Tokushukai Medical Group

Treatment of disorder

medical treatment

Kidney Disease: Chronic Kidney Disease (CKD) and Renal Failure

Early treatment for the disorder of the kidney is proposed in CKD definition.

The disease name of chronic renal failure is used in the past for the clinical condition of chronically dropped kidney function. But in order to understand renal function disorder more clearly and to find it earlier as possible, the concept of Chronic Kidney Disease (CKD) is proposed by American Kidney Foundation in 2002.

CKD designates the clinical conditions including, (1) The drop of kidney function set by Glomerular Filtration Rate (GFR) (GFR<60mL/min/1.73m2) continues more than 3 month, or (2) observations indicating kidney disorder are chronically continued for more than 3 months. (fig.1)

Fig 1.: definition of chronic kidney disease (from CKD diagnosis Guidebook 2012)

Observations indicating the failure of the kidney are;

With this definition, early stage failure of renal function, which do not show any symptoms since disorder level is milder than the stage used to be diagnosed as chronic renal failure, can be diagnosed as CKD. Failure of renal function is not only the problem of kidney itself, but also the problem of increasing the development risk of cardiovascular condition, like cardiac infarct or cerebral stroke, peripheral artery disease (obstructive lower extremity atherosclerosis). So that the purpose of informing not only to doctors but also to ordinally people is that they understand that it is important to diagnose and to start treatment as early as possible.

CKD is increased due to lifestyle-related disease.

CKD includes all clinical condition of chronic renal disorder, so that the causes comes from several diseases.
As a classification,

Like classification, or classification depend on which structure or part of the kidney is damaged;

Above classification is also available (fig.2)

Primary Secondary Hereditary/congenetal
Glomerulardisorder IgA nephropathy
Membranous Nephropathy
Minimal Lesion Nephrotic Syndrome
Focal Segmental Glomerular Sclerosis
Meniscus-forming Nephritis
Membranous Proliferative Glomerular Nephritis
Diabetic
Lupus Nephritis
Microscopic Multiple Vasculitis
(ANCA related Vasculitis)
Hepatitis Virus related kidney disease
Benign Familial Hematuria
Alport Syndrome
Fabry Disease
Vascular Disorder hypertensive nephropathy (Renal Sclerosis)
Renal Artery Stenosis (Fibromuscular Dysplasia)
Aortitis Syndrome (Arterial Sclerosis)
Cholesterol Embolism
Renal Vein Thrombosis
Ischemic Renal Disease
Tubulointerstitial Disorder Chronic Interstitial Nephritis Gout Kidney
Drug-induced Kidney Impairment
Polycystic Kidney disease
Nephronophthisis

Fig. 2 Causative disease of Chronic Renal Disorder (from CKD Diagnosis Guide 2012)

One of the disease which is clinically important among the above diseases is a diabetic nephropathy. In case if affected with diabetes and the control of it is not enough, diabetic nephropathy is developed in 10 to 15 years. They say that 43% of dialyzed person, about one half of the causative disease is diabetic nephropathy.

On the other hand, up until 20 years ago, the most frequent disorder was Chronic Glomerulonephritis, and typical disorder among them is IgA nephropathy.

Also, frequency is decreased, but hypertensive nephropathy (Renal Sclerosis) is a recently increasing disorder, so that chronic renal disorder due to the lifestyle related disease as well as diabetic nephropathy is getting the problem.

The first symptom is frequent micturition while sleeping.

Early stage of CKD, where renal function is relatively maintained well so that only abnormality on Urine observation can be seen, no symptom will appear. First symptom appeared when renal function drops is the frequent micturition, and this is the symptom when amount of urine is increased during the night due to the drop of renal’ s urine concentration ability, so that awake several times for bladder emptying while sleeping. This symptom may appear when renal function drops down to approximately 50%.

In case renal function drops further down to around 30%, symptom, like blood pressure increase and anemia, may come up. Kidney produces hormone named as erythropoietin, and this hormone affect to bone marrow in the bone to give the order of producing the blood. But it becomes unable to produce enough erythropoietin along the drop of renal function, so that blood is not produced even with taking nutrition like iron from meals, then it turns into anemia. This is called as renal anemia.

Furthermore, in case renal function drops down to 30% or less, body inclined to acidity due to the drop of excretion metabolization (metabolic acidosis), and calcic drop, increase of phosphorus, or edema may appear so that the feeling of malaise may appear as well. In case when renal function drops further down to 15% or less, symptoms, like sophisticated high blood pressure, feeling of malaise or breath shortness caused by anasarca (cardiac arrest or lung edema), digestive symptom (anorexia asities, nausea, vomiting), cutaneous symptoms (itch, pigment deposition), lower-limb cramp/leg cramp, may come up. And in case when potassium value gets high, it may lead to abnormal cardiac rhythm and sometimes it reaches to fatal irregular heartbeat. Utmost attention shall be taken.

