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Introduction: Little data is available on biopsy-proven kidney disease in African countries. In this study, we have described the patterns of biopsy-proven kidney disease amongst South African adults encountered over a 23-year period and report whether these have changed over time.

Over the course of the COVID-19 pandemic, numerous studies have aimed to address the challenges faced by patients with kidney disease and their caregivers. These studies addressed areas of concern such as the high infection and mortality risk of patients on in-centre haemodialysis and transplant recipients. However, the ability to draw meaningful conclusions from these studies has in some instances been challenging, owing to barriers in aspects of usual care, data limitations and problematic methodological practices. In many settings, access to SARS-CoV-2 testing differed substantially between patient groups, whereas the incidence of SARS-CoV-2 infection varied over time and place because of differences in viral prevalence, targeted public health policies and vaccination rates. The absence of baseline kidney function data posed problems in the classification of chronic kidney disease and acute kidney injury in some studies, potentially compromising the generalizability of findings. Study findings also require attentive appraisal in terms of the effects of confounding, collider bias and chance. As this pandemic continues and in the future, the implementation of sustainable and integrated research infrastructure is needed in settings across the world to minimize infection transmission and both prevent and plan for the short-term and long-term complications of infectious diseases. Registries can support the real-world evaluation of vaccines and therapies in patients with advanced kidney disease while enabling monitoring of rare complications.

BackgroundDuring the outbreak of coronavirus disease 2019 (COVID-19), many studies have investigated laboratory biomarkers in management and prognostication of COVID-19 patients, however to date, few have investigated arterial blood gas, acid–base and blood pressure patterns. The aim of the study is to assess the arterial blood gas and acid–base patterns, blood pressure findings and their association with the outcomes of COVID-19 patients admitted to an intensive care unit.MethodsA single-centre retrospective, observational study in a dedicated COVID-19 intensive care unit in Cape Town, South Africa. Admission arterial blood gas, serum electrolytes, renal function and blood pressure readings performed on COVID-19 patients admitted between 26 March and 2 June 2020 were analysed and compared between survivors and non-survivors.ResultsA total of 56 intensive care unit patients had admission arterial blood gas performed at the time of intensive care unit admission. An alkalaemia (pH > 7.45) was observed in 36 (64.3%) patients. A higher arterial pH (median 7.48 [interquartile range: 7.45–7.51] versus 7.46 [interquartile range: 7.40–7.48], P = 0.049) and partial pressure of oxygen in arterial blood (median 7.9 kPa [interquartile range: 7.3–9.6] versus 6.5 kPa [interquartile range: 5.2–7.3], P = 3(median: 28.0 mmol/L [interquartile range: 25.7–28.8] versus 26.3 mmol/L [interquartile range: 24.3–27.9], P = 0.059).ConclusionsThe majority of the study population admitted to intensive care unit had an alkalaemia on arterial blood gas. A higher pH and lower partial pressure of oxygen in arterial blood on arterial blood gas analysis were significantly associated with survival.

Introduction: Thiazide diuretics can lower urinary calcium excretion, helping to prevent recurrent calcium kidney stones. As dietary intake and urine chemistry varies throughout the day, a 24-h urine collection may not provide sufficient information to guide the optimal management in individual patients. Using multiple timed urine collections, we sought to identify times during the day when stone-forming risk is higher, allowing for therapy to be more accurately targeted. Methods: In a prospective study, healthy adult volunteers took a 4-week course of either hydrochlorothiazide (HCTZ) 25 mg/d or indapamide 2.5 mg/d. They were assessed at baseline, and at days 7, 14 and 28. At each time point, blood samples were taken for analysis and multiple timed urine samples were collected throughout the day, together with one overnight sample. Results: Diuretic treatment was well tolerated. Daily calcium and citrate excretion decreased, while ionized calcium and phosphate excretion were unchanged. Ionized calcium-divalent phosphate and ionized calcium-oxalate products were unchanged. In the timed urine samples, calcium excretion was decreased, particularly by indapamide, in the morning. Indapamide, but not HCTZ, decreased urinary citrate excretion, most obviously in overnight and early morning urines. No changes in ionized calcium were observed. Decreased divalent phosphate excretion was observed at several time points in the indapamide group. The ionized calcium-divalent phosphate product tended to decrease at most time points in both groups but no significant changes were observed in the ionized calcium-oxalate product. Conclusions: Indapamide 2.5 mg/d has a stronger protective effect against forming calcium kidney stones than HCTZ 25 mg/d. Most of the benefits appear to be achieved during the daytime and it may therefore be beneficial to prescribe medication twice daily or in the evening to maximize the protective effects of these agents. The benefits of indapamide treatment were attenuated by a reduction in urinary citrate excretion, an effect which has not been previously described. Keywords: hydrochlorothiazide, indapamide, kidney stones, urine collection

