Chronic kidney disease (CKD) in the elderly – a geriatrician's perspective

Figures & data

Table I.  Anatomical changes in kidney with aging.

1	Renal mass	Decreased by 30%, mainly due to cortical loss.
2	Glomerular changes	Glomerulosclerosis.
		Ischaemia of cortical glomeruli → decrease in the number of glomeruli by 30 to 50% by age 70.
		Relative sparing of medullary glomeruli.
3	Mesangium	Increase in mesangial volume.
4	Renal tubules	Decrease in number, sclerosis and atrophy leading to distal diverticula. (The diverticula may represent the earliest formation of acquired cysts as seen in aged kidneys or may collect bacteria and debris possibly predisposing to pyelonephritis.)
5	Vascular	Intra-renal vascular changes occur independently of hypertension or other renal disease.
		Increased arteriosclerosis of intrarenal vessels and interlobular and arcuate arteries.
		Cortical efferent arteriole obliteration.
		In juxtamedullary glomeruli, afferent-to-efferent arteriolar shunting rendering redistribution of blood flow to the renal medulla.

Table II.  Functional changes in kidney with aging.

1	Renal plasma flow (RPF)	Reduced rate of approximately 10% per decade from age 30 years [48].
2	Glomerular filtration rate (GFR)	Creatinine clearance decreases linearly from 140 mL/min/1.73 m^2during the third or fourth decade to about 97 mL/min/1.73 m^2 by 80 years of age. This is a decline at the rate of about 0.8 ml/min/1.73 m^2 per year or by about 7% every decade after the age of 40 [48],[50].^☆§†π
3	Renal blood flow	Preferential decrease in cortical blood flow and preservation of medullary flow with age, paralleling histologic changes of loss of selective cortical vasculature [48].
4	Ability to concentrate or dilute urine	Impaired in aging kidney.
		Other contributing factors include: blunted response to anti-diuretic hormone (ADH) and the inhibitory effect of the increased atrial natriuretic peptide (ANP) on renin-angiotensin cascade, aldosterone and ADH in the elderly [6].
5	Acid, base and electrolytes	Ability to conserve sodium in the face of hyponatraemia (possibly secondary to decreased distal reabsorption) or excrete it when required is decreased [6],[46],[51].
		Under the stress of acid load, aged kidney shows impairment in excreting it [46].
		While calcium handling is not affected much by the aging kidney, potassium excretion is affected. This is due to decreased plasma renin and aldosterone, in turn leading to a relative hypoaldosteronism and also due to blunting of the response to aldosterone [46].

^☆It is important to note that observations from the Baltimore Longitudinal Study of Aging indicate that about a third of the patients followed for about a 30-year period showed no such changes [46],[48],[49]. This could imply that such changes are not inevitable with aging alone and there may possibly be other factors influencing the progress of kidney function with time. If these factors are well determined, there is perhaps good potential to help our elderly patients who are more predisposed than the rest for kidney disease.

^†Elderly African Americans showed greater decline in creatinine clearance compared to the elderly white Americans [52].

^§Dr Fliser and colleagues showed in their study of renal functional reserve in healthy elderly subjects that in the elderly without other co-morbid conditions, GFR and RPF are only slightly lower. They also showed renal functional reserve is preserved at least until age 80 years in these subjects [53].

^πCreatinine may not reflect the kidney function accurately in the elderly as the level of creatinine may remain normal due to declining muscle mass even in the face of significant reduction in kidney function [54]. Clinical implication is that we may overestimate GFR by depending on serum creatinine (S_Cr) alone in the elderly.

Table III.  NKF stages of chronic kidney disease and action plan.^☆.

