In
Europe and North America, since the widespread
use of antiretroviral therapy, chronic diseases have bypassed opportunistic
infections as the cause of death in HIV-positive people. In those settings,
kidney disease has emerged as an important cause of morbidity and mortality
among people living with HIV,1
though it still ranks relatively low in the order of individual causes of
death, partly because clinicians and facilities in that part of the world are
well-equipped to diagnose and support patients with kidney problems.2
In Africa, developing a kidney disorder that would be
manageable in industrialised countries often means death.
Even
a middle-income country such as South
Africa has trouble supporting the growing
population that is being diagnosed with severe kidney disease. For instance,
access to haemodialysis — artificial filtration of the blood that is necessary in some
patients with severe loss of kidney function — is extremely limited here and in
most of the continent. A recent BBC article
reported that four out of five people who need dialysis for end-stage renal
disease at the big public hospitals in Cape Town are turned down, and described
the difficult life and death decisions hospitals must make regarding who gets
dialysis. The article stressed that only patients who were good candidates for
having a kidney transplant — and there are very few kidneys available for
transplanting — could qualify for dialysis.
One
dialysis candidate, Karen MacPherson, who was interviewed in the article,
“desperately wanted to live. ‘My daughter needs me,’ the 43-year-old widow with
three children said.” Unfortunately, she was considered overweight, which is
associated with a poorer prognosis after transplantation, so her case was
turned down. Within two weeks of the committee meeting hearing her case, Ms
MacPherson had already been buried.
That
is the fate of almost everyone with end-stage kidney disease (ESKD) in most of
sub-Saharan Africa, especially those living
with HIV, who are actively excluded from renal replacement therapy (dialysis
and kidney transplant) programmes in most countries.3
Even though these policies are being reviewed or revised in some countries in
light of growing access to antiretroviral drugs, there is too little capacity
for kidney transplantation for these policies to change in most of Africa. One possible solution, at least for middle-income
countries, will be discussed in a later part of this clinical review series. Is
it possible to form an organ donor pool among HIV-positive people, as recent work at Groote Schuur
Hospital in Cape Town, has shown that kidneys from other people living with HIV
can safely be transplanted into people living with HIV who need them. 4
But
in most other resource-constrained countries, the huge cost of managing chronic
kidney disease (CKD) with long-term dialysis and kidney transplantation puts
such care beyond the reach of all but a few. In many places, where there is
little or no access to intensive care or dialysis, many people who develop what
should be a treatable and reversible case of acute kidney injury face the same
fate. Making
matters worse, kidney disease often goes unnoticed, with few symptoms until it
is advanced, and patients present with end-stage kidney disease when they have
few other options.
Notably,
there are few, if any, kidney disease specialists (nephrologists) in some
African countries — most have less than ten.5
Even South Africa
has only about 50 nephrologists for a population of almost 50 million people.
Likewise, there are few surgeons to do kidney transplants, or nurses trained to
attend to people with kidney disease.
Kidney
disease has simply not made it onto health agenda in Africa, despite the fact
that it usually strikes Africans in their prime (20-50 years of age) rather
than late in life
and despite the fact that severe kidney disease is three to four times more
common in people of African descent in developed countries.6, 7
The epidemiological data in Africa are
actually rather mixed, however. The incidence of some types of kidney disease
appears to be many times greater than in other parts of the world while other
forms are either not as common, or are significantly under-reported.8
As for acute kidney injuries in Africa, there
are no reliable statistics according to one recent review, though many of the
factors associated with acute kidney damage are abundant on the continent,
including a huge burden of diseases that can cause kidney failure such as
malaria.9 Likewise, it is difficult to
know the burden of chronic kidney disease in Africa
because of
poor diagnostic
capacity, inadequate research and the fact that health systems have not
established
programs and registries to monitor it.10
But
there are reasons to worry that Africa may
have a large unrecognised and growing problem with CKD in particular. It has
often been observed that African-Americans (especially those with HIV) in the
US have a much higher risk of kidney disease than other populations — to such
an extent that ‘black’ race is considered a risk factor for kidney disease and
end-stage renal disease in that country.11 It is not known
whether the drivers of kidney disease in high-income countries will have the
same impact in other settings, or whether the epidemiology of kidney disease
will prove to be shaped by distinct regional forces. Furthermore, it is
inadvisable to make assumptions about what the epidemiology of kidney disease
in people of African descent in other parts of the world means for black
Africans.