Introduction: Hyperkalaemia is a common electrolyte disorder in hospitalised patients and may cause life-threatening cardiac arrythmias and death. There is a lack of consensus regarding its optimal management, which may result in wide variations in practice and the guidance provided to junior staff. Methods: We conducted a survey on a Research Electronic Data Capture (REDCap) platform to evaluate the knowledge of medical specialists regarding the diagnosis and management of hyperkalaemia, with a focus on insulinbased therapy. A convenience sample of 70 specialists in nephrology, internal medicine, emergency medicine and critical-care medicine were invited to participate. Comparisons were also made between nephrologists and nonnephrologists. Results: A total of 51 medical specialists responded, of whom 47% were nephrologists. They were more likely to initiate therapy at a potassium concentration ([K]) of 6 mmol/L, whereas non-nephrologists tended to start at a lower concentration (P < 0.01). Half the respondents regarded blood gas machine measurements as providing an accurate measure of [K]. Non-nephrologists were more likely to perform an ECG before starting treatment (P = 0.02). All respondents regarded insulin and dextrose as the most effective and reliable means for shifting K. Only 22% monitored the serum glucose concentration beyond 2 hours following insulin-based therapy, and 22% thought that hypoglycaemia was an uncommon complication if dextrose also was administered. Conclusions: This is the first comprehensive survey to report on the knowledge of specialists regarding the emergency management of hyperkalaemia. There is a need to address knowledge gaps, particularly around the optimal and safe use of insulin-based therapies. Our findings and recommendations should be useful in informing the development of consensus guidelines and educational resources on hyperkalaemia. Keywords: insulin, dextrose, electrocardiogram, survey, hypoglycaemia

acid-base disorders are very common in critically ill patients and contribute significantly to morbidity and mortality. The aim of this study was to identify the types of acid-base disorders at the time of admission to the intensive care unit (ICU) and its associated ICU and in-hospital mortality.we conducted a retrospective cohort study of all adult patients that were admitted to the ICU and had an arterial blood gas sample at the time of admission from 1a total of 375 patients were included. The median age for the entire cohort was 39 (IQR 30-52) years and 48.3% (n=181) were female. Mixed acid-base disorders were the most common at 48.8% (n=183), followed by no disorder at 24.8% (n=93), metabolic acidosis at 9.3% (n=35), metabolic alkalosis at 6.7% (n=25), respiratory acidosis 6.1% (n=23) and respiratory alkalosis at 4.3% (n=16). A total of 94 (25.0%) patients died. There were no differences in ICU (p = 0.35) or in-hospital death (p = 0.32) by acid-base disorder. Male sex (aOR: 5.8, 95% CI 1.55-21.42; p0.01), APACHE II score (aOR: 1.17, 95% CI 1.06-1.30; p0.01) and the corrected anion gap (aOR: 1.14, 95% CI 1.02-1.27; p = 0.02) were identified as predictors of in-hospital death using multivariable logistic regression.there was no association between acid-base disorders at the time of ICU admission and ICU or in-hospital death. Therefore, in our setting, acid-base disorders at the time of ICU admission should not be used to predict the outcome of patients requiring intensive care.

Funder: AstraZeneca, BACKGROUND: The prevalence and incidence of hyperkalaemia, a potassium abnormality that can potentially have life-threatening consequences, are unclear. METHODS: The objective was to provide the most comprehensive overview of the epidemiology of hyperkalaemia to date within the general population, across different continents, in different healthcare settings and within pre-specified subgroups. Embase and MEDLINE were searched from database inception to 2 February 2021 using the Ovid SP platform. Relevant congress proceedings from 2018 to 2020 were also reviewed for inclusion. There was no language constraint applied. Observational studies from any time period and language reporting prevalence or incidence of hyperkalaemia within both adult and paediatric populations. Four investigators independently screened abstracts and assessed study quality of those meeting the pre-determined inclusion/exclusion criteria. Data extraction was conducted by the lead author with oversight from the senior author and data were pooled using a random-effects model. The measures assessed were the prevalence and incidence of hyperkalaemia. Prevalence was reported as a percentage, whilst incidence was reported as the rate per 100 person years. RESULTS: In total, 542 articles were included from an initial search of 14 112 articles. Across all adult studies, we report a prevalence of hyperkalaemia (by any definition/threshold) of 6.3% [95% confidence interval (CI): 5.8-6.8%], with an incidence of hyperkalaemia in the adult population of 2.8 (2.3-3.3) cases per 100 person years. Prevalence within the general population was 1.3% (1.0-1.8%), whilst incidence was 0.4 (0.2-0.8) cases per 100 person years. There was a variation by sex with a prevalence of 6.3% (4.9-8.0%) in males and 5.1% (4.0-6.6%) in females. Prevalence also varied according to the definition/threshold of hyperkalaemia used: >5 mmol/L-8.0% (7.2-8.9), ≥5.5 mmol/L-5.9% (3.5-10.0) and ≥6.0 mmol/L-1.0% (0.8-1.4); hyperkalaemia (by any definition/threshold) was highest amongst patients with end-stage kidney disease (21.5%; 18.3-25.3), kidney transplant patients (21.8%; 16.1-29.5) and patients with acute kidney injury (24.3%; 19.3-30.7). CONCLUSIONS: This novel review provides a comprehensive and valuable resource on the prevalence and incidence of hyperkalaemia to better inform clinicians, healthcare providers and health policy makers on the burden of hyperkalaemia across different healthcare settings, patient populations and continents.

COVID-19 has now spread to all the continents of the world with the possible exception of Antarctica. However, Africa appears different when compared with all the other continents. The absence of exponential growth and the low mortality rates contrary to that experienced in other continents, and contrary to the projections for Africa by various agencies, including the World Health Organization (WHO) has been a puzzle to many. Although Africa is the second most populous continent with an estimated 17.2% of the world's population, the continent accounts for only 5% of the total cases and 3% of the mortality. Mortality for the whole of Africa remains at a reported 19,726 as at August 01, 2020. The onset of the pandemic was later, the rate of rise has been slower and the severity of illness and case fatality rates have been lower in comparison to other continents. In addition, contrary to what had been documented in other continents, the occurrence of the renal complications in these patients also appeared to be much lower. This report documents the striking differences between the continents and within the continent of Africa itself and then attempts to explain the reasons for these differences. It is hoped that information presented in this review will help policymakers in the fight to contain the pandemic, particularly within Africa with its resource-constrained health care systems.

