Kidney care and renal disease.

The kidneys are essential in the maintenance of homeostasis. Renal

dysfunction causes multiple, complex effects Phase one lab throughout the body. Kidney

function can be impaired acutely, following infection or trauma, or it

may develop slowly as a complication of chronic diseases such as

diabetes or hypertension. The number of people in New Zealand requiring

treatment for renal disease is increasing and incidence is

disproportionately high in Maori and Pacific populations, but this is

not solely due to their higher incidence of diabetes and hypertension.

An appreciation of the roles of the kidney promotes better understanding

of the consequences of renal dysfunction. Recognising, and being

vigilant for, the complex pathophysiological processes in acute and

chronic renal impairment enhances best care for patients.

[FIGURE 1 OMITTED]

INTRODUCTION

Renal disease is expected to place an increasing burden on the

health care system in the coming decades. About 10 per cent of the New

Zealand population is affected by chronic kidney disease (CKD), with a

higher incidence in Maori, Pacific, Asian and Indian groups. (1) The

number of people receiving dialysis increased by eight per cent between

2008 and 2009, with the highest increase in older adults. (2) Risk of

CKD increases with age, diabetes, cardiovascular disease, obesity or

hypertension, smoking and a family history of CKD. (3) The commonest

cause of CKD in this country is diabetes. There is an increased risk of

developing diabetic nephropathy and CKD with prolonged hyperglycaemia,

hypertension, smoking, Maori, Pacific or Asian ethnicity, dyslipidaemia

or retinopathy. (4)

Acute renal failure or acute kidney injury (AKI) can occur

following ischaemic or immune/infectious insult to the kidney. About

four per cent of patients admitted to intensive care units develop AKI,

and the mortality rate for these is greater than 60 per cent. (5) For

general hospital populations, AKI incidence can be as high as 18 per

cent, with a mortality rate of 30-60 per cent. (6) Following recovery

from AKI, approximately 12 per cent of patients require ongoing dialysis

and up to 30 per cent develop CKD. (6) THE ROLE OF THE KIDNEY

The ability of the kidneys to filter, reabsorb and secrete water,

waste molecules and electrolytes determines the composition of both the

body's extracellular fluid and the urinary filtrate. The kidneys

receive 25 per cent of the cardiac output and plasma is filtered through

the glomerular basement membrane at the rate of about 120ml/minute. Of

this, all but l-2ml/minute is reabsorbed.

The glomerular filtration rate (GFR) of plasma is determined by the

filtration pressure. Blood enters the glomerulus through the afferent

arteriole and exits via the efferent arteriole. These two blood vessels

are subject to neural, hormonal and intrinsic control mechanisms that

maintain filtration pressure across a wide range of systemic blood

pressure values. Dilation of the afferent arteriole or constriction of

the efferent arteriole will increase GFR.

The purpose of glomerular filtration is to remove metabolic waste

from the plasma, and to balance extracellular electrolyte and hydrogen

ion concentrations (see figure 1, above). In this process, non-waste

contents such as glucose and amino acids are reabsorbed. The structure

of the glomerular filtration membrane is such that only small molecules

and water can freely cross from the blood stream into the Bowman's

capsule to form the glomerular filtrate: proteins and blood cells are

retained in the plasma.

Excretion of waste

Creatinine is a waste product of muscle metabolism, and is released

from skeletal muscle at a fairly constant rate. Creatinine is filtered

at the glomerulus but does not get reabsorbed by the renal tubules, so

the amount in the blood and urine is a measure of GFR. Rising creatinine

concentration in the plasma indicates decreased glomerular filtration.

Serum creatinine levels are used to determine an estimated

glomerular filtration rate (eGFR), but this can be subject to error,

related to age, variations in body weight and composition, low protein

(vegan) diet and in acute renal failure. It has not been validated as a

measure outside the North American population, so may not accurately

reflect GFR in Maori, Pacific or ethnic minorities. Also, there is

little increase in plasma creatinine until up to 50 per cent of renal

function has been lost, so early stages of renal impairment are not

readily detected by this method. (1,3)

Urea is a by-product of protein metabolism. Nitrogen and ammonia,

formed during the breakdown of proteins in the liver, are converted to

urea. Urea is filtered at the glomerulus and then reabsorbed and

secreted by the renal tubules. Blood urea nitrogen (BUN) is a measure of

renal function: rising levels indicate reduced GFR and slow flow through

the renal tubules (allowing more of the urea to be reabsorbed). However,

BUN also varies with hydration status, dietary intake of protein and

catabolic states in the body, such as following surgery or trauma.

