The impact of vascular calcification among dialysis-dependent South African patients: A 5-year follow-up study
.

BACKGROUND: Vascular calcification is a major risk factor for cardiovascular morbidity and mortality in patients with end-stage renal disease (ESRD). In Western countries, Blacks appear to have lesser degrees of vascular calcification compared to non-Blacks. However, there is no published data from sub-Saharan Africa. MATERIALS AND METHODS: This study assessed the 5-year change in vascular calcification and mortality in a previously published cohort of patients with ESRD. Vascular calcification was assessed by abdominal aortic calcification score and vascular stiffness by pulse wave velocity (PWV). RESULTS: 66 of the original 74 participants studied at baseline were identified. The median age was 46.6 years (37.6 - 59.2), and 57.6% were women. Abdominal aortic calcification showed no progression among Blacks (baseline range 0 - 5, follow-up range 0 - 8 (p = 1.00)), but a trend to progression among non-Blacks (baseline range 0 - 19, follow up range 0 - 22 (p = 0.066)). Black participants did not display a survival advantage (p = 0.870). Non-Blacks had higher parathyroidectomy rates than Blacks with 9/30 cases compared to 2/36 (p = 0.036). After adjustment for parathyroidectomy at follow-up, the odds ratio of having abdominal vascular calcification score of ≥ 1 amongst non-Blacks was 8.6-fold greater compared to Blacks (p = 0.03). A positive correlation (r = 0.5) was observed between PWV and abdominal aortic calcification (p = 0.047). Elevated baseline coronary artery calcification score and FGF-23 level at baseline were not associated with a difference in mortality. CONCLUSION: There was no significant progression in vascular calcification among Blacks. After adjusting for increased parathyroidectomy rates, there was a greater progression of vascular calcification amongst non-Blacks compared to Blacks.

Clinical profile and outcome of patients with biopsy-proven acute interstitial nephritis in Cape Town: a 10-year review
.

BACKGROUND: Acute interstitial nephritis (AIN) is a common cause of acute kidney injury that has not been adequately characterized in Sub-Saharan Africa (SSA) despite an increasing use of potentially inciting agents for the treatment of human immunodeficiency virus (HIV) and tuberculosis in the region. METHODS: A retrospective audit of records of patients with biopsy-proven AIN diagnosed at Groote Schuur Hospital, Cape Town from the 1st of January, 2006, to the 31st of December, 2015. RESULTS: 54 patients with biopsy-proven AIN were reviewed. The majority were of black African origin (59.2%), with HIV (42.8%) and HIV-tuberculosis coinfection (30.5%) as the most common comorbidities. Drug-related AIN was seen in 38 (67.9%) patients, with rifampicin as the most often implicated medication. Probable drug-related AIN was seen in 3 (5.4%) patients, infection-related AIN in 8 (14.3%), and unspecified causes in 4 (7.4%). AIN was suspected in 44.6% of patients before biopsy. 18 patients (34%) received hemodialysis, while 19 (35.2%) were treated with corticosteroids. Complete renal recovery at 30 and 90 days was seen in 23 (42.6%) patients and 24 (45.3%) patients, respectively, with the majority seen among those with drug-induced AIN. Six (11.1%) patients died; 4 (10.5%) of the patients were in the drug-related group. There was no correlation between degree of interstitial inflammation and severity of renal failure (p = 0.10). On multivariate logistic regression, drug-related causes of AIN were predictive of complete recovery at day 30 (OR 16.63; 95% CI: 1.71 - 161.6, p = 0.02), and presence of interstitial fibrosis reduced likelihood of recovery (OR 0.03; 95% CI 0.002 - 0.46, p = 0.012). Steroid use did not influence partial recovery (OR 0.59, 95% CI 0.17 - 1.77; p = 0.32) or complete recovery (OR 3.38, 95% CI 0.38 - 30.39, p = 0.28). CONCLUSIONS: AIN is common in patients with HIV or those on treatment for tuberculosis. Drug-related AIN is often associated with improved outcomes. This is particularly reassuring in the SSA region where the use of potentially-inciting medications is rife from a high burden of HIV and tuberculosis.
.

A Current State of the Art and Science of Exercise in Dialysis: A Narrative Review.