An epidemic of chronic kidney disease (CKD) is being experienced in South Africa. This is driven by a heavy burden of infections, non-communicable diseases, pregnancy-related diseases and injuries. The serious long-term complications of CKD include end-stage renal disease, heart disease and stroke. Competing priorities such as the high burden of HIV, tuberculosis and other infections, unemployment and poverty result in serious constraints to providing comprehensive renal care, especially in the public healthcare sector. The prevention and early detection of CKD by primary care practitioners is therefore of utmost importance. Annual screening is recommended for patients at high risk of developing CKD. This involves checking blood pressure, urine dipstick testing for albuminuria or proteinuria and estimating the glomerular filtration rate from serum creatinine concentrations. In patients with established CKD, renoprotective measures are indicated to arrest or slow down the loss of renal function. These patients are at high risk of cardiovascular disease and close attention should be paid to optimally managing their risk factors.

Background Hypernatremia is a very common electrolyte disorder and is frequently encountered in out-patient as well as in-hospital settings. We describe an adult who was found to have unexplained relative polycythemia and episodic hypernatremia. A diagnosis of idiopathic hypodipsic-hypernatremia syndrome was made and the patient was managed with a water-drinking schedule. Case presentation A 24-year-old South African-Indian man was found to have polycythemia in association with episodes of hypernatremia. Investigations indicated that he had relative polycythemia. He experienced no thirst at a time when his serum sodium concentration was found to be 151 mmol/L. Further testing indicated that his renal response to arginine vasopressin was intact and magnetic resonance imaging of his brain revealed no hypothalamic lesions. A diagnosis of idiopathic hypodipsic-hypernatremia syndrome was made and he was managed with a water-drinking schedule that corrected his hypernatremia. Conclusion Hypodipsia should always be considered when a patient without physical or cognitive disability presents with unexplained episodic hypernatremia or with relative polycythemia.

An epidemic of acute and chronic kidney disease is being experienced in South Africa. This is driven by a heavy burden of infections, non-communicable disease, pregnancy-related disease and injuries. Competing priorities such as the high burden of HIV, tuberculosis and other infections, unemployment and poverty result in serious constraints to providing comprehensive kidney care, especially in the public healthcare sector which serves most of the population.

Introduction: There is an epidemic of chronic kidney disease (CKD) in Africa and human immunodeficiency virus (HIV) infection is among the major drivers. However, the burden of CKD in HIV-infected patients in Africa varies widely by country and study, ranging from 0.5–59.3%. Published data on the prevalence of CKD in the Namibian HIV-infected population are scarce. In this study, we aimed to estimate the prevalence of CKD and associated factors in HIV-infected adults on antiretroviral therapy in northern Namibia. Methods: We conducted a cross-sectional study in the four regions of northern Namibia, using existing electronic records used in the management of HIV-infected patients. Variables captured included the two most recent serum creatinine measurements, date of birth, sex, date of initiating antiretroviral therapy, current antiretroviral treatment, and most recent HIV viral load results. We used standardised serum creatinine measurements to estimate the glomerular filtration rate (GFR) using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. CKD was defined as estimated GFR (eGFR) < 60 mL/min/1.73 m2 on two occasions at least three months apart. Factors associated with CKD were assessed using logistic regression. Results: We included 1 993 participants, of whom 1 362 (68%) were female and mean age was 44.5 ± 11.5 years.The proportion of participants who were virally suppressed was 97% (95% CI 96, 98%) and the median durationon antiretroviral therapy was 107 months (IQR 62–149). The prevalence of CKD was 1.4% (95% CI 1.0, 2.0%).CKD cases were 13 times more likely to be 45 years or older and 3.5 times more likely to be male than those without CKD. Conclusions: Our findings suggest a low prevalence of CKD among the HIV-infected population in northern Namibia. Patients older than 45 years may need additional monitoring for kidney function using eGFR.

South Africa is an upper middle–income country with a population of 59.6 million people (1). Gauteng is the most densely populated province, and houses 26% of the population, followed by KwaZulu-Natal (19%), and the Western Cape (12%). About 29% of the population are

This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess the benefits and harms of less frequent HD (defined as twice‐weekly HD sessions of not less than 3 hours/session) compared to conventional HD (defined as thrice‐weekly sessions of 3 to 5 hours/session) for patients with ESKD on maintenance HD.

