Current Opinion in Nephrology and Hypertension

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Nutritional status assessment: a neglected biomarker in persons with end-stage kidney disease

imagePurpose of review
Malnutrition is a frequent complication and risk factor for adverse outcomes in the dialysis population that is often underrecognized and neglected. This article reviews published literature on the associations between malnutrition, mortality, quality of life and hospitalizations in persons on dialysis in order to raise awareness of the importance of preventing and treating it.
Recent findings
All methods of nutritional assessment namely serum biochemistry, body composition, dietary intake, handgrip strength and nutritional scoring tools are independently associated with increased mortality in dialysis populations. Malnutrition severely affects physical and mental measures of quality of life and increases the number and length of hospitalizations in persons receiving dialysis, resulting in increased healthcare costs. Worsening of nutritional status is also associated with poor survival and higher rates of hospitalizations in this patient population.
Summary
Malnutrition is an unacceptably common complication in dialysis patients that is substantially associated with adverse outcomes and higher hospital costs. Further interventional studies assessing the impact of preventing and treating malnutrition on clinical outcomes are warranted and should be considered a priority.

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https://journals.lww.com/co-nephrolhypertens/Fulltext/2020/11000/Nutritional_status_assessment__a_neglected.2.aspx

Cystatin C is ready for clinical use

imagePurpose of review
The goal of this update is to raise awareness of clinical scenarios where cystatin C has clear and immediate benefits as an alternative glomerular filtration rate (GFR) biomarker to supplement creatinine. An additional goal is to focus the estimated GFR (eGFR) controversy onto medication prescribing for agents with narrow therapeutic windows where better GFR estimation will lead to improved medical care.
Recent findings
Equations that include cystatin C predict GFR more accurately than serum creatinine in children, adults, and older adults with larger effects among persons who are acutely ill. Numerous studies have evaluated medication dosing based on either GFR estimate; vancomycin was the most frequently studied drug and its target level and elimination were better predicted by cystatin C. Overall, approaches to medication dosing and monitoring that include cystatin C concentrations have been shown to result in a better achievement of drug trough levels. Furthermore, cystatin C offers the opportunity to avoid the race coefficient that is required for any current creatinine-based eGFR equation, which has been appropriately criticized for introducing unnecessary imprecision, assumptions and values on GFR estimation.
Summary
Hospital laboratories must make cystatin C available for clinical care to improve the safety and efficacy of medications that have narrow therapeutic windows.

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https://journals.lww.com/co-nephrolhypertens/Fulltext/2020/11000/Cystatin_C_is_ready_for_clinical_use.7.aspx

Current and novel imaging techniques to evaluate myocardial dysfunction during hemodialysis

imagePurpose of review
Patients on hemodialysis have significantly higher rates of cardiovascular mortality resulting from a multitude of myocardial dysfunctions. Current imaging modalities allow independent assessment of cardiac morphology, contractile function, coronary arteries and cardiac perfusion. Techniques such as cardiac computed tomography (CT) imaging have been available for some time, but have not yet had widespread adoption because of technical limitations related to cardiac motion, radiation exposure and safety of contrast agents in kidney disease.
Recent findings
Novel dynamic contrast-enhanced (DCE) CT imaging can be used to acquire high-resolution cardiac images, which simultaneously allow the assessment of coronary arteries and the quantitative measurement of myocardial perfusion. The advancement of recent CT scanners and cardiac protocols have allowed noninvasive imaging of the whole heart in a single imaging session with minimal cardiac motion artefact and exposure to radiation.
Summary
DCE-CT imaging in clinical practice would allow comprehensive evaluation of the structure, function, and hemodynamics of the heart in a short, well tolerated scanning session. It is an imaging tool enabling the study of myocardial dysfunction in dialysis patients, who have greater cardiovascular risk than nonrenal cardiovascular disease populations, both at rest and under cardiac stress associated with hemodialysis itself.

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https://journals.lww.com/co-nephrolhypertens/Fulltext/2020/11000/Current_and_novel_imaging_techniques_to_evaluate.3.aspx

Imaging of renal fibrosis

imagePurpose of review
Fibrosis is an important biomarker of chronic kidney injury, and a powerful predictor of renal outcome. Currently, the only method for measuring fibrotic burden is histologic analysis, which requires a kidney biopsy in humans, or kidney removal in animal models. These requirements have not only hindered our ability to manage patients effectively, but have also prevented a full understanding of renal fibrosis pathogenesis, and slowed the translation of new antifibrotic agents. The development of noninvasive fibrosis imaging tools could thus transform both clinical care and renal fibrosis research.
Recent findings
Conventional imaging modalities have historically failed to image fibrosis successfully. However, recent exciting technological advances have greatly enhanced their capabilities. New techniques, for example, may allow imaging of the physical consequences of scarring, as surrogate measures of renal fibrosis. Similarly, other groups have developed ways to directly image extracellular matrix, either with the use of contrast-enhanced probes, or using matrix components as endogenous contrast agents.
Summary
New developments in imaging technology have the potential to transform our ability to visualize renal fibrosis and to monitor its progression. In doing so, these advances could have major implications for kidney disease care, the development of new antiscarring agents, and our understanding of renal fibrosis in general.