Regulation of ions

Potassium handling via the kidneys is essential to the tight

regulation of extracellular concentration, at about4.8mmol/L.

Differences in potassium concentration between intracellular and

extracellular fluids determine the resting membrane potential of all

excitable cells within the body. Minor alterations in potassium

concentration may be lethal.

Potassium is filtered at the glomerulus and largely reabsorbed in

the proximal convoluted tubules. Potassium is then secreted into the

urinary filtrate in the distal convoluted tubules (DCT). The extent of

potassium loss depends on the concentration gradient across the tubule

walls. Rapid flow of highly dilute filtrate will cause increased loss of

potassium, while low plasma potassium concentration will decrease

secretion. Aldosterone is released in response to high plasma

concentrations of potassium and increases the rate of potassium

secretion in the DCT.

Hydrogen ions also influence the secretion of potassium, linking pH

and potassium balance. During acidosis, hydrogen ions move into the
cells of the DCT in exchange for potassium, thus decreasing their

intracellular potassium levels. The DCT cells react as if potassium in

the body is low, and decrease secretion of potassium into the urinary

filtrate, leading to hyperkalemia. The opposite occurs in alkalosis,

where potassium moves into the cells, triggering Site management organization increased
secretion

into the urinary filtrate and hypokalemia. (7)

The kidney has a complex mechanism for the excretion and buffering

of excess hydrogen ions, thus maintaining acid-base balance in the body.

Filtered bicarbonate is reabsorbed, while hydrogen ions are actively

secreted and buffered with phosphate and ammonia. Bicarbonate

reabsorption involves the formation of new bicarbonate molecules within

the cells lining the tubules and is also affected by sodium and

potassium exchanges in these cells. In renal failure, the inability of

the cells to reabsorb filtered bicarbonate may lead to acidosis.

Renin-angiotensin-atdosterone system (RAAS)

Renal secretion of renin activates the

renin-angiotensin-aldosterone pathway, leading to hormonal regulation of

water and sodium in the extracellular fluid, and to maintenance of blood

pressure via this and vasoconstrictive mechanisms (see fig 1).

Renin release is stimulated by hypovolaemia, hypotension or

decreased sodium in the filtrate passing through the distal tubules. The

classical pathway involves activation of angiotensinogen to angiotensin

I by renin, and conversion of angiotensin I to angiotensin II by

angiotensin-converting enzyme (ACE). Angiotensin II, acting via

receptors, triggers vasoconstriction and increased retention of sodium

and water, enhanced by release of aldosterone. Angiotensin II directly

increases glomerular filtration pressure by causing constriction of the

efferent arterioles. (7)

The RAAS also affects endothelial cell function throughout the

body, triggering vascular remodelling, hypertrophy, increased oxidative

stress, inflammation, atherogenesis and thrombosis. Inappropriate

activation of RAAS in CKD causes ongoing renal hypertension, damaging

the glomerular basement membrane, and inducing a chronic inflammatory

state in the body, contributing to the many systemic effects of CKD.

The kidneys also regulate other body functions (see fig 1).

Activation of vitamin D by the kidneys regulates calcium and phosphate

metabolism and also affects immune function. Secretion of erythropoietin

by the kidney regulates the synthesis of red blood cells; loss of this

function is a major issue for people with CKD.

The kidney is the major site of excretion for drugs and their

metabolites and other foreign substances. Impaired renal function can

have a profound impact on the duration of action and potential toxicity

of many drugs, particularly those excreted in their active form, eg

penicillin.

RENAL INJURY

Regardless of the cause of renal injury, damage to the glomerulus

leads to a sequence of events that, if allowed to progress, culminates

in renal failure. This process may be acute, leading to abrupt loss of

renal function, or more insidious, where chronic damage occurs over a

number of years and renal failure is well advanced before it is

detected. Figure 2 (p22) shows the sequence of events occurring in the

nephrons when the glomerulus suffers injury.

Acute kidney injury (AKI)

AKI is a rapid decline in renal function leading to failure in

fluid, electrolyte and acid-base homeostasis. Urine output falls below

0.5ml/kg/ hour for longer than six hours and serum creatinine levels

increase. (8) The causes of AKI can be pre-renal, intrinsic or

post-renal. Pre-renal causes generally arise due to hypoperfusion of the

nephrons due to shock, heart failure, hypotension, dehydration,

hypovolvaemia or renal arterial stenosis, which all decrease renal blood

flow and may trigger renal failure.