Purpose of the review: The purpose of the review is to discuss current proven benefits and problems of integrating exercise in the care of people receiving dialysis by reviewing literature from the last few years and identifying important questions that still need to be asked and answered. Methods: A focused review and appraisal of the literature were done. Original peer-reviewed articles, review articles, opinion pieces and guidelines were identified from PubMed and Google Scholar databases. Only sources in English were accessed. Search terms "exercise" and "dialysis" were used to find active recruiting randomized trials in various clinical trial registry platforms. Key findings: Numerous studies have demonstrated the benefits of exercise training in individuals receiving dialysis, limited by factors such as short duration of follow-up and inconsistent adverse event reporting and outcomes selected. Notable gaps in exercise research in dialysis include ways to maintain programs and patient motivation, studies in peritoneal dialysis and home hemodialysis patients, and how best to define and measure outcomes of interest. Implications: This review summarizes the current state of exercise in people receiving dialysis and serves as a call to action to conduct large, randomized controlled trials to improve the quality of evidence needed to implement and sustain innovative, exercise interventions, and programs for this population.

Objectif de la revue: Discuter des bienfaits et problèmes avérés de l'intégration de l'exercice physique dans les soins des personnes dialysées en examinant la littérature des dernières années et en identifiant les questions importantes auxquelles il faut encore répondre. Méthodologie: Une revue ciblée et une évaluation de la littérature existante. Des articles originaux évalués par des pairs, des articles-synthèses, des articles d'opinion et des lignes directrices ont été répertoriés dans les bases de données Pubmed et Google Scholar. Seuls les articles en anglais ont été consultés. Les termes de recherche « exercice ¼ et « dialyse ¼ ont été utilisés pour rechercher les essais randomisés en cours de recrutement dans diverses plateformes de registres d'essais cliniques. Principales observations: De nombreuses études ont démontré les bienfaits de l'exercice physique chez les personnes dialysées. Ces études étaient toutefois limitées par des facteurs tels qu'une courte durée du suivi et une incohérence dans le rapport des événements indésirables et la sélection des résultats. Les principales lacunes observées dans les recherches portant sur l'exercice physique en contexte de dialyse concernent les moyens de maintenir les programmes et la motivation des patients, les études sur les patients traités par dialyse péritonéale et hémodialyse à domicile, et les meilleures façons de définir les résultats d'intérêt et de les mesurer. Conclusion: Cette revue résume la situation actuelle en ce qui concerne l'exercice physique chez les personnes dialysées. Elle constitue un appel à l'action pour la tenue d'essais cliniques de grande envergure visant l'amélioration de la qualité des données nécessaires à la mise en œuvre et au maintien d'interventions et de programmes d'exercice novateurs destinés à cette population.

Unmet needs in clinical trials in CKD: questions we have not answered and answers we have not questioned.

Many advances have been made in the field of nephrology over the last decade. These include an increasing focus on patient-centred involvement in trials, exploration of innovative trial designs and methodology, the growth of personalized medicine and, most importantly, novel therapeutic agents that are disease-modifying for large groups of patients with and without diabetes and chronic kidney disease. Despite this progress, many questions remain unanswered and we have not critically evaluated some of our assumptions, practices and guidelines despite emerging evidence to challenge current paradigms and discrepant patient-preferred outcomes. How best to implement best practices, diagnose various conditions, examine better diagnostic tools, treat laboratory values versus patients and understand prediction equations in the clinical context remain unanswered. As we enter a new era in nephrology, there are extraordinary opportunities to change the culture and care. Rigorous research paradigms enabling both the generation and the use of new information should be explored. We identify here some key areas of interest and suggest renewed efforts to describe and address these gaps so that we can develop, design and execute trials of importance to all.

The rationale for the need to study sodium-glucose co-transport 2 inhibitor usage in peritoneal dialysis patients.

The wave of kidney and heart outcome trials, showing multiple potential benefits for sodium-glucose co-transport 2 (SGLT2) inhibitors, have excluded patients with an estimated glomerular filtration rate below 25 ml/min/1.73 m2. However, dialysis patients are at the highest risk of cardiovascular disease and would benefit most from effective cardioprotective therapies. There is emerging evidence from experimental studies and post hoc analyses of randomised clinical trials that SGLT2 inhibitors are well tolerated and may also be effective in preventing cardiovascular and mortality outcomes in patients with severe chronic kidney disease, including patients receiving dialysis. As such, extending the usage of SGLT2 inhibitors to dialysis patients could provide a major advancement in their care. Peritoneal dialysis (PD) patients have an additional unmet need for effective pharmacotherapy to preserve their residual kidney function (RKF), with its associated mortality benefits, and for treatment options that help reduce the risk of transfer to haemodialysis. Experimental data suggest that SGLT2 inhibitors, via various mechanisms, may preserve RKF and protect the peritoneal membrane. There is sound physiological rationale and an urgent clinical need to execute robust randomised control trials to study the use of SGLT2 inhibitors in PD patients to answer important questions of relevance to patients and healthcare systems.

