodium-glucose co-transporter-2 inhibitor (SGLT2i) medications, insufficient medical education in CKD, and most recently - a sustained disruption to routine CKD care during and after the COVID-19 pandemic. Future CKD care in UK primary care must be informed by lessons of the last two decades. Making step change, over incremental improvements in CKD care at scale requires a renewed approach that addresses key barriers to detection, diagnosis, disclosure and management across traditional boundaries of healthcare, social care, and public health. Improved coding accuracy in primary care, increased use of SGLT2i medications, and risk-based care offer promising, cost-effective avenues to improve patient and population-level kidney health. Financial incentives generally improve achievement of care quality indicators - a review of financial and non-financial incentives in CKD care is urgently needed.

New therapeutic perspectives for vascular and valvular calcifications in chronic kidney disease.

PURPOSE OF REVIEW: Vascular and valvular calcification are associated with cardiovascular morbidity and mortality in people with chronic kidney disease (CKD). Uncertainty exists regarding therapeutic strategies to attenuate calcification. This review outlines the pathophysiological mechanisms contributing to vascular and valvular calcification, considers the mechanisms of action of therapeutic interventions, and reports the latest outcomes from interventional studies. RECENT FINDINGS: Conventional therapies targeted at CKD-mineral and bone disorder (MBD) modulation have yielded conflicting or inconclusive results. Magnesium and vitamin K supplementation appear to offer attenuation of coronary artery calcification but inconsistent findings justify the need for further studies. Strategies targeting hydroxyapatite formation such as sodium thiosulphate and hexasodium fytate show promise and are worthy of further evaluation. The serum calcification propensity assay (T50) correlates with severity and progression; it holds promise as a potential future clinical tool for screening monitoring calcification risk. SUMMARY: Whilst knowledge of the pathophysiology of vascular calcification has grown and therapeutic approaches appear promising, as yet no medication has been approved to treat vascular or valvular calcification, or calciphylaxis.

Enhancing clinical service design for multimorbidity management: A comprehensive approach to joined-up care for diabetes, chronic kidney disease, and heart failure.

BACKGROUND AND AIMS: Multimorbidity is becoming the norm rather than the exception, especially among the ageing population and people with lower socio-economic status. In addition to the rising healthcare cost, multimorbidity poses considerable difficulty in the delivery of adequate holistic care for affected patients. METHODS: This review presents a discussion of the current barriers to delivering holistic care to people with multimorbidity and proposes a model of clinical care for people living with cardiovascular-kidney-metabolic (CKM) syndrome as an exemplar of a multimorbidity cluster. RESULTS: Single organ/disease services may not be able to provide optimum care to people with multimorbidity due to the potential complex interactions between multiple disease symptoms and management. In addition, people with multimorbidity may be required to attend multiple appointments in different healthcare centres. This may negatively impact access to services due to time and financial burden. Other barriers include co-ordinating communication between healthcare professionals and reduced continuity of care. Optimising CKM health requires patient-centred care led by an interdisciplinary care team who ideally should possess CKM competencies utilising a shared care protocol to coordinate evidence-based care and use of telehealth to empower patients. Stakeholders and policymakers need to adapt new policy models to establish and enhance CKM care models by allocating funds and implementing frameworks for educational reforms. CONCLUSIONS: A CKM service has the potential to increase the uptake of cardiac and renal protective medications as well as optimising metabolic care, increase capacity in both primary and secondary care, improve quality of life and clinical outcomes, reduce patient inconvenience, and importantly allow rapid translation of advances in cardiorenal metabolic diseases into clinical practice.

Clinical and histopathologic predictors of recurrent glomerulonephritis after kidney transplantation.