These conditions may also cause ischaemia of the renal tubules,

triggering acute tubular necrosis, a form of intrinsic AKI. Other forms

of intrinsic AKI occur with nephrotoxic drugs (eg aminoglycosides such

as gentamycin) or contrast media and the presence of endogenous

nephrotoxic substances, eg haeme-pigment in rhabdomyolysis (abnormal

breakdown of muscle, an adverse effect of statins). The risk of

intrinsic AKI increases with age, presence of diabetes or concurrent

CKD.

One of the hallmarks of acute tubular necrosis is the loss of

ability to concentrate urine. As urinary filtrate travels through the

collecting ducts, it normally encounters a highly concentrated

interstitial zone in the renal medulla that draws water from the urinary

filtrate by osmosis. Establishment of this zone is dependent on the

orchestrated movement of water and electrolytes from the filtrate as it

travels through the loop of Henle, and on adequate blood flow through

the renal capillaries. If the loop of Henle is unable to generate this

osmotic gradient, urinary filtrate cannot be concentrated, so the person

with acute tubular necrosis will produce dilute urine despite being

oliguric (producing low amount of urine). Once the recovery phase

begins, the restoration of glomerular filtrate may occur prior to

re-establishment of tubule function. Resultant polyuria increases the

risk of hypovolemia and further hypoxic injury to the kidney.

[FIGURE 2 OMITTED]

Glomerulonephritis is a form of intrinsic injury that occurs where

antibody-antigen complexes either form or are deposited within the

glomerulus. These damage the glomerular basement membrane and trigger

the sequence of events shown in figure 2. Streptococcal infections

(impetigo, strep throat) may trigger AKI in children seven to 10 days

after infection, but this condition can also arise with other bacteria

or viral infections (acute post-infectious glomerulonephritis). Other

forms of immune-triggered AKI may occur in immune disorders such as

systemic lupus erythematosis. (7)

Post-renal injury may arise where there is prolonged obstruction to

the flow of urine or filtrate, causing a build-up of pressure in the

renal tubules and negation of the filtration gradient from glomerulus

into the Bowman's capsule. This, in turn, triggers renal afferent

arteriolar vasoconstriction, reducing blood flow through the glomerulus

and renal tubule. Sloughing of dead tubule cells from an already damaged

kidney can cause obstruction to flow, increasing the damage from

pre-renal or intrinsic causes.

Recovery depends on rapid correction of the underlying causative

factor(s). Once renal blood flow is restored, surviving nephrons are

able to compensate by increasing their filtration rate (hyperfiltration)

and, over time, their size (hypertrophy). However, if the number of

functional nephrons is too low, this hyperfiltration and hypertrophy

continue leading to a cycle of sclerosis and further nephron loss.

Eventually, despite initial recovery of function, the kidney may fail

completely. (6)

Chronic kidney disease

Loss of renal function over a prolonged period (months to years) is

now described as CKD, rather than chronic renal failure. Stages of CKD

range from kidney damage with normal renal function, through to

end-stage renal disease (ESRD). (9) Underlying causes of CKD

vary--diabetes being the most common. Hypertension, glomerulonephritis,

reflux nephropathy and polycystic kidney disease are other causes.

Regardless of initiating events, CKD progresses due to glomerular

hypertension, glomerulosclerosis, compensatory (and ultimately

pathological) hyperfiltration and hypertrophy, and tubular inflammation

and fibrosis. Symptoms of CKD do not normally manifest until renal

function decreases to less than 25 per cent.7 People with CKD are

particularly vulnerable to AKI, the highest risk being during episodes

in hospital.

CONSEQUENCES OF RENAL DYSFUNCTION

Adverse consequences of AKI depend on the phase of the illness:

initiation (damage is in progess), maintenance (renal injury is

established) and recovery. Generally the first two phases are oliguric,

and polyuria occurs during the recovery phase. In advanced CKD, oliguric

effects predominate. Fluid and electrolyte disturbances (including

hypertension, oedema and heart failure), uraemia, anaemia and infection

may all have a bad effect on the outcomes for patients.

Fluids and electrolytes

Increasing plasma potassium and sodium, and water retention in the

oliguric phase of AKI cause disruption to fluid and electrolyte balance

throughout the body. Hyperkalaemia can induce life-threatening cardiac

dysrhythmias--ventricular tachycardia or fibrillation, bradycardia,

complete heart block or asystole. Also, possible neuromuscular

dysfunction can lead to respiratory failure. Hyperkalaemia is treated

with insulin/ glucose infusion, ion exchange resin (calcium resonium or

resonium A) or, if severe, dialysis. (10) As diuresis sets in with the

recovery phase, the risk of hypokalaemia increases.

