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Target diseases

Hypertension/hypotension

1. Essential hypertension
   Hypertension can be categorized into two types: essential hypertension and secondary hypertension. The former is defined as hypertension with an unknown etiology that occurs due to hereditary reasons or due to a combination of various lifestyle-related factors. Therefore, hypertension is considered a lifestyle-related disease
2. Secondary hypertension (renovascular hypertension, primary aldosteronism, etc.)
   Secondary hypertension is caused by an underlying (primary) disease, which raises the patient's blood pressure. Secondary hypertension may occur as renal hypertension, renovascular hypertension, and endocrine (adrenal in many cases) hypertension, among others. Adequate diagnosis and treatment can result in cure in some cases.
3. Hypertensive emergency (malignant hypertension and other symptoms)
   Hypertensive emergency is a condition defined by not only an abnormally high but also sustained high blood pressure (180/120 mmHg or higher in many cases), resulting in acute impairment of the brain, heart, kidneys, great vessels, and/or other organ systems.
4. Orthostatic hypotension
   Orthostatic hypotension is a condition in which the affected person faints or feels dizzy when standing up due to an excessive drop in blood pressure, which reduces blood flow to the brain. This condition occurs when the compensatory mechanism of an individual fails to promptly respond to a change in blood pressure.
5. Neurally mediated syncope
   Neurally mediated syncope is a collective term that refers to different types of syncope (fainting) caused by various factors such as extended maintenance of an upright position, physical pain, urination/defecation, and emotional/physical stress. It is essential to adequately treat this condition by first identifying the cause.