BackgroundThe majority of South Africans rely on a resource-constrained public healthcare sector, where access to renal replacement therapy (RRT) is strictly rationed. The incidence of RRT in this sector is only 4.4 per million population (pmp), whereas it is 139 pmp in the private sector, which serves mainly the 16% of South Africans who have medical insurance. Data on the outcomes of RRT may influence policies and resource allocation. This study evaluated, for the first time, the survival of South African patients starting RRT based on data from the South African Renal Registry.MethodsThe cohort included patients with end-stage kidney disease who initiated RRT between January 2013 and September 2016. Data were collected on potential risk factors for mortality. Failure events included stopping treatment without recovery of renal function and death. Patients were censored at 1 year or upon recovery of renal function or loss to follow-up. The 1-year patient survival was estimated using the Kaplan–Meier method and the association of potential risk factors with survival was assessed using multivariable Cox proportional hazards regression.ResultsThe cohort comprised 6187 patients. The median age was 52.5 years, 47.2% had diabetes, 10.2% were human immunodeficiency virus (HIV) positive and 82.2% had haemodialysis as their first RRT modality. A total of 542 patients died within 1 year of initiating RRT, and overall 1-year survival was 90.4% [95% confidence interval (CI) 89.6–91.2]. Survival was similar in patients treated in the private sector as compared with the public healthcare sector [hazard ratio 0.93 (95% CI 0.72–1.21)]. Higher mortality was associated with older age and a primary renal diagnosis of ‘Other’ or ‘Aetiology unknown’. When compared with those residing in the Western Cape, patients residing in the Northern Cape, Eastern Cape, Mpumalanga and Free State provinces had higher mortality. There was no difference in mortality based on ethnicity, diabetes or treatment modality. The 1-year survival was 95.9 and 94.2% in HIV-positive and -negative patients, respectively. One-fifth of the cohort had no data on HIV status and the survival in this group was considerably lower at 77.1% (P ConclusionsThe survival rates of South African patients accessing RRT are comparable to those in better-resourced countries. It is still unclear what effect, if any, HIV infection has on survival.

Spurious laboratory results are frequently encountered in patients with haematological disorders and lead to unnecessary additional laboratory investigations and inappropriate treatment. An 80-year-old woman, known with acute myeloid leukaemia, was admitted with suspected sepsis. Laboratory tests revealed a leukocyte count of 358 x 10 9 /L, serum potassium concentration of 2.6 mmol/L and partial pressure of arterial oxygen of 5.3 kPa. The patient did not display any clinical or electrocardiographic features of hypokalaemia and there were no signs of respiratory distress. A diagnosis of pseudohypokalaemia and pseudohypoxaemia was made and inappropriate therapeutic interventions were avoided. Pseudohypokalaemia and pseudohypoxaemia should always be a consideration in patients with hyperleukocytosis due to haematological malignancies, especially when there are no clinical features to support these findings. The inappropriate administration of potassium in such cases may cause serious cardiac arrythmias.

BRASH syndrome (bradycardia, renal failure, atrioventricular nodal blockers, shock and hyperkalemia) is an emerging and distinct condition that occurs due to the synergistic effects of hyperkalaemia and AVN blockers on the heart. Only a few case reports have been described in the medical literature since 2016. We present an 88-year-old woman, known with hypertension, stage 5 chronic kidney disease (not on dialysis) and paroxysmal atrial fibrillation that presented with a history of four syncopal episodes in the past 2-months and had symptoms of heart failure for 1-day. Clinical examination revealed a blood pressure of 105/60 mmHg and a regular pulse rate of 31 beats per minute. Laboratory potassium concentration was 6.7 mmol/L and creatinine was 318 ¼ mol/L. An electrocardiogram revealed a sinus bradycardia without features suggestive of hyperkalaemia. A diagnosis of BRASH syndrome was made. The patient received treatment addressing multiple factors involved in the pathogenesis of the syndrome and responded favourably. She was discharged 1-week later. In patients with syncope, BRASH syndrome should be considered when bradycardia is associated with hyperkalaemia, along with a history of AVN blocker use. It is important to recognise so that appropriate therapy can be instituted that addresses all the elements of the syndrome, rather than focusing on a single component.

Africa trails the rest of the world in COVID-19 cases and deaths. However, as the pandemic spreads through the continent, we expect increases in community infection in the months ahead. Patients with kidney infection, especially those with end-stage kidney disease and those with kidney transplants, are at high risk for acquiring the disease and dying from it. While there is limited evidence for the benefit of interventions, we have the advantage of learning from the experiences of those in China, Europe and the Americas. This document sets forth guidance for dealing with our patients who have acute and chronic kidney disease, including those on renal replacement therapy and the staff involved in their care. Emphasis is placed on preparedness and prevention strategies. As evidence and experience accumulate, it is likely that updated guidance will be needed. L’Afrique suit le reste du monde en termes de nombre de cas et de décès dus à COVID-19. Cependant, alors que la pandémie se propage à travers le continent, nous prévoyons une augmentation de l’infection communautaire dans les mois à venir. Les patients atteints d’une maladie rénale, en particulier ceux atteints d’une maladie rénale chronique en phase terminale et ceux ayant subi une transplantation rénale, courent un risque élevé de contracter la maladie et d’en mourir. Bien que les preuves d’interventions soient limitées, nous avons l’avantage de tirer des enseignements des expériences de ceux qui se trouvent en Chine, en Europe et dans les Amériques. Ce document présente des conseils pour traiter nos patients atteints d’insuffisance rénale aiguë et chronique, y compris ceux sous thérapie de suppléance rénale et le personnel impliqué dans leurs soins. L’accent est mis sur les stratégies de préparation et de prévention. Au fur et à mesure que les preuves et l’expérience s’accumulent, il est probable que des directives actualisées seront nécessaires.

