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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: Kidney transplantation outcomes in resource-limited settings remain underreported. This 10-year retrospective review examined the clinical characteristics, long-term pharmacokinetics, and outcomes of kidney transplant recipients at a South African public hospital. Methods: Data from kidney transplant recipients between January 2012 and December 2022 were analysed. Graft and patient survival were assessed using Kaplan–Meier analysis. Cox proportional hazards models were used to evaluate the associations between clinical and pharmacokinetic variables and outcomes. Results: The one- and five-year graft survival rates were 87.9% and 65.6%, respectively. Acute rejection, as confirmed by biopsy, was associated with graft failure (HR, 2.46; p = 0.010). Increasing recipient age at transplantation increased the graft failure risk by about 5.0% per year (HR: 1.05, p = 0.006). Tacrolimus trough and normalised trough levels were lower in the graft loss group 73% and 93% of the time, respectively, despite similar tacrolimus doses. Whereas achieving optimal tacrolimus concentration did not significantly affect graft survival, maintaining a haemoglobin level >10 g/dL improved the chances of 3-, 4-, and 5-year graft survival (p-value, 0.001, 0.001, and <0.001, respectively). Patient survival rates were more favourable than graft survival rates. The 1-year and 5-year patient survival rates were 90.0% and 77.4%, respectively. Conclusions: This study offers insights into transplant outcomes in low-resource public health settings. The findings emphasise the impact of rejection and age on the risk of graft failure and the significance of maintaining adequate haemoglobin levels after transplantation. The results also indicate the need for more nuanced and personalised approaches to tacrolimus monitoring in the long-term following transplantation.

The COVID-19 pandemic continues to overwhelm health systems across the globe. We aimed to assess the readiness of hospitals in Nigeria to respond to the COVID-19 outbreak. Between April and October 2020, hospital representatives completed a modified World Health Organisation (WHO) COVID-19 hospital readiness checklist consisting of 13 components and 124 indicators. Readiness scores were classified as adequate (score ≥80%), moderate (score 50-79.9%) and not ready (score <50%). Among 20 (17 tertiary and three secondary) hospitals from all six geopolitical zones of Nigeria, readiness score ranged from 28.2% to 88.7% (median 68.4%), and only three (15%) hospitals had adequate readiness. There was a median of 15 isolation beds, four ICU beds and four ventilators per hospital, but over 45% of hospitals established isolation facilities and procured ventilators after the onset of COVID-19. Of the 13 readiness components, the lowest readiness scores were reported for surge capacity (61.1%), human resources (59.1%), staff welfare (50%) and availability of critical items (47.7%). Most hospitals in Nigeria were not adequately prepared to respond to the COVID-19 outbreak. Current efforts to strengthen hospital preparedness should prioritize challenges related to surge capacity, critical care for COVID-19 patients, and staff welfare and protection.

Few studies have linked high levels of plasma C-terminal fibroblast growth factor 23 (FGF23) with poor clinical outcomes in patients on maintenance haemodialysis (MHD), while the association between intact FGF23 and mortality in this group of patients remains inconclusive. Therefore, the aim of this study was to evaluate the association between plasma levels of intact FGF23 and mortality in dialysis patients. A prospective multicenter study involving patients undergoing dialysis at three dialysis centers in Johannesburg was undertaken between 1st October 2014 and 31st December 2017. The study comprised 165 chronic dialysis patients (111 blacks, 54 whites) with a mean age of 46.6 ±14.2 years. During a three year follow up period, there were 46 deaths (1.03 per 100 person-years). The median plasma FGF 23 level was 382 pg/ml (interquartile range [IQR], 145-2977). In adjusted multivariable analyses, there was a non-statistically significant increase in the risk of mortality with higher quartiles of FGF 23 levels: the adjusted hazard ratios (HR) for the second, third and fourth quantiles were HR 3.20 (95% CI, 0.99-10.35; P = 0.052), HR 2.43(95% CI,0.65-9.09; P = 0.19), and HR 2.09 (95% CI, 0.66-7.32; P = 0.25),respectively. Corrected serum calcium 2.38-2.5 mmol/l [HR 2.98 (95% CI, 1.07-8.29; P = 0.04] and > 2.50 mmol/l [HR 5.50 (95% CI, 1.84-16.48; P = 0.002] were independently associated with increased risk of death. Likewise, patients with intact parathyroid hormone > 600 pg/ml had a 3.46-fold higher risk of death (HR 3.46, 95% CI, 1.22-9.82 P = 0.019). These findings persisted in time -dependent analyses. Higher levels of intact FGF 23 appear not to be independently associated with all-cause mortality in our dialysis patients, while hypercalcaemia and severe hyperparathyroidism were found to be independent predictors of mortality in this cohort of patients.