When no treatment has been taken at this stage, there is a case where develops uremic encephalopathy like convulsion or consciousness disturbance, so that it may lead to life-threatening risk.

Diagnose by the abnormality in blood or urine.

Diagnosis of CKD, as it is shown in the definition, is diagnosed with the abnormality of blood or urine, image or tissue examination of the kidney.

There is a serum creatinine in the examination item to evaluate renal function by blood drawing. This is a waste material from body muscle, and material which fixed amount of muscle is broken down every day by metabolism. With observing the density of serum creatinine, renal function is evaluated. Normally it is considered normal if it is 1.2mg/dl or less for male, and 1.0mg/dl or less for female, but this reference is different by facility.

Also, as this creatinine is discharged out in the urine by kidney, by measuring the creatinine and serum creatinine in the one-day pooled urine specimen (collection of urine) at same time, renal glomerulus filtration rate (GFR), indicating how much ratio is the renal working, is calculated.

Also, instead of evaluating GFR using the collection of urine, it is able to presume GFR with simply using serum creatinine density. This is called as estimated renal glomerulus filtration rate (eGFR). Calculation formula is;

eGFR=194 x Blood Serum Cr-1.094 x Age-0.287 (for female, 0.739 is multiplied with this value)

However, it is difficult to calculate with common calculator. This is a problem.

On the other hand, urine test is to observe protein or occult blood reaction in urine, erythrocyte or leucocyte, or cast. Urine protein is important among them. Opinion is normally grouped in (-), (±), (+), (2+), (3+), (4+) according to the density. But the density of urine protein differs by the body condition in that moment. When conserving the intake of liquid, urine is condensed so that the density of urine protein gets thick, and when taking much liquid, urine density will get thinner as urine itself gets thinner.

Therefore, the method, which compensate these urine density level then evaluates it, is g/gcr urine protein determination method. This method compensates urine protein density with the density of creatinine in urine. Calculation formula is; (urine protein density mg/dl) / (density of creatinine in urine mg/dl)

CKD is diagnosed by the degree of aforementioned GFR and urine protein. (fig.3) For Example, when GFR is 35.2mL/min/1.73m2 and protein urina is 0.36g/gCr, CKD stage classification is diagnosed as G3bA2. Protein urina is able to evaluate with protein amount (g) within one-day pooled urine amount. (g/day)

Primary Disease Classification of Protein Urina A1 A2 A3
Diabetes urine albumin determination (mg/day)
Urine albumin/Cr ratio(mg/gCr)
Normal Micro albumin Urine Dominant Albumin Urine
30 or less 30~299 Over 300
Hypertension
Kidney Inflammation
polycystic kidney disease
Renal Transplant
Unknown
Others
Uric protein determination(g/day)
Uric protein/Cr ratio(g/gCr)
Normal Mild Uric Protein Enhanced Uric Protein
0.15 or less 0.15~0.49 Over 0.50
GFR Classification
(mL/min/1.73m2
G1 Normal or elevated value ≧90
G2 Normal or below mild 60~89
G3a Mild to below medium 45~89
G3b Medium to less elevated value 30~44
G4 Less elevated value 15~29
G5 End-stage kidney disease
(ESKD)
<15

Fig.3 disease classification and its severity of chronic kidney disease (from CKD Diagnosis Guide 2012)

Severity is evaluated by the stage which are combined with primary disease, GFR classification and uric protein classification. CKD severity is set the risk of End-stage Kidney disease and cardiovascular onset of death as referenced GREEN stage, and the risk is advanced in the order of YELLOW, ORANGE, and RED.

Besides, in case of polycystic kidney disease, even when uric protein negative (0.15g/gCr or less) and GFR is in good condition like95mL/min/1.73m2), when there is an abnormality where many cysts are developed in the image, it is diagnosed as CKD, and its disease classification turns into G1A0.

Important to treat high-blood pressure which advances impaired renal function.

Since CKD includes many primary diseases, it tends to the selection of the treatment for primary disease. Adrenal cortex steroid drugs or Immunosuppressive drugs is used for some kind of chronic glomerulonephritis or inflammation of blood vessel, and for diabetic nephropathy, hypoglycemic agent is used. Common thing for any CKD is it is important to take general therapy (correction of life-style disease or metabolic syndrome, infection control, discontinuation of smoking, physical exercise), or diet therapy (reduced salt, energy limited meal).

And also, treatment of hypertensive therapy is important. There is a negative spiral where renal function disorder advances, hypertension is getting worse, and when having hypertension, renal function is getting worse. Blood pressure management tales the core position in CKD treatment. Blood Pressure Management is conducted with the target of 130/80mmHg ore less. There is data that the better in blood pressure management, more moderated in the decline rate of renal function by age. (fig.4), but in case of aged person, extreme blood pressure drops (systolic arterial pressure is 110mmHg or less) should be avoided.