INTRODUCTION: We evaluated the long-term outcomes of recurrent glomerulonephritis (RGN) using clinical, histopathological, and demographic predictors. METHODS: A retrospective cohort study of kidney transplant recipients (KTR) in two renal centers between 2005 and 2020. Clinical and native kidney histological data were analyzed. The risk factors and outcomes of each primary glomerulonephritis subtype were assessed using Cox methods. RESULT: 336 recipients with primary glomerulonephritis were analyzed. RGN was diagnosed in 17%, 20%, 25%, and 13% of recipients with IgA nephropathy (IgAN), focal segmental glomerulosclerosis (FSGS), membranous nephropathy (MN) and membranoproliferative glomerulonephritis (MPGN), respectively. Median time to recurrence was shortest in FSGS (.6 years IQR .2-2.9) and longest in MN (6.3 years IQR 3.3-8.0) whereas time to graft loss after diagnosis was shortest in MPGN (.3 years IQR .1-1.7) and longest in IgAN (2.9 year IQR 1.3-4.3). Recipients with recurrent IgAN were likely to be younger, have higher proteinuria at diagnosis, receive living donor allografts, receive cyclosporine treatment, have a history of acute rejection, and have segmental sclerosis in native glomeruli. Younger age of the donors, higher proteinuria at diagnosis, alemtuzumab, proteinuria within the first 12 months, acute rejection, low baseline eGFR, mesangial proliferation, and IgG and IgA deposits were associated with FSGS recurrence. MPGN recurrence was predicted by lower BMI at transplantation, and crescentic native disease. Death-censored graft survival at 5-, 10-, and 15-years was 83%, 51%, and 29% in the RGN group and 95%, 93%, and 84%, respectively in the non-RGN group. Over 15 years, recipients with RGN are nine times more likely than those without RGN to lose their grafts, regardless of donor type, acute rejection, and baseline eGFR. Transplant recipients of related donor allograft were not more likely to have recurrent GN than non-related donors.

The epidemiology of primary FSGS including cluster analysis over a 20-year period.

INTRODUCTION: Focal segmental glomerulosclerosis (FSGS) is one of the leading causes of nephrotic syndrome in adults. This epidemiological study describes a renal centre's 20-year experience of primary FSGS. METHODS: Patients were identified with a diagnosis of primary FSGS after exclusion of known secondary causes. In this retrospective observational study, data was collected for baseline demographics, immunosuppression and outcomes. A two-step cluster analysis was used to identify natural groupings within the dataset. RESULTS: The total cohort was made up of 87 patients. Those who received immunosuppression had lower median serum albumin than those who did not- 23g/L vs 40g/L (p<0.001) and higher median urine protein creatinine ratios (uPCR)- 795mg/mmol vs 318mg/mmol (p <0.001). They were more likely to achieve complete remission (62% vs 40%, p=0.041), but relapsed more 48.6% vs 22% (p=0.027). Overall 5 year mortality was 10.3% and 5 year progression to RRT was seen in 17.2%. Complete remission was observed in 49.4%. The 2-step cluster analysis separated the cohort into 3 clusters: cluster 1 (n=26) with 'nephrotic-range proteinuria'; cluster 2 (n=43) with 'non-nephrotic-range proteinuria'; and cluster 3 (n=18) with nephrotic syndrome. Immunosuppression use was comparable in clusters 1 and 3, but lower in cluster 2 (77.8% and 69.2% vs 11.6%, p<0.001). Rates of complete remission were greatest in clusters 1 and 3 vs cluster 2: 57.7% and 66.7% vs 37.2%. CONCLUSION: People who received immunosuppression had lower serum albumin and achieved remission more frequently, but were also prone to relapse. Our cluster analysis highlighted 3 FSGS phenotypes: a nephrotic cluster that clearly require immunosuppression; a cohort with preserved serum albumin and non-nephrotic range proteinuria who will benefit from supportive care; and lastly a cluster with heavy proteinuria but serum albumin > 30g/L. This group may still have immune mediated disease and thus could potentially benefit from immunosuppression. TRIAL REGISTRATION: This study protocol was reviewed and approved by the 'Research and Innovation committee of the Northern Care Alliance NHS Group', study approval number (Ref: ID 22HIP54).

Peptide GAM immunoadsorption in anti-PLA2 R positive autoimmune membranous nephropathy. The PRISM trial.

