pressure increases in parallel with
worsening stage of CKD ( ie , the lower the eGFR or the greater the albuminu-
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Figure 1 . 3D illustration of the structure of a nephron . |
The eGFR is automatically estimated from serum creatinine levels , patient age and gender , using a mathe- |
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ria and blood pressure , the higher the association with a subsequent risk of kidney failure ). 9 , 10 It has been estimated that up to 90 % of those |
matical formula . An eGFR of less than 60mL / min / 1.73m 2 denotes abnormal kidney function , as it approximates an eGFR of more than two standard |
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with CKD have high blood pressure . 9 Equally , in studies of patients with |
deviations below the mean eGFR of healthy individuals ( ie , it is out of the |
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high blood pressure , at least one in |
normal range or ‘ abnormal ’, see fig- |
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three are reported to have CKD . |
ure 5 ). The formula used to calculate |
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As a diagnosis of ‘ hypertensive |
the eGFR is not perfect and serum |
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kidney disease ’ is one of exclusion , |
creatinine is variable on a day-to-day |
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its reported prevalence is highly var- |
basis because of changes in hydration , |
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iable and mostly determined by the |
physical activity and diet . However , it |
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adequacy of the resources available to exclude other causes . 4 Some have argued that many of these patients actually have other ( undiagnosed ) |
will identify most patients who persistently have an eGFR of less than 60mL / min / 1.73m 2 ( ie , those most at risk of adverse kidney outcomes ). |
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forms of kidney disease , and mild to |
Unless significantly ( greater than |
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moderate high blood pressure is not |
20 %) less than previous values for any |
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the cause of their kidney disease , but rather is the result of it . 11 Indeed , the prevalence of reported hypertensive |
individual , any eGFR found to be in the normal range can be followed with repeat screening at least annually , or |
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CKD does not correlate with that of |
more often in individuals at increased |
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high blood pressure in the same popu- |
risk of CKD ( eg , people with CVD , |
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lations , but instead is associated with |
high blood pressure or eGFR values |
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the prevalence of non-diabetic CKD . 4 Nonetheless , high blood pressure is still |
close to 60 ). Given that eGFR should be measured at least annually in all |
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recorded as a common cause of end- |
patients with high blood pressure , in |
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stage kidney disease ( ESKD ; ie , requiring dialysis or a transplant to survive or death due to kidney failure ), second |
individuals with a ‘ normal eGFR ’ ( ie , eGFR greater than 60mL / min / 1.73m 2 ) observing the rate of decline of eGFR |
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equal with glomerulonephritis , with only diabetes causing more cases . 4 In Australia 12-14 % of patients who enter dialysis are reported as having hypertensive CKD . 12
So-called ‘ hypertensive nephropathy ’ is said to be higher in individuals with recent African and Indigenous ancestry . 13 , 14 Beyond the limited resources to exclude other causes , this association may partly reflect worse blood pressure control , as well as underlying susceptibility including genetic susceptibility ( eg , APOL1 mutation ), reduced nephron endowment , and toxin exposure ( eg , heavy metals
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Figure 2 . Very high magnification micrograph of renal arterial hyalinosis in chronic / sclerosing allograft nephropathy ( periodic acid-Schiff stain ). |
Nephron / CC BY-SA 3.0 / bit . ly / 4bAkAib |
can also provide an early indication of progressive kidney disease . In particular , losses of 10mL / min / 1.73m 2 / three years or greater ( eg , eGFR falls from 80 to 70mL / min / 1.73m 2 over three years ) can be indicative of rapidly declining kidney function and warrants renoprotective intervention ( s ) detailed later .
Figure 6 provides an algorithm for initial detection and diagnosis of CKD .