The Patient-Provider Gap: A Cross-sectional Survey to Understand Barriers and Motivating Factors for Home Blood Pressure Monitoring in a CKD Cohort.

Background: Blood pressure (BP) management can decrease morbidity and mortality in chronic kidney disease (CKD) patients. Evidence-based hypertension guidelines endorse home BP monitoring (HBPM), and the growing use of virtual health has highlighted the need for HBPM. A comprehensive understanding of HBPM adoption in our province is lacking. Objective: To identify the baseline practices, perspectives, barriers, and enablers in both providers and patients in our kidney care clinics regarding HBPM. Ultimately, this will inform the development of a provincial intervention that empowers providers to both increase patient understanding and equip them for accurate and reliable home BP measurement. Design: Cross-sectional, descriptive study using online survey methodology. Setting: Kidney care clinic network in the province of British Columbia, Canada. Patients or Sample or Participants: Kidney care clinic staff and patients who perform HBPM. Methods: Data were collected using semi-structured online surveys, one for staff and one for patients and/or caregivers. These surveys were developed by an interdisciplinary working group that included patient partners and addressed some key components of the implementation of an HBPM program (including perceived barriers to uptake, education, and adoption of best practices). Results: In all, 46 patients and 43 staff responded to the survey from 16 kidney care clinics. Of the patients 53% were women, and the most common age range was 60 to 69 years (25%); 93% of the staff respondents were women and 63% were nurses. We identified numerous areas of discordance between providers and patients and the need for improvement from the perspective of implementing best practices from hypertension guidelines, both in staff teaching and patient usage of HBPM. Blood pressure targets were not known to 18% of patients and 39% of patients had received a BP target from their kidney care clinic team; 89% of patients had not had their upper arm circumference measured for cuff size. Furthermore, 54% of patients knew what to do when their BP is off-target. All recognized the benefits of HBPM, providers were more likely to perceive anxiety as a barrier relative to patients, and patients were more likely to report expense as a barrier than providers. Limitations: This study includes only a single provincial health care system limiting generalizability to other jurisdictions and sampled a small subset of patients and providers. Conclusions: The systematic evaluation of education, understanding, implementation of best practices, and barriers and motivating factors for HBPM from both patient and clinician perspectives is an important step in designing strategies to improve the use of HBPM. Given differences in staff and patient perspectives, targeted interventions based on these responses may lead to improved use of HBPM, and ultimately enhance hypertension self-management and BP control in our CKD patients.

Contexte: La gestion de la pression artérielle (PA) peut réduire la morbidité et la mortalité chez les patients atteints d'insuffisance rénale chronique (IRC). Les lignes directrices pour l'hypertension fondées sur des données probantes appuient la surveillance de la pression artérielle à domicile (SPAD). En outre, le recours croissant à la médecine virtuelle a mis en évidence la nécessité de la SPAD. Une bonne compréhension de ce qui entoure l'adoption de la SPAD dans notre province est manquante. Objectifs: Connaître les pratiques usuelles de SPAD, les facteurs qui favorisent ou freinent son adoption et les perspectives des prestataires de soins et des patients de nos cliniques de soins rénaux. Éventuellement, ces données serviront à orienter l'élaboration d'une intervention provinciale qui permettra aux prestataires de soins d'améliorer la compréhension des patients et de les équiper pour une mesure précise et fiable de la PA à domicile. Conception: Étude transversale descriptive utilisant une méthodologie de sondage en ligne. Cadre: Le réseau des cliniques de soins rénaux de la Colombie-Britannique (Canada). Participants: Le personnel des cliniques et les patients effectuant la SPAD. Méthodologie: Les données ont été recueillies à l'aide de sondages semi-structurés en ligne; un premier destiné au personnel des cliniques, un autre aux patients et/ou aux soignants. Les sondages ont été élaborés par un groupe de travail interdisciplinaire qui comprenait des patients partenaires; ils traitaient de certains éléments clés de la mise en œuvre d'un programme de SPAD (obstacles perçus à l'adoption, enseignement et adoption des meilleures pratiques). Résultats: En tout, 46 patients (53 % de femmes; groupe d'âge le plus représenté: 60 à 69 ans [25 %]) et 43 membres du personnel (93 % de femmes; 63 % d'infirmières), provenant de 16 cliniques, ont répondu au sondage. Nous avons observé de nombreux points de divergence entre les prestataires de soins et les patients, de même qu'en ce qui concerne le besoin d'amélioration du point de vue de la mise en œuvre des meilleures pratiques des lignes directrices pour l'hypertension, tant dans l'enseignement fait par le personnel que dans la pratique de la SPAD par les patients. Seuls 18 % des patients ignoraient les cibles de PA et 39 % avaient reçu une cible de PA de leur équipe soignante à la clinique. La mesure de la circonférence brachiale, qui sert à établir la taille du brassard, n'avait pas été mesurée chez la grande majorité des patients (89 %). En outre, seulement 54 % des patients savaient quoi faire lorsque la PA est hors cible. Tous les répondants ont reconnu les avantages de la SPAD. Les prestataires de soins étaient plus susceptibles de percevoir l'anxiété comme un obstacle pour les patients, et les patients étaient plus susceptibles que les prestataires de percevoir les dépenses comme un obstacle. Limites: Cette étude examine un seul système de santé provincial, ce qui limite la généralisabilité à d'autres administrations. L'étude porte sur de petits sous-ensembles de patients et de prestataires. Conclusion: L'évaluation systématique de l'enseignement, de la compréhension et de la mise en œuvre des meilleures pratiques de SPAD, de même que des obstacles et facilitateurs à son adoption perçus par les patients et les cliniciens, constitue une étape importante dans la conception de stratégies visant à améliorer l'utilisation de la SPAD. Compte tenu des divergences de point de vue entre les prestataires de soins et les patients, des interventions ciblées fondées sur ces réponses pourraient augmenter la SPAD et, éventuellement, améliorer l'autogestion de l'hypertension et le contrôle de la PA chez nos patients atteints d'IRC. Ce que nous savons: La SPAD est un outil pratique et efficace pour optimiser le contrôle de la PA chez les patients; elle peut aider à réduire l'atteinte de leur organe cible et les résultats cliniques défavorables. Interventions: Cette enquête provinciale montre des discordances entre les patients et les prestataires de soins, de même qu'une hétérogénéité dans l'application et la connaissance des pratiques de SPAD, de même qu'en ce qui concerne les obstacles et facilitateurs perçus pour son adoption. Nous soulignons le besoin pour une intervention complète et ciblée de la SPAD dans nos cliniques.