Stage	Description/metabolic consequences	GFR (ml/min/1.73 m^3)	Action plan
–	Risk factors (RF) CKD present	>60	Screen for CKD, RF reduction.
1	Kidney damage with normal or increased GFR	≥90	CKD diagnosis and treatment, interventions to slow CKD progression, treat co-morbid condition and CVD risk reduction.
2	Kidney damage with mild ↓ GFR	60–89	Estimate disease progression.
	• Parathyroid hormone Concentration begins to rise (GFR ∼60–80)
3	Moderate ↓ GFR	30–59	Evaluate and treat complications.
	• Decrease in calcium absorption (GFR ∼60)
	• Malabsorption
	• Lipoprotein activity falls
	• Onset of left ventricular hypertrophy
	• Onset of anaemia (erythropoietin deficiency)
4	Severe ↓ GFR	15–29	Preparation for kidney replacement therapy (dialysis or kidney transplantation).
	• Triglycerides start to ↑
	• Hyperphosphataemia
	• Tendency to hyperkalaemia
	• Metabolic acidosis
5	Kidney failure	<15 (or dialysis)	Kidney replacement therapy (if uraemia present and patient desires).
	• Azotaemia develops

KDOQI Clinical Practice Guidelines for Chronic Kidney Disease: Evaluation, Classification, and Stratification. Accessed at: http://www.kidney.org/professionals/KDOQI/guidelines_ckd/pd4_class_g1.htm. Adapted with permission from the National Kidney Foundation [57].

^☆Includes actions from preceding stages.

Table IV.  Values for proteinuria [57].

	Urine collection method	Normal	Micro-albuminuria	Albuminuria or clinical proteinuria
Total protein	24-hour excretion (varies with method)	<300 mg/day	NA	>300 mg/day
	Spot urine protein-to-creatinine ratio (varies with method)	<200 mg/g	NA	>200 mg/g
Albumin	24-hour excretion	<30 mg/day	30–300 mg/day	>300 mg/day
	Spot urine albumin-to-creatinine ratio	<30 mg/g	30–300 mg/g	>300 mg/g

Table V.  Factors that might influence serum cystatin C levels.

Increase in	Decrease in
• Hypothyroidism [70-72]	• Hyperthyroidism [70-72]
• Steroid use [73]
• Rheumatoid arthritis [73]

Table VI.  Advantages and disadvantages of using cystatin C for estimating GFR.

Advantages	Disadvantages
• A useful alternative in patients whose renal function estimation may be not be so reliable using the creatinine based methods like MDRD due to variations in endogenous creatinine production or high GFR [76].	• Not well studied yet, its accuracy is unknown and is not standardized for clinical practice [65].
	• Preliminary evidence suggesting extra renal excretion increases with reduced GFR is still a concern for it to be a near ideal marker of GFR [65].
• GFR estimates based solely on serum cystatin C levels had the same predictive potential when compared with the MDRD-4 and C-G formulas [77].^☆	• Although there has been clinical data accumulating in the literature, cystatin C has not been widely used. Contributing factors for this may be lack of definitive normal values, conflicting results in clinical studies, lack of clear evidence on when and how to request the test, accessibility and cost factor [64].

^☆MDRD–4–modification of diet in renal disease 4 variable formula; C-G, Cockcroft-Gault formula.

Table VII.  Limitations of both estimation equations (eGFR).

Both CG and MDRD reliability and/or accuracy decreased in	Examples
Unstable renal function as both equations require stable renal function or steady creatinine level for their accurate use [81].	Acute changes in kidney function (e.g. acute kidney failure): wherein GFR has decreased acutely without time for plasma creatinine to accumulate and reflect an increase implying acute renal dysfunction, these equations may not reflect it accurately either [60].
	Interference with creatinine secretion or creatinine assay (diabetic ketoacidosis or administration of certain cephalosporins) either due to medications or medical conditions can lead to inaccurate estimations [79].
Significant variations in diet or muscle mass as these are not specifically taken into account in these equations [60],[82].	Exceptional dietary intake as in vegetarian diet, high protein diet, creatine supplements.
	Malnutrition, muscle wasting, diseases of skeletal muscle, paraplegia, those with high muscle mass, amputees and extremes of body size.

