Journal: Nephrology (Carlton, Vic.)
The options for long-term maintenance therapy in lupus nephritis (LN) remain controversial. This meta-analysis of randomized controlled trials (RCTs) assessed the prognosis and safety of mycophenolate mofetil (MMF) versus azathioprine (AZA) used as maintenance therapy for lupus nephritis.
AIM: Treatment of chronic kidney disease (CKD) includes parenteral iron therapy, and these infusions can lead to iron overload. Secondary iron overload is typically treated with iron chelators, of which deferasirox is one of the most promising. However, it has not been studied in patients with CKD and iron overload. METHODS: A pilot study was conducted to evaluate the pharmacokinetics and safety of deferasirox in 8 haemodialysis-dependent patients, who were receiving intravenous iron for treatment of anaemia of CKD. Deferasirox was administered at two doses (10 mg/kg and 15 mg/kg), either acute (once daily for two days) or steady-state (once daily for two weeks). RESULTS: A dose of 10 mg/kg in either protocol was not sufficient to achieve a plasma concentration in the therapeutic range (acute peak 14.1 and steady-state 22.8 μmol/l), while 15 mg/kg in either protocol maintained plasma concentration well above this range (acute peak 216 and steady-state 171 μmol/l). Plasma concentration observed at 15 mg/kg was well above that expected for this dose (40-50 μmol/l), although no adverse clinical events were observed. CONCLUSION: This study highlights the need to profile drugs such as deferasirox in specific patient groups, such as those with CKD and iron overload.
To derive a simple risk score to predict the individual risk of major complications for patients undergoing a percutaneous renal biopsy procedure of native kidneys.
Patients with diabetic nephropathy develop nephrotic syndrome, and may show limited response to conventional therapy. They often require earlier initiation of renal replacement therapy because they become refractory to diuretics, and experience excessive fluid retention. We aimed to investigate the efficacy of tolvaptan, an oral arginine vasopressin type 2 receptor antagonist, in a case series of 14 severe diabetic renal failure patients who were severely refractory to maximal doses of furosemide and had excessive fluid retention despite preserved cardiac function and residual renal function. All 14 patients experienced immediate and sustained water diuretic effects, resulting in alleviation of congestive heart failure. None required initiation of renal replacement therapy. Tolvaptan promptly increased urine volume and free water clearance, reversed progressive fluid retention, and alleviated congestive heart failure. Thus, tolvaptan could serve as a potential adjunct therapy for severe diabetic renal failure patients with excessive fluid retention and congestive heart failure.
Chronic kidney disease (CKD) is strongly associated with cardiovascular disease and muscle wasting, arising from numerous factors associated with declining renal function and lifestyle factors. Exercise has the ability to impact beneficially on the comorbidities associated with CKD and is accepted as an important intervention in the treatment, prevention and rehabilitation of other chronic diseases, however, the role of exercise in CKD is overlooked, with the provision of rehabilitation programmes well behind those of cardiology and respiratory services. Whilst there is now a large evidence base demonstrating the efficacy and safety of exercise training interventions in patients receiving dialysis, and this is now becoming incorporated into clinical guidelines for treatment of dialysis patients, there is a paucity of research evaluating the effectiveness of exercise in patients with CKD who are not on dialysis. Despite this, existing studies indicate that exercise can improve physical functioning and impact positively on the mediators of co-morbid diseases and upstream factors associated with progression of renal disease. Although preliminary evidence appears positive, more research is required to identify the best modes, frequency and intensities of exercise in order to optimise exercise prescription in pre-dialysis CKD patients. This review summarises what is known about the main effects of exercise in pre-dialysis CKD patients, discusses the potential of exercise in the rehabilitation and treatment of disease and highlights the need for further research.
Symptom and quality of life (QOL) measures in patients with advanced chronic kidney disease (CKD) are recognised indicators of patient-centred care and represent important research, quality and clinical measures. This study examined relationships between symptom burden, QOL and functional status and associations of symptoms and mortality risk. A multisite longitudinal cohort analysis was undertaken in CKD stage 4/5 (no dialysis, ND) and dialysis patients. Patients completed symptom and QOL measures (Palliative Care Outcome Symptom Score (POS-S renal) , World Health Organisation QOL, WHOQOL-BREF)  and Karnofsky Performance scale . Clinical and demographic data were recorded. Participants recruited were 112 dialysis and 40 ND patients. High symptom burden was present and correlated with lower QOL, QOL subdomains and reduced performance status. Comparing groups found a small significant difference in physical QOL suggesting dialysis treatment burden. Further analysis was restricted comparing 102 dialysis and 31 CKD stage 4 (CKD4) patients. Dialysis patients had above target adequacies, but poorer appetite, nausea, vomiting and difficulty sleeping compared with CKD4 patients. Overall, the most prevalent symptoms were also the most severe, specifically pain, dyspnea, weakness, difficulty sleeping. Cox Proportional Hazards regression showed severe pain, nausea, vomiting, poor mobility, itch and skin changes were significantly associated with shorter survival in dialysis patients. Severe symptom score was associated with mortality risk (HR 1.1, 95%CI(1.03,1.17) compared with no increased risk with comorbidity score or age. Patients with advanced CKD had significant symptom burden correlated with poorer QOL. Symptoms may also be useful in considering clinical outcomes, specifically mortality. This article is protected by copyright. All rights reserved.