Nephrology

1. Chronic kidney disease
   Chronic kidney disease (CKD) is a risk factor for end-stage renal failure. The number of patients with CKD has been increasing. As of 2011, approximately 13% of the adult population in Japan, or approximately 13.3 million people, were believed to be afflicted with CKD. Lifestyle-related diseases, such as diabetes and hypertension, are cited as predisposing factors for CKD. As mentioned earlier, CKD is a risk factor for not only end-stage renal failure but also cardiovascular and cerebrovascular diseases, posing a real threat to people's health.
2. Acute kidney injury
   Acute kidney injury is a condition wherein a person's renal function rapidly deteriorates within a few days or even over the span of a few hours. Acute kidney injury leads to overhydration or the inability to remove waste products through the urine, and dialysis is required in some patients.
3. Acute glomerulonephritis
   Acute glomerulonephritis (AGN) refers to renal inflammation that gives rise to symptoms such as hematuria, proteinuria, oliguria, edema, and hypertension. In many cases, it occurs following streptococcal infection. The incidence of acute glomerulonephritis has drastically dropped in recent years owing to the use of antibiotics. Usually, the condition resolves spontaneously, but dialysis is necessary in patients with severe renal failure.
4. Immunoglobulin A nephropathy
   Immunoglobulin A (IgA) nephropathy, a chronic form of glomerulonephritis with hematuria and/or proteinuria, is the most frequently occurring kidney disease. IgA nephropathy results from the renal accumulation of abnormally structured IgA molecules that are generated in tonsils and other locations, resulting in inflammation and subsequent hematuria and/or proteinuria. IgA nephropathy is diagnosed through biopsy, and its treatment usually involves the administration of steroids.
5. Nephrotic syndrome
   Nephrotic syndrome is characterized by excessive protein excretion in urine, causing hypoalbuminemia. It is accompanied by edema in many cases. A renal biopsy is almost always performed for a definitive diagnosis, except in patients with a clear underlying cause (such as diabetes). Treatment mainly involves the administration of steroids, which are combined with immunosuppressive drugs in some cases.
6. Nephrosclerosis (Renal sclerosis)
   Long-term hypertension leads to sclerosis of small blood vessels in the kidneys, causing renal injury. In advanced stages of nephrosclerosis, blood flow to the glomeruli is reduced and renal function deteriorates, leading to renal failure. This disease primarily affects elderly people, in whom its incidence has been increasing, and ranks third among primary diseases requiring dialysis initiation.
7. Diabetic nephropathy
   Since 1998, diabetic nephropathy has ranked first among the primary diseases requiring dialysis initiation. The number of patients with diabetic nephropathy has been increasing in parallel with the increasing number of patients with diabetes. However, with advances in multidisciplinary therapies for diabetic nephrapathy, the percentage of those requiring dialysis among all patients with primary diseases requiring dialysis has stabilized in the last several years.
8. Lupus nephritis (Systemic lupus erythematosus)
   Lupus nephritis refers to renal impairment caused by systemic lupus erythematosus (SLE). SLE tends to cause renal complications that are vital prognostic factors. In patients with positive results for occult hematuria and proteinuria tests, renal biopsy may be performed to assess for SLE and to evaluate the disease. Treatment primarily involves the administration of steroids, which are imperatively combined with immunosuppressant drugs in many cases.
9. Antineutrophil cytoplasmic antibody-associated vasculitis
   Antineutrophil cytoplasmic antibody-associated vasculitis is a collective term used to define diseases characterized by the presence of antineutrophil cytoplasmic antibodies in patients. These diseases are classified into microscopic polyangiitis, granulomatosis with polyangiitis, and eosinophilic granulomatosis with polyangiitis. Among them, microscopic polyangiitis particularly triggers kidney impairment and kidney failure frequently. Diagnosis is made via biopsy. Treatment primarily involves the administration of steroids.
10. Anti-glomerular basement membrane antibody-mediated glomerulonephritis (Goodpasture syndrome)
    Anti-glomerular basement membrane antibody-mediated glomerulonephritis, also known as Goodpasture syndrome, refers to a condition characterized by rapidly progressive glomerulonephritis with positivity for anti-glomerular basement membrane antibody. Alveolar hemorrhage can occur in the lungs. Kidney function deteriorates rapidly, often progressing to end-stage renal failure in a short time period. Renal biopsy is necessary to make a definitive diagnosis. The main treatment comprises a combination of plasmapheresis and steroid administration.
11. Purpura nephritis
    Purpura nephritis is caused by IgA vasculitis and is accompanied by hematuria and proteinuria. Patients with IgA vasculitis always present with purple spots, accompanied with stomachache and joint pain in some cases. Definitive diagnosis requires renal biopsy. Histopathological findings are similar to those of IgA nephritis. Steroids are used for treatment in many cases.
12. Cholesterol embolism
    Cholesterol embolism, distinctively characterized by arteriosclerosis, is the embolism of small peripheral vessels that occurs when cholesterol crystals, which constitute the plaques on the arterial walls, come off due to vascular surgery or intravascular catheterization. The resultant injury can lead to a rapid deterioration of the renal function. If a patient is receiving an anticoagulant therapy, the treatment is suspended. Steroids may also be used depending on the patient's condition.
13. Polycystic kidney disease
    Polycystic kidney disease (PKD) is an autosomal dominant disorder characterized by the development and growth of numerous cysts, which originate in the renal tubules of both kidneys, due to a mutation or mutations in the PKD gene. Renal function rapidly deteriorates, and approximately half of the patients with PKD are diagnosed in the terminal stage of renal failure by the time they reach their 60s. The treatment of PKD has gained momentum since the recent approval of health insurance coverage for tolvaptan (brand name, Samsca) treatment for patients with PKD in Japan.
14. Tubulointerstitial nephritis
    During waste elimination by the kidneys, the tubules reabsorb necessary substances from the filtrate that has passed through the glomeruli and secrete unwanted substances to eliminate them in the urine. Tubulointerstitial nephritis refers to the inflammation of interstitial renal tissue other than the glomeruli and tubules. This condition is caused by medications in many cases. Other causes include latent autoimmune diseases such as Sjogren's syndrome, sarcoidosis, and IgG4-related disease. Diagnosis requires renal biopsy in some cases. Steroids may be administered in patients with particularly severe disease.
15. IgG4-related kidney disease
    IgG4-related kidney disease refers to renal lesions associated with IgG4-related disease and is characterized by a dense infiltration of IgG4-positive plasma cells in the tubular interstices and the growth of fibrous tissue. IgG4-related kidney disease primarily afflicts elderly people. Treatment with steroids proves effective in many cases.

