Chronic kidney disease

Chronic kidney disease (CKD), also known as chronic renal disease, is a progressive loss of
renal function over a period of months or years. The symptoms of worsening kidney function
are unspecific, and might include feeling generally unwell and experiencing a reduced appetite.
Often, chronic kidney disease is diagnosed as a result of screening of people known to be at risk
of kidney problems, such as those with high blood pressure or diabetes and those with a blood
relative with chronic kidney disease. Chronic kidney disease may also be identified when it
leads to one of its recognized complications, such as cardiovascular disease, anemia or
pericarditis.

Chronic kidney disease is identified by a blood test for creatinine. Higher levels of creatinine
indicate a falling glomerular filtration rate (rate at which the kidneys filter blood) and as a result
a decreased capability of the kidneys to excrete waste products. Creatinine levels may be
normal in the early stages of CKD, and the condition is discovered if urinalysis (testing of a
urine sample) shows that the kidney is allowing the loss of protein or red blood cells into the
urine. To fully investigate the underlying cause of kidney damage, various forms of medical
imaging, blood tests and often renal biopsy (removing a small sample of kidney tissue) are
employed to find out if there is a reversible cause for the kidney malfunction.Recent
professional guidelines classify the severity of chronic kidney disease in five stages, with stage
1 being the mildest and usually causing few symptoms and stage 5 being a severe illness with
poor life expectancy if untreated. Stage 5 CKD is also called established chronic kidney
disease and is synonymous with the now outdated terms end-stage renal disease (ESRD),
chronic kidney failure (CKF) or chronic renal failure (CRF).

There is no specific treatment unequivocally shown to slow the worsening of chronic kidney
disease. If there is an underlying cause to CKD, such as vasculitis, this may be treated directly
with treatments aimed to slow the damage. In more advanced stages, treatments may be
required for anemia and bone disease. Severe CKD requires one of the forms of renal
replacement therapy; this may be a form of dialysis, but ideally constitutes a kidney transplant.
Signs and symptoms

Initially it is without specific symptoms and can only be detected as an increase in serum
creatinine or protein in the urine. As the kidney function decreases:

blood pressure is increased due to fluid overload and production of vasoactive hormones,
increasing one's risk of developing hypertension and/or suffering from congestive heart
failure
Urea accumulates, leading to azotemia and ultimately uremia (symptoms ranging from
lethargy to pericarditis and encephalopathy). Urea is excreted by sweating and
crystallizes on skin ("uremic frost").
Potassium accumulates in the blood (known as hyperkalemia with a range of symptoms
including malaise and potentially fatal cardiac arrhythmias)
Erythropoietin synthesis is decreased (potentially leading to anemia, which causes
fatigue)
Fluid volume overload - symptoms may range from mild edema to life-threatening
pulmonary edema
Hyperphosphatemia - due to reduced phosphate excretion, associated with hypocalcemia
(due to vitamin D3 deficiency). The major sign of hypocalcemia being tetany.
o Later this progresses to tertiary hyperparathyroidism, with hypercalcaemia, renal
osteodystrophy and vascular calcification that further impairs cardiac function.
Metabolic acidosis, due to accumulation of sulfates, phosphates, uric acid etc. This may
cause altered enzyme activity by excess acid acting on enzymes and also increased
excitability of cardiac and neuronal membranes by the promotion of hyperkalemia due to
excess acid (acidemia)

People with chronic kidney disease suffer from accelerated atherosclerosis and are more likely
to develop cardiovascular disease than the general population. Patients afflicted with chronic
kidney disease and cardiovascular disease tend to have significantly worse prognoses than those
suffering only from the latter.

Diagnosis

In many CKD patients, previous renal disease or other underlying diseases are already known.
A small number presents with CKD of unknown cause. In these patients, a cause is occasionally
identified retrospectively.[citation needed]

It is important to differentiate CKD from acute renal failure (ARF) because ARF can be
reversible. Abdominal ultrasound is commonly performed, in which the size of the kidneys are
measured. Kidneys with CKD are usually smaller (< 9 cm) than normal kidneys with notable
exceptions such as in diabetic nephropathy and polycystic kidney disease. Another diagnostic
clue that helps differentiate CKD and ARF is a gradual rise in serum creatinine (over several
months or years) as opposed to a sudden increase in the serum creatinine (several days to
weeks). If these levels are unavailable (because the patient has been well and has had no blood
tests) it is occasionally necessary to treat a patient briefly as having ARF until it has been
established that the renal impairment is irreversible.