Table VIII.  Limitations of MDRD equation-derived eGFR.

MDRD reliability and/or accuracy decreased	Examples
In those conditions for which appropriate conclusive, validation studies are lacking [83-92].^☆	Healthy adults and in those with higher GFRs (underestimated in both).
	Elderly.^§
	Some ethnic groups including some of the Asian population.
	Patients with eGFR values above 60 mL/min/1.73 m^2, i.e., in normal renal function or near normal or mild impairment.
	Patients with lowest levels of renal function as in dialysis-dependent patients.
	Calculations for drug dosing.^☆

^☆Drug prescription practice is currently widely based on creatinine clearance. MDRD derived GFR is adjusted to the body surface area (mL/min) but drug dosing modification in renal conditions may require GFR that is not adjusted for it. This can be done by multiplying the value of MDRD estimated GFR by the term body surface area or 1.73 m² without loss of accuracy [79].

^§Validation has been done to an extent [54],[93-95].

Table IX.  Clues to the diagnosis of chronic kidney diseases from the patient's history.

Clue	Potential diagnosis
Review of systems
Symptoms during urination	Usually suggests disorders of the urinary tract such as infection, obstruction or stones.
Recent infections	May suggest post-infectious glomerulonephritis or HIV-associated nephropathy.
Skin rash or arthritis	Suggests autoimmune diseases, e.g. systemic lupus erythematosis or cryoglobinaemia.
Risk factors for parenterally transmitted diseases	May suggest HIV, hepatitis C infection and associated kidney diseases.
Tiredness, decreased energy, impairment in thinking clearly, anorexia, insomnia, pruritus, nocturnal muscle cramps, oedema of extremities or puffiness around the eyes in the morning	CKD from any cause.
Chronic diseases
Heart failure, cirrhosis or gastrointestinal fluid losses	Suggests reduced kidney perfusion (‘pre-renal factors’).
Diabetes^a	As a cause of chronic kidney disease diabetic kidney disease usually follows a typical clinical course after onset, first with microalbuminuria, followed by clinical proteinuria, hypertension and declining GFR.
Hypertension^a	As a cause of chronic kidney disease, hypertensive nephrosclerosis is usually characterized by severely elevated blood pressure readings over a long period of time, with associated end organ-damage in addition to kidney disease. Recent worsening of hypertension, in association with findings of diffuse atherosclerosis, suggests large vessel disease due to atherosclerosis. Recent onset of severe hypertension in young women suggests large vessel disease due to fibromuscular dysplasia.
Past medical history
Findings from past ‘routine’ examinations	May reveal a history of hypertension or proteinuria during childhood, pregnancy, or on examinations for school, military service or insurance.
Past urologic evaluations	Details may disclose radiological abnormalities associated with kidney disease.
Family history of kidney diseases
Every generation; equal susceptibility in males and females	Suggests an autosomal dominant disease, such as polycystic kidney disease.
Every generation; predominant male susceptibility	Suggests a sex-linked recessive disease, such as Alport's syndrome.
Less frequent than every generation	Suggests an autosomal recessive disease, such as medullary cystic kidney disease or autosomal recessive polycystic kidney disease.

KDOQI Clinical Practice Guidelines for Chronic Kidney Disease: Evaluation, Classification, and Stratification. Accessed at: http://www.kidney.org/professionals/KDOQI/guidelines_ckd/p9_approach.htm. Reprinted with permission from the National Kidney Foundation [55].

^aExtremely common in elderly patients and often non-specific.

Table X.  Risk factors for CKD.

Type	Definition	Examples
Susceptibility factors	Factors that increase susceptibility to kidney damage	Older age, family history of CKD, reduction in kidney mass, low birth weight, US racial or ethnic minority status, low income or educational level.
Initiation factors	Factors that directly initiate kidney damage	Diabetes mellitus, high blood pressure, autoimmune diseases, systemic infections, urinary tract infections, urinary stones, obstruction of lower urinary tract, drug toxicity.

