Australian Doctor 8th Nov Issue | Page 26

pressure increases in parallel with

worsening stage of CKD ( ie , the lower the eGFR or the greater the albuminu-

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-

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

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

high blood pressure , at least one in

normal range or ‘ abnormal ’, see fig-

three are reported to have CKD .

ure 5 ). The formula used to calculate

As a diagnosis of ‘ hypertensive

the eGFR is not perfect and serum

kidney disease ’ is one of exclusion ,

creatinine is variable on a day-to-day

its reported prevalence is highly var-

basis because of changes in hydration ,

iable and mostly determined by the

physical activity and diet . However , it

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 ).

forms of kidney disease , and mild to

Unless significantly ( greater than

moderate high blood pressure is not

20 %) less than previous values for any

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

CKD does not correlate with that of

more often in individuals at increased

high blood pressure in the same popu-

risk of CKD ( eg , people with CVD ,

lations , but instead is associated with

high blood pressure or eGFR values

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

recorded as a common cause of end-

patients with high blood pressure , in

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

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

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

and agrichemicals ). 4

PATHOPHYSIOLOGY

A healthy kidney is composed of mil-

advanced stages . 17 Patients with CKD will usually not experience kidney pain or changes in urine colour or output . Some individuals may notice an

lions of filtering units , known as

increase in nocturia , attributable to

nephrons ( see figure 1 ). Nephrons are

impaired nocturnal concentration

specialised structural units compris-

ability , although this will often be

ing a glomerular complex that filters

attributed to ageing bladder / prostate

the plasma , with a tubule running

functions or coincident diabetes .

from it that processes the filtrate and

Many patients with CKD will have a

defines the composition of the urine .

long ( er ) history of high blood pressure ,

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-

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-

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

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

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

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 .