Proteomic signature associated with chronic kidney disease (CKD) progression identified by data-independent acquisition mass spectrometry.

BACKGROUND: Halting progression of chronic kidney disease (CKD) to established end stage kidney disease is a major goal of global health research. The mechanism of CKD progression involves pro-inflammatory, pro-fibrotic, and vascular pathways, but pathophysiological differentiation is currently lacking. METHODS: Plasma samples of 414 non-dialysis CKD patients, 170 fast progressors (with ∂ eGFR-3 ml/min/1.73 m2/year or worse) and 244 stable patients (∂ eGFR of - 0.5 to + 1 ml/min/1.73 m2/year) with a broad range of kidney disease aetiologies, were obtained and interrogated for proteomic signals with SWATH-MS. We applied a machine learning approach to feature selection of proteins quantifiable in at least 20% of the samples, using the Boruta algorithm. Biological pathways enriched by these proteins were identified using ClueGo pathway analyses. RESULTS: The resulting digitised proteomic maps inclusive of 626 proteins were investigated in tandem with available clinical data to identify biomarkers of progression. The machine learning model using Boruta Feature Selection identified 25 biomarkers as being important to progression type classification (Area Under the Curve = 0.81, Accuracy = 0.72). Our functional enrichment analysis revealed associations with the complement cascade pathway, which is relevant to CKD as the kidney is particularly vulnerable to complement overactivation. This provides further evidence to target complement inhibition as a potential approach to modulating the progression of diabetic nephropathy. Proteins involved in the ubiquitin-proteasome pathway, a crucial protein degradation system, were also found to be significantly enriched. CONCLUSIONS: The in-depth proteomic characterisation of this large-scale CKD cohort is a step toward generating mechanism-based hypotheses that might lend themselves to future drug targeting. Candidate biomarkers will be validated in samples from selected patients in other large non-dialysis CKD cohorts using a targeted mass spectrometric analysis.

Does previous stroke modify the relationship between inflammatory biomarkers and clinical endpoints in CKD patients?

BACKGROUND: Chronic kidney disease (CKD) is an independent risk factor for stroke. Stroke is also an independent risk factor for worse CKD outcomes and inflammation may contribute to this bidirectional relationship. This study aims to investigate inflammatory biomarkers in patients with non-dialysis CKD (ND-CKD) with and without stroke. METHODS: A propensity matched sample from > 3000 Salford Kidney Study (SKS) patients, differentiated by previous stroke at study recruitment, had stored plasma analyzed for interleukin- 6 (IL-6), Von Willebrand Factor (VWF) and C-reactive protein (CRP). Multivariable cox regression analysis investigated associations between inflammation and death, end-stage renal disease (ESRD) and future non-fatal cardiovascular events (NFCVE). RESULTS: A total of 157 previous stroke patients were compared against 162 non-stroke patients. There were no significant differences in inflammatory biomarkers between the two groups. Previous stroke was associated with greater mortality risk, hazard ratio (HR) (95% CI) was 1.45 (1.07-1.97). Higher inflammatory biomarker concentrations were independently associated with death but not ESRD or NFCVE in the total population. For each 1 standard deviation (SD) increase in log IL-6, VWF and CRP, the HR for all-cause mortality were 1.35 (1.10-1.70), 1.26 (1.05-1.51) and 1.34 (1.12-1.61), respectively. CRP retained its independent association (HR 1.47 (1.15-1.87)) with death in the stroke population. CONCLUSION: Previous stroke is an important determinant of mortality. However, the adverse combination of stroke and ND-CKD does not seem to be driven by higher levels of inflammation detected after the stroke event. Biomarkers of inflammation were associated with worse outcome in both stroke and non-stroke ND-CKD patients. TRIAL REGISTRATION: 15/NW/0818 .

Technical recommendations for clinical translation of renal MRI: a consensus project of the Cooperation in Science and Technology Action PARENCHIMA.