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https://journals.lww.com/co-nephrolhypertens/Fulltext/2020/11000/Imaging_of_renal_fibrosis.8.aspx

Fluid management in chronic kidney disease: what is too much, what is the distribution, and how to manage fluid overload in patients with chronic kidney disease?

imagePurpose of review
Assessment of fluid status to reach normovolemia in patients with chronic kidney disease (CKD) continues to be a tough task. Besides clinical observation, technological methods have been introduced, yet, the best approach is still uncertain. The present review looks at fluid overload in CKD from three perspectives: the critical fluid threshold leading to adverse cardiovascular outcomes, fluid distribution and its clinical correlates, and direct effect of fluid overload on vascular function related to disturbance of the sodium–skin axis and endothelial glycocalyx dysfunction.
Recent findings
To determine fluid status, both the absolute and relative fluid overload is used as parameter in clinical practice. In addition, the definition of fluid overload is ambivalent and its relation to symptom burden has not been studied well. Studies on the impact of distribution of fluid are scarce and the limited evidence suggests differences based on the cause of CKD. So far, no standardized technologies are available to adequately determine fluid distribution. After discovering the ‘third compartment’ of total body sodium in skin and muscle tissue and its potential direct effect on vascular function, other biomarkers such as VEGF-C are promising.
Summary
We propose a multimodal clinical approach for volume management in CKD. Because there are currently no studies are available demonstrating that correction of fluid overload in CKD will lead to better outcome, these are strongly needed.

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https://journals.lww.com/co-nephrolhypertens/Fulltext/2020/11000/Fluid_management_in_chronic_kidney_disease__what.5.aspx

More precise donor–recipient matching: the role of eplet matching

imagePurpose of review
A precise understanding of the alloimmune risk faced by individual recipients at the time of transplant is an unmet need in transplantation. Although conventional HLA donor–recipient mismatch is too imprecise to fulfil this need, HLA molecular mismatch increases the precision in alloimmune risk assessment by quantifying the difference between donors and recipients at the molecular level.
Recent findings
Within each conventional HLA mismatch the number, type, and position of mismatched amino acids create a wide range of HLA molecular mismatches between recipients and donors. Multiple different solid organ transplant groups from across the world have correlated HLA molecular mismatch with transplant outcomes including de novo donor-specific antibody development, antibody-mediated rejection, T-cell-mediated rejection, and allograft survival.
Summary
All alloimmunity is driven by differences between donors and recipients at the molecular level. HLA molecular mismatch may represent an advancement compared to traditional HLA antigen mismatch as a fast, reproducible, cost-effective way to improve alloimmune risk assessment at the time of transplantation to move the field towards precision medicine.

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https://journals.lww.com/co-nephrolhypertens/Fulltext/2020/11000/More_precise_donor_recipient_matching__the_role_of.13.aspx

Getting the basics right: the monitoring of arteriovenous fistulae, a review of the evidence

imagePurpose of review
Despite being the preferred vascular access for haemodialysis, the arteriovenous fistula (AVF) remains prone to a number of complications, the most common of these being thrombosis secondary to stenosis. This has resulted in the widespread use of monitoring and surveillance programmes. Surveillance uses more resources than monitoring and has not been convincingly shown to improve outcomes. The evidence supporting the use of the various monitoring tools has been relatively neglected and has not been the focus of literature review. This narrative review is the first to appraise the evidence for the use of physical examination, access recirculation, Kt/V and dynamic venous pressures (DVP) as monitoring tools in mature AVF.
Recent findings
The vastly increased number of data points for access recirculation, Kt/V and DVP produced as standard by online clearance monitoring (OCM) on modern dialysis machines is likely to have significantly changed the utility of these metrics in the prediction of AVF failure. Algorithms have been developed to highlight those of highest risk of failure.
Summary
The evidence supporting the use of monitoring in the prediction of AVF failure is predominantly observational, underpowered and more than 20 years old. Access recirculation and Kt/V appears to have higher utility in AVF than in arteriovenous grafts. We suggest that the development of OCM necessitates the reevaluation of these tools.

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https://journals.lww.com/co-nephrolhypertens/Fulltext/2020/11000/Getting_the_basics_right__the_monitoring_of.4.aspx

Apolipoprotein L1: role in the evaluation of kidney transplant donors

imagePurpose of review
To summarize the current state of evidence regarding the role of apolipoprotein L1 (APOL1) genotyping in evaluating donors for kidney transplantation.
Recent findings
African ancestry is associated with an increased risk of kidney failure following living donation. Moreover, kidney transplants from African ancestry deceased donors have an increased risk of graft failure. Preliminary evidence suggests that APOL1 genotype may mediate at least a portion of this racial variation, with high-risk APOL1 genotypes defined by presence of two renal risk variants (RRVs). A pilot study 136 African ancestry living donors found that those with APOL1 high-risk genotypes had lower baseline kidney function and faster rates of kidney function decline after donation. To date, three retrospective studies identified a two-to-three times greater risk of allograft failure associated with kidneys from donors with high-risk APOL1 genotype. Active research initiatives seek to address unanswered questions, including reproducibility in large national samples, the role of ‘second hits’ injuries, and impact of recipient genotype, with a goal to build consensus on applications for policy and practice.
Summary
As evidence evolves, APOL1 genotyping may have applications for organ quality scoring in deceased donor kidney allocation, and for the evaluation and selection of living donor candidates.

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https://journals.lww.com/co-nephrolhypertens/Fulltext/2020/11000/Apolipoprotein_L1__role_in_the_evaluation_of.15.aspx