-
1.
Nuclear Imaging in Pediatric Kidney Diseases.
Dhull, RS, Joshi, A, Saha, A
Indian pediatrics. 2018;(7):591-597
Abstract
Renal scintigraphy is a useful tool in diagnosis and management of various nephro-urological conditions. Tc-99m dimercaptosuccinic acid renal scintigraphy (Tc-99m-DMSA), Tc-99m mercaptoacetyltriglycine (Tc-99m-MAG3) or Tc-99m diethylenetriaminepentaacetic acid (Tc-99m-DTPA) dynamic renal scintigraphy, and Radionuclide micturating cystography are the common scans used in children with kidney diseases. These studies are minimally invasive, easily available, and offer both anatomic details and functional information required for thorough evaluation. At the same time, it is essential to have appropriate knowledge to interpret these studies and be aware of their limitations and pitfalls. The advent of Positron emission tomography-computed tomography/magnetic resonance imaging (PET-CT/MRI) has broadened the scope of nuclear medicine. This article focuses on the technique, interpretation, indication and recent practice guidelines of renal scintigraphy in children with kidney diseases.
-
2.
Innovative Use of Novel Biomarkers to Improve the Safety of Renally Eliminated and Nephrotoxic Medications.
Barreto, EF, Rule, AD, Voils, SA, Kane-Gill, SL
Pharmacotherapy. 2018;(8):794-803
Abstract
Over the last decade, the discovery of novel renal biomarkers and research on their use to improve medication effectiveness and safety has expanded considerably. Pharmacists are uniquely positioned to leverage this new technology for renal assessment to improve medication dosing and monitoring. Serum cystatin C is a relatively new, inexpensive, functional renal biomarker that responds more quickly to changing renal function than creatinine and is not meaningfully affected by age, sex, skeletal muscle mass, dietary intake, or deconditioning. Cystatin C has been proposed as an adjunct or alternative to creatinine for glomerular filtration rate assessment and estimation of drug clearance. Tissue inhibitor of metalloproteinase-2·insulin-like growth factor-binding protein 7 ([TIMP-2]·[IGFBP7]) is a composite of two damage biomarkers released into the urine at a checkpoint in mitosis when renal cells undergo stress or sense a future risk of damage. Concentrations of [TIMP-2]·[IGFBP7] increase before a rise in serum creatinine is evident, thus providing insightful information for evaluation in the context of other patient data to predict the risk for impending kidney injury. This article provides a brief overview of novel renal biomarkers being used as a mechanism to improve medication safety including a discussion of cystatin C, as part of drug-dosing algorithms and specifically for vancomycin dosing, and the use of [TIMP-2]·[IGFBP7] for risk prediction in acute kidney injury and drug-induced kidney disease. Select cases of clinical experience with novel renal biomarkers are outlined, and lessons learned and future applications are described.
-
3.
Nephrotoxicity of Select Rheumatologic Drugs.
Woodell, T, Avasare, RS
Rheumatic diseases clinics of North America. 2018;(4):605-617
Abstract
Several drugs commonly used in the management of rheumatic diseases may lead to nephrotoxicity, electrolyte disturbances, and hypertension. Here the authors focus on nonsteroidal antiinflammatory drugs, uric-acid-lowering therapy, and commonly used immunosuppressant therapies. The authors include a drug dosing table for patients with kidney disease.
-
4.
Adverse Effects of Mineralocorticoid Receptor Antagonist Administration.
Kallistratos, MS, Pittaras, A, Theodoulidis, I, Grassos, C, Poulimenos, LE, Manolis, AJ
Current pharmaceutical design. 2018;(46):5537-5541
Abstract
BACKGROUND Mineralocorticoid receptor antagonists consist of a class of drugs with pleiotropic beneficial effects in several cardiovascular diseases. However, physicians frequently overlook their use due to the adverse effects of such agents. OBJECTIVES To determine the adverse effects of mineralocorticoid receptor antagonists and to suggest clinically meaningful options. We present data on the two most administered agents of this class: spironolactone and eplerenone. METHOD We conducted an in-depth review of the existing international literature to draft a mini review about the mineralocorticoid receptor antagonists-related side effects. RESULT Mineralocorticoid receptor antagonists are associated with increased risk of hyperkalemia and acute deterioration of renal function. Of note, these adverse effects are dose-dependent, more common during the initial period of treatment, and are usually reversed after the withdrawal of therapy. Sex-related adverse events are noted mainly in spironolactone while switching to eplerenone could attenuate those. CONCLUSION Mineralocorticoid receptor antagonists therapy is significantly limited due to their side effects. The development of novel non-steroidal mineralocorticoid receptor antagonists could substantially widen the use of such agents.
-
5.