PURPOSE: The potential of renal MRI biomarkers has been increasingly recognised, but clinical translation requires more standardisation. The PARENCHIMA consensus project aims to develop and apply a process for generating technical recommendations on renal MRI. METHODS: A task force was formed in July 2018 focused on five methods. A draft process for attaining consensus was distributed publicly for consultation and finalised at an open meeting (Prague, October 2018). Four expert panels completed surveys between October 2018 and March 2019, discussed results and refined the surveys at a face-to-face meeting (Aarhus, March 2019) and completed a second round (May 2019). RESULTS: A seven-stage process was defined: (1) formation of expert panels; (2) definition of the context of use; (3) literature review; (4) collection and comparison of MRI protocols; (5) consensus generation by an approximate Delphi method; (6) reporting of results in vendor-neutral and vendor-specific terms; (7) ongoing review and updating. Application of the process resulted in 166 consensus statements. CONCLUSION: The process generated meaningful technical recommendations across very different MRI methods, while allowing for improvement and refinement as open issues are resolved. The results are likely to be widely supported by the renal MRI community and thereby promote more harmonisation.

Consensus-based technical recommendations for clinical translation of renal ASL MRI.

OBJECTIVES: This study aimed at developing technical recommendations for the acquisition, processing and analysis of renal ASL data in the human kidney at 1.5 T and 3 T field strengths that can promote standardization of renal perfusion measurements and facilitate the comparability of results across scanners and in multi-centre clinical studies. METHODS: An international panel of 23 renal ASL experts followed a modified Delphi process, including on-line surveys and two in-person meetings, to formulate a series of consensus statements regarding patient preparation, hardware, acquisition protocol, analysis steps and data reporting. RESULTS: Fifty-nine statements achieved consensus, while agreement could not be reached on two statements related to patient preparation. As a default protocol, the panel recommends pseudo-continuous (PCASL) or flow-sensitive alternating inversion recovery (FAIR) labelling with a single-slice spin-echo EPI readout with background suppression and a simple but robust quantification model. DISCUSSION: This approach is considered robust and reproducible and can provide renal perfusion images of adequate quality and SNR for most applications. If extended kidney coverage is desirable, a 2D multislice readout is recommended. These recommendations are based on current available evidence and expert opinion. Nonetheless they are expected to be updated as more data become available, since the renal ASL literature is rapidly expanding.

Changing Protein Permeability with Nephron Loss: Evidence for a Human Remnant Nephron Effect.

BACKGROUND: If loss of functioning nephrons predisposes to glomerular barotrauma (a "remnant nephron" effect), then glomerular permeability should increase as glomerular filtration rate (GFR) falls, as is observed in animal models of nephron loss. METHODS: Changes in net renal protein permeability, defined as proteinuria or albuminuria per mL/min of GFR, were measured in the setting of nephron loss due to kidney donation (Assessing Long Term Outcomes in Living Kidney Donors cohort) or progressive chronic kidney disease (CKD; Modification of Diet in Renal Disease [MDRD], African American Study of Kidney Disease [AASK], and Chronic Renal insufficiency Cohort [CRIC] studies). RESULTS: Following kidney donation, renal albumin permeability increased by 31% from predonation levels (p < 0.001). With progression of CKD, a 50% loss of residual GFR was accompanied by increases in proteinuria per mL/min GFR of 1.8-, 2.1-, and 1.6-fold in the MDRD, AASK, and CRIC cohorts, respectively (p < 0.001 for all), independent of changes in systolic blood pressure and ACEi/ARB use. A 70% reduction in GFR was associated with permeability increases of 3.1-, 4.4-, and 2.6-fold in the same cohorts. Among MDRD participants with progression of nonglomerular primary disease, the 75th percentile of final permeability was 141 mg/24 h proteinuria per mL/min GFR. This degree of permeability would have resulted in nephrotic range proteinuria had it been present at the baseline mean GFR of 40 mL/min, implying the development of de novo glomerular pathology as GFR fell. Increasing permeability also accompanied CKD progression in participants with nephrotic syndrome at baseline. Consequently, these participants had little improvement in 24 h proteinuria or serum albumin, despite substantial loss of functioning nephron mass across which the protein leak occurred. In the absence of a fall in GFR, there was no increase in permeability in any cohort. CONCLUSION: Nephron loss is accompanied by an increase in renal protein permeability, even in the absence of a primary glomerular disease. This is consistent with a remnant nephron effect in human CKD.

