Publisher: Oxford University Press (Total: 369 journals)
Clinical Kidney Journal
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Open Access journal
ISSN (Print) 2048-8505 - ISSN (Online) 2048-8513
Published by Oxford University Press [369 journals]
Abstract: News from ERA-EDTA:
- Morbidity, mortality and quality of life in the ageing haemodialysis
population: results from the ELDERLY study
Authors: Seckinger J; Dschietzig W, Leimenstoll G, et al.
Abstract: In the original published version of this article the formatting of Table 4 was partially incorrect. This error has now been corrected in the final published version of the article and the correct version of Table 4 is also given below: Table 4.Treatment quality (mean values), comedicationa and QoL parameters (maximum likelihood estimates)MonthAge
- Obesity and kidney disease: hidden consequences of the epidemic
Authors: Kovesdy CP; L. Furth S, Zoccali C, et al.
Abstract: Obesity has become a worldwide epidemic, and its prevalence has been projected to grow by 40% in the next decade. This increasing prevalence has implications for the risk of diabetes, cardiovascular disease and also for chronic kidney disease (CKD). A high body mass index is one of the strongest risk factors for new-onset CKD. In individuals affected by obesity, a compensatory hyperfiltration occurs to meet the heightened metabolic demands of the increased body weight. The increase in intraglomerular pressure can damage the kidneys and raise the risk of developing CKD in the long term. The incidence of obesity-related glomerulopathy has increased 10-fold in recent years. Obesity has also been shown to be a risk factor for nephrolithiasis, and for a number of malignancies including kidney cancer. This year World Kidney Day promotes education on the harmful consequences of obesity and its association with kidney disease, advocating healthy lifestyles and health policy measures that make preventive behaviors an affordable option.
- Does wealth make health' Cherchez la renal replacement therapy
Authors: Sanchez-Niño MD; Ortiz A.
Abstract: In this issue of CKJ, McQuarrie et al. have explored the relationship between socioeconomic status and outcomes among Scottish patients with a renal biopsy diagnosis of primary glomerulonephritis. Patients in the lower socioeconomic category had a twofold higher risk of death. No significant differences were observed on progression to end-stage renal disease (ESRD) requiring renal replacement therapy (RRT), suggesting that overall medical management was appropriate for all socioeconomic categories. The findings are significant since they come from an ethnically homogeneous population with free access to healthcare; they also relate to a specific aetiology of chronic kidney disease (CKD) expected to be less dependent on unhealthy lifestyles than other more frequent aetiologies that dominate studies of CKD in general, such as diabetic or hypertensive nephropathy. A closer look at the data suggests that living in a high socioeconomic area is associated with lower mortality, rather than the other way round. Furthermore, the differences in mortality were most pronounced during the RRT stage of CKD, providing clues for further research. In this regard, Wilmink et al. and Nee et al. point to access to pre-ESRD nephrology care and to the best kidney transplantation options as modifiable factors to be studied in the realm of T3 translational research to improve CKD patient outcomes.
- Quantification of bleeding volume using computed tomography and clinical
complications after percutaneous renal biopsy
Authors: Chikamatsu Y; Matsuda K, Takeuchi Y, et al.
Abstract: Background: The aim of this study was to investigate specific bleeding volume after percutaneous renal biopsy (PRB) and the correlation between bleeding volume and clinical parameters.Methods: A retrospective study of 252 consecutive patients (153 male patients and 99 female patients) who underwent PRB at the Department of Nephrology, Japanese Red Cross Ishinomaki Hospital, between July 2013 and January 2016 was conducted. PRB was performed under ultrasound guidance using an automated spring-loaded biopsy device and a 16-cm, 16-gauge needle. Patients underwent computed tomography (CT) the day after PRB. Bleeding volume after PRB was evaluated using reconstructed CT data.Results: The median bleeding volume after PRB was 38 mL (25th–75th percentile, 18–85 mL), with ≥4 punctures identified as a risk factor for massive bleeding. The incidence rates of macrohematuria, transient hypotension and bladder obstruction were 14.3, 8.7 and 4.7%, respectively. Post-PRB blood transfusion and intervention were required in 4.7 and 0.8% of patients, respectively.Conclusion: Although it is difficult to assess the risk for massive bleeding prior to PRB, we do provide evidence of a specific increased risk with ≥4 puncture attempts, and recommend careful follow-up of these patients.
