Proteinuria in HIV seropositive individuals

ABSTRACT This study was designed to screen antiretroviral therapy (ART)-naïve human immunodeficiency virus (HIV) infected patients for proteinuria, using urine dipsticks, at the HIV outpatient clinic at Johannesburg Hospital in an attempt to detect and treat early renal disease. In those with persistent proteinuria, a marker of kidney disease, renal biopsy was performed, ART with and without angiotensin-converting enzyme inhibitors (ACE-I) was initiated and patients were followed up for immunological and renal responses. After a minimum period of 12 months, a repeat biopsy was performed, where possible, to determine whether the histological lesions had responded to treatment. During urinary screening, proteinuria, leucocyturia and microscopic haematuria were common. Sterile leucocyturia may be associated with co-morbid sexually transmitted infection or tuberculosis. In the group that underwent renal biopsy with treatment, the renal and immunological response, before and after ART was highly statistically significant. Renal and immunological responses to ART were assessed by reduction in proteinuria with increased GFR, increased CD4 count with reduction in HIV viral load, respectively. On biopsy, HIV-associated immune complex disease was more common than HIVAN, a finding that contradicts international and some local data. Resolution of proteinuria was relatively rapid in comparison to the histological response to treatment, an effect not previously shown. This is the first study of its kind, to the author’s knowledge, that prospectively evaluates the effect of ART with/ ACE-I in ART-naïve HIV infected patients with both clinicopathological and histological criteria. It has shown unequivocally, that renal disease, particularly if detected and treated early in HIV infection, is responsive to treatment. These findings suggest screening for early detection and treatment of HIV-associated renal disease should be mandatory in HIV clinics in South Africa

Estimating glomerular filtration rate in African populations

Without a strong bedrock of kidney research in African populations we are vulnerable to extrapolating research findings performed in non-African ancestry populations, mostly in high-income countries, with short- and long-term implications for individual and public health. This review tracks the evolution of kidney function testing, highlighting measured and estimated glomerular filtration rate (GFR) testing. While measured glomerular  filtration rate (mGFR) is the most accurate method, there are potential sources of error for each reference compound and regional preferences and availability dictate choice. Establishing measured GFR testing as a research or clinical service is challenging and remains a barrier to mGFR testing availability in Africa. Estimated GFR is more practical but less accurate, and important for clinicians to understand the trade-offs, especially in an African context. Non-GFR determinants of serum creatinine lead to random error in measurement that is not a true reflection of kidney function: hereditable factors influence biomarker metabolism and excretion; biological variation results in intra-and inter-individual error; non-renal physiological factors include sex, age, environmental temperature (especially hot climes), ingestion of animal protein, levels of exercise, acute illness, chronic liver disease, enhanced gastrointestinal excretion with declining GFR, and concomitant medication that interferes with tubular handling of creatinine. There are likely to be additional factors (still unknown) in African populations; and analytic error that includes Jaffe vs enzymatic, use of standard reference materials and methods for calibration, and adherence to internal and external quality assurance programmes. Laboratories also require age and sex-based population-appropriate reference intervals for creatinine in children, adolescents, adults, and older adults which do not exist in many African countries. While the spotlight on racialised coefficients for eGFR has been largely confined to the USA, the impact of using GFR estimates that are US-based (and their racialised coefficients), throughout Africa remains overlooked. In Africa, recommended equations overestimate GFR, fewer individuals with CKD are diagnosed, and population prevalence is underestimated. Downstream, there are fewer opportunities to investigate causes or initiate treatment to prevent progression – much more relevant since the advent of sodium-glucose co-transporter 2 (SGLT-2) and glucagon-like peptide (GLP)-1 agonists for managing early CKD

On the Trail of Paediatric Liver Transplant in South Africa: Social Challenges to Equitable Distribution in Organ Transplantation

This paper tracks the journey of a family from a remote rural area in South Africa – a 2 year old child born with a life threatening liver disease, and his unemployed mother – who, by a series of contingencies, are sent on the trail of organ transplantation to land at the door of a private organ transplant centre. This case brings into focus the dilemmas that social factors present for equitable distribution of organ transplantation. The paper focuses on two interconnected issues: the link between socio-economic status and access to treatment, and existing practices of rationing. The uncritical conjunction of socio-economic status and organ transplantation disadvantages vulnerable sectors of the population. Yet, social circumstances impact the management of specialized medical treatment, which in itself imposes burdens on those with limited resources.  Similarly, although this paper poses questions about indiscriminate practices, it accepts the inevitable rationing of health care