Impact of prior stroke on major clinical outcome in chronic kidney disease: the Salford kidney cohort study.

BACKGROUND: Chronic kidney disease (CKD) is an independent risk factor for stroke in the general population. The impact of prior stroke on major clinical outcomes in CKD populations is poorly characterised. METHODS: The Salford Kidney Study is a UK prospective cohort of more than 3000 patients recruited since 2002 and followed until March 2018. Multivariable Cox regression examined associations of stroke at two time points; cohort inception, and at dialysis initiation, with risks of death, non-fatal cardiovascular events (NFCVE) and end stage renal disease (ESRD). RESULTS: 277 (9.1%) of 3060 patients suffered a prior stroke and this was associated with mortality, ESRD and future NFCVE after cardiovascular risk factor adjustments. Median survival for prior stroke patients was 40 months vs 77 months in patients without a stroke. Prior stroke was independently associated with mortality (HR 1.20 95%CI 1.0-1.43, p = 0.05). Of 579 patients who reached ESRD and commenced dialysis, a prior stroke (N = 48) was independently associated with mortality. Median survival for the prior stroke group was 29 months compared with 50 months for the non-stroke group. Only 70 and 75% of patients who had suffered an ischaemic stroke were prescribed antiplatelets or statins respectively. CONCLUSIONS: A diagnosis of stroke is strongly and independently associated with several adverse clinical outcomes for patients with CKD. Prior stroke profoundly alters cardiovascular risk in CKD patients. Greater attention to primary and secondary preventive strategies is warranted which may improve these outcomes.

Arterial spin labelling MRI to measure renal perfusion: a systematic review and statement paper.

Renal perfusion provides the driving pressure for glomerular filtration and delivers the oxygen and nutrients to fuel solute reabsorption. Renal ischaemia is a major mechanism in acute kidney injury and may promote the progression of chronic kidney disease. Thus, quantifying renal tissue perfusion is critically important for both clinicians and physiologists. Current reference techniques for assessing renal tissue perfusion have significant limitations. Arterial spin labelling (ASL) is a magnetic resonance imaging (MRI) technique that uses magnetic labelling of water in arterial blood as an endogenous tracer to generate maps of absolute regional perfusion without requiring exogenous contrast. The technique holds enormous potential for clinical use but remains restricted to research settings. This statement paper from the PARENCHIMA network briefly outlines the ASL technique and reviews renal perfusion data in 53 studies published in English through January 2018. Renal perfusion by ASL has been validated against reference methods and has good reproducibility. Renal perfusion by ASL reduces with age and excretory function. Technical advancements mean that a renal ASL study can acquire a whole kidney perfusion measurement in less than 5-10 min. The short acquisition time permits combination with other MRI techniques that might inform drug mechanisms and renal physiology. The flexibility of renal ASL has yielded several variants of the technique, but there are limited data comparing these approaches. We make recommendations for acquiring and reporting renal ASL data and outline the knowledge gaps that future research should address.

Magnetic resonance imaging biomarkers for chronic kidney disease: a position paper from the European Cooperation in Science and Technology Action PARENCHIMA.

Functional renal magnetic resonance imaging (MRI) has seen a number of recent advances, and techniques are now available that can generate quantitative imaging biomarkers with the potential to improve the management of kidney disease. Such biomarkers are sensitive to changes in renal blood flow, tissue perfusion, oxygenation and microstructure (including inflammation and fibrosis), processes that are important in a range of renal diseases including chronic kidney disease. However, several challenges remain to move these techniques towards clinical adoption, from technical validation through biological and clinical validation, to demonstration of cost-effectiveness and regulatory qualification. To address these challenges, the European Cooperation in Science and Technology Action PARENCHIMA was initiated in early 2017. PARENCHIMA is a multidisciplinary pan-European network with an overarching aim of eliminating the main barriers to the broader evaluation, commercial exploitation and clinical use of renal MRI biomarkers. This position paper lays out PARENCHIMA's vision on key clinical questions that MRI must address to become more widely used in patients with kidney disease, first within research settings and ultimately in clinical practice. We then present a series of practical recommendations to accelerate the study and translation of these techniques.