Attitudes and beliefs of South African medical students toward organ transplantation.

The aim of this study was to assess and analyse the attitudes and beliefs of medical students regarding organ donation, procurement, and transplantation. Medical students at the University of Cape Town were prospectively surveyed using a self-administered questionnaire. There were 346 study participants; the mean age was 21 (range 18-33) yr, 38% were male and 62% was female. Only 8% of respondents were registered donors; clinical and white students constituted the majority of this group. Of the 315 "non-donors," the main reason for not donating was "I have not really thought about organ donation" (59%). Most students (91%) would accept an artificial organ; and 87% and 52% of students would accept human and animal organs respectively. Muslim students (11%, p<0.05) and those who believe in an after-life or reincarnation (18%, p=0.00) were less willing to accept human or animal organs. About 95% of respondents stated that they would like to learn more about transplantation and would keep information about it in their practice but only 18% of respondents knew where to find information for potential donors and recipients. Most students have a favorable attitude toward organ transplantation; religion and belief systems impact on willingness to receive organs.

Semaglutide-Associated Acute Interstitial Nephritis: A Case Report.

Glucagon-like peptide 1 receptor agonists (GLP-1RAs) are being investigated to slow the decline of kidney function in type 2 diabetics with chronic kidney disease (CKD). These agents have proven benefits on cardiac outcomes and all-cause mortality as well as in reducing the incidence of macroalbuminuria. Ours is a case of drug-associated acute interstitial nephritis requiring hemodialysis temporally related to a semaglutide dose increase. This case is unique as the index patient had no underlying CKD. Limited cases of acute kidney injury, superimposed on underlying CKD, in patients taking the GLP-1RA semaglutide have been reported. To our knowledge, there are no existing case reports in the literature of GLP-1RA-associated acute interstitial nephritis in a patient with baseline normal kidney function. Because our prescription of these agents is increasing and is anticipated to increase further with growing scientific evidence for their benefit, we sought to highlight this possible, important serious adverse effect of semaglutide.

Peripheral neuropathy in HIV patients on antiretroviral therapy: Does it impact function?