Additional tests may include nuclear medicine MAG3 scan to confirm blood flows and
establish the differential function between the two kidneys. DMSA scans are also used in renal
imaging; with both MAG3 and DMSA being used chelated with the radioactive element
Technetium-99.

In chronic renal failure treated with standard dialysis, numerous uremic toxins accumulate.
These toxins show various cytotoxic activities in the serum, have different molecular weights
and some of them are bound to other proteins, primarily to albumin. Such toxic protein bound
substances are receiving the attention of scientists who are interested in improving the standard
chronic dialysis procedures used today

Stages

A Glomerular filtration rate (GFR) <60 mL/min/1.73 m2 for 3 months are classified as having
chronic kidney disease, irrespective of the presence or absence of kidney damage. The rationale
for including these individuals is that reduction in kidney function to this level or lower
represents loss of half or more of the adult level of normal kidney function, which may be
associated with a number of complications.

All individuals with kidney damage are classified as having chronic kidney disease, irrespective
of the level of GFR. The rationale for including individuals with GFR 60 mL/min/1.73 m 2 is
that GFR may be sustained at normal or increased levels despite substantial kidney damage and
that patients with kidney damage are at increased risk of the two major outcomes of chronic
kidney disease: loss of kidney function and development of cardiovascular disease.

The loss of protein in the urine is regarded as an independent marker for worsening of renal
function and cardiovascular disease. Hence, British guidelines append the letter "P" to the stage
of chronic kidney disease if there is significant protein loss.

Stage 1 CKD

Slightly diminished function; Kidney damage with normal or relatively high GFR (>90
mL/min/1.73 m2). Kidney damage is defined as pathologic abnormalities or markers of damage,
including abnormalities in blood or urine test or imaging studies.
Stage 2 CKD

Mild reduction in GFR (60-89 mL/min/1.73 m2) with kidney damage. Kidney damage is
defined as pathologic abnormalities or markers of damage, including abnormalities in blood or
urine test or imaging studies.

Stage 3 CKD

Moderate reduction in GFR (30-59 mL/min/1.73 m2). British guidelines distinguish between
stage 3A (GFR 45-59) and stage 3B (GFR 30-44) for purposes of screening and referral.

Stage 4 CKD

Severe reduction in GFR (15-29 mL/min/1.73 m2)[1] Preparation for renal replacement therapy

Stage 5 CKD

Established kidney failure (GFR <15 mL/min/1.73 m 2, or permanent renal replacement therapy
(RRT)[1]

Causes

The most common causes of CKD are diabetic nephropathy, hypertension, and
glomerulonephritis. Together, these cause approximately 75% of all adult cases. Certain
geographic areas have a high incidence of HIV nephropathy.

Historically, kidney disease has been classified according to the part of the renal anatomy that is
involved, as

Vascular, includes large vessel disease such as bilateral renal artery stenosis and small
vessel disease such as ischemic nephropathy, hemolytic-uremic syndrome and vasculitis
Glomerular, comprising a diverse group and subclassified into
o Primary Glomerular disease such as focal segmental glomerulosclerosis and IgA
nephritis
o Secondary Glomerular disease such as diabetic nephropathy and lupus nephritis
Tubulointerstitial including polycystic kidney disease, drug and toxin-induced chronic
tubulointerstitial nephritis and reflux nephropathy
Obstructive such as with bilateral kidney stones and diseases of the prostate

Treatment
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The goal of therapy is to slow down or halt the otherwise relentless progression of CKD to
stage 5. Control of blood pressure and treatment of the original disease, whenever feasible, are
the broad principles of management. Generally, angiotensin converting enzyme inhibitors
(ACEIs) or angiotensin II receptor antagonists (ARBs) are used, as they have been found to
slow the progression of CKD to stage 5. Although the use of ACE inhibitors and ARBs
represents the current standard of care for patients with CKD, patients progressively lose kidney
function while on these medications, as seen in the IDNT and RENAAL studies, which reported
a decrease over time in estimated glomerular filtration rate (an accurate measure of CKD
progression, as detailed in the K/DOQI guidelines) in patients treated by these conventional
methods.