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.

Characterisation of cardiomyopathy by cardiac and aortic magnetic resonance in patients new to hemodialysis.

OBJECTIVES: Cardiomyopathy is a key factor in accelerated cardiovascular mortality in haemodialysis (HD) patients. We aimed to phenotype cardiac and vascular dysfunction by tagged cardiovascular magnetic resonance (CMR) imaging in patients recently commencing HD. METHODS: Fifty-four HD patients and 29 age and sex-matched controls without kidney disease were studied. Left ventricular (LV) mass, volumes, ejection fraction (EF), concentric remodelling, peak-systolic circumferential strain (PSS), peak diastolic strain rate (PDSR), LV dyssynchrony, aortic distensibility and aortic pulse wave velocity were determined. RESULTS: Global systolic function was reduced (EF 51 ± 10%, HD versus 59 ± 5%, controls, p < 0.001; PSS 15.9 ± 3.7% versus 19.5 ± 3.3%, p < 0.001). Diastolic function was decreased (PDSR 1.07 ± 0.33s(-1) versus 1.31 ± 0.38s(-1), p = 0.003). LV mass index was increased (63[54,79]g/m(2) versus 46[42,53]g/m(2), p < 0.001). Anteroseptal reductions in PSS were apparent. These abnormalities remained prevalent in the subset of HD patients with preserved EF >50% (n = 35) and the subset of HD patients without diabetes (n = 40). LV dyssynchrony was inversely correlated to diastolic function, EF and aortic distensibility. Diastolic function was inversely correlated to LV dyssynchrony, concentric remodelling, age and aortic pulse wave velocity. CONCLUSION: Patients new to HD have multiple cardiac and aortic abnormalities as characterised by tagged CMR. Cardio-protective interventions are required from initiation of therapy. KEY POINTS: • First characterisation of cardiomyopathy by tagged CMR in haemodialysis patients. • Diastolic function was correlated to LV dyssynchrony, concentric remodelling and aortic PWV. • Reductions in strain localised to the septal and anterior wall. • Bioimpedance measures were unrelated to LV strain, suggesting volume-independent pathogenetic mechanisms. • Multiple abnormalities persisted in the HD patient subset with preserved EF or without diabetes.

An Update on Intradialytic Cardiac Dysfunction.

Cardiac dysfunction is a key factor in the high morbidity and mortality rates seen in hemodialysis (HD) patients. Much of the dysfunction is manifest as adverse changes in cardiac and vascular structure prior to commencing dialysis. This adverse vascular remodeling arises as a dysregulation between pro- and antiproliferative signaling pathways in response to hemodynamic and nonhemodynamic factors. The HD procedure itself further promotes cardiomyopathy by inducing hypotension and episodic regional cardiac ischemia that precedes global dysfunction, fibrosis, worsening symptoms, and increased mortality. Drug-based therapies have been largely ineffective in reversing HD-associated cardiomyopathy, in part due to targeting single pathways of low yield. Few studies have sought to establish natural history and there is no framework of priorities for future clinical trials. Targeting intradialytic cardiac dysfunction by altering dialysate temperature, composition, or ultrafiltration rate might prevent the development of global cardiomyopathy, heart failure, and mortality through multiple pathways. Novel imaging techniques show promise in characterizing the physiological response to HD that is a unique model of repetitive ischemia-reperfusion injury. Reducing HD-associated cardiomyopathy may need a paradigm shift from empirical delivery of solute clearance to a personalized therapy balancing solute and fluid removal with microvascular protection. This review describes the evidence for intradialytic cardiac dysfunction outlining cardioprotective strategies that extend to multiple organs with potential impacts on exercise tolerance, sleep, cognitive function, and quality of life.