Fig.4 Relation of blood pressure and glomerular Filtration Ratio (GFR) drops (from CKD Diagnosis Guide 2012)

In regard to the selection of the kind of antihypertensive drug, for uric protein case, renin-angiotensin-based inhibitors (RAS inhibitors) shall be used. RAS inhibitors reduces uric protein by decreasing glomerular pressure, and it is said that it has kidney protection effect. There are Ca antagonist drug or diuretic medicine, and they are used in accordance with each clinical condition. (fig.5)

CKD complicated with diabetes
CKD uncomplicated with diabetes presented by over-mild uric protein.
Primary Selected Drug
RAS Inhibitor (ARB, ACE Inhibitor)
  1. Able to dose for all CKD stages.
  2. However, for CKD stage G4, G5 and aged person CKD, there merely occur renal function is acutely getting worse at the beginning of dosage or having the risk which fall into high K blood syndrome, so that the dosage should start with low doses for the initial amount.
  3. Unless the pressure drop is recognized or there is no side effect, drug should continue dosage.
Secondary Selected Drug

CVD High-risk
III-degree hypertension

Long-acting type Ca Channel Blocker
  1. Able to dose for all CKD stages
  2. Consider Ca Channel Blocker which has uric protein reducing effect.

Excess of Fluid
(Edema)

Diuretic of the thiazide type
  1. Fundamentally for CKD stage G1 to G3 (able to combine with loop diuretic for CKD stage G4 to G5.)
Long-acting type Lee loop diuretic
  1. CKD stage G4 to G5
Thirdly Selected Drug

Diuretic

Long-acting type Ca Channel Blocker

CKD uncomplicated diabetes of normal Uric protein
Regardless the kind of antihypertensive agent,
Select antihypertensive agent to accommodate with patient clinical condition.
RAS Inhibitor (ARB, ACE Inhibitor)
  1. Able to dose for all CKD stage.
  2. However, for CKD stage G4, G5 and aged person CKD, there merely occur renal function is acutely getting worse at the beginning of dosage or having the risk which fall into high K blood syndrome, so that the dosage should start with low doses for the initial amount.
Long-acting type Ca Channel Blocker
  1. Able to dose for all CKD stage.
  2. CVD High Risk, Consider III-degree Hypertension Case
Diuretic medicine
  1. Consider excess of fluid (edoma) case.
(Diuretic of the thiazide type)
  1. Fundamentally for CKD stage G1 to G3
    (Able to combine with loop diuretic for CKD stage G4 to G5.)
(Long-acting type Loop Diuretic)
  1. For CKD stage G4 to G5
Other antihypertensive drug
  1. Beta Blocker, Alfa Blocker, Central Exchange Nerve Blockers
  2. Continue to dosage unless there is no side-effect and antihypertension is recognized by the combined therapy of single treatment method using antihypertension drug or the usage up to 3 tablets.

Fig.5 Treatment strategy for hypertension in the CKD patient. (from CKD Diagnosis Guideline 2012)

For CKD treatment other than the aforementioned, it becomes necessary to have Drug Therapy which compliment for the maintenance of homeostasis of the body which kidney is assumed, as the substitute for the descended self-kidney. In accordance with the advance of CKD disease condition, disorder in balance of electrolytes or bone metabolism, drop of the hematopoietic capacity may come up, so that below listed drug or agent are administered. (fig.6)

Disorder in balance of electrolytes High K Syndrome Cation exchanger resin
metabolic acidosis Soda (sodium hydrogen carbonate)
Bone Metabolism Disorder hypocalcemia Vitamin D
hyperphosphatemia Phosphate Binder
drop of the hematopoietic capacity Erythropoietin Formulations
High Uric Acid Blood Uric acid descent drugs
High urea nitrogen blood disease/ Uremia Activated Charcoal (absorbent material)

Fig.6 Alternative Drug Therapy accompanied with the decline in renal function

Intend to review daily lifestyle

As described in The Cause of CKD section, recently increased diabetic nephropathy or nephrosclerosis are based on the lifestyle disease, so that it is possible to prevent from the disease development by reviewing daily lifestyle (physical exercise, meals). However to say, in regard for chronic glomerulonephritis or secondary CKD, the mechanism of pathogenesis is still unknown so that it is difficult to prevent them.

Therefore, it is strongly recommended to have periodical urine or blood exam, to check renal function or kidney configuration by abdominal ultrasonography at the health check operated by work office or city government. And when abnormality is reported, visit the kidney specialist doctor’s office as soon as possible. Even these abnormal observation has not reported, in case when eGFR is 60mL/min/1.73m2 or less, it becomes important to have periodical observation check not only for kidney but also for cardiac blood vessel disease, since the risk of cardiac blood vessel disease is getting high.

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