- Multiple socioeconomic deprivation and impact on survival in patients with
Authors: McQuarrie EP; Mackinnon B, Bell S, et al.
Abstract: Background: The impact of multiple socio-economic deprivation on patient outcomes in primary renal diseases is unknown. We aimed to assess whether risk of death or requiring renal replacement therapy (RRT) in patients with primary glomerulonephritis (GN) was higher in patients living in an area of multiple socio-economic deprivation.Methods: Patients undergoing native renal biopsy between 2000 and 2014 were identified. Baseline demographics, postcode at time of biopsy, follow-up blood pressure, proteinuria and time to death or RRT were recorded. The Scottish Index of Multiple Deprivation (SIMD) is a multidimensional model used to measure deprivation based on postcode. Using SIMD, patients were separated into tertiles of deprivation.Results: A total of 797 patients were included, 64.2% were male with mean age of 54.1 (standard deviation 17.0) years. Median follow-up was 6.3 (interquartile range 3.7–9.4) years during which 174 patients required RRT and 185 patients died. Patients in the most deprived tertile of deprivation were significantly more likely to die than those in the least deprived tertile [hazard ratio (HR) 2.2, P < 0.001], independent of age, baseline serum creatinine and blood pressure. They were not more likely to require RRT (P = 0.22). The increased mortality risk in the most deprived tertile was not uniform across primary renal diseases, with the association being most marked in focal segmental glomerulosclerosis (HR 7.4) and IgA nephropathy (HR 2.7) and absent in membranous nephropathy.Conclusion: We have demonstrated a significant independent 2-fold increased risk of death in patients with primary GN who live in an area of multiple socio-economic deprivation at the time of diagnosis as compared with those living in less deprived areas.
- Cognitive function and advanced kidney disease: longitudinal trends and
impact on decision-making
Authors: Iyasere O; Okai D, Brown E.
Abstract: Background: Cognitive impairment commonly affects renal patients. But little is known about the influence of dialysis modality on cognitive trends or the influence of cognitive impairment on decision-making in renal patients. This study evaluated cognitive trends amongst chronic kidney disease (CKD), haemodialysis (HD) and peritoneal dialysis (PD) patients. The relationship between cognitive impairment and decision-making capacity (DMC) was also assessed.Methods: Patients were recruited from three outpatient clinics. Cognitive function was assessed 4-monthly for up to 2 years, using the Montreal Cognitive Assessment (MoCA) tool. Cognitive trends were assessed using mixed model analysis. DMC was assessed using the Macarthur Competency Assessment tool (MacCAT-T). MacCAT-T scores were compared between patients with cognitive impairment (MoCA
- Looking for the needle in the kidney transplantation haystack
Authors: Cruzado JM; Melilli E.
Abstract: The diagnosis of acute rejection still relies on renal allograft biopsy. In fact, histological features including C4d staining can be useful to differentiate cellular and antibody-mediated acute rejection. However, the pathogenic mechanism to define the type of rejection is usually assessed by anti-HLA donor specific antibodies (DSA) monitoring. Suspicion of acute rejection is usually based on renal function deterioration. This method has low sensitivity. Moreover, creatinine increase follows graft injury and therefore the diagnosis is performed when there is an ongoing acute rejection. One strategy to overcome the limitation of serum creatinine as predictor of acute rejection is to perform surveillance protocol biopsies. However, the low incidence of subclinical acute rejection among patients treated with tacrolimus-based immunosuppression makes this procedure questionable in terms of cost-effectiveness. In this scenario new biomarkers predicting acute rejection are urgently needed. Ideally, such biomarkers should anticipate acute rejection, thus allowing preventive actions such as maintenance immunosupression intensification and/or modification. Alternatively, these new biomarkers should at least improve the predictive value of serum creatinine monitoring. Although many of the new biomarkers are promising, none have been translated to the clinic to date because of a lack of validation studies and the existence of major methodological concerns.
- The role of psychological factors in fatigue among end-stage kidney
disease patients: a critical review
Authors: Picariello F; Moss-Morris R, Macdougall IC, et al.