Endogenous markers for kidney function in children: a review.
den Bakker, E, Gemke, RJBJ, Bökenkamp, A
Critical reviews in clinical laboratory sciences. 2018;(3):163-183
Abstract
Although glomerular filtration rate (GFR) in children can be measured using a gold-standard technique following injection of an exogenous marker, this invasive and cumbersome technique is not widely available and GFR is commonly estimated using serum levels of endogenous markers. Creatinine, urea, cystatin C, beta-trace protein, and beta-2 microglobulin are well-established endogenous markers of kidney function. These markers differ in site of production and effects of diet and medication, as well as renal-tubular handling and extra-renal elimination. For each marker, different methods are available for measurement. Importantly, the measurements of creatinine and cystatin C have recently been standardized with the introduction of international reference standards. In order to allow estimation of GFR from serum marker concentrations, different equations for estimated GFR (eGFR) have been developed in children, using simple or more complex regression strategies with gold standard GFR measurements as a dependent variable. As a rule, estimation strategies relying on more than one marker - either by calculating the average of single parameter equations or by using more complex equations incorporating several parameters - outperform eGFR estimations using only a single marker. This in-depth review will discuss the physiology, measurement and clinical use of creatinine, urea, cystatin C, beta-trace protein, and beta-2 microglobulin in children. It will also address the generation of eGFR equations in children and provide an overview of currently available eGFR equations for the pediatric age group.
-
6.
Low protein diets for non-diabetic adults with chronic kidney disease.
Hahn, D, Hodson, EM, Fouque, D
The Cochrane database of systematic reviews. 2018;(10):CD001892
-
-
Free full text
-
Abstract
BACKGROUND Chronic kidney disease (CKD) is defined as reduced function of the kidneys present for 3 months or longer with adverse implications for health and survival. For several decades low protein diets have been proposed for participants with CKD with the aim of slowing the progression to end-stage kidney disease (ESKD) and delaying the onset of renal replacement therapy. However the relative benefits and harms of dietary protein restriction for preventing progression of CKD have not been resolved. This is an update of a systematic review first published in 2000 and updated in 2006 and 2009. OBJECTIVES To determine the efficacy of low protein diets in preventing the natural progression of CKD towards ESKD and in delaying the need for commencing dialysis treatment in non-diabetic adults. SEARCH METHODS We searched the Cochrane Kidney and Transplant Register of Studies up to 2 March 2018 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA We included randomised controlled trials (RCTs) or quasi RCTs in which adults with non-diabetic chronic kidney disease (stages 3 to 5) not on dialysis were randomised to receive a very low protein intake (0.3 to 0.4 g/kg/d) compared with a low protein intake (0.5 to 0.6 g/kg/d) or a low protein intake compared with a normal protein intake (≥ 0.8 g/kg/d) for 12 months or more. DATA COLLECTION AND ANALYSIS Two authors independently selected studies and extracted data. For dichotomous outcomes (death, all causes), requirement for dialysis, adverse effects) the risk ratios (RR) with 95% confidence intervals (CI) were calculated and summary statistics estimated using the random effects model. Where continuous scales of measurement were used (glomerular filtration rate (GFR), weight), these data were analysed as the mean difference (MD) or standardised mean difference (SMD) if different scales had been used. The certainty of the evidence was assessed using GRADE. MAIN RESULTS We identified an additional six studies to include 17 studies with 2996 analysed participants (range 19 to 840). Four larger multicentre studies were subdivided according to interventions so that the review included 21 separate data sets. Mean duration of participant follow-up ranged from 12 to 50 months.Random sequence generation and allocation concealment were considered at low risk of bias in eleven and nine studies respectively. All studies were considered at high risk for performance bias as they were open-label studies. We assessed detection bias for outcome assessment for GFR and ESKD separately. As GFR measurement was a laboratory outcome all studies were assessed at low risk of detection bias. For ESKD, nine studies were at low risk of detection bias as the need to commence dialysis was determined by personnel independent of the study