Renal artery stenosis is a common cause of secondary hypertension and chronic kidney disease. We present here a case of fibromuscular dysplasia that was treated with surgical revascularization, resulting in recovery of kidney function with eventual cessation of chronic dialysis. The case involves a 25-year-old female with coincidentally discovered hypertension, who underwent further investigations revealing a diagnosis of renal artery stenosis due to fibromuscular dysplasia. She subsequently developed two episodes of malignant hypertension, with flash pulmonary oedema and worsening renal failure that resulted in dialysis dependence. After evidence was obtained that the right kidney was still viable, a revascularization procedure was performed, improving blood pressure control and restoring kidney function, thereby allowing dialysis to be stopped. This case highlights the importance of evaluating patients with renal artery stenosis for revascularization before committing them to a life of chronic dialysis.

Background Preliminary studies have shown the potential use of salivary creatinine concentration in the diagnosis of chronic kidney disease (CKD). For saliva to replace serum as a diagnostic tool, studies must be done to determine its effectiveness in the diagnosis and staging of CKD. The aim of the present study was to evaluate the use of salivary creatinine as a safe and non-invasive alternative for identifying patients with CKD. Methods A cross-sectional study was conducted at Tygerberg Hospital in Cape Town, on 230 patients, across all stages of CKD. Ethical approval to conduct the study was obtained from the University of the Western Cape Biomedical Research Ethics Committee, and written informed consent was provided by each participant. Saliva and serum samples were collected for creatinine analysis and the correlation determined using Spearman’s correlation. Receiver operating characteristics (ROC) analysis was used to determine the diagnostic ability of salivary creatinine. A cut-off value for optimal sensitivity and specificity of salivary creatinine to diagnose CKD with glomerular filtration rate (GFR) 2 was obtained. Results Serum creatinine values ranged from 46 μmol/L to 1581 μmol/L, with a median value of 134 μmol/L. Salivary creatinine values ranged from 3 μmol/L to 400 μmol/L, with a median of 11 μmol/L. There was a strong positive correlation (r = 0.82) between serum and salivary creatinine values. Linear regression analysis of serum and salivary creatinine for CKD patients was significant in all CKD stages, except for stage 1. Area under the curve for salivary creatinine was 0.839. A cut-off value of 8.5 μmol/L yielded a sensitivity of 78.3% and specificity of 74.0% for classifying patients as having CKD based on estimated GFR 2. Conclusions The results support the potential of salivary creatinine as a non-invasive diagnostic tool for estimating GFR and identifying patients with CKD.

Introduction The global nephrology workforce is shrinking and, in many countries, is unable to meet healthcare needs. Accurate data pertaining to human resources in nephrology in South Africa is lacking. This data is critical for the planning and delivery of renal services and the training of nephrologists in South Africa to meet the challenge of the growing burden of chronic kidney disease. Methods A cross-sectional study of adult and paediatric nephrologists currently delivering nephrology services in South Africa was conducted. Participants were identified using various data sources, including the register of the Health Professions Council of South Africa. This cohort of doctors was described in terms of their demographics and distribution. A survey was then conducted among these nephrologists to collect additional information on their training, scope of practice, job satisfaction, challenges and future plans. Finally, two focus group interviews were conducted to probe themes identified from the survey data. Results A total of 120 adult nephrologists and 22 paediatric nephrologists were identified (an overall density of 2.5 per million population). There is a male predominance (66%) and the median age is 45 years. The bulk of the workforce (128 nephrologists, 92%) is distributed in three of the nine South African provinces, and two provinces have no nephrologist at all. The survey was completed by 57% of the nephrologists. Most reported positive attitudes to their chosen profession; however, 35 nephrologists (43%) reported an excessive workload, 9 (11%) were planning emigration and 15 (19%) were planning early retirement. A higher frequency of dissatisfaction regarding remuneration (39% vs. 15%) and unsatisfactory work conditions (35% vs. 13%) was observed amongst nephrologists working in the public sector compared to the private sector. A total of 13 nephrologists participated in the focus group interviews. The themes which were identified included that of a rewarding profession, an overall shortage of nephrologists, poor career planning, a need for changes to nephrologists' training, excessive workloads with inadequate remuneration, and challenging work environments. Conclusion There are insufficient numbers of nephrologists in South Africa, with a markedly uneven distribution amongst the provinces and healthcare sectors. Qualitative data indicate that South African nephrologists are faced with the challenges of a high workload, obstructive policies and unsatisfactory remuneration. In the public sector, a chronic lack of nephrologist posts and other resources are additional challenges. A substantial proportion of the workforce is contemplating emigration.

Background The prevalence of chronic kidney disease (CKD) is increasing worldwide and in Africa. Health related quality of life (QOL) has become an essential outcome measure for patients with CKD and end stage renal disease (ESRD). There is growing interest worldwide in QOL of CKD patients but paucity of data in Ghana. This study sought to assess QOL in patients with moderate to advanced CKD (not on dialysis) and establish its determinants. Methods We conducted a cross sectional observational study at the renal outpatient clinic at Komfo Anokye Teaching Hospital (KATH). We collected demographic, clinical and laboratory data. A pretested self-administered Research and Development corporation (RAND®) 36-Item Health Survey questionnaire was administered and QOL scores in physical component summary (PCS) and mental component summary (MCS) were computed. Determinants of QOL were established by simple and multiple linear regression. P value of

