LO KIDNEY WEEK 1

1. Nephritic and nephrotic Syndrome

Nephrotic Syndrome
Nephrotic syndrome (see Figure 1) is usually a chronic condition and with the exception of MCD, most causes
eventually lead to chronic progressive renal failure. Common causes of nephrotic syndrome are listed in Table
3. Most minimal change diseases do respond to corticosteroids and a small fraction of patients are steroid
dependent. Edema in nephrotic syndrome is a combination of hypoalbuminemia and salt and water
retention4. In some could lead to hypertension especially in association with abnormal kidney function.
Proteinuria causes low albumin state and marked negative nitrogen balance and hyperlipidemia5. Loss of
coagulation proteins lead to hypercoagulable state and increased platelet aggregation. These patients have
increased risk of venous and arterial thromboembolism6. Low protein state increases risk for bacterial
infection7. It is not uncommon to have acute renal failure due to volume depletion, renal vein thrombosis, or
adverse drug reactions.

Common Causes of Nephrotic Syndrome

 Minimal change disease

 Focal segmental glomerulosclerosis

 Membranous GN

 Membranoproliferative GN (Type 1 and 2 and associated with cryoglobinemia)

 Daibetic nephropathy

 Amyloid

Nephritic Syndrome

Usually a result of glomerular inflammation (See Figure 1) and is associated with reduced kidney function, non-
nephrotic proteinuria, hematuria with red cell casts, hypertension and edema. A common mode of
presentation, represented by the acute post-streptococcal GN, is oliguria, cola colored urine, weight gain,
edema, and hypertension over a few days. Distinction between nephrotic and nephritic syndrome is usually
straight forward. However, some glomerular diseases especially the MPGN can present as nephrotic or
nephritic. Common causes of nephritic syndrome are listed in Table 4. Rapidly progressive renal failure is a hall
mark of rapidly progressive glomerulonephritis syndrome and presents with nephritic urine picture8.

Common Causes of Nephritic Syndrome

 Post-streptococcal GN

 Infective endocarditis

 Shunt nephritis

 IgA nephropathy

 Lupus Nephritis

 Goodpasture’s

 Vasculitis
 2. Oliguria, Anuria, Polyuria

Oliguria is defined as a urine output that is less than 1 mL/kg/h in infants, less than 0.5 mL/kg/h in children,
and less than 400 mL daily in adults. It is one of the clinical hallmarks of renal failure and has been used as a
criterion for diagnosing and staging acute kidney injury (AKI), previously referred to as acute renal failure. At
onset, oliguria is frequently acute. It is often the earliest sign of impaired renal function and poses a
diagnostic and management challenge to the clinician. (See Presentation and Workup.)  [1, 2] 
A standardized definition of AKI has recently been proposed by the Kidney Disease: Improving Global
Outcomes (KDIGO) AKI working group, which identifies and stages AKI based on changes in serum creatinine
from baseline or a decrease in urine output (oliguria) as shown below.  [3] 
KDIGO Staging of AKI (Open Table in a new window)

Stag
Serum creatinine Urine output
e

Increase by 1.5-1.9 times baseline within 7 days

OR Less than 0.5 mL/kg/h for
1
Increase by 0.3 mg/dL (26.5 µmol/L) or more within 48 6-12 hours
hours

Less than 0.5 mL/kg/h for

2 Increase by 2-2.9 times baseline
12 hours or longer

Increase by 3 times baseline or greater

OR
Less than 0.3 mL/kg/h for
Increase to 4 mg/dL (353.6 µmol/L) or greater
24 hours or longer
OR
3 OR
Renal replacement therapy initiation
Anuria for 12 hours or
OR
longer
In patients younger than 18 years, decrease in estimated
GFR to less than 35 mL/min/1.73m2

Urine formation

Glomerular Filtration

Glomerular filtration occurs as blood passes into the glomerulus producing a plasma-like filtrate (minus
proteins) that gets captured by the Bowman’s (glomerular) capsule and funneled into the renal tubule. This
filtrate produced then becomes highly modified along its route through the nephron by the following
processes, finally producing urine at the end of the collecting duct.