Membranous nephropathy associated with anti-PLA2 R autoantibody is a significant cause of nephrotic syndrome worldwide. Treatment remains empiric with a significant side-effect burden despite an increase in our understanding of the disease. We studied the effect of selectively removing this pathogenic autoantibody using immunoadsorption in adult patients with biopsy proven anti-PLA2 R membranous nephropathy. This was a multicenter, single-arm prospective clinical trial carried out in the United Kingdom. Twelve patients underwent five consecutive sessions of peptide GAM immunoadsorption with 12 months follow-up. Primary outcome was anti-PLA2 R titer at week 2. Secondary outcomes were safety and tolerability of therapy, antibody profile, and change in proteinuria, renal excretory function, serum albumin, total immunoglobulin, and quality of life at weeks 12, 24, and 52. Patients were also stratified by the presence or absence of the high-risk allele (heterozygous or homozygous for HLA-DQA1*05). Median pretreatment anti-PLA2 R was 702.50 U/mL, 1045.00 U/mL at week 2 (P-value .023) and 165.00 U/mL at week 52 (P-value .017). The treatment was well tolerated and safe. Two patients required rescue immunosuppression during the follow-up period. There was a significant improvement in serum albumin with a median at baseline of 20.50 g/L rising to 25.00 g/L at week 52 (P-value <.001). There was no statistical difference over the follow-up period in proteinuria or renal function. Patients in possession of a high-risk allele saw improvement in anti-PLA2 R titers, possibly representing a cohort more likely to benefit from immunoadsorption. Immunoadsorption therapy is a safe treatment and well-tolerated treatment in anti-PLA2 R positive autoimmune membranous nephropathy.

Slowing Progression of Cardiovascular Calcification With SNF472 in Patients on Hemodialysis: Results of a Randomized Phase 2b Study.

BACKGROUND: The high cardiovascular morbidity and mortality in patients with end-stage kidney disease could be partially caused by extensive cardiovascular calcification. SNF472, intravenous myo-inositol hexaphosphate, selectively inhibits the formation and growth of hydroxyapatite. METHODS: This double-blind, placebo-controlled phase 2b trial compared progression of coronary artery calcium volume score and other measurements of cardiovascular calcification by computed tomography scan during 52 weeks of treatment with SNF472 or placebo, in addition to standard therapy, in adult patients with end-stage kidney disease receiving hemodialysis. Patients were randomized 1:1:1 to SNF472 300 mg (n=92), SNF472 600 mg (n=91), or placebo (n=91) by infusion in the hemodialysis lines thrice weekly during hemodialysis sessions. The primary end point was change in log coronary artery calcium volume score from baseline to week 52. The primary efficacy analysis combined the SNF472 treatment groups and included all patients who received at least 1 dose of SNF472 or placebo and had an evaluable computed tomography scan after randomization. RESULTS: The mean change in coronary artery calcium volume score was 11% (95% CI, 7-15) for the combined SNF472 dose group and 20% (95% CI, 14-26) for the placebo group (P=0.016). SNF472 compared with placebo attenuated progression of calcium volume score in the aortic valve (14% [95% CI, 5-24] versus 98% [95% CI, 77-123]; P<0.001) but not in the thoracic aorta (23% [95% CI, 16-30] versus 28% [95% CI, 19-38]; P=0.40). Death occurred in 7 patients (4%) who received SNF472 and 5 patients (6%) who received placebo. At least 1 treatment-emergent adverse event occurred in 86%, 92%, and 87% of patients treated with SNF472 300 mg, SNF472 600 mg, and placebo, respectively. Most adverse events were mild. Adverse events resulted in discontinuation of SNF472 300 mg, SNF472 600 mg, and placebo for 14%, 29%, and 20% of patients, respectively. CONCLUSIONS: Compared with placebo, SNF472 significantly attenuated the progression of coronary artery calcium and aortic valve calcification in patients with end-stage kidney disease receiving hemodialysis in addition to standard care. Future studies are needed to determine the effects of SNF472 on cardiovascular events. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02966028.

SNF472: mechanism of action and results from clinical trials.

PURPOSE OF REVIEW: Vascular calcification (VC) is associated with increased cardiovascular event rates, particularly in patients with end-stage kidney disease (ESKD). Dysregulated mineral metabolism and inflammation have been shown to promote VC, however, treatment options targeting VC specifically are not available. This review outlines the pathophysiological mechanisms contributing to VC in ESKD and describes recent studies evaluating the effects of the first-in-class inhibitor of VC, SNF472. RECENT FINDINGS: SNF472 directly inhibits calcium phosphate crystal formation and aggregation. SNF472 has completed early phase clinical trials with a favourable safety profile and Phase 2 clinical trial data have shown attenuation of coronary artery and aortic valve calcification in patients receiving hemodialysis. SUMMARY: Therapeutic agents that directly target VC may prevent the multiple complications associated with dystrophic calcification in patients with ESKD.