Randomized clinical trial of dialysate cooling and effects on brain white matter.

Hemodialysis is associated with significant circulatory stress that could produce recurrent and cumulative ischemic insults to multiple organs, such as the brain. We aimed to characterize hemodialysis-induced brain injury by longitudinally studying the effects of hemodialysis on brain white matter microstructure and further examine if the use of cooled dialysate could provide protection against hemodialysis-associated brain injury. In total, 73 patients on incident hemodialysis starting within 6 months were randomized to dialyze with a dialysate temperature of either 37°C or 0.5°C below the core body temperature and followed up for 1 year. Brain white matter microstructure was studied by diffusion tensor magnetic resonance imaging at baseline and follow-up (38 patients available for paired analysis). Intradialytic hemodynamic stress was quantified using the extrema points analysis model. Patients on hemodialysis exhibited a pattern of ischemic brain injury (increased fractional anisotropy and reduced radial diffusivity). Cooled dialysate improved hemodynamic tolerability, and changes in brain white matter were associated with hemodynamic instability (higher mean arterial pressure extrema points frequencies were associated with higher fractional anisotropy [peak r=0.443, P<0.03] and lower radial diffusivity [peak r=-0.439, P<0.02]). Patients who dialyzed at 0.5°C below core body temperature exhibited complete protection against white matter changes at 1 year. Our data suggest that hemodialysis results in significant brain injury and that improvement in hemodynamic tolerability achieved by using cooled dialysate is effective at abrogating these effects. This intervention can be delivered without additional cost and is universally applicable.

The pathophysiology of the chronic cardiorenal syndrome: a magnetic resonance imaging study.

OBJECTIVE: To study the association of renal function with renal perfusion and renal parenchymal structure (T1 relaxation) in patients with chronic heart failure (HF). METHODS: After IRB approval, 40 participants were enrolled according to HF and renal function status [10 healthy volunteers < 40 years; 10 healthy age-matched volunteers; 10 HF patients eGFR > 60 ml/min/1.73 m(2); 10 HF patients eGFR < 60 ml/min/1.73 m(2)] and assessed by MRI. To be eligible for enrolment all HF patients with renal dysfunction (RD) needed to be diagnosed as having chronic cardiorenal syndrome based on current guidelines. Patients with primary kidney disease were excluded. RESULTS: Renal cortical perfusion correlated with eGFR values (r = 0.52;p < 0.01) and was similar between HF patients with and without RD (p = 0.27). T1 relaxation correlated negatively with eGFR values (r = -0.41;p > 0.01) and was higher in HF patients compared to volunteers (1121 ± 102 ms vs. 1054 ± 65 ms;p = 0.03). T1 relaxation was selectively prolonged in HF patients with RD (1169 ms ± 100 vs. HF without RD 1067 ms ± 79;p = 0.047). In linear regression analyses coronary artery disease (p = 0.01), hypertension (p = 0.04), and diabetes mellitus (p < 0.01) were associated with T1 relaxation. CONCLUSION: RD in HF is not primarily mediated by decreased renal perfusion. Instead, chronic reno-parenchymal damage, as indicated by prolonged T1 relaxation, appears to underly chronic cardiorenal syndrome. KEY POINTS: • The pathophysiology underlying chronic cardiorenal syndrome is not completely understood. • Chronic cardiorenal syndrome is independent of cardiac output or renal perfusion. • Renal T 1 relaxation appears to be prolonged in HF with renal impairment. • Renal T 1 relaxation is associated with classic cardiovascular risk factors. • Association of renal T 1 relaxation with parenchymal damage should be validated further.

Hemodialysis-associated cardiomyopathy: a newly defined disease entity.