HIV-associated distal sensory polyneuropathy (DSP), with or without neuropathic symptoms, can develop after anti-retroviral therapy (ART). Symptoms frequently involve small fibres but reports on autonomic dysfunction in HIV-DSP are sparse. We studied an HIV-infected cohort after 5 years of ART, and report on the frequency and severity of autonomic symptoms and the impact of DSP on everyday function. This cross-sectional study comprised of participants from a community-based South African HIV-clinic. The Brief Peripheral Neuropathy Screen and reduced Total Neuropathy Score evaluated neuropathic symptoms/signs. DSP was defined as ≥2 symmetrical DSP-signs, and symptomatic DSP when accompanied by neuropathic symptoms. Autonomic symptoms questionnaires, heart rate variability and postural blood pressure changes were assessed. The Lower Extremity Functional Scale (LEFS) was completed. The 67 participants had a median age of 42 years and median ART exposure of 7 years with viral suppression in 84%. Most (81%) met our criteria for DSP and 36% had additional neuropathic symptoms. Autonomic symptoms and signs (above normative values) were present in 15% and more likely in those with symptomatic DSP (P < .001). Participants with DSP, even without symptoms, had lower LEFS scores (P ≤ .039) than those without. HIV-DSP is prevalent and impacts on daily living.

The Effects of Angiotensin Converting Enzyme Inhibitors (ACE-I) on Human N-Acetyl-Seryl-Aspartyl-Lysyl-Proline (Ac-SDKP) Levels: A Systematic Review and Meta-Analysis.

BACKGROUND: Tuberculous pericardial effusion is a pro-fibrotic condition that is complicated by constrictive pericarditis in 4% to 8% of cases. N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) is a ubiquitous tetrapeptide with anti-fibrotic properties that is low in tuberculous pericardial effusion, thus providing a potential mechanism for the heightened fibrotic state. Angiotensin-converting enzyme inhibitors (ACE-I), which increase Ac-SDKP levels with anti-fibrotic effects in animal models, are candidate drugs for preventing constrictive pericarditis if they can be shown to have similar effects on Ac-SDKP and fibrosis in human tissues. OBJECTIVE: To systematically review the effects of ACE-Is on Ac-SDKP levels in human tissues. METHODS: We searched five electronic databases (1996 to 2014) and conference abstracts with no language restrictions. Two reviewers independently selected studies, extracted data and assessed methodological quality. The protocol was registered in PROSPERO. RESULTS: Four studies with a total of 206 participants met the inclusion criteria. Three studies (106 participants) assessed the change in plasma levels of Ac-SDKP following ACE-I administration in healthy humans. The administration of an ACE-I was associated with an increase in Ac-SDKP levels (mean difference (MD) 5.07 pmol/ml (95% confidence intervals (CI) 0.64 pmol/ml to 9.51 pmol/ml)). Two studies with 100 participants further assessed the change in Ac-SDKP level in humans with renal failure using ACE-I. The administration of an ACE-I was associated with a significant increase in Ac-SDKP levels (MD 8.94 pmol/ml; 95% CI 2.55 to 15.33; I2 = 44%). CONCLUSION: ACE-I increased Ac-SDKP levels in human plasma. These findings provide the rationale for testing the impact of ACE-I on Ac-SDKP levels and fibrosis in tuberculous pericarditis.

Ambulatory blood pressure profiles in a subset of HIV-positive patients pre and post antiretroviral therapy.

OBJECTIVES: Human immunodeficiency virus (HIV) and antiretroviral therapy (ART) are associated with renal disease and increased cardiovascular risk. The relationship between HIV and ambulatory blood pressure (ABP) non-dipping status, a risk factor for cardiovascular events and target-organ damage, has never been assessed in South Africa. Study objectives were to establish the prevalence of chronic kidney disease, and assess the ABP profile in asymptomatic HIV-positive clinic out-patients. METHODS: This was a prospective cohort study. Office blood pressure (BP), urinary microalbumin-creatinine ratio, urine dipsticks, serum creatinine and estimated glomerular filtration rate (eGFR) were measured at baseline and six months after ART initiation. A subset of HIV-positive subjects and an HIV-negative control group underwent 24-hour ABP monitoring. RESULTS: No patient had an eGFR < 60 ml/min, three patients (4.7%) had microalbuminuria and one had macroalbuminuria. Mean office systolic BP was 111 ± 14 mmHg at baseline and increased by 5 mmHg to 116 ± 14 mmHg (p = 0.05) at six months. This increase was not confirmed by ABP monitoring. In the HIV-positive and -negative patients, the prevalences of non-dipping were 80 and 52.9%, respectively (p = 0.05, odds ratio = 3.56, 95% CI: 0.96-13.13). No relationship between dipping status and ART usage was found. CONCLUSION: The prevalence of chronic kidney disease (CKD) was lower than anticipated. HIV infection was associated with an ambulatory non-dipping status, which suggests an underlying dysregulation of the cardiovascular system. In the short term, ART does not seem to improve loss of circadian rhythm.