Cystatin C should be routinely available for estimating kidney function.

PURPOSE OF REVIEW: In this report, we summarize why the availability of cystatin C is important across a variety of clinical scenarios, the recent literature on when, why and in whom cystatin C testing should be considered, and how nephrologists can take practical steps to incorporate cystatin C testing into their practice. RECENT FINDINGS: Large intra-individual discrepancies between estimated glomerular filtration rate by creatinine (eGFRcr) and estimated glomerular filtration rate by creatinine eGFRcys (known as eGFRdiff) are observed in at least 1 in 4 people. These differences are seen more commonly among more vulnerable individuals: older adults, females, non-White individuals and those living with multiple medical conditions. A large eGFRdiff, where eGFRcys is lower than eGFRcr, is associated with a plethora of adverse outcomes, including medication-associated adverse events, acute kidney injury, cardiovascular disease, kidney failure and all-cause mortality. Among studies that have measured GFR, eGFRcr-cys usually provides the most accurate estimation of kidney function compared to mGFR, including among participants with large discrepancies between eGFRcr and eGFRcys. SUMMARY: Cystatin C improves sensitivity and specificity of chronic kidney disease diagnosis, improves detection of harmful acute and chronic changes in kidney function, improves precision of treatment eligibility and safety, and may reduce healthcare inequalities. Better education, curiosity, and motivation among nephrologists could substantially improve the availability and utilization of cystatin C.

Genome-wide association analysis of cystatin-C kidney function in continental Africa.

BACKGROUND: Chronic kidney disease is becoming more prevalent in Africa, and its genetic determinants are poorly understood. Creatinine-based estimated glomerular filtration rate (eGFR) is commonly used to estimate kidney function, modelling the excretion of the endogenous biomarker (creatinine). However, eGFR based on creatinine has been shown to inadequately detect individuals with low kidney function in Sub-Saharan Africa, with eGFR based on cystatin-C (eGFRcys) exhibiting significantly superior performance. Therefore, we opted to conduct a GWAS for eGFRcys. METHODS: Using the Uganda Genomic Resource, we performed a genome-wide association study (GWAS) of eGFRcys in 5877 Ugandans and evaluated replication in independent studies. Subsequently, putative causal variants were screened through Bayesian fine-mapping. Functional annotation of the GWAS loci was performed using Functional Mapping and Annotation (FUMA). FINDINGS: Three independent lead single nucleotide polymorphisms (SNPs) (P-value <5 × 10-8 (based on likelihood ratio test (LRT))) were identified; rs59288815 (ANK3), rs4277141 (OR51B5) and rs911119 (CST3). From fine-mapping, rs59288815 and rs911119 each had a posterior probability of causality of >99%. The rs911119 SNP maps to the cystatin C gene and has been previously associated with eGFRcys among Europeans. With gene-set enrichment analyses of the olfactory receptor family 51 overlapping genes, we identified an association with the G-alpha-S signalling events. INTERPRETATION: Our study found two previously unreported associated SNPs for eGFRcys in continental Africans (rs59288815 and rs4277141) and validated a previously well-established SNP (rs911119) for eGFRcys. The identified gene-set enrichment for the G-protein signalling pathways relates to the capacity of the kidney to readily adapt to an ever-changing environment. Additional GWASs are required to represent the diverse regions in Africa. FUNDING: Wellcome (220740/Z/20/Z).

Identifying the prevalence and correlates of multimorbidity in middle-aged men and women: a cross-sectional population-based study in four African countries.

OBJECTIVES: To determine the prevalence of multimorbidity, to identify which chronic conditions cluster together and to identify factors associated with a greater risk for multimorbidity in sub-Saharan Africa (SSA). DESIGN: Cross-sectional, multicentre, population-based study. SETTING: Six urban and rural communities in four sub-Saharan African countries. PARTICIPANTS: Men (n=4808) and women (n=5892) between the ages of 40 and 60 years from the AWI-Gen study. MEASURES: Sociodemographic and anthropometric data, and multimorbidity as defined by the presence of two or more of the following conditions: HIV infection, cardiovascular disease, chronic kidney disease, asthma, diabetes, dyslipidaemia, hypertension. RESULTS: Multimorbidity prevalence was higher in women compared with men (47.2% vs 35%), and higher in South African men and women compared with their East and West African counterparts. The most common disease combination at all sites was dyslipidaemia and hypertension, with this combination being more prevalent in South African women than any single disease (25% vs 21.6%). Age and body mass index were associated with a higher risk of multimorbidity in men and women; however, lifestyle correlates such as smoking and physical activity were different between the sexes. CONCLUSIONS: The high prevalence of multimorbidity in middle-aged adults in SSA is of concern, with women currently at higher risk. This prevalence is expected to increase in men, as well as in the East and West African region with the ongoing epidemiological transition. Identifying common disease clusters and correlates of multimorbidity is critical to providing effective interventions.