KDOQI Clinical Practice Guidelines for Chronic Kidney Disease: Evaluation, Classification, and Stratification. Accessed at http://www.kidney.org/professionals/KDOQI/guidelines_ckd/p9_approach.htm. Reprinted with permission from the National Kidney Foundation [55].

Table XI.  Clinical evaluation of patients at increased risk of CKD.

All patients

a) Measurement of blood pressure.

b) Serum creatinine to estimate GFR.

c) Protein-to-creatinine ratio or albumin-to-creatinine ratio in a first-morning or random untamed ‘spot’ urine specimen.

d) Examination of the urine sediment or dipstick for red blood cells and white blood cells.

Selected patients, depending on risk factors

a) Ultrasound imaging (for example, in patients with symptoms of urinary tract obstruction, infection or stone, or family history of polycystic kidney disease).

b) Serum electrolytes (sodium, potassium, chloride and bicarbonate).

c) Urinary concentration or dilution (specific gravity or osmolality).

d) Urinary acidification (pH).

KDOQI Clinical Practice Guidelines for Chronic Kidney Disease: Evaluation, Classification, and Stratification. Accessed at: http://www.kidney.org/professionals/KDOQI/guidelines_ckd/p9_approach.htm. Reprinted with permission from the National Kidney Foundation [55].

Table XII.  Simplified classification of CKD based on diagnosis.

Disease	Major types (examples)
Diabetic kidney disease	Type 1 and type 2 diabetes
Non-diabetic kidney diseases	Glomerular diseases (Autoimmune diseases, systemic infections, drugs, neoplasia)
	Vascular diseases (Large vessel disease, medium sized vessel diseases, hypertension, microangiopathy)
	Tubulo-interstitial diseases (Urinary tract infections, stones, obstructions and drug toxicity)
	Cystic diseases (Polycystic kidney diseases)
Diseases in the transplant	Chronic rejection
	Drug toxicity Cyclosporine or tacrolimus
	Recurrent diseases Glomerular diseases
	Transplant glomerulopathy

KDOQI Clinical Practice Guidelines for Chronic Kidney Disease: Evaluation, Classification, and Stratification. Accessed at: http://www.kidney.org/professionals/KDOQI/guidelines_ckd/p9_approach.htm. Reprinted with permission from the National Kidney Foundation [55].

Table XIII.  Clinical evaluation of elderly individuals with GFR of 60–80 ml/min/1.73 m².

All individuals

1. Assessment of CKD risk factors.

2. Measurement of blood pressure.

3. Albumin-to-creatinine ratio in a ‘spot’ urine specimen.

4. Examination of the urine sediment of dipstick for red blood cells and white blood cells.

KDOQI Clinical Practice Guidelines for Chronic Kidney Disease: Evaluation, Classification, and Stratification. Accessed at: http://www.kidney.org/professionals/KDOQI/guidelines_ckd/p9_approach.htm. Reprinted with permission from the National Kidney Foundation [55].

Table XIV.  Possible additional parameters to assess (see other guidelines).

Clinical problem	Parameters to assess	Possible additional parameters to assess
Anaemia	Haemoglobin	If anaemic:
		• Red blood cell indices
		• Reticulocyte count
		• Iron studies (serum iron, total binding capacity, percent transferrin saturation and ferritin)
		• Test for occult blood in stool
		• Medical evaluation for co-morbid conditions
Malnutrition	1. Weight	If malnourished:
	2. Serum albumin	• 24-hour urine collection for urea nitrogen excretion
	3. Dietary history	• Food recall/records for protein and total energy intake
	4. Subjective global assessment	• Medical evaluation for co-morbid conditions
Bone disease	1. Serum PTH	If abnormal:
	2. Serum calcium	• Consider vitamin D levels
	3. Serum phosphorous	• Consider bone x-rays
		• Consider DEXA scan
Neuropathy	1. Parasthesias	If symptomatic:
	2. Mental status Abnormalities	• Neurologic exam, including mental status
	3. Sleep disturbances	• Serum electrolytes
	4. Restless legs	• Medical evaluation for co-morbid conditions
		• Consider nerve conduction velocity
		• Consider EEG/sleep studies
Reduced functioning and well-being^☆	Standardized, Self-administered instruments such as:	If abnormal:
		• Medical evaluation for comorbid conditions
	Dartmouth	• Self-management education
	COOP charts	• Physical rehabilitation
	Duke/DUSOI	• Mental health treatment
	SF-36	• Social support
	KDQOL	• Vocational rehabilitation