Abnormal activation of the RAAS and reduced sodium excretion affect

body water balance. Oedema and congestive heart failure develop due to

fluid retention. Fluid losses in the recovery phase of AKI may cause

dehydration and further renal injury.

Hyponatremia may occur with some forms of CKD and during the

recovery phase of AKI. It must be corrected slowly due to the impact of

rapidly altered osmotic pressures on the brain.

[FIGURE 3 OMITTED]

ESRD can induce severe metabolic acidosis due to loss of renal

compensatory mechanisms and bicarbonate handling.

Uraemia

Accumulation of nitrogenous and other toxic wastes leads to

development of gastrointestinal symptoms (anorexia, nausea, vomiting,

cramps). As BUN increases, neurological.
symptoms of lethargy, confusion

and seizures may develop. Uraemia causes platelet dysfunction that can

lead to life-threatening haemorrhage; (10) it also impairs immune

function, increasing the risk of developing infections, especially

pneumonia. Infection is the commonest cause of morbidity and death for

patients with AKI (10) and the second most common, after cardiovascular

disease, for CKD. (1)

Other effects of uraemia include pruritis, peripheral neuropathy,

mouth ulcers, pancreatitis, sexual dysfunction and infertility.

Anaemia

Red blood cell production may be reduced due to loss of

erythropoietin (EPO) secretion from the damaged kidneys. Bone marrow

becomes less sensitive to the action of EPO, possibly due to chronic

systemic inflammation. (3) Blood loss may also occur via the kidneys or

due to haemorrhage. Water retention causes a dilution anaemia.

Hypertension

Water and sodium retention increase blood volume and thus blood

pressure. Abnormal activation of the reninangiotensin pathway increases

aldosterone secretion, so that sodium retention is increased in

remaining

functional nephrons. Angiotensin II causes vasoconstriction,

including of the afferent arterioles, increasing glomerular hypertension

and damage.

Cardiac disease

The majority of people with CKD will die from cardiovascular

disease: patients on dialysis are 10-20 times more likely to die of

cardiovascular disease than the general population. (3,11) CKD is an

independent risk factor for cardiovascular disease, and cardiovascular

disease increases risk of CKD. Therapies aimed at reducing

cardiovascular risk will slow progression of CKD. Underlying mechanisms

in the development of cardiovascular disease with CKD include

hypertension, dyslipidaemia, abnormal endothelial cell function and

chronic inflammation.

Bone changes

Reduced activation of vitamin D, combined with phosphate retention,

cause hyperparathyroidism and hypocalcaemia. Osteomalacia and osteitis

fibrosa ensue, with bone pain and increased risk of fractures.

Persistent elevated parathyroid hormone also induces soft tissue

calcification and cardiovascular disease. (7)

Malnutrition

Weight loss in renal disease is not solely due to reduced food

intake. Loss of protein in the urine and a catabolic metabolic state

lead to reduced plasma proteins and muscle wasting. Loss of plasma

proteins increases the development of oedema.

DIET IN RENAL DISEASE

Restricting protein intake in CKD can delay progression of the

disease and reduce adverse cardiovascular effects and uraemia (12).

While those with CKD generally suffer from low serum albumin, this

reduction is probably more due to loss of protein through the damaged

kidneys, metabolic acidosis, dialysis and on-going inflammation, rather

than malnutrition. (12)

A low-protein diet reduces production of nitrogenous wastes,

reducing renal damage, inflammation and gastrointestinal symptoms.

Low-protein diets are also associated with reduced sodium, phosphate and

acid intake, reducing development of hypertension, hyperphosphataemia

and acidosis. Very low protein diets must be accompanied by supplements

of essential amino acids and ketoacids.

Sticking to restrictive diets long-term is difficult for many

people and there is an associated risk of malnutrition, increased in the

presence of underlying disease. Research evidence is not conclusive on

the effectiveness of low-protein diets, particularly in early stages of

CKD and this intervention is not recommended until late in the disease.

(13,14) Malnutrition may require high-energy dietary interventions. Of

particular concern is where calorie deficits increase the use of protein

as an energy source, increasing production of nitrogenous waste. Reduced

appetite and other gastrointestinal effects of uraemia can contribute to

this state. The high risk of cardiovascular disease for people with CKD

affects the types of protein and carbohydrates that should be included

in the diet. Specialist renal dieticians are an essential component of

care for people with CKD.