Kidney dysfunction: prevalence and associated risk factors in a community-based study from the North West Province of South Africa.

BACKGROUND: Globally, the World Health Organization ranks chronic kidney disease (CKD) as one of the top 10 causes of mortality. In South Africa, where noncommunicable diseases have become leading causes of mortality, the true population prevalence of CKD is unknown and associated risk factors remain understudied. This study aimed to describe the prevalence of kidney dysfunction and associated risk factors in a community from the North West province of South Africa. METHODS: This cross-sectional study included 1999 participants older than 30 years. Kidney dysfunction was defined as (i) estimated glomerular filtration rate (eGFR) < 90 ml/min/1.73m2, or (ii) urine albuminuria-to-creatinine ratio (uACR) ≥ 3.0 mg/mmol, or a combination (i and ii). Risk factors included age, sex, urban/rural locality, body mass index (BMI), blood pressure (BP), lipid profile, haemoglobin A1c (HbA1C), C-reactive protein (CRP), gamma-glutamyl transferase (GGT), tobacco use, and HIV status. RESULTS: Mean age of participants was 48 (42;56) years, and 655/1999 (33%) had eGFR < 90 ml/min/1.73m2 and/or uACR ≥ 3.0 mg/mmol. Compared to those with normal kidney function, participants with eGFR < 90 ml/min/1.73m2 and/or uACR ≥ 3.0 mg/mmol were older, female, had higher measures of adiposity, systolic, diastolic, and mean arterial blood pressure, serum lipids and C-reactive protein (CRP) (all p ≤ 0.024). In multiple regression analyses eGFR was associated with systolic BP (ß = 0.11) and HIV infection (ß = -0.09), and albuminuria was associated with elevated CRP (ß = 0.12) and HIV infection (ß = 0.11) (all p < 0.026). In both groups (individuals with and without kidney dysfunction respectively), eGFR was associated with age (ß = -0.29, ß = -0.49), male sex (ß = 0.35, ß = 0.28), BMI (ß = -0.12, ß = -0.09), low-density/high-density lipoprotein cholesterol ratio (ß = -0.17, ß = -0.09) and CRP (ß = 0.10, ß = 0.09) (all p < 0.005); and uACR was associated with female sex (ß = 0.10, ß = -0.14), urban locality (ß = -0.11, ß = -0.08), BMI (ß = -0.11, ß-0.11), and systolic BP (ß = 0.27, ß = 0.14) (all p < 0.017). CONCLUSION: In this study from the North West province, South Africa, eGFR < 90 ml/min/1.73m2 and/or uACR ≥ 3.0 mg/mmol was prevalent and associated with modifiable risk factors. The findings may inform screening strategies for kidney disease prevention, focusing on women, obesity, blood pressure control, dyslipidaemia, identifying and treating inflammation, and HIV diagnosis and treatment.

Emphasising Organisational Routine: A Qualitative Study of Patient and Health Professional Experiences of Inpatient Oncology Care.

BACKGROUND: Although the experience of hospitalisation for cancer management has been widely researched, such research from the African sub-continent is limited. OBJECTIVE: This study explored experiences of patient care in a tertiary, inpatient oncology setting in urban South Africa, from the point of view of patients and health professionals. METHODS: In-depth interviews and focus groups were conducted with participants. Participants included oncology inpatients, oncologists, nurses and nursing management (N = 46) at an oncology unit in Johannesburg, South Africa. Data were analysed by a multidisciplinary research group using reflexive thematic analysis principles. RESULTS: Our results suggest that barriers to establishing effective organisational routines included communication breakdowns between patients and healthcare providers, a lack of predictability in interactions with doctors, deficient access to information and diminished confidence in nurses. CONCLUSIONS: Oncology inpatients may not feel in control of their circumstances, in part due to lacking routine in the hospital setting. Ironically, nurses, who are often at the frontline of patient management, appear to be underutilised or disabled by the healthcare system as conveyors of information. IMPLICATIONS FOR PRACTICE: Robust organisational routines for oncology inpatients may be a good mechanism for allaying uncertainty and conferring a sense of control. Nursing staff, as the individuals with the most direct patient contact, could be instrumental in nurturing organisational routines towards improving patient perceptions of care.

