Conservative kidney management and kidney supportive care: core components of integrated care for people with kidney failure.

Integrated kidney care requires synergistic linkage between preventative care for people at risk for chronic kidney disease and health services providing care for people with kidney disease, ensuring holistic and coordinated care as people transition between acute and chronic kidney disease and the 3 modalities of kidney failure management: conservative kidney management, transplantation, and dialysis. People with kidney failure have many supportive care needs throughout their illness, regardless of treatment modality. Kidney supportive care is therefore a vital part of this integrated framework, but is nonexistent, poorly developed, and/or poorly integrated with kidney care in many settings, especially in low- and middle-income countries. To address this, the International Society of Nephrology has (i) coordinated the development of consensus definitions of conservative kidney management and kidney supportive care to promote international understanding and awareness of these active treatments; and (ii) identified key considerations for the development and expansion of conservative kidney management and kidney supportive care programs, especially in low resource settings, where access to kidney replacement therapy is restricted or not available. This article presents the definitions for conservative kidney management and kidney supportive care; describes their core components with some illustrative examples to highlight key points; and describes some of the additional considerations for delivering conservative kidney management and kidney supportive care in low resource settings.

Kidney adolescent and young adult clinic: A transition model in Africa.

Adolescents and Young Adults (AYAs) with chronic kidney disease (CKD) have challenges unique to this developmental period, with increased rates of high-risk behavior and non-adherence to therapy which may impact the progression of kidney disease and their requirement for kidney replacement therapy (KRT). Successful transition of AYA patients are particularly important in low- and middle-income countries (LMICs) where KRT is limited, rationed or not available. Kidney AYA transition clinics have the potential to improve clinical outcomes but there is a paucity of data on the clinical translational impact of these clinics in Africa. This review is a reflection of the 20-year growth and development of the first South African kidney AYA transition clinic. We describe a model of care for patients with CKD, irrespective of etiology, aged 10-25 years, transitioning from pediatric to adult nephrology services. This unique service was established in 2002 and re-designed in 2015. This multidisciplinary integrated transition model has improved patient outcomes, created peer support groups and formed a training platform for future pediatric and adult nephrologists. In addition, an Adolescent Centre of Excellence has been created to compliment the kidney AYA transition model of care. The development of this transition pathway challenges and solutions are explored in this article. This is the first kidney AYA transition clinic in Africa. The scope of this service has expanded over the last two decades. With limited resources in LMICs, such as KRT, the structured transition of AYAs with kidney disease is not only possible but essential. It is imperative to preserve residual kidney function, maximize the kidney allograft lifespan and improve adherence, to enable young individuals an opportunity to lead productive lives.

Task shifting roles, interventions and outcomes for kidney and cardiovascular health service delivery among African populations: a scoping review.

BACKGROUND: Human resources for health (HRH) shortages are a major limitation to equitable access to healthcare. African countries have the most severe shortage of HRH in the world despite rising communicable and non-communicable disease (NCD) burden. Task shifting provides an opportunity to fill the gaps in HRH shortage in Africa. The aim of this scoping review is to evaluate task shifting roles, interventions and outcomes for addressing kidney and cardiovascular (CV) health problems in African populations. METHODS: We conducted this scoping review to answer the question: "what are the roles, interventions and outcomes of task shifting strategies for CV and kidney health in Africa?" Eligible studies were selected after searching MEDLINE (Ovid), Embase (Ovid), CINAHL, ISI Web of Science, and Africa journal online (AJOL). We analyzed the data descriptively. RESULTS: Thirty-three studies, conducted in 10 African countries (South Africa, Nigeria, Ghana, Kenya, Cameroon, Democratic Republic of Congo, Ethiopia, Malawi, Rwanda, and Uganda) were eligible for inclusion. There were few randomized controlled trials (n = 6; 18.2%), and tasks were mostly shifted for hypertension (n = 27; 81.8%) than for diabetes (n = 16; 48.5%). More tasks were shifted to nurses (n = 19; 57.6%) than pharmacists (n = 6; 18.2%) or community health workers (n = 5; 15.2%). Across all studies, the most common role played by HRH in task shifting was for treatment and adherence (n = 28; 84.9%) followed by screening and detection (n = 24; 72.7%), education and counselling (n = 24; 72.7%), and triage (n = 13; 39.4%). Improved blood pressure levels were reported in 78.6%, 66.7%, and 80.0% for hypertension-related task shifting roles to nurses, pharmacists, and CHWs, respectively. Improved glycaemic indices were reported as 66.7%, 50.0%, and 66.7% for diabetes-related task shifting roles to nurses, pharmacists, and CHWs, respectively. CONCLUSION: Despite the numerus HRH challenges that are present in Africa for CV and kidney health, this study suggests that task shifting initiatives can improve process of care measures (access and efficiency) as well as identification, awareness and treatment of CV and kidney disease in the region. The impact of task shifting on long-term outcomes of kidney and CV diseases and the sustainability of NCD programs based on task shifting remains to be determined.