Haemodialysis (HD) was the first procedure that had demonstrated the ability to partially replace renal function, and became the most widely utilized treatment for patients with end-stage renal disease (ESRD). In a great majority of countries around the world, conventional in-centre HD had become the predominant renal replacement therapy, being touted as able to achieve better solute clearance and more successful in attaining euvolemia than patients on peritoneal dialysis. This is despite the antecedent hemodynamic risks, more rapid loss of residual renal function, greater infectious perils, excessive erythropoietin requirements and higher infrastructure costs. In addition, quality of life had been suggested to be worse among patients on HD, though this had been challenged repeatedly. Consequently, the concept of integrated ESRD care over the last few decades had placed HD, as a complementary rather than a competitive treatment modality to the entire armamentarium of renal replacement therapies. Incorporating HD as part of integrated care into health-care policies and national resource planning will become an essential strategy in improving access and outcome to care among the ESRD population. The improvement in technologies and innovation in prescription had brought forth enhanced dialyzer membrane and machine upgrades, and expanded modalities including more frequent HD and haemodiafiltration. While boasting of controversial improvement in outcomes, many of these therapies remain expensive and insurmountable for widespread utility in many countries. In addition, the results of these new technologies had been conflicting across studies, with some even suggesting that they could be detrimental. Therefore, judicial consideration has to be undertaken to appropriate their use in clinical practice.
Diabetic nephropathy is one of the leading causes of end-stage renal disease and creates heavy healthcare burdens globally. Dysfunction of mesangial cells and podocytes contributes to diabetic nephropathy. Dysregulation of signaling involved in renal development and regeneration may cause diabetic kidney damages. Growing evidences suggest the importance of dysregulated dickkopf-1 (DKK1)/Wnt/ β-catenin signaling pathways in the pathogenesis of diabetic glomerular injuries. The inhibition of Wnt signaling in injured mesangial cells is likely attributed to the high glucose-induced Ras/Rac1 dependent superoxide formation. When DKK1, the cellular inhibitor of Wnt signaling, binds to the Kremen-2 receptor, depositions of extracellular matrix increase in the mesangium of diabetic kidneys. Additionally, reactivation of Notch-1 signaling has been implicated in podocytopathy during diabetic proteinuria development. Knocking down Notch-1 alleviates vascular endothelial growth factor (VEGF) expression, nephrin repression and proteinuria in diabetic kidneys. It is also found that epigenetic modulations by histone deacetylase 4 (HDAC4) and miR-29a could lead to diabetic nephropathy. High glucose increases the expression of HDAC4, which causes deacetylation with subsequent ubiquitination of nephrin. Overexpression of miR-29a in diabetic transgenic mice would decrease the expression of HDAC4 and stabilize nephrin. Surprisingly, reprogramming or reactivation of signaling involved in renal development or regeneration often brings about diabetic glomerular sclerosis in mesangial cells and podocytes. Better knowledge about modifications of embryonic stem cell signaling will have a chance to implement strategically focused pharmacological research programs aiming to the development of new drugs for diabetic kidney injuries.
It is increasingly recognized that maternal obesity is implicated in developmental programming, contributing to the future risk of chronic disease development in offspring. The exact mechanisms of the role of maternal obesity in the development of chronic kidney disease in offspring remain unclear and animal models used are not without limitation. Human studies are limited by the effects of postnatal environmental conditions, which may have a direct impact on disease phenotype; and animal models are limited by use of species that differ significantly. This review will examine the most recent evidence from animal models on the impact of maternal factors during pregnancy/lactation on the future risk of chronic kidney disease development in offspring, emphasising the role of maternal obesity in exacerbating the deleterious effects of diet-induced obesity and/or diabetes on renal health.
Cardiorenal syndromes are disorders of the heart and kidneys whereby dysfunction in one organ may lead to dysfunction in the other organ. Cardiorenal syndrome type I (CRS I) is defined as acute kidney injury caused by acute cardiac dysfunction such as acute decompensated heart failure and acute coronary syndrome. Traditional markers like serum creatinine may delay the diagnosis of acute kidney injury and provide limited information regarding the underlying pathophysiology in the setting of CRS I. Herein, we briefly review some emerging biomarkers, including brain natriuretic peptide, soluble ST2, angiopoietin, soluble thrombomodulin, neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, cystatin C, interleukin-18 and calprotectin. These biomarkers may help early detecting, differential diagnosis, assessing disease severity and prognosis in patients with CRS I, therefore improve patient management and outcomes.