TREATMENT OF CKD

Figure 3 (see p23) illustrates the progression of CKD and the

nature of interventions provided at each stage. Screening for, and

purposeful management of, modifiable risk factors can prevent, delay and

sometimes reverse the onset of the disease.

Early renal damage is indicated by the presence of persistent

microalbuminuria/ proteinuria or haematuria, and abnormal urine

microscopy or renal defects on ultrasound or radiology. At this stage,

giving drugs that prevent the actions of angiotensin II has been shown

to delay further deterioration in renal function. (1)

ACE-inhibitors (eg lisinopril, enalapril) are the first-line drugs

used or, if these are not well tolerated, angiotensin II receptor

blockers (ARBs) such as losartan or candesartan. By inhibiting the

actions of angiotensin II, these drugs reduce afferent arteriolar

vasoconstriction, decreasing glomerular hypertension and its

consequences on glomerular structure and function. The systemic chronic

inflammatory effects of angiotensin II are also reduced. (15) The

effects of RAAS blockade are enhanced when sodium intake is restricted.

(16)

As renal function deteriorates and GFR declines, the focus of

treatment shifts to include protection of remaining renal function. The

increased vulnerability of the failing kidneys to injury is of prime

concern. All medications should be reviewed for their potential to

damage the kidneys. Fluid and electrolyte management becomes especially

important during any form of health intervention, eg surgery. Prevention

of infection is also essential and vaccination against seasonal

influenza and pneumococcus should be encouraged. (1,3)

Decisions on kidney transplant need to be made as ESRD approaches.

In 2010, 2378 patients were receiving dialysis in New Zealand and there
were 1442 people with functioning transplants. (17)

Haemodialysis, peritoneal dialysis and kidney transplant are

expensive, with variable outcomes for patients. Survival rates following

transplantation are about 90 per cent at one year, dropping to 40 per

cent at 10 years. (3) Survival rates with dialysis are substantially

lower. Overall survival rates on haemodialysis (HD) and peritoneal

dialysis (PD) are similar, although older patients with diabetes have

worse outcomes with peritoneal dialysis. (18)

Dialysis involves the exchange of substances between the blood and

another fluid (dialysate) by diffusion and ultrafiltration across a semi

permeable membrane. In the case of PD, this is the peritoneal membrane

surrounding the abdominal organs. With haemodialysis, an artificial

membrane is used and blood must be extracted and returned to the body.

CONCLUSION

The kidneys provide complex and essential support to the

maintenance of homeostasis of fluids and electrolytes, blood pressure

and acid-base balance. They are also responsible for the removal of

waste products of metabolism and drugs from the body. Renal failure is

manifested across this wide range of functions and offers an interesting

challenge to those providing care for people with AKI or CKD.

Understanding the pathophysiology involved allows nurses to deliver

optimal care and support to these patients.

* For this article's references, go to CPD4nurses.co.nz and

click under the 'News' link.

LEARNING OUTCOMES

After reading this article and completing the accompanying online

learning activities, you should be able to:

* Outline the roles of the kidney in maintaining homeostasis.

* Describe the causes and consequences of acute kidney injury.

* Describe the course of chronic kidney disease and its progression

to end-stage renal disease.

* Discuss common measurements of renal function.

Georgina Casey, RN, BSc, PGDipSci, MPhil (nursing), is the director

of CPD4nurses.co.nz. She has an extensive background in nursing

education and clinical experience in a wide variety of practice

settings.

Table 1. Advantages and disadvantages of haemodialysis and

peritoneal dialysis ... (19)

HAEMODIALYSIS PERITONEAL DIALYSIS

Advantages High clearance of solutes Less risk of

allows intermittent treatment. hypotension than HD.

Easier to detect and manage Patient-controlled.

under dialysis. Less restriction of

mobility during
sessions. No

anticoagulation

required.

Disadvantages Loss of patient control over Risk of malnutrition

dialysis. due to abdominal

fullness and loss of

larger solutes in

PD.

Loss of mobility during High risk of

dialysis. peritonitis.

Risk of hypotension. Risk of catheter

Risk of infection or malfunction or

thrombosis in vascular insertion site

access site. infection.

Risk associated with need for

anticoagulant therapy. Lower clearance of

Increased incidence of solutes than HD so

anaemia. more frequent

dialysis required.

Discomfort, leakage

and burnout may

reduce compliance.