Diagnostic methods

Blood pressure measurement

1. Clinic blood pressure
   Clinic blood pressure is a patient's blood pressure that is correctly measured using a mercury manometer or an equally accurate automated sphygmomanometer in a hospital clinic or a physician's office.
2. Non-clinic blood pressure
   Outside a medical institution, blood pressure can be measured at home (home blood pressure).Additionally, ambulatory blood pressure monitoring (ABPM) can be used for continual measurement of blood pressure while the patient spends his or her time freely during a 24-hour period. Home blood pressure measurement and ABPM are considered to provide more reliable data in patients whose blood pressure levels tend to rise in the presence of a physician due to anxiety or other reasons.

Diagnosis of hypertension-induced organ damage and complications

The following tests are conducted to screen for hypertension-induced organ damage and complications and, if present, to determine their severity.

1. Echocardiography
   Echocardiography is performed to examine the movements of the heart and to assess for cardiomegaly and valvular disease.
2. Carotid ultrasonography
   Carotid ultrasonography is performed to observe the thickness of the carotid artery wall and to assess for plaques.
3. Renal blood flow detection using Doppler ultrasonography
   Doppler ultrasonography is conducted to assess the presence of renal artery stenosis and to observe blood flow in the kidneys.
4. Pulse wave velocity
   Pulse wave velocity is conducted to evaluate the thickness of blood vessel walls, so as to assess the severity of arteriosclerosis, based on the velocity of blood flow.
5. Flow-mediated dilation
   Flow-mediated dilation is performed to examine the state of blood vessels in a non-invasive, real-time setting.
6. Radioisotope tests
   Radioisotope tests are used to examine the heart to assess changes in the coronary blood flow and the kidneys to assess the morphology and function of both kidneys.
7. Computed tomography
   Computed tomography is performed to examine the brain to assess for asymptomatic cerebral infarction, among others, as well as to examine the chest and abdomen to assess for aortic aneurysms and observe the morphology of the kidneys and adrenal glands, among other purposes.
8. Ophthalmoscopy (Fundoscopy)
   Ophthalmoscopy is performed to assess for arteriosclerosis, hypertension in the blood vessels at the back of the eye, and ophthalmological changes due to diabetes.
9. Ambulatory blood pressure monitoring
   ABPM is conducted to determine average daily blood pressure levels and blood pressure fluctuations over a period of 24 hours using a portable automated sphygmomanometer.

Diagnosis of secondary hypertension

Various underlying diseases can cause secondary hypertension. Therefore, tests that are necessary for differential and definitive diagnoses are tailored for each case according to the predicted causes based on patient's medical history, condition, physical traits, and examination findings, among others.

Diagnosis of orthostatic hypotension

It is important to obtain the patient's medical history before and after the occurrence of syncope. The diagnosis is based on the measurement of blood pressure before and after the patient stands up.

Diagnosis of neurally mediated syncope

It is important to interview the patient to establish his or her medical history before and after the occurrence of syncope. If deemed necessary, a head-up tilt test is performed. During this test, the patient's blood pressure is measured; furthermore, any changes in the physical condition before and after the head of the patient (lying on a special table) is passively raised are noted.

Diagnosis of kidney diseases

1. Urinalysis
   Urinalysis is imperative in the diagnosis of kidney diseases. Among the urinalysis findings, urine protein and blood measurements are particularly important. Because urine tests are relatively inexpensive, they must be conducted without fail if any kidney disease is suspected. We suggest that physicians refer patients with a single urine protein value of 2+ or higher and those who test positive for both protein and blood in urine to the Department of Hypertension and Nephrology at the NCVC.
2. Renal function tests
   To examine renal function, measurement of blood urea nitrogen and serum creatinine levels is essential. These tests can serve as a good indicator of the severity of CKD and the timing to introduce dialysis. Patients with severely deteriorating renal function should be referred to the Department of Hypertension and Nephrology at the NCVC. Patients who correspond to the description under "1. Urinalysis"should be referred to the NCVC regardless of the state of their renal function.
3. Imaging-based diagnosis
   Simple computed tomography and renal ultrasound are performed to evaluate the kidney size, which is an extremely important parameter in the diagnosis of kidney diseases. In some cases, these test results determine whether a biopsy is necessary. Imaging-based tests can clarify the probability of PKD or eliminate the possibility of postrenal failure.
4. Renal biopsy
   Renal biopsy might be necessary for the definitive diagnosis of some kidney diseases. Accurate histological diagnosis that can be obtained via biopsy allows to determine treatment approaches and to evaluate renal function prognosis. A rebiopsy may be performed to evaluate the efficacy of the treatment provided. The Department of Hypertension and Nephrology performs approximately 20 biopsies per year.