Currently, several compounds are in development for CKD. These include, but are not limited
to, bardoxolone methyl, olmesartan medoxomil, sulodexide, and avosentan

Replacement of erythropoietin and vitamin D3, two hormones processed by the kidney, is
usually necessary in patients with CKD, as is calcium. Phosphate binders are used to control the
serum phosphate levels, which are usually elevated in chronic kidney disease.

When one reaches stage 5 CKD, renal replacement therapy is required, in the form of either
dialysis or a transplant.

In some cases, dietary modifications have been proven to slow and even reverse further
progression. Generally this includes limiting a persons intake of protein

Prognosis

The prognosis of patients with chronic kidney disease is guarded as epidemiological data has
shown that all cause mortality (the overall death rate) increases as kidney function decreases.
The leading cause of death in patients with chronic kidney disease is cardiovascular disease,
regardless of whether there is progression to stage 5.

While renal replacement therapies can maintain patients indefinitely and prolong life, the
quality of life is severely affected.[13][14] Renal transplantation increases the survival of patients
with stage 5 CKD significantly when compared to other therapeutic options; however, it is
associated with an increased short-term mortality (due to complications of the surgery).
Transplantation aside, high intensity home hemodialysis appears to be associated with improved
survival and a greater quality of life, when compared to the conventional three times a week
hemodialysis and peritoneal dialysis.

Why separate acute from chronic renal failure?

- Management is different
- Manifestations may be similar
- Prognosis is different: Chronic Renal Failure irreversible; Acute Renal Failure
reversible

Functions of the Kidney Measure

d using:
Excretory function BUN,
creatinin
e
Maintenance of Acid Base pH,
Balance HCO3,
pCO2
Maintenance of Fluid and Osmolali
Electrolyte Balance ty, water,
Na, K,
Cl
Maintenance of Ca-Phosphate Ca,
Balance Phosphat
es
(Mineral balance) (Mg)
Vitamin D production Calcium
Erythropoeitin Production Hgb, hct
for
confirma
tion

Chronic Renal Failure (CRF)

-Pathophysiologic process which is a result of varied conditions that leads to irreversible

destruction of nephrons, ultimately leading to End Stage Kidney Disease (ESRD).
-Sum of all processes that happen cause by various diseases such as DM, hpn, GN,
lupus, secondary causes due to multiple myeloma, etc.
- Slow deterioration of kidney function
- Loss of nephrons other nephrons try to compensate
during CRF phase, you dont see manifestations of ESRD
- Normal GFR men:100ml/min; women:85ml/min
- Just keep in mind that the key word in CRF is COMPENSATION
- DO NOT MAKE THE MISTAKE OF DIALYSING A PATIENT WITH CRF!

Spectrum of CRF:

Normal kidney CRF (>3mos) ESRD

Pathophysiology
-Long term reduction of renal mass / function which initially leads to compensatory
hypertrophy and function. Eventually this leads to sclerosis of the remaining nephron,
resulting to ESRD.

Stages of Chronic Renal Disease

Stag Description GFR,

e mL/min per
1.73 m2
1 At increased risk of 90 (with CRD
kidney damage with risk factors)
normal or increased 90
GFR
2 Kidney damage 60-89
with mildly
decreased GFR
3 Moderately 30-59
decreased GFR
4 Severely decreased 15-29
GFR
5 Renal Failure < 15
(ESRD)

GFR

CRF: 16-89 mL/min

ESRD: <15 mL/min

Difference between CRF & ESRD in terms of Pathophysiology

CRF there is hyperfiltration, some amount of compensation

ESRD no more compensation; all other organ systems will end up with some kind of
dysfunction