Background. The Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations are two commonly used formulae to estimate glomerular filtration rate (GFR) in adults. The CKD-EPI equation is recommended in current international and local guidelines for the diagnosis and management of chronic kidney disease (CKD), unless an alternative equation has been shown to have superior accuracy. Validation and comparison of the equations in local populations are therefore required. Previous studies have reported on the accuracy of these prediction equations in black South Africans and those of Indian ancestry. Objectives. To evaluate the MDRD and CKD-EPI equations in South African (SA) adults of mixed ancestry. Methods. In all participants, GFR was measured (mGFR) from plasma clearance of 99m Tc-diethylenetetraaminepenta-acetic acid ( 99m Tc-DTPA), using a standardised technique. Serum creatinine assays were isotope dilution mass spectrometry traceable. GFR was estimated (eGFR) using the MDRD and CKD-EPI equations, with and without the black ethnicity factor. The agreement, bias, precision and accuracy of each equation was determined. Results. Eighty adults were included (30 male, median age 39 years, median GFR 59 mL/min/1.73 m 2 ). Sixty-eight had a diagnosis of CKD, 10 were potential kidney donors, and 2 were healthy volunteers. Both equations, without the black ethnicity factor, had good agreement with measured GFR. The equations tended to overestimate GFR, with bias of 1.6 and 7.9 mL/min/1.73 m 2 for the MDRD and CKD-EPI equations, respectively. The interquartile ranges of the differences were 15.9 and 20.2 mL/min/1.73 m 2 , and as a measure of accuracy, the percentages of estimates that fell within 30% of the mGFR (P30) were 80% and 72.5% ( p =0.18). For identification of individuals with a GFR

Multidrug-resistant Mycobacterium tuberculosis infection (MDR-TB) is a highly prevalent communicable disease in South Africa and often occurs in those with HIV infection. We describe three HIV-infected patients with pulmonary MDR-TB who received treatment with a regimen that included kanamycin and subsequently developed a Bartter-like syndrome. The clinical presentation varied from asymptomatic to severely symptomatic electrolyte disturbances, with one fatal outcome. This report highlights the importance of the routine monitoring of electrolytes in MDR-TB patients receiving treatment that includes kanamycin.

Background. Calcific uraemic arteriolopathy (calciphylaxis) is an unusual and potentially fatal condition characterised by small-vessel calcification and ischaemic skin necrosis. It mainly affects patients with end-stage renal disease (ESRD) on haemodialysis, but may rarely occur in the absence of ESRD in conditions such as primary hyperparathyroidism, malignancy, alcoholic liver disease and connective tissue disease. Methods. We reviewed the records of all patients diagnosed with calciphylaxis while on renal replacement therapy at Tygerberg Hospital, Cape Town, South Africa, between 1990 and 2014, to describe its presentation, course and final outcome. Results. Nineteen patients developed calciphylaxis over this period. Their median age was 34 years and 13 (68.4%) were female. Fifteen (78.9%) had received a kidney transplant. All patients had painful skin lesions that rapidly progressed to infarction. Small-vessel calcification was seen on skin biopsy in 13 patients. Twelve patients had hyperparathyroidism. Several of the transplanted patients had been treated for graft rejection in the year preceding the diagnosis. Treatment consisted of good wound care and efforts to normalise serum calcium and phosphate levels. Five patients received an urgent parathyroidectomy. The outcome was fatal in 17 patients, with sepsis being the main cause of death. Conclusions. In our patients, calciphylaxis carried a worse prognosis than previously reported internationally. It should always be considered in the differential diagnosis of painful skin lesions in the dialysis or transplant patient.

Optimizing the usability of e-learning materials is necessary to reduce extraneous cognitive load and maximize their potential educational impact. However, this is often neglected, especially when time and other resources are limited. We conducted a randomized trial to investigate whether a usability evaluation of our multimedia e-learning resource, followed by fixing of all problems identified, would translate into improvements in usability parameters and learning by medical residents. Two iterations of our e-learning resource [ version 1 (V1) and version 2 (V2)] were compared. V1 was the first fully functional version and V2 was the revised version after all identified usability problems were addressed. Residents in internal medicine and anesthesiology were randomly assigned to one of the versions. Usability was evaluated by having participants complete a user satisfaction questionnaire and by recording and analyzing their interactions with the application. The effect on learning was assessed by questions designed to test the retention and transfer of knowledge. Participants reported high levels of satisfaction with both versions, with good ratings on the System Usability Scale and adjective rating scale. In contrast, analysis of video recordings revealed significant differences in the occurrence of serious usability problems between the two versions, in particular in the interactive HandsOn case with its treatment simulation, where there was a median of five serious problem instances (range: 0–50) recorded per participant for V1 and zero instances (range: 0–1) for V2 ( P < 0.001). There were no differences in tests of retention or transfer of knowledge between the two versions. In conclusion, usability evaluation followed by a redesign of our e-learning resource resulted in significant improvements in usability. This is likely to translate into improved motivation and willingness to engage with the learning material. In this population of relatively high-knowledge participants, learning scores were similar across the two versions.

Background: Hyperkalemia is a common medical emergency that may result in serious cardiac arrhythmias. Standard therapy with insulin plus glucose reliably lowers the serum potassium concentration ([K+]) but carries the risk of hypoglycemia. This study examined whether an intravenous glucose-only bolus lowers serum [K+] in stable, nondiabetic, hyperkalemic patients and compared this intervention with insulin-plus-glucose therapy. Methods: A randomized, crossover study was conducted in 10 chronic hemodialysis patients who were prone to hyperkalemia. Administration of 10 units of insulin with 100 ml of 50% glucose (50 g) was compared with the administration of 100 ml of 50% glucose only. Serum [K+] was measured up to 60 min. Patients were monitored for hypoglycemia and EKG changes. Results: Baseline serum [K+] was 6.01 ± 0.87 and 6.23 ± 1.20 mmol/l in the insulin and glucose-only groups, respectively (p = 0.45). At 60 min, the glucose-only group had a fall in [K+] of 0.50 ± 0.31 mmol/l (p < 0.001). In the insulin group, there was a fall of 0.83 ± 0.53 mmol/l at 60 min (p < 0.001) and a lower serum [K+] at that time compared to the glucose-only group (5.18 ± 0.76 vs. 5.73 ± 1.12 mmol/l, respectively; p = 0.01). In the glucose-only group, the glucose area under the curve (AUC) was greater and the insulin AUC was smaller. Two patients in the insulin group developed hypoglycemia. Conclusion: Infusion of a glucose-only bolus caused a clinically significant decrease in serum [K+] without any episodes of hypoglycemia.

