South African experts believe it is crucial to get the balance right between scaling up kidney dialysis capacity and investing in transplantation, and called for screening to be increased, especially for HIV positive people.
People with HIV have an increased risk of developing several opportunistic infections and co-morbidities, including chronic kidney disease (CKD) – that happens over a period of time – but delayed diagnosis limits the ability to treat sufferers, writes Elri Voigt in Spotlight.
CKD is damage that happens over at least three months, affecting the kidneys’ filtration of waste products and elimination of fluid, said Dr Nina Diana, consultant nephrologist based at Charlotte Maxeke Johannesburg Academic Hospital and lecturer at Wits University.
Sometimes CKD results from when the kidney stops working properly due to a physical injury, certain medications, an infection or other medical conditions, said Dr Nicola Wearne, an associate professor and head of the Nephrology and Hypertension clinical unit at Groote Schuur Hospital.
The disease is classified in stages, with stage one being the mildest and stage five the most severe. Determining whether someone has CKD and its stage is done by measuring the glomerular filtration rate (GFR).
Someone with normal kidney function, said Wearne, has a GFR greater than 90. When the GFR drops to below 90, it can indicate stage one CKD. Between 90 and 60 is seen as stage two, 60-30 indicates stage three, and 15-30 is stage four. When the GFR drops to below 15, it’s classed as stage five disease.
There are several risk factors for developing CKD, including high blood pressure, diabetes, TB, or other opportunistic infections.
Large decline in HIV-associated nephropathy
HIV is also a risk factor, with the risk of HIV-associated nephropathy. Wearne said this was when the virus entered the body and started replicating everywhere, including in the kidneys. The virus gets into the small filtering units (the glomeruli) in the kidneys and causes collapse.
The condition was previously essentially a death sentence and progressed to end-stage rapidly, but that was before antiretroviral therapy became widely available.
“In the beginning (of the HIV epidemic), loads of people had HIV-associated nephropathy because we didn’t have ARVs and the mortality was high. You can go to end stage kidney disease, less than 15 GFR, within three months,” she added.
Over the past 16 years she’s noticed a big, stabilising change in CKD affecting HIV+ patients.
She heads up the HIV renal clinic within the Renal Unit at Groote Schuur Hospital. The clinic opened in 2008 and since then Wearne has seen less HIV-associated nephropathy – those developing the condition usually stabilise on HIV treatment.
Transplant breakthrough
South Africa made medical history when the first kidney from a donor with HIV was transplanted into another patient with HIV at Groote Schuur in 2008, the programme being led by Professor Elmi Muller in response to a “huge healthcare crisis with HIV and renal failure”.
Previously, said Muller, now dean of the Faculty of Medicine and Health Sciences at Stellenbosch University, people with HIV with end-stage kidney disease did not qualify for dialysis and there was nothing doctors could offer them.
They were not considered as good kidney transplant candidates; and because dialysis was a scarce resource in the public health sector, it was “ring-fenced” for people who were considered good candidates.
Muller sought to increase access to kidney transplants for HIV patients through a programme in which the kidneys of brain-dead donors with HIV were donated to other HIV+ people who had end-stage kidney disease.
About 60 of these transplants were performed at Groote Schuur. Overall, the transplant recipients had good outcomes, which helped change views on such transplants around the world.
Now, said Muller, there are no restrictions on the organs that can be transplanted into people with HIV, who are considered candidates if they’ve been on ARVs for at least three months.
The role of tenofovir
Another HIV-related complication is the use of the drug tenofovir. Though safe for most people, it can, in rare cases, cause kidney damage. Tenofovir forms part of the three-drug combination comprising the standard HIV treatment in South Africa.
Because of this risk, the Southern African HIV Clinicians Society recommends HIV patients are screened for kidney disease when starting ARV therapy, and then again at three months, six months, and then six to 12 monthly after that. Monitoring is done through a blood test that determines creatinine levels
For patients at high risk for CKD or who show signs of kidney damage, the risk can be managed by choosing first line antiretrovirals that are safe or by changing the existing ARVs, or simply adjusting dosage.
Lack of data
Wearne said there were not much data on the prevalence of CKD in HIV patients, but a systematic review and meta-analysis in 2018 found that the overall prevalence of chronic kidney disease in HIV+ people globally was 6.4%, with the highest rates of around 8% in sub-Saharan Africa.
The lack of data affects how CKD is defined in studies, as not all studies classify chronic kidney disease the same way, making it difficult to compare the research.
South Africa does, however, have data from the renal registry that was last published in 2021, said Wearne, and which shows that in 2019 there were 10 000 patients on dialysis – just under 1 000 of them with HIV.
The 2020 report showed 8 700 people had kidney replacement therapy – either dialysis or a kidney transplant – but the lower numbers were probably due to disruptions from the pandemic.
In a BMJ 2018 systematic review assessing the CKD burden throughout Africa, one meta-analysis showed the prevalence in sub-Saharan Africa was 13.2%.
‘Prevention, prevention, prevention’
Because people do not generally develop symptoms until the disease is at its end stage, screening is vital in preventing or detecting it early.
“Prevention, prevention, prevention – that’s where we make the biggest impact,” Wearne said, and this would be a blood test to check GFR levels, and urine tests for the presence of protein and blood, using a dipstick.
Regularly monitoring blood pressure and ensuring any pre-existing conditions are under control is also necessary, and both Wearne and Diana said there should be more screening efforts at a population level.
How CKD is treated
In the public health sector, Wearne saud, stages one and two can be managed at a primary healthcare level, while from stage three onwards, a patient must be seen by a nephrologist.
Treating stages one and two involves making sure that no additional damage is done to the kidneys – making sure patients with other medical conditions like high BP, diabetes and HIV, have those conditions under control and are not taking any medications that can damage their kidneys.
At stages three and four, a nephrologist will step in, and by stage five, the patient will require dialysis and/or a kidney transplant.
Diana said because CKD can have so many different causes, the exact treatment will depend on the underlying cause of the damage.
“If it’s a drug, you would stop or change the drug. If it were an infection, you treat the infection. So, it (treatment) would depend on the underlying cause. The aim of treatment is often not to recover to normal, but to keep at baseline.”
Dialysis versus transplant
The outlook for patients with end-stage CKD, whether HIV+ or not, is variable but the prognosis of the long-term survival of someone who receives a transplant is better than on dialysis.
It is therefore crucial, Muller said, to get the balance right between investing in scaling up dialysis capacity and investing in transplantation.
“I personally think we are getting the balance wrong. More money, funding and effort must go into transplantation as a treatment modality for any renal failure, and less for dialysis,” she said.
“Dialysis should be seen as a bridge for transplantation, and that’s not happening for various reasons. We are not doing enough to create opportunities for people to be either living or deceased donors, and so the dialysis industry is just growing and growing.”
See more from MedicalBrief archives:
Chronic kidney diseases surge in SA
Provincial and public/private sector disparities in kidney treatment – SA study
Older age and baseline kidney function the key risk factors for CKD in people with HIV