The association between lifestyle-related risk factors and survival in patients with colorectal cancer in an urban South African cohort.

Background: Lifestyle-related factors have been linked with risk for colorectal cancer. Data describing the relationship between lifestyle factors of South African patients who present with colorectal cancer and their survival is sparse. Objectives: The objectives were to describe the profile of patients with colorectal cancer; to determine the association between lifestyle-related factors and survival, and to compare results of patients in the private and public sectors. Methods: A retrospective review and secondary analysis of information of patients with colorectal cancer were conducted. The independent samples t-test and Mann Whitney U test were administered to determine differences in the clinical presentation. Pearson's Chi-Squared and Eta (η) tests were used to determine the association between survival and lifestyle-related factors. Results: Data of 441 patients were included. When compared to the public sector cohort, patients in the private sector cohort were older (p=0.0110), had earlier stages of cancer at the time of diagnosis (p<0.001), had a higher percentage of current alcohol consumption (p<0.001) and had higher survival rates (p<0.001). Waist circumference was shown to have a large-strength effect on survival (η2=0.266). Conclusion: Emphasis should be placed on anthropometric screening and education to effect long-term behaviour change. Physiotherapists are well placed to provide screening and non-pharmacological interventions for patients with colorectal cancer.

Measurement of kidney function in Malawi, South Africa, and Uganda: a multicentre cohort study.

BACKGROUND: The burden of kidney disease in many African countries is unknown. Equations used to estimate kidney function from serum creatinine have limited regional validation. We sought to determine the most accurate way to measure kidney function and thus estimate the prevalence of impaired kidney function in African populations. METHODS: We measured serum creatinine, cystatin C, and glomerular filtration rate (GFR) using the slope-intercept method for iohexol plasma clearance (mGFR) in population cohorts from Malawi, Uganda, and South Africa. We compared performance of creatinine and cystatin C-based estimating equations to mGFR, modelled and validated a new creatinine-based equation, and developed a multiple imputation model trained on the mGFR sample using age, sex, and creatinine as the variables to predict the population prevalence of impaired kidney function in west, east, and southern Africa. FINDINGS: Of 3025 people who underwent measured GFR testing (Malawi n=1020, South Africa n=986, and Uganda n=1019), we analysed data for 2578 participants who had complete data and adequate quality measurements. Among 2578 included participants, creatinine-based equations overestimated kidney function compared with mGFR, worsened by use of ethnicity coefficients. The greatest bias occurred at low kidney function, such that the proportion with GFR of less than 60 mL/min per 1·73 m2 either directly measured or estimated by cystatin C was more than double that estimated from creatinine. A new creatinine-based equation did not outperform existing equations, and no equation, including the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2021 race-neutral equation, estimated GFR within plus or minus 30% of mGFR for 75% or more of the participants. Using a model to impute kidney function based on mGFR, the estimated prevalence of impaired kidney function was more than two-times higher than creatinine-based estimates in populations across six countries in Africa. INTERPRETATION: Estimating GFR using serum creatinine substantially underestimates the individual and population-level burden of impaired kidney function in Africa with implications for understanding disease progression and complications, clinical care, and service provision. Scalable and affordable ways to accurately identify impaired kidney function in Africa are urgently needed. FUNDING: The GSK Africa Non-Communicable Disease Open Lab. TRANSLATIONS: For the Luganda, Chichewa and Xitsonga translations of the abstract see Supplementary Materials section.

Osteoporosis, Rather Than Sarcopenia, Is the Predominant Musculoskeletal Disease in a Rural South African Community Where Human Immunodeficiency Virus Prevalence Is High: A Cross-Sectional Study.