Pain management in patients with end-stage renal disease and calciphylaxis- a survey of clinical practices among physicians.

BACKGROUND: Calciphylaxis is a rare condition usually seen in patients with end-stage renal disease. Pain is a hallmark of this condition and can be extremely difficult to control. Anecdotal data suggests that pain management in calciphylaxis is challenging with variable approaches across the United Kingdom (UK) and internationally. A knowledge and practice survey was conducted to establish current practice in the management of pain in patients with calciphylaxis, in the UK. Based on the results and clinical experience the authors suggest a clinical practice guideline. METHODS: An online questionnaire was circulated among physicians (renal and palliative care) involved in the management of pain in calciphylaxis. The questionnaire included a mix of open-ended questions and questions with drop down options. RESULTS: One hundred and six clinicians responded to the survey of which 60 (57%) respondents were from palliative medicine; the remaining 46 (43%) were from renal medicine. 31 (30%) respondents across both specialties had not encountered any patients with a diagnosis of calciphylaxis (renal-2, palliative care-29). A referral to the palliative care team was undertaken by 18% of renal physicians, 32% referred to the pain team and 50% referred to both. Only 3% of the palliative medicine respondents indicated that they had received a referral from the renal team at the time of diagnosis. Opioids were the preferred initial drug of choice for the management of all types of pain. Paracetamol was universally selected as the preferred first-choice adjuvant agent for management of all types of pain. The importance of advance care planning was highlighted with 72% undertaking advanced care planning discussions often or most of the time. CONCLUSION: There was wide variation in the current practice of pain management in patients with calciphylaxis, with variation between renal specialists and palliative care specialists. Referral to specialists in pain management is not universal despite the severe nature of the pain experienced by patients with calciphylaxis. The data generated has facilitated the development of a clinical practice guideline to support complex pain management in a group of patients with multiple comorbidities.

Safely reducing haemodialysis frequency during the COVID-19 pandemic.

BACKGROUND: Patients undergoing haemodialysis (HD) are at higher risk of developing worse outcomes if they contract COVID-19. In our renal service we reduced HD frequency from thrice to twice-weekly in selected patients with the primary aim of reducing COVID 19 exposure and transmission between HD patients. METHODS: Dialysis unit nephrologists identified 166 suitable patients (38.4% of our HD population) to temporarily convert to twice-weekly haemodialysis immediately prior to the peak of the COVID-19 pandemic in our area. Changes in pre-dialysis weight, systolic blood pressure (SBP) and biochemistry were recorded weekly throughout the 4-week project. Hyperkalaemic patients (serum potassium > 6.0 mmol/L) were treated with a potassium binder, sodium bicarbonate and received responsive dietary advice. RESULTS: There were 12 deaths (5 due to COVID-19) in the HD population, 6 of which were in the twice weekly HD group; no deaths were definitively associated with change of dialysis protocol. A further 19 patients were either hospitalised and/or developed COVID-19 and thus transferred back to thrice weekly dialysis as per protocol. 113 (68.1%) were still receiving twice-weekly HD by the end of the 4-week project. Indications for transfer back to thrice weekly were; fluid overload (19), persistent hyperkalaemia (4), patient request (4) and compliance (1). There were statistically significant increases in SBP and pre-dialysis potassium during the project. CONCLUSIONS: Short term conversion of a large but selected HD population to twice-weekly dialysis sessions was possible and safe. This approach could help mitigate COVID-19 transmission amongst dialysis patients in centres with similar organisational pressures.

Improved management of acute kidney injury in primary care using e-alerts and an educational outreach programme.

