Clinical Features

Management and Treatment of Chronic Kidney Disease

An interview with Theresa Lowry Lehnen (PhD), Clinical Nurse Practitioner and Associate Lecturer South East Technological University

Chronic kidney disease (CKD) is a progressive renal disorder that commonly occurs in the adult population, especially in those with hypertension and diabetes. There is no cure, and the condition is associated with high morbidity and mortality rates. Approximately 10% of adults globally are affected by some form of chronic kidney disease, which results in 1·2 million deaths and 28 million years of life lost annually.

We spoke with Theresa Lowry Lehnen, RGN, RNP, BSc, MSc, PG. Dip. Ed, M. Ed, PhD Clinical Nurse Practitioner and Associate Lecturer South East Technological University to find out more about the current management and treatment options available. CKD affects 1:10 people in the whole population, and over 500 people in Ireland develop kidney failure every year. By 2040, it is estimated that chronic kidney disease will become the fifth leading cause of death globally.

Theresa begins by explaining, “CKD is defined as a reduction in kidney function, with estimated glomerular filtration rate (eGFR) of < 60 mL/min per 1·73 m2, or markers of kidney damage, such as albuminuria, haematuria, or abnormalities detected through laboratory testing or imaging, and that are present for at least 3 months. “Chronic kidney disease is usually insidious, develops slowly over time and most people affected are asymptomatic until the disease becomes advanced (eGFR < 30 mL/min per 1·73 m2). The rate of kidney function loss varies by aetiology, exposures, and interventions but, in most cases, progression to kidney failure takes between months and decades to develop.” Signs and symptoms of kidney failure result from progressive uraemia, anaemia, volume overload, electrolyte abnormalities, mineral and bone disorders, and acidaemia, and lead to death if left untreated.

Theresa adds, “Kidney function can decline gradually over several years, or rapidly over several months. In some people, function can drop so low that dialysis treatment or a kidney transplant will be required. This is known as End Stage Kidney Disease (ESKD).” Cardiovascular disease is a leading cause of death in patients with chronic kidney disease, and is a major focus of preservative care in this population. Theresa adds, “Diabetes, which affects more than 250, 000 people in Ireland, is one of the leading causes of CKD.

Diabetes Ireland highlights the importance of screening for chronic kidney disease. Diabetes check-ups include the routine monitoring of kidney function so that changes can be detected early. “Diabetes Ireland urges all people with diabetes to attend for their routine diabetes checkups, have their kidney function monitored regularly and ensure that discussions on kidney health becomes an integral part of their review Risk factors for chronic kidney disease include older age (>50 years), low birth weight, obesity, smoking, high blood pressure, diabetes, a family history of kidney disease, being of African-American decent, and long-term use of over-thecounter medications. “Both genomic and environmental factors contribute to this complex heterogeneous disease, and CKD heritability is estimated to be high at 30–75%. There is a higher incidence and prevalence in women than men, however, women have a lower risk of CKD progression, and men are more likely to develop end stage renal failure (ESRD).” In addition to known causes, CKD can also be idiopathic, she adds.

The most common causes of CKD are diabetes (type 1 and type 2) and hypertension. Other causes include primary glomerulonephritis, chronic tubulointerstitial nephritis; hereditary or cystic diseases, secondary glomerulonephritis or vasculitis and plasma cell dyscrasias or neoplasm. “Autoimmune diseases such as lupus can damage blood vessels and can make antibodies against kidney tissue.” CKD may result from disease processes in any of the three categories: prerenal – decreased renal perfusion pressure; intrinsic renal – pathology of the vessels, glomeruli, or tubules-interstitium; or postrenal -obstructive. Theresa continues, “Chronic prerenal disease occurs in patients with chronic heart failure or cirrhosis with persistently decreased renal perfusion, which increases the tendency for multiple episodes of an intrinsic kidney injury, such as acute tubular necrosis (ATN).

This leads to progressive loss of renal function over time. “Intrinsic occurs when direct damage to the kidneys causes a sudden loss in kidney function. The most common chronic renal vascular disease is nephrosclerosis, which causes chronic damage to blood vessels, glomeruli, and tubulointerstitium. “The other renal vascular diseases are renal artery stenosis from atherosclerosis or fibro-muscular dysplasia which over months or years, cause ischemic nephropathy, characterised by glomerulosclerosis and tubulointerstitial fibrosis. Chronic obstruction may be due to prostatic disease, nephrolithiasis or abdominal/pelvic tumour with mass effect on ureter(s).

Retroperitoneal fibrosis is a rare cause of chronic ureteral obstruction.” Signs and Symptoms Kidney disease tends not to cause symptoms at the early stage, therefore routine screening using urine and blood tests is important. “Symptoms develop over time and can include weight loss, anorexia, oedema of the ankles, feet and hands, dyspnoea, fatigue, nocturia, haematuria, nausea, headaches, muscle cramps, headaches, and erectile dysfunction in men,” she says. Diagnosis A thorough medical history, physical examination and investigative tests are required to form a diagnosis for CKD. Early CKD stages are usually asymptomatic, and symptoms manifest in stages 4 or 5.

“Chronic kidney disease is typically identified through routine screening with blood serum chemistry profile (Serum creatinine concentration should be measured, allowing calculation of eGFR) and urine studies (ACRalbumin: creatinine ratio) or as an incidental finding. Urine dipstick is first performed, and is a useful screening tool although it only provides a semi quantitative assessment of level of proteinuria, as the reported value can vary according to the hydration status of the patient.