This article reports on the development and evaluation of a Web-based application that provides instruction and hands-on practice in managing electrolyte and acid-base disorders. Our teaching approach, which focuses on concepts rather than details, encourages quantitative analysis and a logical problem-solving approach. Identifying any dangers to the patient is a vital first step. Concepts such as an “appropriate response” to a given perturbation and the need for electroneutrality in body fluids are used repeatedly. Our Electrolyte Workshop was developed using Flash and followed an iterative design process. Two case-based tutorials were built in this first phase, with one tutorial including an interactive treatment simulation. Users select from a menu of therapies and see the impact of their choices on the patient. Appropriate text messages are displayed, and changes in body compartment sizes, brain size, and plasma sodium concentrations are illustrated via Flash animation. Challenges encountered included a shortage of skilled Flash developers, budgetary constraints, and challenges in communication between the authors and the developers. The application was evaluated via user testing by residents and specialists in internal medicine. Satisfaction was measured with a questionnaire based on the System Usability Scale. The mean System Usability Scale score was 78.4 ± 13.8, indicating a good level of usability. Participants rated the content as being scientifically sound; they liked the teaching approach and felt that concepts were conveyed clearly. They indicated that the application held their interest, that it increased their understanding of hyponatremia, and that they would recommend this learning resource to others.

There are four themes in this teaching exercise for Professor McCance. The first challenge was to explain how a premature infant with Bartter's syndrome could survive despite having such a severe degree of renal salt wasting. Second, the medical team wanted to know why there was such a dramatic decrease in the natriuresis in response to therapy, despite the presence of a permanent molecular defect that affected the loop of Henle. Third, Professor McCance was asked why this patient seemed to have a second rare disease, AQP2 deficiency type of nephrogenic diabetes insipidus. The fourth challenge was to develop a diagnostic test to help the parents of this baby titrate the dose of indomethacin to ensure an effective dose while minimizing the likelihood of developing nephrotoxicity. The missing links in this interesting story emerge during a discussion between the medical team and its mentor.

Background: Cyclophosphamide (CPM) is still considered to be the first-line treatment for many life-threatening autoimmune conditions. It does, however, carry a significant risk of serious adverse events, especially infections. At present CPM is administered as either a daily oral dose (DOC) or an intravenous pulse (PIVC). There is uncertainty regarding the safety profiles of both regimens in settings with a high burden of infectious diseases. Objective: To compare the frequency and nature of adverse events related to the use of DOC and PIVC in such a setting. Methods: A cohort of patients treated with CPM for autoimmune diseases at Tygerberg Academic Hospital, Cape Town, South Africa, from 1 January 2008 to 31 May 2013 was studied. We compared participants receiving DOC and PIVC with regard to disease characteristics and the occurrence of major adverse events. Results: A total of 134 participants (92 DOC and 42 PIVC) were included. Participants in the DOC group were treated for longer (174 v. 101 days; p

This teaching exercise demonstrates how the application of principles of physiology can identify the cause of a severe degree of hyperglycaemia (plasma glucose concentration 80 mmol/l) in a very young patient with newly diagnosed diabetes mellitus, determine whether the patient has diabetic ketoacidosis, and highlight the potential risks for this patient on admission and during initial therapy. A consultation with Professor McCance was sought to determine whether this patient had an unusual degree of 'insulin resistance'. There were also uncertainties regarding the acid-base diagnosis. The patient did not appear to have an important degree of metabolic acidosis as judged from his pH of 7.39 and plasma bicarbonate concentration of 20 mmol/l in arterial blood; hence the diagnostic impression was that he had a hyperglycaemic hyperosmolar state. However, his plasma anion gap was significantly elevated, and remained so for 60 h, despite the administration of insulin. Issues in management concerning the basis for this severe degree of hyperglycaemia and how to minimize the risk of developing cerebral oedema are addressed. The missing links in this interesting story emerge during a discussion between the medical team and their mentor, Professor McCance.

A 46-year-old female had a history of recurrent uric acid stone formation, but the reason why uric acid precipitated in her urine was not obvious, because the rate of urate excretion was not high, urine volume was not low, and the pH in her 24-h urine was not low enough. In his discussion of the case, Professor McCance provided new insights into the pathophysiology of uric acid stone formation. He illustrated that measuring the pH in a 24-h urine might obscure the fact that the urine pH was low enough to cause uric acid to precipitate during most of the day. Because he found a low rate of excretion of NH(4)(+) relative to that of sulphate anions, as well as a high rate of citrate excretion, he speculated that the low urine pH would be due to a more alkaline pH in proximal convoluted tubule cells. He went on to suspect that there was a problem in our understanding of the function of renal medullary NH(3) shunt pathway, and he suggested that its major function might be to ensure a urine pH close to 6.0 throughout the day, to minimize the likelihood of forming uric acid kidney stones.