Purpose: Acute kidney injury (AKI) detected in primary care is associated with increased morbidity and mortality. AKI electronic alerts (e-alerts) and educational programmes have recently been implemented but their contribution to improve AKI care is unknown. This project aimed to improve response to AKI detected in primary care and used a factorial design to evaluate the impact of the UK National Health Service (NHS) AKI e-alert and AKI educational outreach sessions on time to response to primary care AKI stages 2 and 3 between April and August 2016. Methods: A total of 46 primary care practices were randomized into four groups. A 2 × 2 factorial design exposed each group to different combinations of two interventions. The primary outcome was 'time to repeat test' or hospitalization following AKI e-alert for stages 2 and 3. Yates algorithm was used to evaluate the impact of each intervention. Time to response and mortality pre- and post-intervention were analysed using Mann-Whitney U test and chi-square test respectively. The factorial design included two interventions: an AKI educational outreach programme and the NHS AKI e-alerts. Results: 1807 (0.8%) primary care blood tests demonstrated AKI 1-3 (78.3% stage 1, 14.8% stage 2, 6.9% stage 3). There were 391 stage 2 and 3 events from 251 patients. E-alerts demonstrated a reduction in mean response time (-29 hours). Educational outreach had a smaller effect (-3 hours). Median response time to AKI 2 and 3 pre- and post-interventions was 27 hours versus 16 hours respectively (P = 0.037). Stage 2 and 3 event-related 30-day all-cause mortality decreased following the interventions (15.6% versus 3.9% P = 0.036). Conclusion: AKI e-alerts in primary care hasten response to AKI 2 and 3 and reduce all-cause mortality. Educational outreach sessions further improve response time.

Presentation of laboratory test results in patient portals: influence of interface design on risk interpretation and visual search behaviour.

BACKGROUND: Patient portals are considered valuable instruments for self-management of long term conditions, however, there are concerns over how patients might interpret and act on the clinical information they access. We hypothesized that visual cues improve patients' abilities to correctly interpret laboratory test results presented through patient portals. We also assessed, by applying eye-tracking methods, the relationship between risk interpretation and visual search behaviour. METHODS: We conducted a controlled study with 20 kidney transplant patients. Participants viewed three different graphical presentations in each of low, medium, and high risk clinical scenarios composed of results for 28 laboratory tests. After viewing each clinical scenario, patients were asked how they would have acted in real life if the results were their own, as a proxy of their risk interpretation. They could choose between: 1) Calling their doctor immediately (high interpreted risk); 2) Trying to arrange an appointment within the next 4 weeks (medium interpreted risk); 3) Waiting for the next appointment in 3 months (low interpreted risk). For each presentation, we assessed accuracy of patients' risk interpretation, and employed eye tracking to assess and compare visual search behaviour. RESULTS: Misinterpretation of risk was common, with 65% of participants underestimating the need for action across all presentations at least once. Participants found it particularly difficult to interpret medium risk clinical scenarios. Participants who consistently understood when action was needed showed a higher visual search efficiency, suggesting a better strategy to cope with information overload that helped them to focus on the laboratory tests most relevant to their condition. CONCLUSIONS: This study confirms patients' difficulties in interpreting laboratories test results, with many patients underestimating the need for action, even when abnormal values were highlighted or grouped together. Our findings raise patient safety concerns and may limit the potential of patient portals to actively involve patients in their own healthcare.

Non-recruitment to and selection bias in studies using echocardiography in haemodialysis patients.

BACKGROUND: It is unknown whether patients recruited to renal cardiac imaging studies are fully representative of the investigated population and whether there are differences in characteristics and survival between participants and non-participants (excluded or declined consent). Subjects and Methods Four hundred thirty-five maintenance haemodialysis patients were screened in an observational, prospective study. Baseline demographics, laboratory results, social deprivation scores and survival data were collected from patient records. All patients were followed-up until death, renal transplantation or 16 November 2015. RESULTS: Forty-four patients were excluded (16 language barrier, 10 mental incapacity, 9 severe co-morbid illness and 9 because of immobility), 172 patients declined consent (84% due to reluctance to attend for an extra visit) and 219 patients were recruited. Excluded patients had a lower mean haemoglobin (10.2 g/dL vs 10.7 g/dL), phosphate (4.15 mg/dL vs 4.74 mg/dL), albumin (3.6 g/dL vs 3.8 g/dL) and higher C-reactive protein (3.2 mg/dL vs 1.6 mg/dL) compared with recruited patients. No difference was identified between groups for Charleston comorbidity index (P = 0.115) or social deprivation scores. After a median follow-up of 29.7 (25th-75th percentile, 21.1-34.3) months, there were 141 deaths. In a multivariable Cox regression model adjusting for BMI, age, Charleston comorbidity index, haemoglobin, albumin, smoking status and diabetes mellitus, patients who declined consent had an adjusted HR of 1.70, 95% CI 1.10-2.52, and excluded patients had an adjusted HR of 1.30, 95% CI 0.75-2.25, for all-cause mortality compared with recruited patients. CONCLUSIONS: Patients recruited to the study had longer survival compared with non-participants. Research studies should document phenotypes of non-participants to aid interpretation and generalizability of results.