Tubular Reabsorption

As the filtrate travels along the length of the nephron, the cells lining the tubule selectively, and often
actively, take substances from the filtrate and move them out of the tubule into the blood. Recall that the
glomerulus is simply a filter and anything suspended in the plasma that can fit through the holes in the
filtration membrane can end up in the filtrate. This includes very physiologically important molecules such as
water, sodium, chloride, and bicarbonate (along with many others) as well as molecules that the digestive
system used a lot of energy to absorb, such as glucose and amino acids. These molecules would be lost in
the urine if not reclaimed by the tubule cells. These cells are so efficient that they can reclaim all of the
glucose and amino acids and up to 99% of the water and important ions lost due to glomerular filtration.
The filtrate that is not reasbsorbed becomes urine at the base of the collecting duct.

Tubular Secretion

Tubular secretion occurs mostly in the PCT and DCT where unfiltered substances are moved from the
peritubular capillary into the lumen of the tubule. Secretion usually removes substances from the blood that
are too large to be filtered (ex: antibiotics, toxins) or those that are in excess in the blood (ex: H +, K+). These
substances secreted into the tubule are destined to leave the body as components of urine.

Substances Secreted or Reabsorbed in the Nephron and Their Locations (Table 25.5)

Substance PCT Loop of Henle DCT Collecting ducts

Almost 100
percent
Glucose reabsorbed;
secondary active
transport with Na+

Almost 100
Oligopeptides,
percent
proteins, amino
reabsorbed;
acids
symport with Na+

Vitamins Reabsorbed

Lactate Reabsorbed

Creatinine Secreted
Substances Secreted or Reabsorbed in the Nephron and Their Locations (Table 25.5)

Substance PCT Loop of Henle DCT Collecting ducts

50 percent
Secretion, Reabsorption in
reabsorbed by
Urea diffusion in medullary collecting
diffusion; also
descending limb ducts; diffusion
secreted

25 percent
5 percent
65 percent reabsorbed in
5 percent reabsorbed,
Sodium actively thick ascending
reabsorbed; active stimulated by
reabsorbed limb; active
aldosterone; active
transport

Reabsorbed in
Reabsorbed, thin and thick
Reabsorbed;
Chloride symport with Na+, ascending limb; Reabsorbed; symport
diffusion
diffusion diffusion in
ascending limb

67 percent 15 percent Variable amounts

8 percent
reabsorbed reabsorbed in reabsorbed,
Water reabsorbed if
osmotically with descending limb; controlled by ADH,
ADH; osmosis
solutes osmosis osmosis

Reabsorbed,
80–90 percent
symport with
symport Reabsorbed antiport
Bicarbonate Na+ and antiport
reabsorption with with Cl–
with Cl–; in
Na+
ascending limb
Substances Secreted or Reabsorbed in the Nephron and Their Locations (Table 25.5)

Substance PCT Loop of Henle DCT Collecting ducts

H+ Secreted; diffusion Secreted; active Secreted; active

Secreted;
NH4+ Secreted; diffusion Secreted; diffusion
diffusion

Reabsorbed;
Reabsorbed; Reabsorbed; Reabsorbed; antiport
HCO3– diffusion in
diffusion diffusion with Na+
ascending limb

Some drugs Secreted Secreted; active Secreted; active

20 percent
65 percent Secretion controlled
reabsorbed in
Potassium reabsorbed; Secreted; active by aldosterone;
thick ascending
diffusion active
limb; symport

Reabsorbed in Reabsorbed if
Reabsorbed;
Calcium thick ascending parathyroid hormone
diffusion
limb; diffusion present; active

Reabsorbed in
Reabsorbed;
Magnesium thick ascending Reabsorbed
diffusion
limb; diffusion
 Substances Secreted or Reabsorbed in the Nephron and Their Locations (Table 25.5)

Substance PCT Loop of Henle DCT Collecting ducts

85 percent
reabsorbed,
inhibited by Reabsorbed;
Phosphate
parathyroid diffusion
hormone,
diffusion

KIDNEY ANATOMY

EXTERNAL ANATOMY

The left kidney is located at about the T12 to L3 vertebrae, whereas the right is lower due to slight
displacement by the liver. Upper portions of the kidneys are somewhat protected by the eleventh and
twelfth ribs (Figure 1). Each kidney weighs about 125–175 g in males and 115–155 g in females. They are
about 11–14 cm in length, 6 cm wide, and 4 cm thick, and are directly covered by a fibrous capsule
composed of dense, irregular connective tissue that helps to hold their shape and protect them. This capsule
is covered by a shock-absorbing layer of adipose tissue called the renal fat pad, which in turn is
encompassed by a tough renal fascia. The fascia and, to a lesser extent, the overlying peritoneum serve to
firmly anchor the kidneys to the posterior abdominal wall in a retroperitoneal position.