The rollout of antiretroviral therapy globally has increased life expectancy across Southern Africa, where 20.6 million people now live with human immunodeficiency virus (HIV). We aimed to determine the prevalence of age-related osteoporosis and sarcopenia, and investigate the association between HIV, bone mineral density (BMD), muscle strength and lean mass, and gait speed. A cross-sectional community-based study of individuals aged 20-80 years in rural South Africa collected demographic and clinical data, including HIV status, grip strength, gait speed, body composition, and BMD. Sarcopenia was defined by the European Working Group on Sarcopenia in Older People 2 (EWGSOP2) guidelines, and osteoporosis as BMD T-score ≤ -2.5 (if age ≥50 years). The mean ± standard deviation (SD) age of 805 black South African participants was 44.6 ± 14.8 years, 547 (68.2%) were female; 34 (13.2%) were men, and 129 (23.6%) women had HIV, with 88% overall taking anti-retroviral therapy. A femoral neck T-score ≤ -2.5, seen in four of 95 (4.2%) men and 39 of 201 (19.4%) women age ≥50 years, was more common in women with than without HIV (13/35 [37.1%] versus 26/166 [15.7%]; p = 0.003). Although no participant had confirmed sarcopenia, probable sarcopenia affected more men than women (30/258 [11.6%] versus 24/547 [4.4%]; p = .001]. Although appendicular lean mass (ALM)/height2 index was lower in both men and women with HIV, there were no differences in grip strength, gait speed, or probable sarcopenia by HIV status. Older age, female sex, lower ALM/height2 index, slower gait speed, and HIV infection were all independently associated with lower femoral neck BMD. In conclusion, osteoporosis rather than sarcopenia is the common musculoskeletal disease of aging in rural South Africa; older women with HIV may experience greater bone losses than women without HIV. Findings raise concerns over future fracture risk in Southern Africa, where HIV clinics should consider routine bone health assessment, particularly in aging women. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Corrigendum: Predicting Colorectal Cancer Recurrence and Patient Survival Using Supervised Machine Learning Approach: A South African Population-Based Study.

[This corrects the article DOI: 10.3389/fpubh.2021.694306.].

Use of Machine Learning and Statistical Algorithms to Predict Hospital Length of Stay Following Colorectal Cancer Resection: A South African Pilot Study.

The aim of this pilot study was to develop logistic regression (LR) and support vector machine (SVM) models that differentiate low from high risk for prolonged hospital length of stay (LOS) in a South African cohort of 383 colorectal cancer patients who underwent surgical resection with curative intent. Additionally, the impact of 10-fold cross-validation (CV), Monte Carlo CV, and bootstrap internal validation methods on the performance of the two models was evaluated. The median LOS was 9 days, and prolonged LOS was defined as greater than 9 days post-operation. Preoperative factors associated with prolonged LOS were a prior history of hypertension and an Eastern Cooperative Oncology Group score between 2 and 4. Postoperative factors related to prolonged LOS were the need for a stoma as part of the surgical procedure and the development of post-surgical complications. The risk of prolonged LOS was higher in male patients and in any patient with lower preoperative hemoglobin. The highest area under the receiving operating characteristics (AU-ROC) was achieved using LR of 0.823 (CI = 0.798-0.849) and SVM of 0.821 (CI = 0.776-0.825), with each model using the Monte Carlo CV method for internal validation. However, bootstrapping resulted in models with slightly lower variability. We found no significant difference between the models across the three internal validation methods. The LR and SVM algorithms used in this study required incorporating important features for optimal hospital LOS predictions. The factors identified in this study, especially postoperative complications, can be employed as a simple and quick test clinicians may flag a patient at risk of prolonged LOS.

Preoperative physical activity and functional performance levels are predictors of acute postoperative outcomes in a private South African colorectal cancer cohort.

BACKGROUND: For patients with colorectal cancer, surgical resection of the primary tumour remains the best treatment option. Surgery for colorectal cancer is being performed on patients who would previously not have been considered as suitable candidates. It remains to be seen which factors influence hospital length of stay (LOS) and the development of acute postoperative complications in South African patients. OBJECTIVES: The objectives of our study were to determine the modifiable factors that influence patients' development of postoperative complications and hospital LOS and, to identify the types of postoperative complications that develop. METHOD: A retrospective review and secondary analysis of information in an existing database of patients with colorectal cancer were conducted. Regression analysis statistics were used to determine the predictors of postoperative outcomes. The level of significance at which testing was performed was set at 5% (p ≤ 0.05). RESULTS: Data of 125 patients were included. Surgical site infections and postoperative paralytic ileus were the most frequently reported postoperative complications. Preoperative vigorous-intensity physical activity (p = 0.048, ß = -0.000) and functional performance status (p = 0.05, ß = 0.926) significantly predicted hospital LOS and the incidence of postoperative complications, respectively. CONCLUSION: Preoperative physical activity and functional performance levels are predictors of acute postoperative outcomes in a private South African cohort of patients with colorectal cancer. Future research which includes other modifiable factors is required to make informed suggestions for changes in clinical practice. CLINICAL IMPLICATIONS: Patients requiring surgery for colorectal cancer should be screened for signs of physical deconditioning and referred for physiotherapy intervention before elective surgery to optimise their recovery.