Abstract: Fatigue is a common and debilitating symptom, affecting 42–89% of end-stage kidney disease patients, persisting even in pre–dialysis care and stable kidney transplantation, with huge repercussions on functioning, quality of life and patient outcomes. This paper presents a critical review of current evidence for the role of psychological factors in renal fatigue. To date, research has concentrated primarily on the contribution of depression, anxiety and subjective sleep quality to the experience of fatigue. These factors display consistent and strong associations with fatigue, above and beyond the role of demographic and clinical factors. Considerably less research is available on other psychological factors, such as social support, stress, self-efficacy, illness and fatigue-specific beliefs and behaviours, and among transplant recipients and patients in pre-dialysis care. Promising evidence is available on the contribution of illness beliefs and behaviours to the experience of fatigue and there is some indication that these factors may vary according to treatment modality, reflecting the differential burdens and coping necessities associated with each treatment modality. However, the use of generic fatigue scales casts doubt on what specifically is being measured among dialysis patients, illness-related fatigue or post-dialysis-specific fatigue. Therefore, it is important to corroborate the available evidence and further explore, qualitatively and quantitatively, the differences in fatigues and fatigue-specific beliefs and behaviours according to renal replacement therapy, to ensure that any model and subsequent intervention is relevant and grounded in the experiences of patients.
- Palliative care for patients with end-stage renal disease: approach to
treatment that aims to improve quality of life and relieve suffering for
patients (and families) with chronic illnesses
Authors: Rak A; Raina R, Suh TT, et al.
Abstract: Providing end-of-life care to patients suffering from chronic kidney disease (CKD) and/or end-stage renal disease often presents ethical challenges to families and health care providers. However, as the conditions these patients present with are multifaceted in nature, so should be the approach when determining prognosis and treatment strategies for this patient population. Having an interdisciplinary palliative team in place to address any concerns that may arise during conversations related to end-of-life care encourages effective communication between the patient, the family and the medical team. Through the use of a case study, the authors demonstrate how an interdisciplinary palliative team can be used to make decisions that satisfy the patient's and the medical team's desires for end-of-life care.
- B cell-depleting therapy with rituximab or ofatumumab in immunoglobulin A
nephropathy or vasculitis with nephritis
Authors: Lundberg S; Westergren E, Smolander J, et al.
Abstract: BackgroundApproximately 30% of adult patients with immunoglobulin A (IgA) nephropathy (IgAN) or IgA vasculitis with nephritis (IgAVN) develop end-stage renal disease during long-term follow-up. In particular, patients with nephritic–nephrotic syndrome have an increased risk of rapid progression. Conventional immunosuppressive therapy with corticosteroids (CSs) may be insufficient for disease control and is associated with a number of side effects. Rituximab (RTX) has been shown to be well tolerated and effective in a range of glomerular diseases, but there is little information on its therapeutic potential in IgAN. The humanized anti-CD20 monoclonal antibody ofatumumab (OFAB) may be an alternative drug for patients intolerant or unresponsive to RTX, but so far there is no report on its use in IgAVN or IgAN.MethodsWe describe clinical outcomes after 17–22 months in four adult patients with biopsy-confirmed IgAVN or IgAN treated with RTX or OFAB as well as CS soon after diagnosis. All presented with nephritic–nephrotic syndrome and one had crescentic IgAN. Rebiopsy was performed in two cases.ResultsRTX and OFAB were well tolerated. Albuminuria was
- Assessment of physical performance and quality of life in
kidney-transplanted patients: a cross-sectional study
Authors: Esposito P; Furini F, Rampino T, et al.