COVID-19 and the kidney: A South African state healthcare experience.

The first documented case of SARS-CoV-2 infection was confirmed in South Africa (SA) in March 2020. The Western Cape (WC) province was the initial epicenter. The pandemic peaked in July 2020 when 76,851 cases were documented and 2,323 deaths reported. COVID-19 can have multisystem involvement. Acute kidney injury (AKI) is well-documented and associated with increased mortality. We report our experience as the pandemic evolved in the WC province, focusing on those patients with a SARS-CoV-2 positive test presenting with AKI. We also reviewed our chronic dialysis cohort and renal transplant recipients who tested positive to assess incidence and outcomes. All patients presenting to nephrology services at the four main public hospitals were included. Information regarding demographics, co-morbidities, medical care, laboratory data, and outcomes were recorded. There were 86 patients referred with AKI, 48 required dialysis, and 47 died. There were 52 patients admitted to the intensive care unit with AKI (37 received dialysis, 1 of whom survived). In those presenting with AKI, diabetes, obesity, hypertension, and HIV were the most common comorbidities. Of the 295 patients receiving chronic dialysis within our services, 31 tested positive for SARS-CoV-2, and 6 died. Of the 45 kidney transplant recipients who tested positive, 9 died. Only 3 required dialysis. In conclusion, we report a high rate of AKI and poor prognosis in those requiring kidney replacement therapy, a better prognosis than anticipated was found in our chronic dialysis cohort, and high numbers of admissions were required for renal transplant recipients.

Building optimal and sustainable kidney care in low resource settings: The role of healthcare systems.

Healthcare systems in low-income and lower-middle income countries (LLMICs) face significant challenges in the provision of health services, for example, kidney care to the population. Although this is linked to several high-level factors such as poor infrastructure, socio-demographic and political factors, healthcare funding has often been cited as the major reason for the wide gap in availability, accessibility and quality of care between LLMICs and rich countries. With the steady rising incidence and prevalence of kidney diseases globally, as well as cost of care, LLMICs are likely to suffer more consequences of these increases than rich countries and may be unable to meet targets of universal health coverage (UHC) for kidney diseases. As health systems in LLMICs continue to adapt in finding ways to provide access to affordable kidney care, various empirical and evidence-based strategies can be applied to assist them. This review uses a framework for healthcare strengthening developed by the World Health Organization (WHO) to assess various challenges that health systems in LLMICs confront in providing optimal kidney care to their population. We also suggest ways to overcome these barriers and strengthen health systems to improve kidney care in LLMICs.

Diagnostic performance of glomerular PLA2R and THSD7A antibodies in biopsy confirmed primary membranous nephropathy in South Africans.

BACKGROUND: Serum and tissue-based tests using phospholipase A2 receptor 1 (PLA2R) and thrombospondin type-1 domain containing 7A (THSD7A) are established immune biomarkers for the diagnosis of primary membranous nephropathy (PMN). This study assessed the diagnostic performance of these biomarkers in the diagnosis of PMN in South Africans. METHODS: This was a cross-sectional analysis from a single centre in Cape Town, South Africa. Relevant biodata was collected from all patients. Histology, including slides for PLA2R and THSD7A were processed and assessed by typical microscopic and immunohistochemical features. Biopsy tissues of patients with membranous lupus nephritis (LN-V) and diabetic nephropathy (DN) were used as controls. The diagnostic accuracy for diagnosis of PMN using positive PLA2R and THSD7A were evaluated. RESULTS: Of the 88 patients included, 41 had PMN with a mean age of 44.5 ± 17.5 years and 61.0% were female. Histologically, PLA2R and THSD7A were only positive in the PMN group (51.2% and 4.9%, respectively) but negative in both control groups. The sensitivity of PLA2R and THSD7A for identifying PMN was 51.2% and 4.9%, respectively. The sensitivity of both tests together was 53.7% while the specificity and positive predictive values (PPV) for any of the tests (alone or in combination) was 100%. There was no difference in the sensitivity and specificity when using PLA2R alone compared to combining the two tests (p=0.32). CONCLUSION: Glomerular staining of PLA2R and THSD7A could have potential diagnostic values in South Africans. This has implications on how immunotherapies can be initiated and used in these settings.