“Spot urine sample is sent to the laboratory to measure Protein/ Albumin to Creatinine Ratio. This will detect even small levels of proteinuria and is essential for diagnosis, but is not useful for routine follow up of patients who already have established macroalbuminuria. At the same time, a midstream urine specimen (MSU) should be sent for culture to exclude urinary tract infection. The eGFR is a useful and accurate measure of renal function, and is calculated using serum creatinine as well as the variables of age, gender and race. In the following circumstances however, eGFR may not be accurate: acute renal failure; patients less than 18 years of age; patients with advanced muscle wasting and amputations; and pregnancy.”

Theresa goes to note that less commonly, patients may present with symptoms such as gross haematuria, foamy urine, nocturia, flank pain, or decreased urine output. “If CKD is advanced, patients may report fatigue, poor appetite, nausea, vomiting, metallic taste, unintentional weight loss, pruritus, changes in mental status, dyspnoea, or peripheral oedema. In assessing a patient, additional symptoms that might suggest a systemic cause such as haemoptysis, rash, lymphadenopathy, hearing loss, neuropathy; or urinary obstruction such as hesitancy, urgency, frequency or incomplete bladder emptying should be enquired about.

“Patients should be assessed for risk factors of kidney disease including; prior exposure to potential nephrotoxins such as nonsteroidal anti-inflammatory drugs (NSAIDs); antibiotic therapies such as gentamicin and chemotherapies; history of nephrolithiasis or recurrent urinary tract infections; the presence of comorbidities; family history of kidney disease; and other known genetic risk factors. “A detailed physical examination may provide additional information regarding the underlying cause of CKD. Signs of volume depletion may reflect poor oral intake, vomiting, diarrhoea, or over diuresis, whereas signs of volume overload may be due to decompensated heart failure, liver failure, or nephrotic syndrome.

The presence of arterial-venous nicking or retinopathy on retinal examination suggests long-standing hypertension or diabetes. Patients with carotid or abdominal bruits may have renovascular disease. Flank pain or enlarged kidneys should prompt consideration of obstructive uropathy, nephrolithiasis, pyelonephritis, or polycystic kidney disease. “Neuropathy may be due to diabetes or less commonly vasculitis, or amyloidosis. Skin findings may include rash, palpable purpura, telangiectasias, or extensive sclerosis. Patients with advanced CKD may exhibit pallor, skin excoriations, muscle wasting, asterixis, myoclonic jerks, altered mental status, and pericardial rub.

“Other diagnostic investigations carried out may include an ultrasound, MRI or CT scan and a biopsy. Once a diagnosis of CKD has been established, the next step is to determine staging.” Stages and classification of CKD The stages of CKD range from 1-5. Most patients who are diagnosed as having stage 1, 2 or 3, have mild to moderate kidney disease and usually do not progress to end stage kidney failure (ESKF). Once stage 4 is reached, damage is more severe and is usually not reversible. Dialysis or a kidney transplant may be required.

Theresa adds, “A patient is considered to have chronic kidney disease if they have abnormalities of kidney function or structure present for more than 3 months. The definition of CKD includes all individuals with markers of kidney damage or those with an eGFR of less than 60 ml/min/1.73m2 on at least two occasions, 90 days apart with or without markers of kidney damage. Markers of kidney disease may include: albuminuria (ACR > 3 mg/mmol), haematuria (presumed or confirmed renal origin), electrolyte abnormalities due to tubular disorders, renal histological abnormalities, structural abnormalities detected by imaging (e.g. polycystic kidneys, reflux nephropathy) or a history of kidney transplantation. CKD is classified based on the eGFR and the level of proteinuria and helps to risk stratify patients. Patients are classified as G1-G5, based on the eGFR, and A1- A3 based on the ACR albumin: creatinine ratio.”

The stages include:

• G1: GFR 90 ml/min per 1.73 m2 and above
• G2: GFR 60 to 89 ml/min per 1.73 m2
• G3a: GFR 45 to 59 ml/min per 1.73 m2
• G3b: GFR 30 to 44 ml/min per 1.73 m2
• G4: GFR 15 to 29 ml/min per 1.73 m2
• G5: GFR < 15 ml/min per 1.73 m2 or treatment by dialysis

The 3 levels of albuminuria include albumin-creatinine ratio (ACR):

• A1: ACR less than 3 mg/mmol (normal to mild)
• A2: ACR 3 to 30 mg/mmol (moderately increased)
• A3: ACR greater than 30 mg/ mmol (severely increased)

Treatment and Management

Theresa concludes, “There is no cure for chronic kidney disease, but treatment and management can help relieve the symptoms and improve the patient’s quality of life. Treatment options and prognosis will depend on the stage of CKD. Lifestyle measures include, stopping smoking, a healthy diet, restricted salt intake of less than 6g. “The main goals of management of CKD are to reduce overall cardiovascular risk, delay progression to renal failure and avoid complications.

Regular reviews are recommended and should include blood pressure measurement, assessment of kidney function, review of all medications, and immunisation with Influenza vaccine and Pneumococcal vaccine, in addition to lifestyle advice regarding smoking, reduced salt intake and weight loss. Anaemia is common in more advanced disease and a target of 10–11.5gm/dL should be sought. If the Haemoglobin is low, nonrenal causes should be excluded. Management of “renal” anaemia can include the provision of iron and the use of erythropoiesis stimulating agents. Regular review of medication is important to minimise nephrotoxic drugs particularly NSAIDs, and ensure doses of others are appropriate to renal function. Metformin should be avoided in patients with CKD stage G4 and G5.”

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