Abstract: BackgroundInformation on physical and mental wellness in renal transplantation is limited. Therefore, we performed a cross-sectional study to evaluate and describe the different components of physical performance and quality of life (QoL) in a cohort of kidney-transplanted patients.MethodsPhysical performance and QoL were determined through the administration of validated tests and questionnaires [muscle strength, dynamometer handgrip, tactile sensitivity, visual analogue scale (VAS) for pain, Timed Up and Go (TUG) test, Fatigue Severity Scale (FSS) and the 36-item Short Form Health Survey]. The patients were divided into three groups based on time elapsed since transplantation: early (in the first 6 months), middle (from 7 to 60 months) and late (>60 months).ResultsOf 132 enrolled patients, 11 patients (8.3%) presented a severe reduction of muscle strength, 63 patients (47%) had significant bilateral impaired handgrip and tactile sensitivity was altered in 23 patients (17.4%). TUG assessment showed significant mobility limitation in 29 patients (21.9%). The FSS presented a pathological value in 50 patients (37.3%), while the mean VAS was 1.8 ± 2.7. There were no significant differences in physical performance parameters among the three patient groups. There were inverse correlations among different components of physical performance and age, comorbidity and dialysis vintage, and there was a direct correlation with renal function. During the first months after transplantation there were limitations in physical, social and emotional activities. Overall, the self-perceived physical performance was significantly lower in transplanted patients with respect to the normal reference level.ConclusionKidney-transplanted patients may present different degrees of impairment in physical performance and quality of life. Systematic functional assessment is essential to identify patients needing intensive and personalized rehabilitation programmes.
- The efficacy of rituximab in adult frequently relapsing minimal change
Authors: King C; Logan S, Smith SW, et al.
Abstract: BackgroundCorticosteroids are the basis of treatment for nephrotic syndrome due to minimal change disease (MCD), but 25% of patients have frequently relapsing nephrotic syndrome (FRNS) and 30% become steroid dependent. Prolonged use of conventional immunosuppressants causes significant toxicity. Rituximab (RTX) is now included in guidelines for childhood MCD. Evidence for use in adult MCD is limited. We describe a single-centre experience of RTX use in adult MCD.MethodsOutcomes of all adult MCD patients treated with RTX for FRNS between 2008 and 2015 were retrospectively analysed.ResultsThirteen patients received RTX; 11/13 had childhood-onset MCD. All had FRNS and 10 were steroid dependent. Eleven patients experienced one or more major treatment side effect from conventional therapy. At the time of RTX treatment, six patients were relapsing. All entered remission after RTX. The median length of follow-up after the first RTX treatment was 20 months (range 6–85). After RTX, the rate of relapse was reduced from 4 to 0.4/year (Wilcoxon signed rank P ≤ 0.05). Seven patients relapsed after RTX after a median of 10 months (range 1–11). All seven relapsing patients were successfully re-treated with RTX and none developed RTX-resistant nephrosis. The median number of courses of RTX per patient was 1 (range 1–5). The number of additional immunosuppressants, steroid dependency and antihypertensive agents were also reduced. At the last follow-up, two patients remained on low-dose steroids. No RTX-related adverse events were observed.ConclusionRTX is safe and effective in adults with FRNS due to MCD. The median rate of relapse is significantly reduced following RTX treatment and additional immunosuppressant exposure is minimized.
- Impact of poverty and race on pre-end-stage renal disease care among
dialysis patients in the United States
Authors: Nee R; Yuan CM, Hurst FP, et al.
Abstract: BackgroundAccess to nephrology care prior to end-stage renal disease (ESRD) is significantly associated with lower rates of morbidity and mortality. We assessed the association of area-level and individual-level indicators of poverty and race/ethnicity on pre-ESRD care provided by nephrologists.MethodsIn this retrospective cohort study using the US Renal Data System database, we identified 739 537 patients initiated on maintenance dialysis from 1 January 2007 through 31 December 2012. We assessed the Medicare–Medicaid dual eligibility status as an indicator of individual-level poverty and ZIP code–level median household income (MHI) data obtained from the 2010 US census. We conducted multivariable logistic regression of pre-ESRD nephrology care as the outcome variable.ResultsAmong patients in the lowest area-level MHI quintile, 61.28% received pre-ESRD nephrology care versus 67.68% among those in higher quintiles (P < 0.001). Similarly, the proportions of dual-eligible and nondual-eligible patients who had pre-ESRD nephrology care were 61.49 and 69.84%, respectively (P < 0.001). Patients in the lowest area-level MHI quintile were associated with significantly lower likelihood of pre-ESRD nephrology care (adjusted odds ratio [aOR] 0.86 [95% confidence interval (CI) 0.85–0.87]) compared with those in higher quintiles. Both African American (AA) and Hispanic patients were significantly less likely to have received pre-ESRD nephrology care [aOR 0.85 (95% CI 0.84–0.86) and aOR 0.72 (95% CI 0.71–0.74), respectively].ConclusionsIndividual- and area-level measures of poverty, AA race and Hispanic ethnicity were independently associated with a lower likelihood of pre-ESRD nephrology care. Efforts to improve pre-ESRD nephrology care may require focusing on the poor and minority groups.