Granulomatous interstitial nephritis on renal biopsy in human immunodeficiency virus positive patients: Prevalence and causes in Cape Town, South Africa.

South Africa continues to be burdened by human immunodeficiency virus (HIV) and tuberculosis (TB). In Cape Town, the epidemic of HIV-TB co-infection is as high as 70%. Granulomatous interstitial nephritis (GIN) has increased in frequency on renal biopsy. This study aimed to determine GIN prevalence and causes in HIV-positive patients as well as renal outcomes, patient survival and associated factors. This observational cohort study reviewed HIV-positive renal biopsies for GIN from 2005 to 2012. Causes of GIN (medications, TB, fungal and other), and baseline characteristics were analysed. A comparison of baseline data, renal function and survival was made between GIN and non-GIN cohorts. There were 45/316 biopsies demonstrating GIN. TB was the likely cause of GIN in 27 (60%) and 9 (20%) were due to a drug. Low estimated glomerular filtration rate was a statistically significant factor associated with mortality in both GIN (P = 0.045) and non-GIN cohorts (P < 0.000). In the GIN group, there were 12 (26.7%) deaths. Mortality for all patients was greatest in the first 6 months (P = 0.057). TB co-infection in both cohorts was associated with a higher mortality. The multivariate logistic regression demonstrated that a higher urine protein/creatinine ratio (uPCR) and lower estimated glomerular filtration rate were statistically associated with death. GIN is common in HIV-positive renal biopsies in Cape Town. TB-GIN was the commonest cause and associated with a high early mortality. GIN should be considered in HIV-positive patients with acute kidney injury, its presence conveys a survival benefit. There is a need for improved diagnostic accuracy and treatment strategies of TB-GIN.

The effects of add-on corticosteroids on renal outcomes in patients with biopsy proven HIV associated nephropathy: a single centre study from South Africa.

BACKGROUND: The aim of this study was to assess, the efficacy and safety of add-on corticosteroids to antiretroviral therapy [ART] in patients with biopsy proven HIV associated nephropathy. METHODS: All included patients had histological evidence of either collapsing or non-collapsing focal segmental glomerulosclerosis (FSGS) or podocyte and/or parietal cell hypertrophy or hyperplasia. All patients had evidence of tubulointerstitial inflammation with microcysts. Patients were randomized to ART with the addition of 1 mg/kg of corticosteroids [ART+C] or remained in the group [ART Alone] and followed for 2 years. A repeat biopsy was performed at 6 months. RESULTS: Twenty-one patients were randomized to [ART+C] and 17 to [ART Alone]. The baseline estimated glomerular filtration rate (eGFR) was significantly lower in the [ART+C] vs. [ART Alone] group [35mls/min/1.73m2 vs. 47 mls/min/1.73m2, p = 0.015]. The [ART+C] cohort had a statistically significant improvement in median (eGFR) from baseline to last follow up compared with [ART Alone] i.e. [Δ = 25mls/min (IQR: 15;51) vs 9 mls/min (IQR: 0-24), p = 0.008]. There were no statistically significant differences between the groups when proteinuria and histology were analyzed. There were 8 deaths during the trial period, 7 from [ART+C] (Log rank p = 0.071). CONCLUSIONS: In the [ART+C] cohort there was a significant improvement in eGFR over 2-years with increased mortality. Routine corticosteroid use cannot currently be recommended. Further investigation to define which subgroup of this cohort would safely benefit from the positive effects is required. TRIAL REGISTRATION: ISRCTN study ID ( 56112439 ] was retrospectively registered on the 5 September 2018.

Kidney disease in the setting of HIV infection: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference.