Cardiovascular disease is the most common cause of the greatly elevated rates of mortality characteristic of patients undergoing maintenance hemodialysis. This article is an attempt to describe the complex and evolving features of cardiac disease routinely encountered in HD patients. Furthermore, by trying to appreciate the pathophysiological drivers, and the crucial interaction with the HD treatment itself, this article seeks to define cardiac disease in this setting (HD-associated cardiomyopathy) as a unique and complex entity. By understanding the phenotype and basis of HD-associated cardiomyopathy, we can develop an evolved understanding of the dominant processes involved in its development and offer up dialysis-based interventions specifically designed to mitigate the cumulative ischemic insults consequent to conventional HD treatment. This article explores the justification of this approach and recent evidence of its efficacy.

Characterising haemodynamic stress during haemodialysis using the extrema points analysis model.

BACKGROUND AND AIMS: It is becoming recognised that the process of haemodialysis (HD) itself induces circulatory stress that could be implicated in the observed higher rate of end-organ damage. We aimed to study the haemodynamic performance during HD using the extrema points (EP) analysis model, and to examine the determinants of the model and its relation to circulatory stress. METHODS: 63 incident HD patients were studied. Mean arterial blood pressure (MAP) EP frequencies and baroreflex sensitivity during HD were computed for continuous non-invasive haemodynamic monitoring. Pulse-wave velocity as a measure of arterial stiffness was performed. High-sensitivity troponin-T was also measured. RESULTS: The time of each dialysis session was divided into four quarters. Repeated measures ANOVA of the MAP EP frequencies for all subjects during HD demonstrated a gradual significant increase reaching peak levels at the third quarter of dialysis time and remaining at that peak during the fourth quarter (F(3,171228) = 392.06, p < 0.001). In multivariate regression, lower baroreflex sensitivity was the only independent predictor of higher MAP EP frequencies (ß = -0.642, p = 0.001, adjusted R(2) for the whole model = 0.385). In linear regression analysis, higher MAP EP frequencies were associated with higher troponin-T levels (ß = 0.442, p = 0.002, R(2) = 0.19, B = 103.29, 95% CI 38.88-167.70). CONCLUSION: The EP analysis model using MAP is a novel functional haemodynamic measure that can represent and quantify circulatory stress during HD. This measure seems to be determined by the integrity of the autonomic function in HD and could represent the link between circulatory stress and end-organ damage in HD patients.

Exploring haemodynamics of haemodialysis using extrema points analysis model.

BACKGROUND: Haemodialysis is a form of renal replacement therapy used to treat patients with end stage renal failure. It is becoming more appreciated that haemodialysis patients exhibit higher rates of multiple end organ damage compared to the general population. There is also a strong emerging evidence that haemodialysis itself causes circulatory stress. We aimed at examining haemodynamic patterns during haemodialysis using a new model and test that model against a normal control. METHODS: We hypothesised that blood pressures generated by each heart beat constantly vary between local peaks and troughs (local extrema), the frequency and amplitude of which is regulated to maintain optimal organ perfusion. We also hypothesised that such model could reveal multiple haemodynamic aberrations during HD. Using a non-invasive cardiac output monitoring device (Finometer®) we compared various haemodynamic parameters using the above model between a haemodialysis patient during a dialysis session and an exercised normal control after comparison at rest. RESULTS: Measurements yielded 29,751 data points for each haemodynamic parameter. Extrema points frequency of mean arterial blood pressure was higher in the HD subject compared to the normal control (0.761Hz IQR 0.5-0.818 vs 0.468Hz IQR 0.223-0.872, P < 0.0001). Similarly, extrema points frequency of systolic blood pressure was significantly higher in haemodialysis compared to normal. In contrary, the frequency of extrema points for TPR was higher in the normal control compared to HD (0.947 IQR 0.520-1.512 vs 0.845 IQR 0.730-1.569, P < 0.0001) with significantly higher amplitudes. CONCLUSION: Haemodialysis patients potentially exhibit an aberrant haemodynamic behaviour characterised by higher extrema frequencies of mean arterial blood pressure and lower extrema frequencies of total peripheral resistance. This, in theory, could lead to higher variation in organ perfusion and may be detrimental to vulnerable vascular beds.