Predicting Colorectal Cancer Recurrence and Patient Survival Using Supervised Machine Learning Approach: A South African Population-Based Study.

Background: South Africa (SA) has the highest incidence of colorectal cancer (CRC) in Sub-Saharan Africa (SSA). However, there is limited research on CRC recurrence and survival in SA. CRC recurrence and overall survival are highly variable across studies. Accurate prediction of patients at risk can enhance clinical expectations and decisions within the South African CRC patients population. We explored the feasibility of integrating statistical and machine learning (ML) algorithms to achieve higher predictive performance and interpretability in findings. Methods: We selected and compared six algorithms:- logistic regression (LR), naïve Bayes (NB), C5.0, random forest (RF), support vector machine (SVM) and artificial neural network (ANN). Commonly selected features based on OneR and information gain, within 10-fold cross-validation, were used for model development. The validity and stability of the predictive models were further assessed using simulated datasets. Results: The six algorithms achieved high discriminative accuracies (AUC-ROC). ANN achieved the highest AUC-ROC for recurrence (87.0%) and survival (82.0%), and other models showed comparable performance with ANN. We observed no statistical difference in the performance of the models. Features including radiological stage and patient's age, histology, and race are risk factors of CRC recurrence and patient survival, respectively. Conclusions: Based on other studies and what is known in the field, we have affirmed important predictive factors for recurrence and survival using rigorous procedures. Outcomes of this study can be generalised to CRC patient population elsewhere in SA and other SSA countries with similar patient profiles.

Evaluating chronic kidney disease in rural South Africa: comparing estimated glomerular filtration rate using point-of-care creatinine to iohexol measured GFR.

OBJECTIVES: The prevalence of chronic kidney disease is rising rapidly in low- and middle-income countries. Serum creatinine and estimation of glomerular filtration rate (GFR) are critical diagnostic tools, yet access to centralised laboratory services remains limited in primary care resource-limited settings. The aim of this study was to evaluate point-of-care (POC) technologies for serum creatinine measurement and to compare their performance to a gold standard measurement using iohexol measured GFR (mGFR). METHODS: POC creatinine was measured using iSTAT® and StatSensor® devices in capillary and venous whole blood, and laboratory creatinine was measured using the compensated kinetic Jaffe method in 670 participants from a rural area in South Africa. GFR estimating equations Chronic Kidney Disease Epidemiology Collaboration and Modification of Diet in Renal Disease (CKD-EPI and MDRD) for POC and laboratory creatinine were compared to iohexol mGFR. RESULTS: Calculated GFR for laboratory and POC creatinine measurements overestimated GFR (positive bias of 1.9-34.1 mL/min/1.73 m2). However, all POC devices had less positive bias than the laboratory Jaffe method (1.9-14.7 vs. 34.1 for MDRD, and 8.4-19.9 vs. 28.6 for CKD-EPI). Accuracy within 30% of mGFR ranged from 0.56 to 0.72 for POC devices and from 0.36 to 0.43 for the laboratory Jaffe method. POC devices showed wider imprecision with coefficients of variation ranging from 4.6 to 10.2% compared to 3.5% for the laboratory Jaffe method. CONCLUSIONS: POC estimated GFR (eGFR) showed improved performance over laboratory Jaffe eGFR, however POC devices suffered from imprecision and large bias. The laboratory Jaffe method performed poorly, highlighting the need for laboratories to move to enzymatic methods to measure creatinine.

Liver Transplant for Nonresectable Colorectal Cancer Liver Metastases in South Africa: A Single-Center Case Series.