HIV-positive individuals are at increased risk for kidney disease, including HIV-associated nephropathy, noncollapsing focal segmental glomerulosclerosis, immune-complex kidney disease, and comorbid kidney disease, as well as kidney injury resulting from prolonged exposure to antiretroviral therapy or from opportunistic infections. Clinical guidelines for kidney disease prevention and treatment in HIV-positive individuals are largely extrapolated from studies in the general population, and do not fully incorporate existing knowledge of the unique HIV-related pathways and genetic factors that contribute to the risk of kidney disease in this population. We convened an international panel of experts in nephrology, renal pathology, and infectious diseases to define the pathology of kidney disease in the setting of HIV infection; describe the role of genetics in the natural history, diagnosis, and treatment of kidney disease in HIV-positive individuals; characterize the renal risk-benefit of antiretroviral therapy for HIV treatment and prevention; and define best practices for the prevention and management of kidney disease in HIV-positive individuals.

Adolescent nephrology: An emerging frontier for kidney care in sub-Saharan Africa.

Adolescents make up a quarter of the world's population and are important users of health services. In South Africa little is known about the extent of renal disease or outcomes in this group. Adolescents are a vulnerable age group, due to their neurocognitive development, engagement in high-risk social activities, prevalence of mental illness and increasing rates of HIV infection. In Africa access to renal replacement therapy is rationed, therefore the focus of renal disease must be one of prevention rather than dealing with the management of end stage renal disease. Treating adolescents is a challenging field, as compliance is essential as a preventative strategy. This review will outline how a cost effective adolescent service was established in a resource limited setting. The adolescent friendly clinic aims to ease transition of adolescents, improve engagement within the health service and ultimately aims to improve compliance. In order to treat adolescents, it is important to deliver age-appropriate treatment that can be implemented in any chronic disease setting to give the adolescent the greatest chance of success.

HIV-associated renal disease - an overview.

The cause of the human immunodeficiency virus (HIV) epidemic in South Africa (SA) was worsened by the denial by key political players that HIV causes acquired immunodeficiency syndrome (AIDS). South Africa continues to have the highest rate of HIV world-wide, which has had a huge impact on the development of both chronic kidney disease and acute kidney injury. Fortunately, there is now an effective antiretroviral therapy (ART) roll-out program. SA is also dealing with a collision of epidemics of HIV, tuberculosis, and non-communicable disease, particularly hypertension and diabetes. This has been evidenced by recent data seen in the reinstated SA renal registry. There is also an unacceptably high rate of tuberculosis in regions of SA, this has led to high rates of granulomatous interstitial nephritis (GIN) and case reports of TB-GIN immune reconstitution inflammatory syndrome (IRIS). HIV-associated nephropathy (HIVAN) remains common in SA and responds well to ART. The definitive diagnosis requires a renal biopsy, which is often not possible in many regions of sub-Saharan Africa. Unfortunately, there is still a high rate of HIVAN in SA due to late presentation and lack of effective screening for renal disease in HIV-positive patients. Transplantation for HIV-positive donors to positive recipients offers a unique and encouraging way forward for these patients.

Pain management and the use of opioids in adults with kidney failure receiving conservative kidney management.

Conservative kidney management (CKM) is an active treatment for kidney failure (KF) for people who will either not benefit from kidney replacement therapy (KRT), do not wish to pursue KRT, or do not have access to KRT. CKM aims to improve patients' quality-of-life through meticulous attention to symptom management. KF is associated with a high symptom burden globally that is experienced across age, sex, and race with chronic pain being one of the most severe and common symptoms. The delivery of CKM therefore requires the integration of effective pain management strategies. This review will provide a detailed insight into CKM globally and will offer an approach to pain management for people with KF who are receiving CKM. Specifically, this review will provide an overview of the clinical characteristics of people receiving CKM across both high and low resource settings and the epidemiology of pain in this population. While it will provide some high-level considerations for the non-pharmacologic management of pain, it will focus predominantly on pharmacologic approaches. This will include considerations of non-opioid analgesics and strategies for the use of opioids in people receiving CKM. Furthermore, we will explore global disparities in kidney care, CKM, and pain management resources, including access to opioids and will discuss some of the additional challenges faced in low resource settings.

Advance Care Planning in South Africa.