Figure 1. Kidneys. The kidneys are slightly protected by the ribs and are surrounded by fat for protection
(not shown).

On the superior aspect of each kidney is the adrenal gland. The adrenal cortex directly influences renal
function through the production of the hormone aldosterone to stimulate sodium reabsorption.

INTERNAL ANATOMY

A frontal section through the kidney reveals an outer region called the renal cortex and an inner region
called the medulla (Figure 2). The renal columns are connective tissue extensions that radiate downward
from the cortex through the medulla to separate the most characteristic features of the medulla, the renal
pyramids and renal papillae. The papillae are bundles of collecting ducts that transport urine made by
nephrons to the calyces of the kidney for excretion. The renal columns also serve to divide the kidney into
6–8 lobes and provide a supportive framework for vessels that enter and exit the cortex. The pyramids and
renal columns taken together constitute the kidney lobes.

RENAL HILUM

The renal hilum is the entry and exit site for structures servicing the kidneys: vessels, nerves, lymphatics,
and ureters. The medial-facing hila are tucked into the sweeping convex outline of the cortex. Emerging
from the hilum is the renal pelvis, which is formed from the major and minor calyxes in the kidney. The
smooth muscle in the renal pelvis funnels urine via peristalsis into the ureter. The renal arteries form
directly from the descending aorta, whereas the renal veins return cleansed blood directly to the inferior
vena cava. The artery, vein, and renal pelvis are arranged in an anterior-to-posterior order.

NEPHRONS AND VESSELS

The renal artery first divides into segmental arteries, followed by further branching to form interlobar
arteries that pass through the renal columns to reach the cortex (Figure 3). The interlobar arteries, in turn,
branch into arcuate arteries, cortical radiate arteries, and then into afferent arterioles. The afferent
arterioles service about 1.3 million nephrons in each kidney.

Nephrons are the “functional units” of the kidney; they cleanse the blood and balance the constituents of
the circulation. The afferent arterioles form a tuft of high-pressure capillaries about 200 µm in diameter,
the glomerulus. The rest of the nephron consists of a continuous sophisticated tubule whose proximal end
surrounds the glomerulus in an intimate embrace—this is Bowman’s capsule. The glomerulus and
Bowman’s capsule together form the renal corpuscle. As mentioned earlier, these glomerular capillaries
filter the blood based on particle size. After passing through the renal corpuscle, the capillaries form a
second arteriole, the efferent arteriole (Figure 4). These will next form a capillary network around the more
distal portions of the nephron tubule, the peritubular capillaries and vasa recta, before returning to the
venous system. As the glomerular filtrate progresses through the nephron, these capillary networks recover
most of the solutes and water, and return them to the circulation. Since a capillary bed (the glomerulus)
drains into a vessel that in turn forms a second capillary bed, the definition of a portal system is met. This is
the only portal system in which an arteriole is found between the first and second capillary beds. (Portal
systems also link the hypothalamus to the anterior pituitary, and the blood vessels of the digestive viscera to
the liver.)

Figure 4. Blood Flow in the Nephron. The two capillary beds are clearly shown in this figure. The efferent
arteriole is the connecting vessel between the glomerulus and the peritubular capillaries and vasa recta.

CORTEX

In a dissected kidney, it is easy to identify the cortex; it appears lighter in color compared to the rest of the
kidney. All of the renal corpuscles as well as both the proximal convoluted tubules (PCTs) and distal
convoluted tubules are found here. Some nephrons have a short loop of Henle that does not dip beyond
the cortex. These nephrons are called cortical nephrons. About 15 percent of nephrons have long loops of
Henle that extend deep into the medulla and are called juxtamedullary nephrons.

Renal insufficiency
What is renal insufficiency?

Renal insufficiency is poor function of the kidneys that may be due to a reduction in blood-flow to the
kidneys caused by renal artery disease. Normally, the kidneys regulate body fluid and blood pressure, as
well as regulate blood chemistry and remove organic waste. Proper kidney function may be disrupted,
however, when the arteries that provide the kidneys with blood become narrowed, a condition called renal
artery stenosis. Some patients with renal insufficiency experience no symptoms or only mild symptoms.
Others develop dangerously high blood pressure, poor kidney function, or kidney failure that requires
dialysis.
Symptoms of renal insufficiency

Patients suffering from renal insufficiency can have no symptoms or mild ones. Others can experience
severe hypertension (see renovascular hypertension).
Risk factors of renal insufficiency