OBJECTIVES: Publication in 2013 of the first Secondary Cancer cohort study returned attention to liver transplant for nonresectable colorectal cancer, demonstrating excellent outcomes for a procedure that was historically contraindicated. The Wits Donald Gordon Medical Centre in Johannesburg, South Africa, hosts the largest liver transplant program in sub-Saharan Africa. The persistent shortage of deceased donor organs in our setting has compelled us to innovate solutions unique to our context, which allows us to perform as many transplants as possible and maximize our resource utilization. Therefore, we initiated a research study to transplant organs in patients with nonresectable colorectal carcinoma with expanded criteria using marginal deceased donor organs that would otherwise have been discarded. MATERIALS AND METHODS: Institutional Review Board approval was obtained for this study. We used criteria from the 2013 Secondary Cancer cohort study to determine eligibility of patients with nonresectable colorectal carcinoma for liver transplant. Unlike the study from 2013, we utilized expanded criteria and marginal liver allografts for transplant. RESULTS: Five patients have undergone liver transplant for nonresectable colorectal carcinoma. At a median follow-up of 36 months (range, 10-52 months), 4 of the 5 (80%) patients are alive. The patient who died had progressive disease on chemotherapy pretransplant and was the only patient who tested positive for the Kirsten rat sarcoma viral oncogene homolog mutant. Recurrence occurred in all patients at a median time of 6 months after transplant (range, 3-13 months). CONCLUSIONS: To our knowledge, this is the only published case series of patients undergoing liver transplant for nonresectable colorectal carcinoma in Africa and is internationally unique in its use of expanded criteria and marginal grafts for this type of transplant. Despite the use of such grafts in our recipients, thus far, these outcomes align with those of the 2013 Secondary Cancer cohort studies from Norway.

Needs must: living donor liver transplantation from an HIV-positive mother to her HIV-negative child in Johannesburg, South Africa.

The world's first living donor liver transplant from an HIV-positive mother to her HIV-negative child, performed by our team in Johannesburg, South Africa (SA) in 2017, was necessitated by disease profile and health system challenges. In our country, we have a major shortage of donor organs, which compels us to consider innovative solutions to save lives. Simultaneously, the transition of the HIV pandemic, from a death sentence to a chronic illness with excellent survival on treatment required us to rethink our policies regarding HIV infection and living donor liver transplantation . Although HIV infection in the donor is internationally considered an absolute contraindication for transplant to an HIV-negative recipient, there have been a very small number of unintentional transplants from HIV-positive deceased donors to HIV-negative recipients. These transplant recipients do well on antiretroviral medication and their graft survival is not compromised. We have had a number of HIV-positive parents in our setting express a desire to be living liver donors for their critically ill children. Declining these parents as living donors has become increasingly unjustifiable given the very small deceased donor pool in SA; and because many of these parents are virally suppressed and would otherwise fulfil our eligibility criteria as living donors. This paper discusses the evolution of HIV and transplantation in SA, highlights some of the primary ethical considerations for us when embarking on this case and considers the new ethical issues that have arisen since we undertook this transplant.

Design and methodology of a study on colorectal cancer in Johannesburg, South Africa.

BACKGROUND AND AIM: Cancer is one of the foremost causes of morbidity and mortality worldwide. Globally, colorectal cancer (CRC) is the third most diagnosed and fourth most important cause of cancer death. A total of 70% of all CRC-related deaths occur in low- and middle-income countries. In Sub-Saharan Africa (SSA), estimating the burden of CRC is difficult. Only 27 of 43 SSA countries have formalized cancer registration systems; data quality is variable and national coverage rare. METHODS: This is a multidisciplinary, longitudinal cohort study started in January 2016. Patients >18 years with histologically confirmed primary adenocarcinoma of the colon and rectum, diagnosed within the previous 12 months, are eligible. Participants were assessed and were followed up for 3 years. Baseline information, including demographics, socioeconomic status, family history, medical and surgical non-cancer-related history, dietary history, colonoscopic findings, staging at presentation, treatment, and disease recurrence, is collected, as well as blood tests and histology results. Outcomes include disease recurrence (local and metastatic) and survival. RESULTS AND CONCLUSION: This study aims to describe the clinical presentation, management, and outcomes of adults with CRC in a multiethnic, urban South African population. It will be the first prospective study to describe clinical presentation, demographics, risk factors, treatment, and outcomes according to population group, from both private and state health-care facilities in Johannesburg, South Africa. The results of this study will be relevant not only to South Africa but also to other SSA countries undergoing similar rates of rapid urbanization and epidemiological transition.

Living donor liver transplant from an HIV-positive mother to her HIV-negative child: opening up new therapeutic options.