A 22-year-old male developed a severe degree of metabolic acidosis (plasma pH 7.20, bicarbonate 8 mmol/l), with a large increase in the plasma anion gap (26 mEq/l). Ketoacidosis was suspected because of the odour of acetone on his breath and a positive qualitative test for acetone in plasma (to a 1:4 dilution). Later, his plasma beta-hydroxybutyrate concentration was found to be 4.5 mmol/l. After receiving an infusion of 1 l of half-isotonic saline and 1 l of 5% dextrose in water over 24 h, as well as curtailing his large oral intake of sweetened beverages, all blood tests became normal. Diabetic ketoacidosis, alcoholic ketoacidosis, starvation ketosis and hypoglycaemic ketoacidosis were all ruled out, and his toxin screen was negative for salicylates. Finding another possible cause for ketoacidosis became the focus of this case.

Osmotic demyelination of the brain (ODS) is a dreaded complication that typically occurs several days after aggressive therapy for chronic hyponatraemia, but is eminently avoidable. In this teaching exercise, Professor McCance, an imaginary consultant, is asked to explain how he would have treated a 28-year-old female who had hyperkalaemia, hypoglycaemia, hypotension and hyponatraemia (118 mM) to prevent the development of ODS. He begins with a review of the physiology, including his own landmark work on chronic hyponatraemia associated with a contracted extracellular fluid volume. Adding quantitative analysis, the cause of the excessive rise in plasma sodium concentration is revealed, and a better plan for therapy is proposed.

The aim of this masterclass is to develop a rational plan of therapy to deal with a severe degree of hyponatraemia (90 mmol/l) and hyperglycaemia (100 mmol/l) that occurred 100 min after the start of laproscopic surgery in a young woman. The lavage fluid used in this procedure was 10% dextrose.H(2)O in water (505 mmol glucose/l). To focus attention on specific issues, three questions are posed to the reader, as they were to a panel of 59 modern-day experts. Two imaginary consultants from the past were asked the same (and additional) questions. Their responses were restricted to knowledge available before the molecular era, to show the power of integrative physiology at the bedside. An analysis of intracellular events was helpful in answering the first question: 'Is an infusion of hypertonic saline required to treat her acute hyponatremia?' Similarly, a quantitative analysis of changes in the composition of the extracellular fluid compartment was helpful in answering the second question: 'Is an infusion of isotonic saline required to treat her hypotension?' A metabolic analysis was used to answer the third question, 'Should insulin be administered?'

Background Events in the gastrointestinal tract that might contribute to a high absorption of calcium were simulated in vitro to evaluate why only a small proportion of individuals who ingest alkaline calcium salts develop hypercalcaemia, hypokalaemia and metabolic alkalosis. Methods A patient who chewed and swallowed around 40 betel nuts daily developed hypercalcaemia, metabolic alkalosis, hypokalaemia with renal potassium wasting, and renal insufficiency. The quantities of calcium and alkali per betel nut preparation were measured. Factors that might increase intestinal absorption of calcium were evaluated. Results Hypercalcaemia in the index case was accompanied by a high daily calcium excretion (248 mg, 6.2 mmol). Circulating levels of 1,25-dihydroxyvitamin D(3) and parathyroid hormone were low. Hypokalaemia with a high transtubular K(+) concentration gradient, metabolic alkalosis, a low excretion of phosphate and a very low glomerular filtration rate were prominent features. Conclusions Possible explanations for the pathophysiology of metabolic alkalosis and hypokalaemia are provided. We speculate that a relatively greater availability of ionized calcium than inorganic phosphate in the lumen of the intestinal tract could have enhanced dietary calcium absorption.

Preoperative localization of parathyroid lesions is potentially beneficial in renal patients with hyperparathyroidism. The aim of this study was to determine the localizing value of hybrid single-photon emission computed tomography combined with low-dose x-ray computed tomography (SPECT/LDCT) compared with SPECT alone and whether the LDCT improved reader confidence.A retrospective study examined parathyroid scintigraphy results of patients previously referred with a diagnosis of renal hyperparathyroidism. All patients underwent planar scintigraphy using technetium-99m (Tc)-pertechnetate, which was immediately followed with Tc-sestamibi and SPECT/LDCT ∼60 min after sestamibi injection and a delayed static image to assess differential washout. Planar subtraction images were generated. Two nuclear physicians, assisted by a radiologist, reported on planar+SPECT images followed by planar+SPECT/LDCT images.Thirty-seven patients (males: 21; females: 16) were included (mean age 39 years, range: 23.9-55.5). Mean creatinine level was 878 μmol/l (109-1839), mean corrected calcium level was 2.42 mmol/l (1.77-3.64), and median parathyroid hormone level was 156.2 pmol/l (2.4 to201). Twenty-three patients had positive planar and SPECT results (46 lesions), six had positive planar results only, and eight had negative scintigraphy results. In the patients with positive planar and SPECT results, 35 lesions were classified as eutopic and 11 as ectopic. After the addition of LDCT, localization of five eutopic lesions (on SPECT) was amended to ectopic locations (on SPECT/LDCT), principally by identifying posteriorly situated glands. The addition of LDCT led to increased confidence in localization in all cases.Compared with SPECT alone, SPECT/LDCT is beneficial in preoperative localization of lesions in renal hyperparathyroidism.