Background: Endothelial dysfunction constitutes an early pathophysiological event in atherogenesis and cardiovascular disease. This study aimed to assess the prevalence, determints, and degree of endothelial dysfunction in antiretroviral therapy (ART)–treated people living with HIV (PLWH) in northwestern Nigeria using brachial flow-mediated dilatation (FMD).Methods: This was a comparative, cross-sectiol study. A total of 200 ART-treated adults living with HIV with no evidence of kidney disease were compared with 200 HIV-negative participants attending a tertiary hospital in Kano, Nigeria, between September 2020 and May 2021. Endothelial function was evaluated by measuring FMD with a high-resolution vascular ultrasound transducer. FMD was calculated as the ratio of the brachial artery diameter after reactive hyperemia to baseline diameter and expressed as a percentage of change. Blood and urine samples were obtained from participants in both arms. Urine albumin-to-creatinine ratio (uACR) was calculated using the 2021 CKD-EPI estimated glomerular filtration rate (eGFR) creatinine-cystatin C equation without the race variable, and low-density lipoprotein (LDL) cholesterol was measured using enzymatic method.Results: The overall mean age (± standard deviation) of the study participants was 42 ± 11 years. Participants in the comparison arm were younger than PLWH (38 ± 11 versus 46 ± 10 years, respectively). The median (interquartile range) uACR was 41.6 (23.2–162.9) mg/g for the ART-treated PLWH versus 14.5 (7.4–27.0) mg/g for healthy controls. PLWH had a significantly lower mean percent FMD when compared to HIV-negative participants (9.8% ± 5.4 versus 12.1% ± 9.2, respectively). Reduced FMD was independently associated with HIV infection (β = –2.83%, 95% CI, –4.44% to –1.21%, p = 0.001), estimated glomerular filtration rate (β = –0.04%, 95% CI, –0.07% to –0.01%, p = 0.004) and LDL cholesterol (β = –1.12%, 95% CI, –2.13% to –0.11%, p = 0.029).Conclusion: HIV-positive status, lower estimated GFR, and higher LDL cholesterol levels were independently associated with endothelial dysfunction. Future prospective studies with larger cohorts of persons living with HIV (and age- and sex-matched HIV-negative controls) are needed to gain further insight into these important findings. In the interim, aggressive magement of modifiable risk factors is warranted.

Background It remains unclear whether genetic factors may explain the reported variation in the levels of biochemical markers of chronic kidney disease mineral and bone disorders (CKD- MBD) across ethnic groups. Therefore, the aim of this study was to examine the influence of vitamin D receptor (VDR) polymorphisms on secondary hyperparathyroidism and its association with vitamin D levels in black and white South African study participants. Methods This was a cross sectional study involving 272 CKD stage 3- 5D patients and 90 healthy controls. The four major VDR polymorphisms ( Bsm 1, Fok 1, Taq 1, and Apa1 ) were genotyped using the polymerase chain reaction- restriction fragment length polymorphism (PCR –RFLP) method. In addition, biochemical markers of CKD-MBD were measured to determine their associations with the four VDR polymorphisms. Results With the exception of Taq I polymorphism, the distribution of the VDR polymorphisms differed significantly between blacks and whites. In hemodialysis patients, the Bb genotype was significantly associated with moderate secondary hyperparathyroidism (OR, 3.88; 95 CI 1.13–13.25, p  = 0.03) and severe hyperparathyroidism (OR, 2.54; 95 CI 1.08–5.96, p  = 0.03). This was consistent with the observed higher levels of median parathyroid hormone, fibroblast growth factor 23 and mean phosphate in patients with Bb genotype. This candidate risk genotype (Bb) was over represented in blacks compared to whites (71.0% versus 55.6%, p  < 0.0001). In an unadjusted regression model, FokFf genotype was found to be significantly associated with the risk of developing severe vitamin D deficiency < 15 ng/ml (OR, 1.89; 95 CI 1.17–3.07, p  = 0.01). Conclusion The VDR Bb genotype is an independent predictor of developing secondary hyperparathyroidism in patients with end stage kidney disease. In addition, study participants with FokFf genotype are at increased of developing severe 25 -hydroxyvitamin D [25(OH)D] deficiency.

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. 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. 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, -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, -value =0.005) had a strong association with anemia among the CKD participants. 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.

