The changing landscape of HIV-associated kidney disease.

The HIV epidemic has devastated millions of people globally, with approximately 40 million deaths since its start. The availability of antiretroviral therapy (ART) has transformed the prognosis of millions of individuals infected with HIV such that a diagnosis of HIV infection no longer automatically confers death. However, morbidity and mortality remain substantial among people living with HIV. HIV can directly infect the kidney to cause HIV-associated nephropathy (HIVAN) - a disease characterized by podocyte and tubular damage and associated with an increased risk of kidney failure. The reports of HIVAN occurring primarily in those of African ancestry led to the discovery of its association with APOL1 risk alleles. The advent of ART has led to a substantial decrease in the prevalence of HIVAN; however, reports have emerged of an increase in the prevalence of other kidney pathology, such as focal segmental glomerulosclerosis and pathological conditions associated with co-morbidities of ageing, such as hypertension and diabetes mellitus. Early initiation of ART also results in a longer cumulative exposure to medications, increasing the likelihood of nephrotoxicity. A substantial body of literature supports the use of kidney transplantation in people living with HIV, demonstrating significant survival benefits compared with that of people undergoing chronic dialysis, and similar long-term allograft and patient survival compared with that of HIV-negative kidney transplant recipients.

Clinicopathological correlation of kidney disease in HIV infection pre- and post-ART rollout.

The spectrum of HIV-associated kidney disease has expanded significantly with the introduction of antiretroviral therapy (ART). In the pre-ART era there was prominence of HIV-associated nephropathy (HIVAN). More recently, the spectrum of disease additionally reflects comorbid illness in the ageing HIV population and ART-related nephrotoxicity. We performed a clinicopathological correlation of kidney disease in HIV-positive individuals who underwent kidney biopsy between 1989 and 2014, utilizing the 2018 Kidney Disease Improving Global Outcomes pathologic classification. ART rollout began in 2004 in South Africa. Patients biopsied pre-ART rollout were compared to those biopsied post-ART rollout with respect to demographics, clinical parameters and histology. We assessed kidney survival in a cohort of these patients following biopsy. Six hundred and ninety biopsies were included, 99 (14.3%) were undertaken pre- and 591 (85.7%) post-ART rollout. Most patients were of Black African descent (97.5%). The post-ART rollout patients were older (p = 0.007), had higher eGFR at presentation (p = 0.016) and fewer presented with eGFR of less than 15ml/min/1.73m2 (p = 0.0008). There was a decrease in the prevalence of classic HIVAN (p = 0.00001); and an increase in FSGS (NOS) in the setting of HIV (p = 0.0022) and tubulointerstitial diseases (p = 0.009) post-ART rollout. Kidney function survival over 5 years was poorest in patients with classic HIVAN (p = 0.00005) and best in minimal change nephropathy (p = 0.0013). Kidney biopsy is crucial for the correct diagnosis and management of HIV-related kidney disease. ART rollout has shifted the spectrum of kidney disease away from classic HIVAN but has not eliminated it. Histological diagnosis prognosticates kidney survival.

Living kidney donation in a developing country.

BACKGROUND: Living kidney donation has been advocated as a means to ameliorate the chronic shortage of organs for transplantation. Significant rates of comorbidity and familial risk for kidney disease may limit this approach in the local context; there is currently limited data describing living donation in Africa. METHODS: We assessed reasons for non-donation and outcomes following donation in a cohort of 1208 ethnically diverse potential living donors evaluated over a 32-year period at a single transplant centre in South Africa. RESULTS: Medical contraindications were the commonest reason for donor exclusion. Black donors were more frequently excluded (52.1% vs. 39.3%; p<0.001), particularly for medical contraindications (44% vs. 35%; p<0.001); 298 donors proceeded to donor nephrectomy (24.7%). Although no donor required kidney replacement therapy, an estimated glomerular filtration rate below 60 ml/min/1.73 m2 was recorded in 27% of donors at a median follow-up of 3.7 years, new onset albuminuria >300 mg/day was observed in 4%, and 12.8% developed new-onset hypertension. Black ethnicity was not associated with an increased risk of adverse post-donation outcomes. CONCLUSION: This study highlights the difficulties of pursuing live donation in a population with significant medical comorbidity, but provides reassurance of the safety of the procedure in carefully selected donors in the developing world.

Age significantly influences the sensitivity of SARS-CoV-2 rapid antibody assays.

BACKGROUND: Point-of-care serological assays are a promising tool in COVID-19 diagnostics but do have limitations. Our study evaluated the sensitivity of five rapid antibody assays and explored factors influencing their sensitivity in detecting SARS-CoV-2-specific IgG and IgM antibodies. METHODS: Finger-prick blood samples from 102 participants, within 2-6 weeks of PCR-confirmed COVID-19 diagnosis, were tested for IgG and IgM using five rapid serological assays. The assay sensitivities were compared, and patient factors evaluated in order to investigate potential associations with assay sensitivity. RESULTS: Sensitivity ranged from 36% to 69% for IgG and 13% to 67% for IgM. Age was the only factor significantly influencing the likelihood of a detectable IgG or IgM response. Individuals aged 40 years and older had an increased likelihood of a detectable IgG or IgM antibody response by rapid antibody assay. CONCLUSION: Rapid serological assays demonstrate significant variability when used in a real-world clinical context. There may be limitations in their use for COVID-19 diagnosis among the young.

Update on current management of chronic kidney disease in patients with HIV infection.

The prevalence of HIV-associated chronic kidney disease (CKD) varies geographically and depends on the definition of CKD used, ranging from 4.7% to 38% globally. The incidence, however, has decreased with the use of effective combined antiretroviral therapy (cART). A wide variety of histological patterns are seen in HIV-associated kidney diseases that include glomerular and tubulointerstitial pathology. In resource-rich settings, there has been a plateau in the incidence of end-stage renal disease secondary to HIV-associated nephropathy (HIVAN). However, the prevalence of end-stage renal disease in HIV-positive individuals has risen, mainly due to increased longevity on cART. There is a disparity in the occurrence of HIVAN among HIV-positive individuals such that there is an 18- to 50-fold increased risk of developing kidney disease among HIV-positive individuals of African descent aged between 20 and 64 years and who have a poorer prognosis compared with their European descent counterparts, suggesting that genetic factors play a vital role. Other risk factors include male sex, low CD4 counts, and high viral load. Improvement in renal function has been observed after initiation of cART in patients with HIV-associated CKD. Treatment with an angiotensin-converting enzyme inhibitor/angiotensin receptor blocker is recommended, when clinically indicated in patients with confirmed or suspected HIVAN or clinically significant albuminuria. Other standard management approaches for patients with CKD are recommended. These include addressing other cardiovascular risk factors (appropriate use of statins and aspirin, weight loss, cessation of smoking), avoidance of nephrotoxins, and management of serum bicarbonate and uric acid, anemia, calcium, and phosphate abnormalities. Early diagnosis of kidney disease by screening of HIV-positive individuals for the presence of kidney disease is critical for the optimal management of these patients. Screening for the presence of kidney disease upon detection of HIV infection and annually thereafter in high-risk populations is recommended.