investigators. Five studies were assessed at high risk of attrition bias with eleven studies at low risk. Ten studies were at high risk for reporting bias as they did not include data which could be included in a meta-analysis. Eight studies reported funding from government bodies while the remainder did not report on funding.Ten studies compared a low protein diet with a normal protein diet in participants with CKD categories 3a and b (9 studies) or 4 (one study). There was probably little or no difference in the numbers of participants who died (5 studies 1680 participants: RR 0.77, 95% CI 0.51 to 1.18; 13 fewer deaths per 1000; moderate certainty evidence). A low protein diet may make little or no difference in the number of participants who reached ESKD compared with a normal protein diet (6 studies, 1814 participants: RR 1.05, 95% CI 0.73 to 1.53; 7 more per 1000 reached ESKD; low certainty evidence). It remains uncertain whether a low protein diet compared with a normal protein intake impacts on the outcome of final or change in GFR (8 studies, 1680 participants: SMD -0.18, 95% CI -0.75 to 0.38; very low certainty evidence).Eight studies compared a very low protein diet with a low protein diet and two studies compared a very low protein diet with a normal protein diet. A very low protein intake compared with a low protein intake probably made little or no difference to death (6 studies, 681 participants: RR 1.26, 95% CI 0.62 to 2.54; 10 more deaths per 1000; moderate certainty evidence). However it probably reduces the number who reach ESKD (10 studies, 1010 participants: RR 0.65, 95% CI 0.49 to 0.85; 165 per 1000 fewer reached ESKD; moderate certainty evidence). It remains uncertain whether a very low protein diet compared with a low or normal protein intake influences the final or change in GFR (6 studies, 456 participants: SMD 0.12, 95% CI -0.27 to 0.52; very low certainty evidence).Final body weight was reported in only three studies. It is uncertain whether the intervention alters final body weight (3 studies, 89 participants: MD -0.40 kg, 95% CI -6.33 to 5.52; very low certainty evidence).Twelve studies reported no evidence of protein energy wasting (malnutrition) in their study participants while three studies reported small numbers of participants in each group with protein energy wasting. Most studies reported that adherence to diet was satisfactory. Quality of life was not formally assessed in any studies. AUTHORS' CONCLUSIONS This review found that very low protein diets probably reduce the number of people with CKD 4 or 5, who progress to ESKD. In contrast low protein diets may make little difference to the number of people who progress to ESKD. Low or very low protein diets probably do not influence death. However there are limited data on adverse effects such as weight differences and protein energy wasting. There are no data on whether quality of life is impacted by difficulties in adhering to protein restriction. Studies evaluating the adverse effects and the impact on quality of life of dietary protein restriction are required before these dietary approaches can be recommended for widespread use.
-
7.
Calciphylaxis in end-stage liver and renal disease patients before and after transplant.
Couri, T, Stier, M, Mikolajczyk, A, Aronsohn, A
Clinical transplantation. 2018;(6):e13272
Abstract
Calciphylaxis is a rare vascular disorder characterized by calcification of arterioles which causes tissue inflammation and necrosis. It is associated with the metabolic disturbances seen in end-stage renal disease (ESRD) and has also been described in patients with cirrhosis with preserved kidney function. Characteristic calciphylaxis lesions are black eschars surrounded by retiform purpura, and the gold standard for diagnosis is skin biopsy. Reported 1-year mortality rates range between 45% and 80%. No treatment modality has been evaluated in a prospective randomized trial, and reports of treatment efficacy vary. Kidney transplant has been reported as a successful therapy for calciphylaxis; however, cases exist of the initial onset of calciphylaxis following kidney transplant as well as simultaneous liver-kidney (SLK) transplant. The decision to maintain a patient with end-stage renal and liver disease on the waiting list for SLK transplant following the onset of calciphylaxis must consider the high 1-year mortality associated with this condition. More research is necessary to understand how to allocate donor allografts to manage patients with calciphylaxis and ESRD and/or cirrhosis effectively.
-
8.
Empagliflozin reduces cardiovascular events, mortality and renal events in participants with type 2 diabetes after coronary artery bypass graft surgery: subanalysis of the EMPA-REG OUTCOME® randomised trial.