South Africa (SA), an upper middle-income country, faces significant challenges, including severe inequality, poverty, high unemployment rates, unequal access to basic services, and a long history of human rights violations. It is a diverse nation with eleven official languages. The country also bears a heavy burden of communicable and non-communicable diseases, with many patients seeking healthcare services too late. Despite the pressing need, palliative care is still an emerging field in South Africa, with limited funding allocated for its integration. Advance Care Planning (ACP) is a recommended practice in SA for patients with serious illnesses while they are still in good health and can function independently. Non-Governmental Organizations (NGOs) in SA have played a significant role in integrating ACP planning within their settings through advocacy and training. ACP has been included in both formal academic training and training programs offered by NGOs. Additionally, research has been initiated to evaluate the acceptability and validity of the Serious Illness Conversation Guide within the cultural diversity and complexities of the SA context. Acceptance of ACP amongst SA healthcare workers and the public faces many challenges. Many South Africans still have a low level of trust and acceptance towards the public healthcare system. In many South African cultures discussing death and dying is considered culturally taboo. Traditional cultures interpret and apply the concept of individual autonomy differently. The philosophy of "Ubuntu", which translates to "I am because we are", is widely endorsed in the country, prioritising community needs over individual needs. It is, therefore, essential for healthcare professionals engaging in ACP conversations not to make assumptions about a person's preferences for communication, decision-making and care, based on external attributes. Instead, they should respectfully explore these preferences and be adaptable in their approach to ACP. The implementation of ACP in SA is still in its early stages, requiring further research to inform culturally sensitive approaches to advance care planning.

HIV and Associated TB: A Lethal Association for Kidney Health?

Human immunodeficiency virus (HIV) and tuberculosis (TB) are the leading infectious causes of death globally. The combined brunt of these diseases is experienced mainly in low-income and lower-middle-income countries. HIV/TB have devastating effects on the kidneys, leading to accelerated decline of kidney function as well as mortality. Managing the triad of TB/HIV and kidney disease is challenging. We discuss the epidemiology of HIV/TB coinfection and the kidney and the key mechanisms of kidney disease including genetic susceptibility. The clinical presentation and pathology, as well as the challenges of diagnosing CKD in these patients, also are discussed. The strategies to prevent and manage HIV/TB-related kidney disease such as proper assessment, avoiding nephrotoxic regimens, drug dose adjustments, kidney function monitoring, avoidance of drug-drug interactions, and other interventions are explored. We also briefly discuss the complexities around HIV/TB patients on dialysis and kidney transplantation. HIV/TB coinfection presents an increased risk for kidney-related morbidity and mortality; patients with this triad need to be given special consideration for future research and management.

Primary Sjögren's syndrome with renal tubular acidosis and central pontine myelinolysis: An unusual triad.

Primary Sjögren's syndrome (pSS) is a complex, multisystem autoimmune disorder. It is characterized by lymphocytic infiltration of the exocrine glands. In the setting of pSS, the presence of systemic disease is an important prognostic determinant, but involvement of the kidney is uncommon. The triad of pSS, distal renal tubular acidosis (dRTA), and central pontine myelinolysis (CPM) is rare and potentially fatal. A 42-year-old woman presented with dRTA, profound hypokalemia, and CPM characterized by progressive global quadriparesis, ophthalmoplegia, and encephalopathy. Sjögren's syndrome was diagnosed based on sicca symptoms, clinical features, and strongly positive anti-SSA/Ro and anti-SSB/La autoantibodies. The patient responded well to electrolyte replacement, acid-base correction, corticosteroids, and subsequent cyclophosphamide therapy. Early recognition and appropriate treatment resulted in good kidney and neurological outcomes in this case. This report highlights the need to consider the diagnosis of pSS in unexplained dRTA and CPM, as it has a favorable prognosis if recognized and managed timeously.

Management of Type 2 Diabetes Mellitus and Kidney Failure in People with HIV-Infection in Africa: Current Status and a Call to Action.

There is an increasing global burden of diabetes mellitus (DM) and chronic kidney disease (CKD), coupled with a high burden of people with HIV (PWH). Due to an increased lifespan on ART, PWH are now at risk of developing non-communicable diseases, including DM. Africa has the greatest burden of HIV infection and will experience the greatest increase in prevalence of DM over the next two decades. In addition, there is a rising number of people with CKD and progression to kidney failure. Therefore, there is an urgent need for the early identification and management of all 3 diseases to prevent disease progression and complications. This is particularly important in Africa for people with CKD where there is restricted or no access to dialysis and/or transplantation. This review focuses on the epidemiology and pathophysiology of the interaction between HIV infection and DM and the impact that these diseases have on the development and progression of CKD. Finally, it also aims to review the data on the management, which stems from the growing burden of all three diseases.

The Evolving Spectrum of Kidney Histology in HIV-Positive Patients in South Africa.