OBJECTIVE: Transplant a liver from an HIV-positive mother to her HIV-negative child to save the child's life. DESIGN: A unique case of living donor liver transplantation from an HIV-positive mother to her HIV-negative child in South Africa. Two aspects of this case are ground-breaking. First, it involves living donation by someone who is HIV-positive and second it involves controlled transplant of an organ from an HIV-positive donor into an HIV-negative recipient, with the potential to prevent infection in the recipient. METHODS: Standard surgical procedure for living donor liver transplantation at our centre was followed. HIV-prophylaxis was administered preoperatively. Extensive, ultrasensitive HIV testing, over and above standard diagnostic assays, was undertaken to investigate recipient serostatus and is ongoing. RESULTS: Both mother and child are well, over 1 year posttransplantation. HIV seroconversion in our recipient was detected with serological testing at day 43 posttransplant. However, a decline in HIV antibody titres approaching undetectable levels is now being observed. No plasma, or cell-associated HIV-1 DNA has been detected in the recipient at any time-point since transplant. CONCLUSION: This case potentially opens up a new living liver donor pool which might have clinical relevance in countries where there is a high burden of HIV and a limited number of deceased donor organs or limited access to transplantation. However, our recipient's HIV status is equivocal at present and additional investigation regarding seroconversion events in this unique profile is ongoing.

The clinical and histological response of HIV-associated kidney disease to antiretroviral therapy in South Africans.

BACKGROUND: Little is known about the progression of kidney disease in HIV-infected patients in developing countries in the era of antiretroviral therapy (ART). METHODS: HIV-infected patients were screened for kidney disease. Kidney biopsies were performed before and after initiation of ART to assess the clinical and histological response to treatment. Data were collected from all participants in accordance with the study protocol. The mean follow-up was 2.4 patient years on ART. RESULTS: There was a rapid immunological and renal response to ART. The renal response was reflected by a significant rise in the estimated glomerular filtration rate (eGFR) and rapid regression of proteinuria. The histological patterns were highly variable, ranging from non-specific lesions such as mesangial hyperplasia and interstitial nephritis to HIV-immune complex disease (HIV-ICD) with or without features of HIV-associated nephropathy (HIVAN). In the follow-up biopsies, the histological response to treatment was variable with a combination of no change, progression or regression of lesions. CONCLUSIONS: This study demonstrated a spectrum of renal histological lesions in HIV-associated kidney disease. Initiation of ART produced a rapid and sustained clinical renal response in all participants, irrespective of the histology. Follow-up biopsies showed an inconsistent histological response of lesions to treatment. In lesions that regressed, there appeared to be a discrete lag in histological response when compared with the rapid clinical response.

Urinary screening abnormalities in antiretroviral-naive HIV-infected outpatients and implications for management--a single-center study in South Africa.

Few urinary screening studies have been performed to determine the incidence of urinary abnormalities in antiretroviral therapy-naive, HIV-infected outpatients. From published data, the incidence appears to be high, particularly when compared with populations outside sub-Saharan Africa. In South Africa, urinary screening in antiretroviral therapy clinics is not routinely practiced. The aim of this descriptive study was to screen antiretroviral therapy-naive, HIV-infected outpatients attending the HIV clinic for urinary abnormalities, namely leukocyturia, microscopic hematuria, and microalbuminuria/proteinuria. This study showed that 84% of the screened population had AIDS (CD4 count < 200 cells/ mm3), and the incidence of abnormalities on urinary dipstick testing was high: 30% had leukocyturia, 33% had microscopic hematuria, and 44% had microalbuminuria/proteinuria. In patients with leukocyturia, an infective organism was cultured in only 29.1% of cases, predominantly Escherichia coli (70%) with sterile leukocyturia comprising the remainder. There may be an association with tuberculosis (TB) or sexually transmitted infections (STI) in the sterile leucocyturia group, but this remains to be confirmed. In those with a culture positive result the most common organism was E. coli (70%), which exhibited 90% resistance to cotrimoxazole, demonstrating that cotrimoxazole prophylaxis is not effective to prevent urinary tract infection in this group. On the basis of these findings, it has been proposed that urinary screening be considered standard of care in HIV clinics in South Africa. An algorithm has been proposed for use in antiretroviral therapy clinics in South Africa to guide clinicians regarding the cost-effective management of urinary dipstick abnormalities.