An overview of tenofovir and renal disease for the HIV-treating clinician

Tenofovir disoproxil fumarate (TDF, commonly termed ‘tenofovir’) is the antiretroviral most commonly implicated in antiretroviral-induced nephrotoxicity. As patients on successful antiretroviral therapy (ART) age, their risk for developing renal disease may increase in part because of ART itself, but more importantly, because of HIV-associated and non-HIVassociated comorbidity. Therefore, clinicians need an approach to managing renal disease in people on TDF. TDF as a cause of acute kidney injury (AKI) or chronic kidney disease (CKD) is uncommon, and clinicians should actively exclude other causes (Box 1). In TDF-associated AKI, TDF should be interrupted in all cases, and replaced, or ART interrupted altogether. Tenofovir disoproxil fumarate toxicity can present as AKI or CKD, and as a full or partial Fanconi’s syndrome. TDF has a small but definite negative impact on kidney function (up to a 10% decrease in glomerular filtration rate [GFR]). This occurs because of altered tubular function in those exposed to TDF for treatment and as pre-exposure prophylaxis. Renal function should be assessed using creatinine-based estimated GFR at the time of initiation of TDF, if ART is changed, at 1–3 months, and then ideally every 6–12 months if stable. Specific tests of tubular function are not routinely recommended; in the case of clinical concern, a spot protein or albumin: creatinine ratio is preferable, but in resource-limited settings, urine dipstick can be used. More frequent monitoring may be required in those with established CKD (estimated glomerular filtration rate [eGFR] < 50 mL/min/1.73 m2) or risk factors for kidney disease. The most common risk factors are comorbid hypertension, diabetes, HIV associated kidney disease, hepatitis B or C co-infection, and TDF in combination with a ritonavir-boosted protease inhibitor. Management of these comorbid conditions must be prioritised in this group. If baseline screening eGFR is < 50 mL/min/1.73 m2, abacavir (the preferred option), and dose-adjusted TDF (useful if concomitant hepatitis B), zidovudine or stavudine (d4T) remain alternatives to full-dose TDF. If there is a rapid decline in kidney function (eGFR drops by more than 25% and decreases to < 50 mL/min/1.73 m2 from of baseline function), or there is new onset or worsening of proteinuria or albuminuria, clinicians should review ART and other potentially nephrotoxic medications and comorbidity and conduct further testing if indicated. If kidney function does not improve after addressing reversible causes of renal failure, then referral to a nephrologist is appropriate. In the case of severe CKD, timeous referral for planning for renal replacement therapy is recommended. Tenofovir alafenamide, a prodrug of tenofovir, appears to have less renal toxicity and is likely to replace TDF in future

Perceptions of nurses’ roles in end-of-life care and organ donation – imposition or obligation?

South Africa has a rich organ-transplant history, and studies suggest that the SA public supports organ donation. In spite of this, persistently low donor numbers are a significant challenge. This may be due to a lack of contextually appropriate awareness and education, or to barriers to referring patients and families in clinical settings. It may also be due to ad hoc regulations that are not uniformly endorsed or implemented. In this article we present the findings of a study in Johannesburg that explored the attitudes and roles of nurses in end-of-life care and organ donation. A total of 273 nurses participated. Most were female and <50 years old. The majority expressed positive attitudes towards both end-of-life care and organ donation, but there was ambiguity as to whether referring patients and families for these services was within nursing scope of practice. The vast majority of participants noted that they would refer patients themselves if there was a mandatory, nationally endorsed referral policy. These findings have implications for clinical practice and policy, and suggest that the formulation and implementation of robust national guidelines should be a priority. Because nurses would follow such guidelines, this might lead to an increase in donor rates and circumvent some uncertainty regarding referral

HIV-positive kidney transplants for HIV-positive individuals: Attitudes and concerns of South African patients and health care workers

In South Africa, an estimated 30% of the cadaveric donor pool is HIV-infected; in consequence, these organs are discarded. An undersupply of donor organs combined with limited resources, tends to exclude HIV-positive patients from renal replacement programmes. We evaluated the acceptance of using HIV-positive donor kidneys for transplantation into HIV-infected recipients, and found that the vast majority (90% of health care workers and 80% of patients, N=20 and 80, respectively) found this approach acceptable for expanding the organ donor pool, which indicates broad patient and health care worker support for using HIV-infected donor kidneys.Participants: 80 patients were recruited from four different groups: those with HIV on stable antiretroviral (ARV) therapy but with no kidney disease; stable antiretroviral therapy, with kidney disease, including on dialysis; and HIV-uninfected patients, both on dialysis and those with functional kidney transplants. Discussions with 20 health care workers were also conducted. Results: The vast majority (90% of health care workers and 80% of patients, n=20 and 80 respectively) found transplant of HIV-infected organs to HIV-positive recipients an acceptable method for expanding the organ donor pool. This study found no significant difference between the groups of patients regarding whether they approved of using HIV-positive donors; HIV positive patients were willing to accept kidneys from HIV-infected family members, while HIV-negative patients were very unlikely to accept HIV-infected organs. Health care workers expressed concern about initiatives to expand the donor pool and educate patients concerning transplant eligibility. Conclusion: These findings indicate broad patient and health care worker support for the use of HIV-infected donor kidneys for some types of renal patients

Symptomatic hyperlactataemia in adults on anti-retroviral therapy: A single centre experience

Objectives: There is little data on symptomatic hyperlactataemia due to antiretroviral therapy (ART) in resource-limited settings. This retrospective record review assessed individuals who developed symptomatic hyperlactataemia on ART in an outpatient clinic in South Africa. Design: A retrospective record review was performed on patients attending the clinic from January 2004 to December 2005. Results: 35 patients developed symptomatic hyperlactataemia, all on stavudine-containing regimens. The incidence in this population was 20.5 cases per 1000 person-years of ART with an associated mortality of 21%. The major risk factor was being female (RR 3.27). Significant clinical symptoms preceding symptomatic hyperlactataemia include non-specific gastrointestinal symptoms, weight loss, and development of symptomatic neuropathy Conclusions: The incidence of symptomatic hyperlactataemia in our population was high. Simple clinical measures, such as neuropathy symptoms and monitoring of weight may alert the clinician to impending symptomatic hyperlacataemia. Early diagnosis allows for safe outpatient care, and for switching of ART regimens without interruption in many cases