Treatment modalities

Treatment of hypertension

Hypertension is mainly treated using two approaches: pharmacotherapy with the use of hypotensive drugs and non-pharmacological treatment with a focus on lifestyle improvement.

1. Lifestyle improvement (non-pharmacological treatment)
   

   According to the Guidelines for the Management of Hypertension of the Japanese Society of Hypertension (2014 edition), the recommended lifestyle improvements for individuals with hypertension are (1) limited salt intake, (2) fruit and vegetable consumption and limited cholesterol and saturated fatty acid intake, (3) weight loss, (4) physical exercise, (5) limited alcohol consumption, and (6) quitting smoking. These lifestyle improvements are believed to be more effective if implemented togehter.

2. Pharmacotherapy
   

   There are several classes of hypotensive drugs. For treatment, drugs are selected with consideration of the concomitant complications present in patients. In general, hypotensive drugs are initially administered as monotherapy and in low dosages. If they do not prove sufficiently effective, the dosage may be increased or other drugs may be added in small dosages.

3. Catheter-based treatment for renovascular hypertension (treatment in collaboration with the Division of Radiology)
   

   As needed, catheter-based treatments are provided to patients with renovascular hypertension due to renal artery stenosis, aneurysm, or embolism.

Treatment of kidney diseases

1. Education about renal failure
   To treat patients with renal failure, dietary and pharmacological therapies should be implemented in a complementary manner. At the NCVC, patients are hospitalized for 1-2 weeks for educational purposes, that is, to help them acquire new dietary habits that include a limited intake of salt, protein, and/or potassium while monitoring and regulating their pharmacotherapy.
2. Pharmacotherapies for CKD
   CKD is associated with various complications, including hypertension, renal anemia, overhydration, hyperpotassemia, metabolic acidosis, and potassium/phosphorus metabolism disorders. Considering these complications, various pharmacotherapies are proposed for CKD; these include the use of hypotensive agents, erythropoietin, diuretics, potassium adsorbents, sodium bicarbonate, and phosphorus adsorbents.
3. Immunosuppressant drugs
   To treat patients with IgA nephropathy, nephrotic syndrome, and kidney diseases complicated by collagen diseases, immunosuppressant drugs, primarily adrenocortical steroids, are prescribed in many cases; these drugs are also used in combination with other immunosuppressant drugs, such as cyclosporine, tacrolimus, cyclophosphamide, mizoribine, and mycophenolic acid.
4. Introduction of tolvaptan
   The health insurance-covered indications of the vasopressin receptor antagonist tolvaptan (brand name, Samsca) have recently been expanded to include PKD. Moreover, PKD has recently been added to the list of intractable/rare diseases recognized by law in Japan. As a result of these developments, it is now possible to prescribe tolvaptan for the treatment of PKD.
5. Hemodialysis
   Once patients reach end-stage renal failure, it becomes necessary to introduce hemodialysis, which is performed by the Department of Hypertension and Nephrology on a regular basis, with hemodialysis initiated for approximately 30 cases per year. We actively receive and treat patients with stroke and heart diseases who require maintenance dialysis. Our dialysis room has eight beds and is staffed with three nephrologists and internists/hypertension specialists, four nurses, and three clinical engineers. We conduct 1,800-2,000 dialysis sessions per year.
6. Special hemocatharsis methods
   We perform plasma exchange, double-filtration plasmapheresis, and plasma adsorption according to patients' condition and as the need arises.

last updated : 2021/10/01