Chronic End-Stage
Kidney Renal Renal
Function Failure Disease
(CRF) (ESRD)
Excretory No signs / Nausea /
Function symptoms vomiting
BUN BUN
Creatinine,
Creatinine,
Cystatin C Cystatin C
Maintenan No RR
ce of ManifestatioKussmaul
Acid- ns breathing
Base Normal acid-Metabolic
Balance base balanceAcidosis
Maintenan RR
ce of BP Arrythmia
Fluid & NVE NVE
Electrolyt Crackles Crackles
e Balance Edema Edema
Na Normal Na Normal
K Normal K
or
Maintenan No Osteitis
ce of manifestatio fibrosa
Calcium- ns cystica
Phosphat Phosphate Phosphate
e Balance Ca Ca
Vitamin D No Osteomalacia
Productio manifestatio Calcitriol
n ns
Calcitriol
(see diagram
below)
Erythropoi Weakness Weakness
 etin Dizziness Dizziness
Productio Pallor Pallor
n Easy Easy
Fatigability Fatigability

Hemoglobin Hemoglobin

Excretory function:
1.5mg creatinine
10-20 BUN depending on level of hydration
Cystatin- only used in lab research for now
Maintenance of Acid-Base Balance:
Still with compensation
Maintenance of Fluid & Electrolyte Balance:
For fluids, think also of sodium going along with it
Creatinine clearance >60, accumulation of Na
Increased BP: CM, lupus, GN
No signs/symptoms, normal BP: may also have renal failure, creatinine worsening
Buko juice: causes hyperkalemia; so AVOID DRINKING BUKO JUICE WHEN YOU
HAVE KIDNEY PROBLEMS UNLESS YOU HAVE LOW POTASSIUM
Buko juice, bananas good fore people with diarrhea
Nephrologists should therefore identify patients are Na or K wasters. If this is the case then
dont let them avoid Na of K.
Maintenance of Calcium-Phosphate Balance
>25% creatinine clearance is still normal
Vitamin D Production
Calcitriol- only in lab research for now
(Please refer to table at last page) Why is there an increase in phosphates in ESRD?
because the poorly functioning kidney cant eliminate them all. The phosphate binds with
calcium leading to a decrease in ionized calcium leading to secondary
hypoparathyroidism
Erythropoietin Production
In DM, anemia occurs early

Management of Chronic Renal Failure

A. Comprehensive strategy for renoprotection in patients with chronic renal disease

Intervention Therapeutic Goal
Specific
renoprotective Proteinuria <0.5
therapy g/day
ACE inhibitor or GFR decline <2
ARB treatment ml/min/year
Specific
renoprotective Proteinuria <0.5
therapy g/day
ACE inhibitor or GFR decline <2
ARB treatment ml/min/year
Adjunctive
cardiorenal
protective therapy <130/80 mm Hg
Additional
antihypertensive
therapy
Dietary protein
restriction 0.6-0.8 g/kg/day
Dietary salt 3-5 g/day
restriction
Tight glycemic AIC < 6.05 %
control in Normal values
diabetes
Reduce elevated
calcium-
phosporous
Lipid lowering LDC-C <100mg/dl
therapy
Anti-platelet therapy Thrombosis
prophylaxis
Consider correction Hb > 12g/dl
of anemia
Smoking cessation Abstinence
Weight control Ideal body weight

Level of proteinuria determines the level of dietary protein restriction in patients

Reduce elevated electolyte Ca and P if <25%, it merits checking
The lecturer considers correction of anemia if Hb 11-12g/dl
Lipid lowering therapy (Statins)

B. Avoid insults to the kidney

 Volume depletion- diarrhea
Nephrotoxins- aminoglycosides, radiocontrast material
NSAID- COX2 inhibitors, mefenamic acid, naproxene, indomethacin

C. Preparation for ESRD management

Psychological
Renal Replacement Therapy, options
o Dialysis Vascular Access
o Transplant Recipient Donor Work-Up
* with a creatinine clearance of 20 or 25, you can start discussing dialysis with the patient

End Stage Renal Disease

Please see table on first page
Excretory function:
Nausea and vomiting- SSX of accumulation of BUN, creatinine
Maintenance of Acid-Base Balance:
metabolic acidosis
Maintenance of Fluid & Electrolyte Balance:
body cant eliminate waste products because it cant compensate; arrhythmia due to
increased K
Maintenance of Calcium-Phosphate Balance
Phosphate retained, binds to Ca, absence of Vit D3 decreased gut absorption of Ca
Vitamin D Production
Erythropoietin Production
Anemia insidious in onset so you may have SSX in ESRD