- Effect of ethnicity and socioeconomic status on vascular access provision
and performance in an urban NHS hospital
Authors: Wilmink T; Wijewardane A, Lee K, et al.
Abstract: BackgroundThe aim of this study was to examine the effect of ethnicity, socioeconomic group (SEG) and comorbidities on provision of vascular access for haemodialysis (HD).MethodsThis was a retrospective review of two databases of HD sessions and access operations from 2003–11. Access modality of first HD session and details of transplanted patients were derived from the renal database. Follow-up was until 1 January 2015. Primary failure (PF) was defined as an arteriovenous fistula (AVF) used for fewer than six consecutive dialysis sessions. AVF survival was defined as being until the date the AVF was abandoned. Ethnicity was coded from hospital records. SEG was calculated from postcodes and 2011 census data from the Office of National Statistics. Comorbidities were calculated with the Charlson Comorbidity Index.ResultsFive hundred incident patients started chronic HD in the study period. Mode of starting HD was not associated with ethnicity (P = 0.27) or SEG (P = 0.45). Patients from ethnic minorities were younger when starting dialysis (P < 0.0001). Some 928 AVF patients' first AVF operations were analysed: 68% Caucasian, 26% Asian and 6% Afro-Caribbean. Half were in the most deprived SEG and 11% in the least deprived SEG. PF did not differ by ethnicity (P = 0.29), SEG (P = 0.75) or comorbidities (P = 0.54). AVF survival was not different according to ethnicity (P = 0.13) or SEG (P = 0.87). AVF survival was better for patients with a low comorbidity score (P = 0.04). The distribution of transplant recipients by ethnic group and SEG was similar to the distributions of all HD starters.ConclusionEthnicity and socioeconomic group had no effect on mode of starting HD, primary AVF failure rate or AVF survival. Ethnic minorities were younger at start of dialysis and at their first AVF operation.
- Does size matter' Kidney transplant donor size determines kidney
function among living donors
Authors: Narasimhamurthy M; Smith LM, Machan JT, et al.
Abstract: BackgroundKidney donor outcomes are gaining attention, particularly as donor eligibility criteria continue to expand. Kidney size, a useful predictor of recipient kidney function, also likely correlates with donor outcomes. Although donor evaluation includes donor kidney size measurements, the association between kidney size and outcomes are poorly defined.MethodsWe examined the relationship between kidney size (body surface area-adjusted total volume, cortical volume and length) and renal outcomes (post-operative recovery and longer-term kidney function) among 85 kidney donors using general linear models and time-to-chronic kidney disease data.ResultsDonors with the largest adjusted cortical volume were more likely to achieve an estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 over a median 24-month follow-up than those with smaller cortical volumes (P
- Serum osteoprotegerin and renal function in the general population: the
Authors: Vik A; Brodin EE, Mathiesen EB, et al.
Abstract: BackgroundSerum osteoprotegerin (OPG) is elevated in patients with chronic kidney disease (CKD) and increases with decreasing renal function. However, there are limited data regarding the association between OPG and renal function in the general population. The aim of the present study was to explore the relation between serum OPG and renal function in subjects recruited from the general population.MethodsWe conducted a cross-sectional study with 6689 participants recruited from the general population in Tromsø, Norway. Estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration equations. OPG was modelled both as a continuous and categorical variable. General linear models and linear regression with adjustment for possible confounders were used to study the association between OPG and eGFR. Analyses were stratified by the median age, as serum OPG and age displayed a significant interaction on eGFR.ResultsIn participants ≤62.2 years with normal renal function (eGFR ≥90 mL/min/1.73 m2) eGFR increased by 0.35 mL/min/1.73 m2 (95% CI 0.13–0.56) per 1 standard deviation (SD) increase in serum OPG after multiple adjustment. In participants older than the median age with impaired renal function (eGFR
- Course of chronic kidney disease in French patients
Authors: Janus N; Launay-Vacher V, Juillard L, et al.