However,
there is now evidence suggesting that a genetic adaptation that may have conferred a
survival benefit in Africa, which was passed
down in many African populations as well as among people of African descent,
may increase susceptibility to specific types of kidney injury.12
Some studies suggest one of these mutations is fairly widespread, though it is
not found in every population.13
Already, there is evidence that glomerular kidney disease
(explained later in this series) is more prevalent in Africa, and according to
Dr Saraladevi Naicker of the University of Witwatersrand,
it “seems to be of a more severe form than that found in western countries, and
is characterized by poor response to treatment and progression to renal
failure."14
Hypertension is already one of the most common causes of kidney disease among
Africans, and it appears
likely that CKD could become even more common as Africans are increasingly
exposed to a more urban westernised lifestyle and diet, with its attendant vascular
risk factors, diabetes and hypertension which commonly lead to kidney problems in
industrialised countries.15
On
top of this, there is sub-Saharan Africa’s
burden of HIV disease (and associated infections/conditions), which plainly
increases the risk of kidney disorders. HIV can cause severe kidney disease
directly — including acute kidney injuries, (possibly) thrombotic
microangiopathies, HIV-associated nephropathy (HIVAN), and HIV immune complex
kidney disease (HIVICK). Likewise, tuberculosis (TB), sexually transmitted
infections, opportunistic infections, hepatitis B & C, bacterial
infections, and neoplasms that are more common in the context of HIV infection
can cause a variety of kidney disorders. Kidney damage may also be the result
of some of the medications used to treat these infections.
Concern
about one medication, tenofovir, a cause of kidney injury in some individuals,
which is now entering into much more widespread use, finally has more HIV
clinicians thinking about kidney disease, and ART programmes are beginning to
consider whether they need, can afford or have the capacity to begin monitoring
their patients’ kidney function. However, the scope of this concern is at
present rather narrow, centred primarily on the safety of this drug, or to make
appropriate dosage adjustments on other drugs the patient is taking.
HIV
programmes may have a much greater problem lying in wait as people living with
HIV on ART begin aging — especially as other chronic health problems such as
diabetes and cardiovascular disease become more common in people living with
HIV. How this will play out in populations that may be more susceptible to
kidney injury from the start and where there is a huge burden of illnesses that
can cause kidney injury, is anyone’s guess. However, if measures of kidney
function are reliable across populations
— and this is not yet clear (see below) — a number of cross-sectional
surveys have already identified very high rates of renal impairment in people
living with HIV in a variety of sub-Saharan African settings. For instance, an
analysis of more than 25,000 Zambians starting ART suggests that approximately
8500 (33%) had mild to severe renal impairment (though other ways of measuring suggest kidney impairment was
not as common).16
But findings such as these have led one international kidney journal to ask
whether sub-Saharan Africa might be on the
cusp of an epidemic of HIV-related chronic kidney disease.17
“We believe that the epidemic of HIV renal
disease in Africa has arrived but has not been
widely announced due to lack of documentation,” said Dr Nicola Wearne, Senior
Registrar of Groote Schuur Hospital last year at a meeting of the South African
Congress of Nephrology.18
“The extent of the HIV epidemic and its associated burden of kidney disease, makes
management of these patients extremely difficult given limited resources –
especially for renal replacement.”
Indeed,
before effective ART regimens became available, renal impairment was shown to
be associated with faster progression to AIDS and death in HIV-positive US
women.19
In
the current treatment era, kidney disease at the time of ART initiation was
associated with a higher risk of death in a cohort of 1415 US women during 8148
person-years of follow-up.20 A
similar finding emerged from the Zambian study — those who had renal impairment
when they initiated treatment were found to be more likely than their
counterparts to die during a two-year follow-up period.21
Other consequences of kidney disease have important
implications in HIV-positive populations as well. A US study comparing HIV-positive
people who had experienced either a heart attack or stroke with those who had
not done so found a below-normal kidney function to be a significant risk
factor for those events. The association persisted after controlling for
confounding factors such as diabetes and high blood pressure.22
Other recent research that appears to confirm that renal impairment is strongly
associated with the risk of cardiovascular disease and heart failure in people
living with HIV is discussed later in this article. These and other findings
raise the prospect of kidney disease greatly complicating HIV clinical care.
For instance, aside from high blood pressure, kidney disease can lead to bone
thinning and anaemia — both of which are already considerable problems in some
HIV-positive populations — as well as a variety of other conditions that are
difficult to diagnose or which may complicate the diagnosis of other
HIV-related illness.
Unfortunately,
such complex clinical problems don’t always seem to fit into streamlined
target-driven ART programmes. But
data are beginning to show that a ‘get the patient in and out’ by the numbers
approach is leading to more and more losses to follow-up, possibly because
people feel their needs are going unmet. 23
“We like saying that we're going to be looking after our patients on ART into old age,” Dr Kevin Rebe of Health4Men in Cape Town told HATIP, “but our ART programmes aren’t actually prepared to deal with the illnesses
such as CKD affecting ageing patients.”
However,
adopting a palliative care approach, which aims both to address the causes of
illness and to treat the symptoms to alleviate suffering, could better help
families living with kidney disease and its related complication, and may help
those with advanced CKD cope with progressive loss of kidney functions, and
perhaps even slow down that loss over time. It is also important to remember
that, in resource-constrained settings where there is little or no screening
for kidney disease, people may only present once their condition is terminal.
They will need end-of-life care and their families, support, beyond what the
health services alone can offer. This goes beyond what any already overburdened
health provider can do by themselves — and will require a multidisciplinary
approach that employs the strengths of civil society, different community-based
and faith-based organisations.
Nevertheless,
many potentially serious kidney problems are reversible or can be slowed if
recognised in time. In light of this, and the high costs of managing chronic or
end-stage disease, prevention and early detection and treatment of kidney
disease are especially critical for people living with HIV in Africa.