Verma, S, Mazer, CD, Fitchett, D, Inzucchi, SE, Pfarr, E, George, JT, Zinman, B
Diabetologia. 2018;(8):1712-1723
-
-
Free full text
-
Abstract
AIMS/HYPOTHESIS After coronary artery bypass graft (CABG) surgery in individuals with type 2 diabetes, there remains a considerable residual cardiovascular risk. In the EMPA-REG OUTCOME® trial in participants with type 2 diabetes and established cardiovascular disease, empagliflozin reduced the risk of cardiovascular death by 38%, all-cause mortality by 32%, hospitalisation for heart failure by 35% and incident or worsening nephropathy by 39% vs placebo when given in addition to standard of care. The aim of this post hoc analysis of the EMPA-REG OUTCOME® trial was to determine the effects of the sodium glucose cotransporter 2 inhibitor empagliflozin on cardiovascular events and mortality in participants with type 2 diabetes and a self-reported history of CABG surgery. METHODS The EMPA-REG OUTCOME® trial was a randomised, double-blind, placebo-controlled trial. Participants with type 2 diabetes and established cardiovascular disease were randomised 1:1:1 to receive placebo, empagliflozin 10 mg or empagliflozin 25 mg, once daily, in addition to standard of care. In subgroups by self-reported history of CABG (yes/no) at baseline, we assessed: cardiovascular death; all-cause mortality; hospitalisation for heart failure; and incident or worsening nephropathy (progression to macroalbuminuria, doubling of serum creatinine, initiation of renal replacement therapy or death due to renal disease). Differences in risk between empagliflozin and placebo were assessed using a Cox proportional hazards model. RESULTS At baseline, 25% (1175/4687) of participants who received empagliflozin and 24% (563/2333) of participants who received placebo had a history of CABG surgery. In participants with a history of CABG surgery, HRs (95% CI) with empagliflozin vs placebo were 0.52 (0.32, 0.84) for cardiovascular mortality, 0.57 (0.39, 0.83) for all-cause mortality, 0.50 (0.32, 0.77) for hospitalisation for heart failure and 0.65 (0.50, 0.84) for incident or worsening nephropathy. Results were consistent between participants with and without a history of CABG surgery (p > 0.05 for treatment by subgroup interactions). CONCLUSIONS/INTERPRETATION In participants with type 2 diabetes and a self-reported history of CABG surgery, treatment with empagliflozin was associated with profound reductions in cardiovascular and all-cause mortality, hospitalisation for heart failure, and incident or worsening nephropathy. These data have important implications for the secondary prevention of cardiovascular events after CABG in individuals with type 2 diabetes. TRIAL REGISTRATION ClinicalTrials.gov NCT01131676.
-
9.
Intravenous fluid therapy in critically ill adults.
Finfer, S, Myburgh, J, Bellomo, R
Nature reviews. Nephrology. 2018;(9):541-557
Abstract
Intravenous fluid therapy is one of the most common interventions in acutely ill patients. Each day, over 20% of patients in intensive care units (ICUs) receive intravenous fluid resuscitation, and more than 30% receive fluid resuscitation during their first day in the ICU. Virtually all hospitalized patients receive intravenous fluid to maintain hydration and as diluents for drug administration. Until recently, the amount and type of fluids administered were based on a theory described over 100 years ago, much of which is inconsistent with current physiological data and emerging knowledge. Despite their widespread use, various fluids for intravenous administration have entered clinical practice without a robust evaluation of their safety and efficacy. High-quality, investigator-initiated studies have revealed that some of these fluids have unacceptable toxicity; as a result, several have been withdrawn from the market (while others, controversially, are still in use). The belief that dehydration and hypovolaemia can cause or worsen kidney and other vital organ injury has resulted in liberal approaches to fluid therapy and the view that fluid overload and tissue oedema are 'normal' during critical illness; this is quite possibly harming patients. Increasing evidence indicates that restrictive fluid strategies might improve outcomes.
-
10.
Magnetic resonance imaging T1- and T2-mapping to assess renal structure and function: a systematic review and statement paper.
Wolf, M, de Boer, A, Sharma, K, Boor, P, Leiner, T, Sunder-Plassmann, G, Moser, E, Caroli, A, Jerome, NP
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2018;(suppl_2):ii41-ii50
-
-
Free full text
-
Abstract
This systematic review, initiated by the European Cooperation in Science and Technology Action Magnetic Resonance Imaging Biomarkers for Chronic Kidney Disease (PARENCHIMA), focuses on potential clinical applications of magnetic resonance imaging in renal non-tumour disease using magnetic resonance relaxometry (MRR), specifically, the measurement of the independent quantitative magnetic resonance relaxation times T1 and T2 at 1.5 and 3Tesla (T), respectively. Healthy subjects show a distinguishable cortico-medullary differentiation (CMD) in T1 and a slight CMD in T2. Increased cortical T1 values, that is, reduced T1 CMD, were reported in acute allograft rejection (AAR) and diminished T1 CMD in chronic allograft rejection. However, ambiguous findings were reported and AAR could not be sufficiently differentiated from acute tubular necrosis and cyclosporine nephrotoxicity. Despite this, one recent quantitative study showed in renal transplants a direct correlation between fibrosis and T1 CMD. Additionally, various renal diseases, including renal transplants, showed a moderate to strong correlation between T1 CMD and renal function. Recent T2 studies observed increased values in renal transplants compared with healthy subjects and in early-stage autosomal dominant polycystic kidney disease (ADPKD), which could improve diagnosis and progression assessment compared with total kidney volume alone in early-stage ADPKD. Renal MRR is suggested to be sensitive to renal perfusion, ischaemia/oxygenation, oedema, fibrosis, hydration and comorbidities, which reduce specificity. Due to the lack of standardization in patient preparation, acquisition protocols and adequate patient selection, no widely accepted reference values are currently available. Therefore this review encourages efforts to optimize and standardize (multi-parametric) protocols to increase specificity and to tap the full potential of renal MRR in future research.