Abstract: BackgroundIn 1998, a French survey showed that the referral of patients with chronic kidney disease to a nephrologist was delayed, resulting in many emergency initiations of dialysis. In 2009, the ORACLE study aimed to describe the renal course of dialysis patients from their first nephrology visit to their first dialysis session.MethodsThe ORACLE study was a multicentre retrospective study of all patients who started chronic dialysis. Data were collected at the first nephrology visit and at the first dialysis session.ResultsIn total, 720 patients were included (69 centres). At the first nephrology visit, the mean Cockcroft–Gault (CG) indicator was 31.8 mL/min (22.7 in 1998) and 52.4% of patients (73% in 1998) had a CG
- Cuff extrusion in peritoneal dialysis: single-centre experience with the
cuff-shaving procedure in five patients over a 4-year period
Authors: Debowski JA; Wærp C, Kjellevold SA, et al.
Abstract: Catheter-related infections in peritoneal dialysis (PD) remain a significant complication, and some patients with recurrent exit-site (ESI) and/or tunnel infections may experience external cuff extrusion. In these cases, cuff-shaving has been described as a possible course of treatment. During a 4-year period, there were 44 patients with PD at our department; all received double-cuffed Tenckhoff catheters. Six (13%) never started on PD. Five (13%) of the 38 active PD patients experienced cuff extrusion. Causes of end-stage renal disease (ESRD) were diabetic nephropathy (n = 1), toxic nephropathy (n = 1), hypertensive nephrosclerosis (n = 1), systemic disease (n = 1) and one with unknown cause. PD catheters were inserted by the Department of Surgery and our patients waited a mean of 3.71 weeks (0.57–7.86) from catheter insertion to PD start. Patients were followed up by monthly and even fortnightly during infections. Our cohort experienced two (1–5) ESIs per patient prior to cuff extrusion. Cultures showed growth of Staphylococcus aureus and the patients received dicloxacillin orally 500 mg qid for 3–4 weeks. Of the 38 active PD patients, 5 (13%) developed cuff extrusion with an incidence of 0.20 episodes/patient/year, manifesting on average at 32 weeks (17.3–40.6), due to repeated ESI in four patients and substantial weight loss in one patient. All five underwent cuff-shaving and the ESIs resolved completely in 80% of the cases assisted by supplemental treatment with mupirocin and/or dicloxacillin. There were no complications to the cuff-shaving procedure itself. None of the five patients experienced new ESIs after cuff-shaving had been performed. Cuff-shaving reduces the rate of recurring ESIs. The procedure is safe, if performed correctly, and poses no risk to the patient or the catheter.
- Non-invasive approaches in the diagnosis of acute rejection in kidney
Authors: Erpicum P; Hanssen O, Weekers L, et al.
Abstract: Kidney transplantation (KTx) represents the best available treatment for patients with end-stage renal disease. Still, the full benefits of KTx are undermined by acute rejection (AR). The diagnosis of AR ultimately relies on transplant needle biopsy. However, such an invasive procedure is associated with a significant risk of complications and is limited by sampling error and interobserver variability. In the present review, we summarize the current literature about non-invasive approaches for the diagnosis of AR in kidney transplant recipients (KTRs), including in vivo imaging, gene-expression profiling and omics analyses of blood and urine samples. Most imaging techniques, such as contrast-enhanced ultrasound and magnetic resonance, exploit the fact that blood flow is significantly lowered in case of AR-induced inflammation. In addition, AR-associated recruitment of activated leucocytes may be detectable by 18F-fluorodeoxyglucose positron emission tomography. In parallel, urine biomarkers, including CXCL9/CXCL10 or a three-gene signature of CD3ε, CXCL10 and 18S RNA levels, have been identified. None of these approaches has yet been adopted in the clinical follow-up of KTRs, but standardization of analysis procedures may help assess reproducibility and comparative diagnostic yield in large, prospective, multicentre trials.
- Loss of kAE1 expression in collecting ducts of end-stage kidneys from a
family with SLC4A1 G609R-associated distal renal tubular acidosis
Authors: Vichot AA; Zsengellér ZK, Shmukler BE, et al.