The risk factors for renal insufficiency due to renal artery disease are those associated with atherosclerosis:
 Older age
 Gender
 Family history
 Race or ethnicity
 Genetic factors
 Hyperlipidemia (elevated fats in the blood)
 Hypertension (high blood pressure)
 Smoking
 Diabetes
 Obesity

Patients known to have atherosclerosis and diagnosed with coronary artery disease or peripheral artery
disease are at greater risk for renal insufficiency.
Chronic Renal Failure
The guidelines define CKD as either kidney damage or a decreased glomerular filtration rate (GFR) of less
than 60 mL/min/1.73 m2 for at least 3 months. Whatever the underlying etiology, once the loss of nephrons
and reduction of functional renal mass reaches a certain point, the remaining nephrons begin a process of
irreversible sclerosis that leads to a progressive decline in the GFR.  [4]

Signs and symptoms

Patients with CKD stages 1-3 are generally asymptomatic. Typically, it is not until stages 4-5 (GFR < 30
mL/min/1.73 m²) that endocrine/metabolic derangements or disturbances in water or electrolyte balance
become clinically manifest.
Signs of metabolic acidosis in stage 5 CKD include the following:
 Protein-energy malnutrition
 Loss of lean body mass
 Muscle weakness
Signs of alterations in the way the kidneys are handling salt and water in stage 5 include the following:
 Peripheral edema
 Pulmonary edema
 Hypertension
Anemia in CKD is associated with the following:
 Fatigue
 Reduced exercise capacity
 Impaired cognitive and immune function
 Reduced quality of life
 Development of cardiovascular disease
 New onset of heart failure or the development of more severe heart failure
 Increased cardiovascular mortality
Other manifestations of uremia in ESRD, many of which are more likely in patients who are being
inadequately dialyzed, include the following:
 Pericarditis: Can be complicated by cardiac tamponade, possibly resulting in death if unrecognized
 Encephalopathy: Can progress to coma and death
 Peripheral neuropathy, usually asymptomatic
 Restless leg syndrome
 Gastrointestinal symptoms: Anorexia, nausea, vomiting, diarrhea
 Skin manifestations: Dry skin, pruritus, ecchymosis
 Fatigue, increased somnolence, failure to thrive
 Malnutrition
 Erectile dysfunction, decreased libido, amenorrhea
 Platelet dysfunction with tendency to bleed
Screen adult patients with CKD for depressive symptoms; self-report scales at initiation of dialysis therapy
reveal that 45% of these patients have such symptoms, albeit with a somatic emphasis.

Etiology
Causes of chronic kidney disease (CKD) include the following:
 Diabetic kidney disease
 Hypertension
 Vascular disease
 Glomerular disease (primary or secondary)
 Cystic kidney diseases
 Tubulointerstitial disease
 Urinary tract obstruction or dysfunction
 Recurrent kidney stone disease
 Congenital (birth) defects of the kidney or bladder
 Unrecovered acute kidney injury
Vascular diseases that can cause CKD include the following:
 Renal artery stenosis
 Cytoplasmic pattern antineutrophil cytoplasmic antibody (C-ANCA)–positive and perinuclear
pattern antineutrophil cytoplasmic antibody (P-ANCA)–positive vasculitides
 ANCA-negative vasculitides
 Atheroemboli
 Hypertensive nephrosclerosis
 Renal vein thrombosis
Primary glomerular diseases include the following:
 Membranous nephropathy
 Alport syndrome
 Immunoglobulin A (IgA) nephropathy
 Focal and segmental glomerulosclerosis (FSGS)
 Minimal change disease
 Membranoproliferative glomerulonephritis (MPGN)
 Complement-related diseases (eg, atypical hemolytic-uremic syndrome [HUS], dense deposit
disease)
 Rapidly progressive (crescentic) glomerulonephritis
Secondary causes of glomerular disease include the following:
 Diabetes mellitus
 Systemic lupus erythematosus
 Rheumatoid arthritis
 Mixed connective tissue disease
 Scleroderma
 Granulomatosis with polyangiitis (formerly known as Wegener granulomatosis)
 Mixed cryoglobulinemia
 Endocarditis
 Hepatitis B and C
 Syphilis
 Human immunodeficiency virus (HIV) infection
 Parasitic infection
 Heroin use
 Gold
 Penicillamine
 Amyloidosis
 Light-chain deposition disease
 Neoplasia
 Thrombotic thrombocytopenic purpura (TTP)
 Shiga-toxin or Streptococcus pneumoniae – related HUS
  Henoch-Schönlein purpura
 Reflux nephropathy
Causes of tubulointerstitial disease include the following:
 Drugs (eg, sulfonamides, allopurinol)
 Infection (viral, bacterial, parasitic)
 Sjögren syndrome
 Tubulointerstitial nephritis and uveitis (TINU) syndrome
 Chronic hypokalemia
 Chronic hypercalcemia
 Sarcoidosis
 Multiple myeloma cast nephropathy
 Heavy metals
 Radiation nephritis
 Polycystic kidneys
 Cystinosis and other inherited diseases
Urinary tract obstruction may result from any of the following:
 Benign prostatic hypertrophy
 Urolithiasis (kidney stones
 Urethral stricture
 Tumors
 Neurogenic bladder
 Congenital (birth) defects of the kidney or bladder
 Retroperitoneal fibrosis