CLINICAL PRESENTATION OF CHRONIC KIDNEY DISEASE
CKD is usually silent until the
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and agrichemicals ). 4
PATHOPHYSIOLOGY
A healthy kidney is composed of mil-
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advanced stages . 17 Patients with CKD will usually not experience kidney pain or changes in urine colour or output . Some individuals may notice an |
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lions of filtering units , known as |
increase in nocturia , attributable to |
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nephrons ( see figure 1 ). Nephrons are |
impaired nocturnal concentration |
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specialised structural units compris- |
ability , although this will often be |
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ing a glomerular complex that filters |
attributed to ageing bladder / prostate |
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the plasma , with a tubule running |
functions or coincident diabetes . |
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from it that processes the filtrate and |
Many patients with CKD will have a |
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defines the composition of the urine . |
long ( er ) history of high blood pressure , |
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High blood pressure can damage crit- |
and manifest symptoms and signs |
ical components of the nephron , |
high blood pressure . Tubular atrophy , |
volume expansion and neurohormonal |
estimated by measuring the urinary |
of longstanding high blood pressure , |
contributing to a progressive loss of |
tubulointerstitial fibrosis and capillary |
activation driving high blood pressure |
albumin to creatinine ratio ( ACR ), as |
including left ventricular hypertrophy , |
nephron integrity and kidney func- |
rarefaction are the final common path- |
and impairing responsiveness to treat- |
the urinary creatinine adjusts for the |
heart failure , oedema , atherosclerosis |
tion . In particular , following chronic exposure to high blood pressure , the |
way to nephron loss and replacement by scar tissue . |
ment . In particular , CKD is associated with increased activity of the renin |
void volume and urine concentration . 17 The first or second void in the morning |
and hypertensive retinopathy . These may suggest a diagnosis of ‘ hyperten- |
blood vessels that supply the nephron become thickened and the vascular |
Taken together , these histopathological changes are known as ‘ arteriolar |
angiotensin aldosterone system ( RAAS ) and sympathetic nervous system . |
is generally considered best , but other voids ( eg , at a clinic visit ) can also be |
sive kidney disease ’. As stated earlier , all these signs may also be present in a |
lumen narrowed . Hyaline-like ( pink , amorphous , homogeneous ) material is exuded into the wall of preglomerular arterioles ( see figure 2 ). This is known as ‘ arteriolosclerosis ’. This process can progressively decrease glomerular blood flow and eventually lead to |
nephrosclerosis ’ or ‘ nephroangiosclerosis ’ ( see figure 3 ); however , they are not specific or diagnostic of hypertensive kidney damage . Nephrosclerosis can also be observed in all of the most common forms of CKD , including diabetes , obesity , smoking , ageing and in |
SCREENING FOR CHRONIC KID- NEY DISEASE IN PATIENTS WITH HIGH BLOOD PRESSURE
ALL people with high blood pres-
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used for analysis without much loss of value . Regardless of the method , there is usually substantial day-today variability in the urinary albumin excretion rate . This means that any abnormal result should always be confirmed by undertaking two additional |
patient with longstanding CKD , and it is almost impossible to tell which came first . In order to develop abnormal kidney function , more than half of the filtering nephron units must have been progressively lost over many years , during which time the kidney disease |
ischaemic collapse and obsolescence |
advanced stages of glomerulonephri- |
sure require screening for CKD , at |
samples over the next 3-6 months . If |
may have adversely impacted on the |
of the glomeruli . Equally , vascular |
tis , in part due to remnant hyperfunc- |
least annually , from the time of their |
albumin excretion is within the nor- |
patient ’ s blood pressure but the CKD |
stiffening impairs healthy autoregulation of kidney blood flow , transmitting elevated systemic blood pressure to the delicate structures of the glomeruli , resulting in their remodelling and progressive dysfunction .
As kidney damage develops , the glomeruli are partly or wholly replaced by scar tissue ( known as focal , segmental or global glomerulosclerosis , respectively ). The extent of glomerular sclerosis correlates with the progres-
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tion ( ie , the remaining nephrons carry a heavier burden leading to accelerated injury and progressive dropout ).
As the kidney has little or no regenerative capacity , once a nephron is lost , it cannot return . The remaining nephrons have substantial capacity to buffer losses in the short term . However , the extra workload that nephron loss creates acts to perpetuate further losses .
Reduced kidney function ( of any
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diagnosis with elevated blood pressure . 15 The purpose of this screening is to identify those with high blood pressure in whom a different treatment ( kidney-protective ) strategy is needed to improve clinical outcomes . Screening encompasses the testing of both urinary albumin excretion rate and eGFR , as both are independently and additively associated with prognosis . 16 This is conceptualised in the Australian Kidney Health Check pro- |
mal range in both tests , future screening can be repeated on an annual basis . If one or both urinalyses are abnormal , then a diagnosis of CKD can be recorded , and a new treatment plan initiated ( as detailed later ).
Urine dipstick tests ( to estimate urinary albumin or protein ) are not generally recommended . Although an elevated urine albumin concentration on a dipstick is almost always associated with an abnormal ACR , less than
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was not diagnosed until their kidney function ultimately became abnormal .
DIAGNOSIS OF CHRONIC KID- NEY DISEASE IN PATIENTS WITH HIGH BLOOD PRESSURE
CONSIDER additional investigations in
any patient presenting with impaired kidney function to determine the
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sive decline in kidney function , as well |
cause ) progressively leads to endothe- |
gram ( see figure 4 ). 17 |
half of those with an abnormal ACR |
potential cause ( s ), optimal treatment |
as other clinical features like secondary |
lial dysfunction , sodium retention , |
Urinary albumin excretion is best |
will be dipstick positive . 18 |
and likely prognosis . |