N-terminal Pro-B-type natriuretic peptide and its correlation to haemodialysis-induced myocardial stunning.

BACKGROUND: Haemodialysis (HD) is able to induce recurrent myocardial ischemia and segmental left-ventricular dysfunction (myocardial stunning). The association of N-terminal Pro-B-type natriuretic peptide (NTpro-BNP) with HD-induced myocardial stunning is unclear. METHODS: In 70 prevalent HD patients, HD-induced myocardial stunning was assessed echocardiographically at baseline and after 12 months. The extent to which pre-dialysis NTpro-BNP was associated with the occurrence of HD-induced myocardial stunning was assessed as the primary endpoint. RESULTS: The median Ntpro-BNP concentration in this cohort was 2,154 pg/ml (IQR 1,224-3,014). Patients experiencing HD-induced myocardial stunning at either time point displayed elevated NTpro-BNP values (2,418 pg/ml, IQR, 1,583-3,474 vs. 1,751 pg/ml, IQR (536-2,029), p = 0.02). NTpro-BNP levels did not differ between patients showing HD-induced stunning at baseline and those developing stunning during the observational period (p = 0.8). NTpro-BNP levels drawn at the beginning of the dialysis session achieved a poor diagnostic accuracy for the detection of myocardial stunning (area under the ROC curve 0.61, 95% CI 0.45-0.77), but provided an accurate rule out for myocardial stunning during the subsequent year (AUC 0.85, 95% CI 0.70-0.99). The calculated cut-off of 1,570 pg/ml achieved a sensitivity of 66% and a specificity of 78% for the exclusion of myocardial stunning at any time point. In logistic regression analysis, only low NTpro-BNP levels (OR 0.92 for every additional 100 pg/ml, 95% CI 0.85-0.99, p = 0.03) were significantly associated with absence of myocardial stunning at any time point. CONCLUSION: Predialytic NTpro-BNP levels fail to adequately diagnose current dialysis-induced myocardial stunning, but help to identify patients with a propensity to develop dialysis-induced myocardial stunning at any time during the next 12 months.

MRI for the assessment of organ perfusion in patients with chronic kidney disease.

PURPOSE OF REVIEW: Recent data have highlighted the importance of quantitative measures of organ perfusion and functional reserve. Magnetic resonance imaging allows the assessment of markers of perfusion without the use of contrast media. Techniques such as arterial spin labelling (ASL) and blood oxygen level-dependent (BOLD) imaging have been available for some time, but advances in the technology and concerns over the safety of contrast media in renal disease have spurred renewed interest and development. RECENT FINDINGS: ASL measures perfusion, whereas BOLD imaging provides a marker of blood oxygenation, arising from the compound effect of a number of measures including perfusion, blood volume and oxygen consumption; thus, the techniques are complementary rather than analogous. They were initially confined to brain imaging as inherently low signal, susceptibility effects and motion limited their use in thoracic and abdominal organs. Advances in technology have led to robust sequences that can quantify clinically relevant changes and correlate well with reference standards. Novel approaches are likely to accelerate translation into clinical practice. SUMMARY: The noninvasive and repeatable nature of ASL and BOLD imaging makes it likely that they will be increasingly used in clinical research. Using a developmental framework, we suggest that the application of these techniques to thoracic and abdominal organs requires validation before they are suitable for generalized clinical use. The demand for these techniques is likely to be driven by the incentive to avoid the use of contrast media.

Volume is not the only key to hypertension control in dialysis patients.

There is a widely held belief that hypervolaemia due to excess intake or inadequate removal of salt and water is the principal cause of hypertension in dialysis patients. The risk of failing to consider additional pathophysiological elements is that inadequate or inappropriate therapeutic strategies may be adopted. This review aims to highlight multiple alternative mechanisms for hypertension in this setting along with the risks of probing for normotension by empirical dry weight reduction if dry weight is imprecisely defined.