Novel Approach to Cardiovascular Outcome Prediction in Haemodialysis Patients.

BACKGROUND: Cardiovascular mortality is high in haemodialysis (HD) patients. Arterial stiffness and global longitudinal strain (GLS) are important non-atheromatous cardiovascular risk predictors. No study has encompassed both parameters in a combined model for prediction of outcomes in HD patients. This is important because left ventricular (LV) dysfunction can result from fibrotic remodelling secondary to increased arterial stiffness. METHODS: Two hundred and nineteen HD patients had pulse wave velocity (PWV) and echocardiography (including GLS) assessments. Patients were followed-up until death, transplantation or November 16, 2015, whichever happened first. Pearson's correlation coefficient was used to determine factors associated with PWV and GLS. A multivariable Cox regression model investigated factors associated with all-cause, cardiac death and events. RESULTS: One hundred and ninety eight HD patients had full datasets (median age 64.2, 68.7% males) with a mean LV ejection fraction (LVEF) of 61.7 ± 10.1% and GLS -13.5 ± 3.3%; 51% had LV hypertrophy. Forty eight deaths (15 cardiac) and 44 major cardiac events occurred during a median follow-up of 27.6 (25th-75th percentile, 17.3-32.7) months. In separate survival models, PWV and GLS were independently associated with all-cause mortality; however, in a combined model, LV mass indexed to height2.7 (LVMI/HT2.7; adjusted hazard ratio (HR) 1.02, 95% CI 1.00-1.04) and PWV (adjusted HR 1.23, 95% CI 1.03-1.47) were significant. PWV was neither associated with cardiac death nor associated with related cardiac events. However, GLS was associated with cardiac death (adjusted HR 1.24, 95% CI 1.00-1.54) and cardiac events (adjusted HR 1.13, 95% CI 1.03-1.25). CONCLUSIONS: PWV and LVMI/HT2.7 were superior to GLS in prediction of all-cause mortality. However, GLS was associated with cardiac death and events even when accounting for LVEF and LVMI/HT2.7.

Lack of evidence does not justify neglect: how can we address unmet medical needs in calciphylaxis?

Calcific uraemic arteriolopathy (CUA), or calciphylaxis, is a rare disease predominantly occurring in comorbidity with dialysis. Due to the very low frequency of CUA, prospective studies on its management are lacking and even anecdotal reports on treatment remain scarce. Therefore, calciphylaxis is still a challenging disease with dismal prognosis urgently requiring adequate strategies for diagnosis and treatment.In an attempt to fill some of the current gaps in evidence on various, highly debated and controversial aspects of dialysis-associated calciphylaxis, 13 international experts joined the 1st Consensus Conference on CUA, held in Leuven, Belgium on 21 September 2015. The conference was supported by the European Calciphylaxis Network (EuCalNet), which is a task force of the ERA-EDTA scientific working group on Chronic Kidney Disease-Mineral and Bone Disorders (CKD-MBD). After an intense discussion, a 9-point Likert scale questionnaire regarding 20 items on calciphylaxis was anonymously answered by each participant. These 20 items addressed unsolved issues in terms of diagnosis and management of calciphylaxis. On the one hand, the analysis of the expert opinions identified areas of general consensus, which might be a valuable aid for physicians treating such a disease with less experience in the field. On the other hand, some topics such as the pertinence of skin biopsy and administration of certain treatments revealed divergent opinions. The aim of the present summary report is to provide some guidance for clinicians who face patients with calciphylaxis in the current setting of absence of evidence-based medicine.

Association of serum sodium levels with all-cause and cardiovascular mortality in chronic kidney disease: Results from a prospective observational study.