ACUTE RENAL FAILURE – Acute kidney injury (AKI), formerly known as acute renal failure (ARF) denotes a
sudden and often reversible reduction in the kidney function, as measured by glomerular filtration rate
(GFR).
Signs and symptoms
Skin
Skin examination may reveal the following in patients with AKI:
 Livedo reticularis, digital ischemia, butterfly rash
 Palpable purpura: systemic vasculitis
 Maculopapular rash: Allergic interstitial nephritis
 Track marks (ie, intravenous drug abuse): Endocarditis
Eyes
Eye examination may reveal the following:
 Keratitis, iritis, uveitis, dry conjunctivae: Autoimmune vasculitis
 Jaundice: Liver diseases
 Band keratopathy (ie, hypercalcemia): Multiple myeloma
 Signs of diabetes mellitus
 Signs of hypertension
 Atheroemboli: Retinopathy (ie, Hollenhorst plaque in cholesterol microembolism)
Ears
Examination of the patient’s ears may reveal the following signs:
 Hearing loss: Alport disease and aminoglycoside toxicity
 Mucosal or cartilaginous ulcerations: Granulomatosis with polyangiitis (Wegener granulomatosis)
Cardiovascular system
Cardiovascular examination may reveal the following:
 Irregular rhythms (ie, atrial fibrillation): Thromboemboli
 Murmurs: Endocarditis
 Pericardial friction rub: Uremic pericarditis
 Increased jugulovenous distention, rales, S 3: Heart failure
Abdomen
The following signs of acute kidney injury may be discovered during an abdominal examination:
 Pulsatile mass or bruit: Atheroemboli
 Abdominal or costovertebral angle tenderness: Nephrolithiasis, papillary necrosis, renal artery
thrombosis, renal vein thrombosis
 Pelvic, rectal masses; prostatic hypertrophy; distended bladder: Urinary obstruction
 Limb ischemia, edema: Rhabdomyolysis
Pulmonary system
Pulmonary examination may reveal the following:
 Rales: Pulmonary edema, infectious pulmonary process 
 Hemoptysis: ANCA (antineutrophilic cytoplasmic antibodies) vasculitis, anti–glomerular basement
membrane (anti-GBM, Goodpasture) syndrome

PITTING NON PITTING EDEMA

What is non-pitting edema?

Edema is the medical term for swelling that’s caused by extra fluid. Many things can cause edema, from
warm weather to thyroid conditions.

Doctors usually classify edema as either pitting or non-pitting. If you press a swollen area with your finger
and it doesn’t cause an indentation in the skin, it’s considered non-pitting edema.

Pitting edema is a general problem caused by a variety of issues such as:

 heart valve problems

 low protein levels
 deep venous thrombosis (DVT) — blood clots, usually in the legs
 severe lung disease
 congestive heart failure
 venous insufficiency
 liver disease
 kidney failure
 obesity
 pregnancy
 administration of intravenous fluids
 medications
 hot weather

Pitting vs. non-pittin edema

Areas of pitting edema respond to pressure, usually from a hand or finger. For example, when you press on
the skin with your finger, it’ll leave an indentation, even after you remove your finger. Chronic pitting edema
is often a sign of liver, heart, or kidney problems. It can also be a symptom of a problem with nearby veins.

Applying pressure to non-pitting edema, on the other hand, doesn’t cause any lasting indentation. It’s often
a sign of a condition affecting the thyroid or lymphatic system.

What causes non-pitting edema?

Lymphedema

Lymphedema is a condition that makes it difficult for lymph fluid to properly drain due to a blockage. It’s
often caused by a surgical procedure or as a secondary condition. You can also be born with it.

When lymph fluid can’t drain it accumulates and causes swelling. Lymphedema can be either pitting or non-
pitting.