Pathophysiology: fibrosis no more compensation in whatever aspect of excretion

Management of ESRD

A. Supportive
1. Nutrition
2. Psychological
3. Control BP
4. Maintain Hb at 110-120 g/dl with erythropoietin oral iron is not absorbed very\well by
uremic patient; its better to give it to them IV
5. Fluid and electrolyte balance
6. Acid-base homesotasis
 7. Maintain Ca and Phosphate balance give Calcium carbonate or Calcium acetate with
meals. You eat meat, and meat has phosphate. Para habang nakakapagbigay ka ng
calcium, nakakapag prevent ka na rin ng absorption ng phosphate. You shoot two
birds with one stone
B. Renal Replacement Therapy
1. Dialysis
2. Hemodialysis
3. Peritoneal Dialysis
4. Transplant
5.
- Consider dialysis if creatinine clearance is about 20ml/min
- Uremic symptoms present with nausea and vomiting. If the disease is not ESRD, consider
other etiologies for the said symptoms
- Excess fluid in the body volume overload diuretics wont help coz kidneys are already
sclerosed

Renal Replacement Therapy in CRF

- indicated when metabolic abnormalities can no longer be controlled with conservative
management or when signs and symptoms of uremia developed
- No absolute value in terms of CR by which you will start your RRT

Indications for Dialysis

- volume overload
- intractable metabolic acidosis
- hyperkalemia
- uremic state (encephalopathy, pericarditis)
- azotemia without uremic manifestations

CASE

A 24-year old male diagnosed with chronic glomerulonephritis was admitted for nausea and
vomiting. Maintenance of ACE inhibitors with HCTZ (Hydrochlorothiazide) was given.

His last follow-up a week ago showed a Cr 1.8 mg%. Three days PTA he had copious diarrhea
and was unable to take anything including medicines. He noted decreased urine output. He felt
weak and later developed nausea and vomiting.

PE: BP = 90/60 PR = 110/min RR = 25/min

Sunken eyeballs, dry skin and mucous membranes
BUN 80mg/dL; Cr 10mg/dL; K 6meq/L; Na 132 meq/L
ABG: pH 7.2; HCO3 11meq/L; CO2 20meq/L
Hgb: 15gm/dl (N14-17)
Hematocrit: 45 (hemoconcentrated)
Urinalysis: Sp gr = 1.010, (4+) protein, () sugar
4-5 RBCs/hpf, 10-15 WBCs/hpf

What is your diagnosis?

a. Acute renal failure
b. Chronic renal failure
c. End stage renal failure
d. Acute on chronic renal failure

Answer: Acute on Chronic Renal Failure

What finding tells us that the patient has renal failure?

a. K
b. pH
c. creatinine
d. urinalysis just a reflection that somethings wrong, but not specific for renal failure

Answer: Creatinine
What is the cause of the ABG finding?
e. Chronic GN
f. Diarrhea
g. Vomiting
h. Acute renal failure

Answer: Diarrhea and ARF (acidosis)

How should you manage this patient?

a. kidney transplant
b. dialysis
c. supportive management
d. observe

Answer: Supportive Management

Management:
Hydrate patient
 For increased K, give sodium bicarbonate- shoot two birds with one stone not only do
you decrease K you also replace the lost HCO3
Treat the cause of diarrhea
Nutrition: dont focus on it yet. Just follow treatment for diarrhea
Follow up BUN, creatinine. If it improves, dont do anything. Take note that theres a 3-4
day period before creatinine drops.

Hypovolemia: low BP, sunken eyeballs, dry skin, mucous membrane

Increased RR implies metabolic acidosis
Hemoconcentration due to diarrhea

If the creatinine changed from 1.8 to 9mg, but the patient has nausea and vomiting,
Bp=130/80, no diarrhea, eyeballs not sunken, (+)edema, what is the management?

Answer: Dialysis

If anemic (Hb 10g/dl), what is the

mgt?

Answer: Give erythropoietin. If <10

g/dl, transfusion

From block B:
Hyperkalemia dont give
diuretics because patient is
dehydrated; give sodium
bicarbonate -> push K inside the