AIMS: The prevalence of hyponatraemia in the outpatient setting has not been thoroughly explored, and little is known about the prognostic implication of dysnatraemia in chronic kidney disease (CKD) patients, in particular accommodating the effect of concurrent medications. METHODS: This is a prospective observational study of non-dialysis-dependent CKD patients managed in a nephrology clinic. Patients enrolled between 2002 and 2012 in the Chronic Renal Insufficiency Standards Implementation Study were assessed. Survival analyses were performed using baseline sodium and 12-month time-averaged sodium, with adjustment for co-morbid diseases, laboratory findings and concurrent medications. RESULTS: At baseline (n = 2093), mean estimated glomerular filtration rate was 32.8 ± 15.9 ml/min per 1.73 m(2) , median age was 67 (interquartile range 56-75) years and median serum sodium concentration was 140 (138-142) mmol/l. After a follow up of 41 (18-67) months, there were 684 deaths, 174 from cardiovascular causes; 1925 time-averaged sodium values were analysed. In the Cox multivariate adjusted regression, baseline hyponatraemia, but not hypernatraemia, was independently associated with all-cause mortality (hazard ratio (HR) 1.35, 95% confidence interval (CI) 1.02-1.78, P = 0.04, and HR 1.15, 95% CI 0.84-1.57, P = 0.39, respectively). This was similarly the case for time-averaged hyponatraemia and hypernatraemia (HR 2.15, 95% CI 1.59-2.91, P < 0.01, and HR 1.47, 95% CI 0.93-2.38, P = 0.10, respectively). However, the association of baseline and time-averaged hyponatraemia with cardiovascular mortality was not significant. CONCLUSION: Hyponatraemia in the ambulatory setting is associated with all-cause but not cardiovascular mortality in CKD, independent of concomitant medications and co-morbidities.

Risks for mortality and renal replacement therapy in atherosclerotic renovascular disease compared with other causes of chronic kidney disease.

AIM: Patients with atherosclerotic renovascular disease (ARVD) have an increased risk for death and likelihood of initiating renal replacement therapy (RRT) compared with the general population. No data exist to describe prognosis in ARVD compared with other causes of chronic kidney disease (CKD). We compare patient outcomes between ARVD and other causes of CKD. METHODS: Patients were selected from two prospective observational cohort studies of outcome in ARVD and CKD. Multivariate Cox regression was used to compare risk for RRT and death (both prior to and following initiation of RRT) between patients with ARVD and other causes of CKD. RESULTS: Of 1472 patients (563 (38%) ARVD, 909 (62%) non-ARVD), 242 (16%) progressed to RRT and 640 (44%) died over a median follow-up period of 4.1 (2.4-5.6) years. Patients with ARVD had an increased risk for death (HR 1.5 (1.2-1.8), P < 0.001) but not for RRT (HR 1.0 (0.7-1.4), P = 0.9). The largest increase in risk for death was observed relative to renal limited diseases, e.g. pyelonephritis (HR 2.4 (1.3-4.5), P = 0.004) and interstitial/infiltrative disease (HR 2.2 (1.3-4.5), P = 0.02). Following initiation of RRT, patients with ARVD had a significantly increased risk for death compared with patients without ARVD (HR 3.3 (2.2-5.0), P < 0.001). CONCLUSIONS: Patients with ARVD as a cause of CKD have an increased risk for death both prior to and following initiation of RRT. Further work should seek to identify modifiable risk factors relevant to prognosis.

Echocardiography in hemodialysis patients: uses and challenges.

Patients with end-stage renal disease undergoing hemodialysis have high rates of morbidity and mortality. Cardiovascular disease accounts for almost half of this mortality, with the single most common cause being sudden cardiac death. Early detection of abnormalities in cardiac structure and function may be important to allow timely and appropriate cardiac interventions. Echocardiography is noninvasive cardiac imaging that is widely available and provides invaluable information on cardiac morphology and function. However, it has limitations. Echocardiography is operator dependent, and image quality can vary depending on the operator's experience and the patient's acoustic window. Hemodialysis patients undergo regular hemodynamic changes that also may affect echocardiographic findings. An understanding of the prognostic significance and interpretation of echocardiographic results in this setting is important for patient care. There are some emerging techniques in echocardiographic imaging that can provide more detailed and accurate information compared with conventional 2-dimensional echocardiography. Use of these novel tools may further our understanding of the pathophysiology of cardiac disease in patients with end-stage renal disease undergoing hemodialysis.