^☆Symptoms, physical functioning, depression, employment and usual activities, social functioning; DEXA-dual energy x-ray absorptiometry (bone densitometry); EEG-Electroencephalogram.

KDOQI Clinical Practice Guidelines for Chronic Kidney Disease: Evaluation, Classification, and Stratification. Accessed at: http://www.kidney.org/professionals/KDOQI/guidelines_ckd/p9_approach.htm. Reprinted with permission from the National Kidney Foundation [55].

Table XV.  Treatments to slow the progression of CKD in adults.

	Diabetic kidney disease	Non-diabetic kidney disease	Kidney disease in the transplant
Strict glycaemic control	Yes^a	NA	Not tested
ACE-inhibitors or	Yes	Yes (greater effect in patients with proteinuria)	Not tested
Angiotensin-receptor blockers
Strict blood pressure control	Yes	Yes	Not tested
	<125/75 mm Hg	<130/85 mm Hg (Effect > in patients with proteinuria)
		<125/75 mm Hg (in patients with proteinuria)
Dietary protein restriction	Inconclusive	Inconclusive	Not tested

^aPrevents or delays the onset of diabetic kidney disease. Inconclusive with regard to progression of established disease.

KDOQI Clinical Practice Guidelines for Chronic Kidney Disease: Evaluation, Classification, and Stratification. Accessed at: http://www.kidney.org/professionals/KDOQI/guidelines_ckd/p9_approach.htm. Reprinted with permission from the National Kidney Foundation [55].

Table XVI.  Epoetin alfa use in CKD patients [171],[172],[176].^§.

	Initial administration		Adjustments
	SC	IV	When to increase the dose and how?	When to decrease the dose and how?
Monitoring Hgb:	80 to 120 U/Kg/week in 2 to 3 divided doses.	120 to 180 U/Kg/week in 3 divided doses (note: higher dosage in IV than SC route).	Increase by 25% after 4 weeks if initial dosing levels fail to increase Hgb by 0.3 to 0.5 g/dl per week.	If Hgb increases by 2.5 to 3 g/dl per month, reduce by 10 to 25%. Some clinicians recommend holding the dose for a week especially in rapid responders.
Weekly with initiation or adjustment of dose till target Hgb reached, thereafter, every 2 to 4 weeks.
	Switching from IV to SC dose in haemodialysis (HD) patients.		Switching from SC to IV in HD patients intolerant to SC administration.
	If target Hgb not yet reached.	If target Hgb is already reached.	If dosage is known, 50% higher than SC dose should be used; if not known, 120 to 180 U/Kg/week in 2 to 3 divided doses should be used.
	Total weekly IV dose should be administered in 2 to 3 SC divided doses.	The initial SC dose should be two thirds the weekly IV dose.

^§Following renal transplant, erythropoietin production is delayed for 8 to 30 days but there is no data to support with supplement during the immediate post transplant period. Side effects of erythropoietin: hypertension, headache, influenza-like syndrome, pure red cell aplasia. Adjust the antihypertensive medication rather than withholding the ESA treatment if blood pressure increases. Calcium channel blockers may be preferable in erythropoietin induced hypertension treatment in haemodialysis patients [134].

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