Abstract: Distal renal tubular acidosis caused by missense mutations in kidney isoform of anion exchanger 1 (kAE1/SLC4A1), the basolateral membrane Cl−/HCO3− exchanger of renal alpha-intercalated cells, has been extensively investigated in heterologous expression systems but rarely in human kidneys. The preferential apical localization of distal renal tubular acidosis (dRTA)-associated kAE1 mutants R901X, G609R and M909T in cultured epithelial monolayers has not been examined in human kidney. Here, we present kidney tissues from dRTA-affected siblings heterozygous for kAE1 G609R, characterized by predominant absence rather than mistargeting of kAE1 in intercalated cells. Thus, studies of heterologous recombinant expression of mutant proteins should be, whenever possible, interpreted in comparison to affected patient tissues.
- Circulating miRNAs as biomarkers of kidney disease
Authors: Hüttenhofer A; Mayer G.
Abstract: Interest in microRNAs (miRNAs) has dramatically increased in recent years not only because they regulate mRNA expression, and thus many physiological or pathophysiological processes, but also because they could serve as biomarkers. Next to analysis of tissue miRNA expression, measurement in body fluids such as blood or urine is attractive because miRNA in microvesicles or bound to protein is very stable. Currently it is unclear whether these circulating miRNAs are tissue and disease specific or represent more general pathologies like inflammation. In addition pre-analytical sample handling and variable analysis techniques affect the results and thus much more work needs to be done before one can draw a final conclusion about their clinical utility.
- Non-invasive approaches in the diagnosis of acute rejection in kidney
transplant recipients. Part I. In vivo imaging methods
Authors: Hanssen O; Erpicum P, Lovinfosse P, et al.
Abstract: Kidney transplantation (KTx) represents the best available treatment for patients with end-stage renal disease. Still, full benefits of KTx are undermined by acute rejection (AR). The diagnosis of AR ultimately relies on transplant needle biopsy. However, such an invasive procedure is associated with a significant risk of complications and is limited by sampling error and interobserver variability. In the present review, we summarize the current literature about non-invasive approaches for the diagnosis of AR in kidney transplant recipients (KTRs), including in vivo imaging, gene expression profiling and omics analyses of blood and urine samples. Most imaging techniques, like contrast-enhanced ultrasound and magnetic resonance, exploit the fact that blood flow is significantly lowered in case of AR-induced inflammation. In addition, AR-associated recruitment of activated leukocytes may be detectable by 18F-fluoro-deoxy-glucose positron emission tomography. In parallel, urine biomarkers, including CXCL9/CXCL10 or a three-gene signature of CD3ε, IP-10 and 18S RNA levels, have been identified. None of these approaches has been adopted yet in the clinical follow-up of KTRs, but standardization of procedures may help assess reproducibility and compare diagnostic yields in large prospective multicentric trials.
- Serum microRNAs are altered in various stages of chronic kidney disease: a
Authors: Brigant B; Metzinger-Le Meuth V, Massy ZA, et al.
Abstract: BackgroundMicroRNAs (miRNAs) are innovative and informative blood-based biomarkers involved in numerous pathophysiological processes. In this study and based on our previous experimental data, we investigated miR-126, miR-143, miR-145, miR-155 and miR-223 as potential circulating biomarkers for the diagnosis and prognosis of patients with chronic kidney disease (CKD). The primary objective of this study was to assess the levels of miRNA expression at various stages of CKD.MethodsRNA was extracted from serum, and RT-qPCR was performed for the five miRNAs and cel-miR-39 (internal control).ResultsSerum levels of miR-143, -145 and -223 were elevated in patients with CKD compared with healthy controls. They were further increased in chronic haemodialysis patients, but were below control levels in renal transplant recipients. In contrast, circulating levels of miR-126 and miR-155 levels, which were also elevated in CKD patients, were lower in the haemodialysis group and even lower in the transplant group. Four of the five miRNA species were correlated with estimated glomerular filtration rate, and three were correlated with circulating uraemic toxins.ConclusionsThis exploratory study suggests that specific miRNAs could be biomarkers for complications of CKD, justifying further studies to link changes of miRNA levels with outcomes in CKD patients.