Despite the availability of global and regional guidelines to curtail the adverse clinical outcomes associated with chronic kidney disease–mineral and bone disorder (CKD-MBD), most CKD patients are still affected by the consequences of abnormalities of CKD-MBD. This important clinical complication of CKD continues to be studied, in order to improve the understanding and management of CKD-MBD. Some notable discoveries include the role of fibroblast growth factor 23 (FGF23) in the pathogenesis of CKD-MBD, leading to a shift from the previous well-established classic trade-off hypothesis to the updated trade-off hypothesis. More recently, there has been a shift from the treatment of CKD-MBD based on a single level of biomarkers to serial measurements of calcium, phosphate and parathyroid hormone (PTH). Furthermore, some clinical trials have emerged after the 2009 Kidney Disease-Improving Global Outcomes (KDIGO) Guidelines, leading to the 2017 KDIGO updated recommendations. Hence, this review gives an overview of the rapidly evolving trends in CKD-MBD, linking the past and current concepts of CKD-MBD.

Background: Preeclampsia is the leading cause of maternal and fetal mortality due to the inability to diagnose and treat the disorder early in pregnancy. This is attributed to the complex pathophysiology and unknown etiology of the disorder, which is modulated by several known and unknown factors. Exosomes have recently been implicated as possible mediators of the pathogenesis of preeclampsia, with, however, no evidence linking these nanovesicles to the pathophysiology of preeclampsia and its subtypes. Methods: To better understand the pathophysiological role of exosomes in preeclampsia, we have analyzed the exosomal microRNA in early and late onset preeclamptic women in comparison to their gestationally matched normotensive controls using Digital Direct Detection (NanoString Technologies). Results: For the first time, distinct exosomal microRNA signatures in early and late onset preeclampsia have been identified. Moreover, these signatures indicate that exosomes are involved in key pathological features associated with preeclampsia and differentiate between the subtypes. Conclusion: This study forms the basis for the diagnostic and functional validation of the identified signatures as biomarkers of preeclampsia and its subtypes.

Introduction: Anemia is a complication of chronic kidney disease (CKD) that can greatly impact on its prognosis. However, the risk factors for anemia, including the influence of ethnicity, are not well established among the CKD population in Johannesburg. Methods: This was a cross-sectional study of 353 adult CKD patients attending the renal outpatient clinic of the Charlotte Maxeke Johannesburg Academic Hospital (Johannesburg, South Africa) from June 1, 2016 to December 30, 2016. Sociodemographic and clinical characteristics were obtained using a proforma. Blood samples were collected for serum electrolytes and hematological parameters. Predictors of low hemoglobin and iron deficiency anemia (IDA) were evaluated using multivariable binary logistic regression. Results: The mean age and prevalence of anemia among the CKD participants were 55.3±15.0 years and 43.18% (95% CI: 38.1%–48.4%), respectively. Blacks had the highest prevalence of anemia (46.9%), while Indians/Asians had the lowest (18.2%). Although the odds of anemia was 3.8-fold higher (odds ratio =3.8, P-value =0.059) among CKD stage V participants as compared to CKD stage I, the relationship between anemia and stages of CKD was non-linear. Diabetes mellitus (odds ratio =2.31, P-value =0.005) had a strong association with anemia among the CKD participants. Conclusion: Almost half of the CKD participants were anemic, and the odds of anemia did not increase linearly with increasing severity of CKD. There was a marked ethnic disparity in anemia prevalence. Our study highlights the need for risk-based management of anemia among CKD patients.

Background. Serum creatinine is suboptimal as a biomarker in the early diagnosis of contrast-induced nephropathy (CIN). In this study, we investigated a panel of novel biomarkers in the early diagnosis of CIN and in assessing patient outcomes. Methods. This single-centre, nested, prospective case-controlled study included 30 patients with CIN and 60 matched controls. Serum and urine samples were collected before contrast administration and at 24 hours, 48 hours, and ≥5 days after contrast administration. Concentrations of NGAL, cystatin C, β₂M, IL18, IL10, KIM1, and TNFα were determined using Luminex and ELISA assays. Outcomes were biomarker diagnostic discrimination performance for CIN and mortality after generation of area under receiver operating characteristic curves (AUROCs). Results. Median serum levels for 24 h cystatin C (p<0.01) and 48 h β₂M levels (p<0.001) and baseline urine NGAL (p=0.02) were higher in CIN patients compared to controls with AUROCs of 0.75, 0.78, and 0.74, respectively, for the early diagnosis of CIN. Serum β₂M levels were higher in CIN patients at all time points. Elevated baseline serum concentrations of IL18 (p<0.001), β₂M (p=0.04), TNFα (p<0.001), and baseline urine KIM (p=0.01) and 24 h urine NGAL (p=0.02) were significantly associated with mortality. Baseline serum concentrations of IL18, β₂M, and TNFα showed the best discrimination performance for mortality with AUROCs, all >0.80. Baseline NGAL was superior for excluding patients at risk for CIN, with positive and negative predictive ranges of 0.50–0.55 and 0.81–0.88, respectively. Cystatin C (p=0.003) and β₂M (p=0.03) at 24 h independently predicted CIN risk. β₂M predicted increased mortality of 40% at baseline and 50% at 24 hours. Conclusion. Serum cystatin C at 24 h was the best biomarker for CIN diagnosis, while baseline levels of serum IL18, β₂M, and TNFα were best for predicting prognosis.

Background. Transforming growth factor-β (TGF-β) may inhibit the development of atherosclerosis. We evaluated serum levels of TGF-β isoforms concurrently with serum levels of endotoxin and various inflammatory markers. In addition, we determined if any association exists between polymorphisms in the TGF-β1 gene and atherosclerosis in South African CKD patients. Methods. We studied 120 CKD patients and 40 healthy controls. Serum TGF-β1, TGF-β2, TGF-β3, endotoxin, and inflammatory markers were measured. Functional polymorphisms in the TGF-β1 genes were genotyped using a polymerase chain reaction-sequence specific primer method and carotid intima media thickness (CIMT) was assessed by B-mode ultrasonography. Results. TGF-β isoforms levels were significantly lower in the patients with atherosclerosis compared to patients without atherosclerosis (p<0.001). Overall, TGF-β isoforms had inverse relationships with CIMT. TGF-β1 and TGF-β2 levels were significantly lower in patients with carotid plaque compared to those without carotid plaque [TGF-β1: 31.9 (17.2 – 42.2) versus 45.9 (35.4 – 58.1) ng/ml, p=0.016; and TGF-β2: 1.46 (1.30 – 1.57) versus 1.70 (1.50 – 1.87) ng/ml, p=0.013]. In multiple logistic regression, age, TGF-β2, and TGF-β3 were the only independent predictors of subclinical atherosclerosis in CKD patients [age: odds ratio (OR), 1.054; 95% confidence interval (CI): 1.003 – 1.109, p=0.039; TGF-β2: OR, 0.996; 95% CI: 0.994–0.999, p=0.018; TGF-β3: OR, 0.992; 95% CI: 0.985–0.999, p=0.029). TGF-β1 genotypes did not influence serum levels of TGF-β1 and no association was found between the TGF-β1 gene polymorphisms and atherosclerosis risk. Conclusion. TGF-β isoforms seem to offer protection against the development of atherosclerosis among South African CKD patients.