Introduction: Sub-Saharan Africa remains challenged by the highest burden of human immunodeficiency virus (HIV), an epidemic of tuberculosis (TB), and increasing number of people with HIV (PWH) on antiretroviral therapy (ART), all of which may result in kidney injury. Methods: This observational cohort study describes the spectrum of kidney disease in PWH in South Africa, between 2005 and 2020. Kidney biopsies were analyzed in 4 time periods as follows: early ART rollout (2005-2009), tenofovir disoproxil (TDF) introduction (2010-2012), TDF-based fixed dose combination (2013-2015), and ART at HIV diagnosis (2016-2020). Logistic regression was used to identify factors associated with HIV-associated nephropathy or focal segmental glomerulosclerosis (HIVAN/FSGS) and tubulointerstitial disease (TID). Results: We included 671 participants (median age 36, interquartile range, 21-44 years; 49% female; median CD4 cell count 162 [interquartile range, 63-345] cells/mm3). Over time, ART (31%-65%, P < 0.001), rate of HIV suppression (20%-43%, P < 0.001), nonelective biopsies (53%-72%, P < 0.001), and creatinine at biopsy (242-449 µmol/l, P < 0.001) increased. A decrease in HIVAN (45%-29% P < 0.001) was accompanied by an increase in TID (13%-33%, P < 0.001). Granulomatous interstitial nephritis accounted for 48% of TID, mostly because of TB. Exposure to TDF was strongly associated with TID (adjusted odds ratio 2.99, 95% confidence interval 1.89-4.73 P < 0.001). Conclusion: As ART programs intensified and increasingly used TDF, the spectrum of kidney histology in PWH evolved from a predominance of HIVAN in the early ART era to TID in recent times. The increase in TID is likely due to multiple exposures that include TB, sepsis, and TDF as well as other insults.

The evolution of our knowledge of HIV-associated kidney disease in Africa.

Human immunodeficiency virus (HIV) infection started in Africa circa 1930. South Africa has the highest prevalence rate in the world. Although reports of HIV-associated nephropathy (HIVAN) appeared in the early 1980s, the earliest report from sub-Saharan Africa (SSA) came in 1994. Geographical, socioeconomic, political, and ethical factors have worked in concert to shape the character of HIV disease as it is seen in SSA. Political leaders within SSA have, through their actions, significantly contributed to the incidence of HIV infection. Black females, who often face cultural suppression and disadvantage, have a higher prevalence of HIV than males. Too few studies and outcomes data have bedeviled the statistics in SSA in relation to HIVAN prevalence and its management. Much of what is written is approximation and anecdotal. The largest reliable biopsy series comes from the University of Cape Town, where a workable classification of HIVAN has been developed to enable standardization of terminology. Histologic and clinical prognostic indicators with outcomes have been evaluated using this classification. Patients with HIV who present with acute kidney injury appear to have mainly acute tubular necrosis due to sepsis, dehydration, and nephrotoxic drugs. Since the rollout of combination antiretroviral therapy, the extent of HIV infection and kidney disease continues to be modified and possibly retarded.

The spectrum of renal histologies seen in HIV with outcomes, prognostic indicators and clinical correlations.

BACKGROUND: Two hundred and twenty-one HIV-positive renal biopsies were analysed from Groote Schuur Hospital to determine outcomes and prognostic indicators based on histology and clinical features. METHODS: The histology findings were compared with patient demographics, clinical and renal parameters, mortality, CD4 count and date of commencing combined anti-retroviral therapy (cART). Follow-up was between 1 and 3.5 years. RESULTS: We found a spectrum of renal histologies in HIV-positive patients of which HIV-associated nephropathy (HIVAN) was the most common histology. cART reduced the mortality in those with any feature of HIVAN by 57% [adjusted hazard ratio (AHR) 0.43, 95% confidence interval (CI) 0.22-0.85]. Of those patients with HIVAN who died, 79% died of renal failure as registered on their death certificate. Proteinuria and microcysts were shown to be poor prognostic indicators (AHR 1.36: 1.09-1.70 and 2.04: 1.24-3.37). In patients with HIVAN alone followed for up to 2 years on cART, estimated glomerular filtration rate remained stable and there was a trend towards decreased proteinuria. cART improved survival in patients with isolated immune complex disease. CONCLUSIONS: As mortality is improved in patients with any feature of HIVAN or isolated immune complex disease, cART should be initiated once any of these histological features are established. We believe the spectrum of disease that constitutes HIVAN needs to be more specifically defined. The ultimate outcome may be determined by the histological subtype.