Myxedema

Some people with severe or advanced hypothyroidism develop a condition called myxedema. It tends to

cause swollen legs and feet, but it can also cause swollen eyelids and lips. In some cases, it can also cause
tongue swelling.

Lipedema

Lipedema causes fat cells to grow and proliferate, and leads to increased fluid retention around the cells
which results in non-pitting edema that’s often tender or painful. It usually affects the legs and feet and
occurs almost exclusively in women.

FRANK STARLING LAW

The left ventricular performance (Frank-Starling) curves relate preload, measured as left ventricular end-
diastolic volume (EDV) or pressure, to cardiac performance, measured as ventricular stroke volume or
cardiac output. On the curve of a normally functioning heart, cardiac performance increases continuously as
preload increases. During states of increased left ventricular contractility, for example, due to
norepinephrine infusion, there is greater cardiac performance for a given preload. This is represented
graphically as an upward shift of the normal curve. Conversely, during states of decreased left ventricular
contractility associated with systolic heart failure, there is less cardiac performance for a given preload as
compared to the normal curve.  This is represented by a downward shift of the normal curve. Decreased
contractility also can result from a loss of myocardium as with myocardial infarction, beta-blockers (acutely),
non-dihydropyridine Ca++ channel blockers, and dilated cardiomyopathy.[4][5][6]

Changes in afterload, which is the force of resistance that the ventricle must overcome to empty contents at
the beginning of systole, will also shift the Frank-Starling curve. A decrease in afterload will cause an upward
shift of the ventricular performance curve in a similar fashion to an increase in inotropy. Conversely, an
increase in afterload will cause a downward shift of the curve in a similar fashion to a decrease in inotropy.  

Increase in catecholamines, such as norepinephrine, during exercise will result in an upward shift of the
Frank-Starling curve. Catecholamines achieve this increase by binding to a myocyte beta1-adrenergic
receptor, a g-protein coupled receptor, ultimately resulting in increased Ca++ channel release from the
sarcoplasmic reticulum which enhances the force of contraction.
RENAL FUNCTION TESTS USES AND LIMITATIONS

SERUM CREATININE

Uses
1. Serum creatinine measurement is used as a test of renal function. It is superior in this respect to [urea],
which is influenced considerably by non‐renal factors including protein turnover (whether derived from the
diet or endogenously) and the state of hydration.
2. Serum [creatinine] is used to monitor progression and treatment in acute kidney injury and chronic kidney
disease (CKD). In acute kidney injury, the frequency of measurements will usually be guided by clinical
factors and the need to monitor serum [potassium] but is unlikely to be less than once in 24 h.

In patients with CKD stages 1‐3 (i.e. eGFR ≥60 mL/min) measurements should be made 6‐ or at least 12‐
monthly according to whether eGFR is changing by more or less than 15 mL/min, respectively, between
successive measurements; in patients with more advanced CKD, the corresponding figures are 3‐ and 6‐
monthly.

3. Serum [creatinine] can be combined with measurements of urine creatinine in timed urine specimens to
generate the creatinine clearance, an indicator of the glomerular filtration rate (GFR). Such measurements
have poor reproducibility owing to the imprecision imposed by the difficulty in collecting accurately timed
urine specimens.
4. Serum [creatinine] can be used together with demographic information (e.g. age, race, sex) to calculate
an estimated GFR (eGFR). In the UK, it is recommended that eGFR should be based on the MDRD
(Modification of Diet in Renal Disease) 4‐variable formula (e.g. Levey AS, Coresh J, Greene T et al for the
Chronic Kidney Disease Epidemiology Collaboration. Using Standardized Serum Creatinine Values in the
Modification of Diet in Renal Disease Study Equation for Estimating Glomerular Filtration Rate. Ann Int Med
2006;145:247‐254). However, this concept is open to criticism (e.g Giles PD, Fitzmaurice DA. Formula
estimation of glomerular filtration rare: have we gone wrong? BMJ 2007;334:1198‐2000) and is not
applicable to several clinical situations e.g. acute kidney disease, children, individuals with muscle‐wasting
etc.

3.1 Limitations
Serum [creatinine] has a wide normal reference interval; it is inversely related to GFR. As a result, GFR may
fall to half normal before serum [creatinine] exceeds the upper reference limit. The influence of muscle bulk
and, to a much lesser extent, dietary protein intake, on creatinine production, means that a (slightly)
elevated [creatinine] may not indicate impaired renal function