Objective. To determine the association between serum total alkaline phosphatase (TAP) and mortality in African maintenance haemodialysis patients (MHD). Patients and Methods. The study enrolled a total of 213 patients on MHD from two dialysis centers in Johannesburg between January 2009 and March 2016. Patients were categorized into a low TAP group (≤112 U/L) versus a high TAP group (>112 U/L) based on a median TAP of 112 U/L. Results. During the follow-up period of 7 years, there were 55 (25.8%) deaths. After adjusting for cofounders such as age, other markers of bone disorder, and comorbidity (diabetes mellitus), patients in the high TAP group had significantly higher risk of death compared to patients in the low TAP group (hazard ratio, 2.50; 95% CI 1.24–5.01, P = 0.01). Similarly, serum calcium >2.75 mmol/L was associated with increased risk of death compared to patients within levels of 2.10–2.37 mmol/L (HR 6.34, 95% CI 1.40–28.76; P = 0.02). The HR for death in white patients compared to black patients was 6.88; 95% CI 1.82–25.88; P = 0.004. Conclusion. High levels of serum alkaline phosphatase, hypercalcaemia, and white race are associated with increased risk of death in MHD patients.

Background The risk of various types of kidney disease is significantly increased in the presence of APOL1 high-risk genotype (carriage of two risk alleles), particularly HIV-associated nephropathy (HIVAN). However, there are discrepancies in the existing evidence about the level of association between APOL1 high-risk genotype and the risk of kidney diseases in people living with HIV (PLWHIV). Methods This systematic review and meta-analysis was conducted to assess the relationship between the APOL1 genotypes and kidney disease in the HIV population. An a priori protocol registered on PROSPERO (ID: CRD42021253877), was followed by a systematic search of five electronic databases. Database-specific search terms were used to identify observational studies that evaluated the outcomes chosen in the review, based on a set of prespecified eligibility criteria. Using a random effect model, the odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were pooled for the meta-analysis. Results After screening 4418 citations, 14 articles comprising 11,069 participants were included in this review. The risk of chronic kidney disease (CKD) in the HIV positive population was significantly increased in the presence of two APOL1 risk alleles (OR 4.65 [95% CI 3.51–6.15]). Also, a significant association was observed between the carriage of two risk APOL1 variants and proteinuria (OR 2.58 [95% CI 2.05–3.25]), HIVAN (OR 16.67 [95% CI 10.22–27.19]), and progression to end-stage kidney disease (ESKD) hazard ratio: 1.79 (95% CI 1.20–2.66). Conclusion This review highlights a strong association between the presence of two risk APOL1 variants and an increased risk of kidney disease in PLWHIV, and provides a more precise estimate of the effect size, with smaller 95% CIs for CKD, HIVAN, and progression to ESKD.

Introduction Despite a decline in developed countries, pregnancy-related acute kidney injury (PRAKI) remains a significant contributor to maternal mortality and adverse fetal outcomes in resource-constrained settings. Little is known about the impact of pregnancy-related acute kidney injury in Nigeria. Therefore, this study aimed to assess the incidence and maternal-fetal outcomes associated with pregnancy-related acute kidney injury among a cohort of high-risk women in Nigeria. Methods This prospective multicenter study included women at high risk of acute kidney injury, who were more than 20 weeks pregnant or within 6 weeks postpartum and admitted to the Obstetrics and Gynecology units of two large public hospitals between September 1, 2019, and July 31, 2022. Acute kidney injury was defined and classified using the Kidney Disease Improving Global Outcomes (KDIGO) criteria. Results A total of 433 women, with mean age (± standard deviation) of 28 ± 6 years, were included in the evaluation. Pregnancy-related acute kidney injury occurred in 113 women (26.1%; 95% confidence interval [CI]: 21.1%-30.2%). The leading cause was preeclampsia ( n  = 57; 50.1%); 19 women died (4.4%), with 17 deaths (15%) occurring in the PRAKI group. Increasing severity of pregnancy-related acute kidney injury was independently associated with maternal mortality: adjusted odds ratio (aOR) for KDIGO stage 2 = 4.40; 95% CI 0.66–29.34, p  = 0.13, and KDIGO stage 3 aOR = 6.12; 95% CI 1.09–34.34, p  = 0.04. The overall perinatal mortality was 15% ( n  = 65), with 28 deaths (24.8%) occurring in the PRAKI group. Pregnancy-related acute kidney injury was also associated with an increased risk of perinatal mortality, aOR = 2.23; 95 CI 1.17–4.23, p  = 0.02. Conclusions The incidence of pregnancy-related acute kidney injury was high, and significantly associated with maternal and perinatal mortality. The leading causes were hypertensive disorders of pregnancy. Graphical abstract