Definetion • Etiology • Pathogenesis • Clinical Manifestations • Diagnosis and Differential Diagnosis • Prevention • Treatment
Chronic renal failure(CRF) is defined as a substantial and irreversible reduction in renal function over a period of months to less than 20% of normal. It is a gradual and progressive loss of the ability of the kidneys to excrete wastes, concentrate urine, and conserve electrolytes.
Loss of <75% of glomerular filtration rate (GFR) does not usually result in pronounced symptoms, as the remaining glomeruli adapt with hyperfiltration, and the surviving tubules adjust by maintaining adequate acid-base, fluid, and electrolyte balance. For example, the doubling of serum creatinine(Cr) from 0.7 mg/dl to l.4 mg/dl signifies a loss of approximately 50% GFR, emphasizing the importance of early recognition and intervention at this early stage.
CRF typically occurs in three stages: 1.Compensatory stage. 50ml/min<GFR<80ml/min, Cr<178umol/L(2mg/dl), BUN<9mmol/L (25mg/dl), and no symptoms. 2.Decompensatory stage. 25ml/min<GFR<50ml/min, Cr>178umol/L, BUN>9mmol/L, lightly gastrointestinal signs(anorexia, nausea, and vomiting) and anemia. 3.Uremic stage.GFR<25ml/min, Cr>445umol/L(5mg/dl), BUN>20mmol/L(55mg/dl), typical uremic symptoms.
The most common etiologies of renal insufficiency ultimately leading to endstage renal disease (ESRD)
Unlike acute renal failure with its sudden reversible failure of kidney function, chronic renal failure is slowly progressive. It most often results from any disease that causes gradual destruction of the kidneys. It can range from mild dysfunction to severe kidney failure. Progression may continue to end-stage renal disease.
Chronic renal failure occurs in approximately 2 out of 10,000 people. Causative diseases include glomerulonephritis of any type (one of the most common causes), polycystic kidney disease, hypertension, Alport syndrome, reflux nephropathy, obstructive uropathy, kidney stones and infection, and analgesic nephropathy. Diabetes mellitus is a major cause of chronic renal failure.
The pathogenesis of CRF is too complex to be clarified until now. The main theories include: 1. The Remaining Nephrons Theory and Maladaptive Mechanisms To ensure adequate solute, water, and acid-base balance, the surviving nephrons in the diseased kidney must adjust by increasing their filtration and excretion rates.
Figure 1 illustrates different pathways through which these maladaptive mechanisms can result in progression of renal insufficiency and, ultimately, ESRD.
2. Glomerular Hyperfiltration Theory Glomerular hypertrophy and glomerular capillary hypertension leading to glomerulosclerosis have been implicated as important factors in the development of progressive renal insufficiency. For example, decreased glomerular capillary pressure with angiotensin-converting enzyme (ACE) inhibitors has been found in animal and human studies to retard such progression in renal failure.
3. Renal Tubular Hypermetabolic Theory Compensatory glomerular hypertrophy is invariably associated with tubular hypertrophy in the remaining nephrons. Although this adaptive mechanism can be beneficial in maintaining fluid, electrolyte, and acid-base balance, the long-term consequence is perpetuation of tubulointerstitial damage.
Clinical Manifestations • Symptoms: initial、later • Sign • Tests • The Uremic Syndrome • Specific Manifestations of Uremia
Symptoms • Initial symptoms (may be nonspecific) • unintentional weight loss • nausea, vomiting • general ill feeling • fatigue • headache • frequent hiccups • generalized itching (pruritus)
Later symptoms • increased or decreased urine output, need to urinate at night • easy bruising or bleeding; may have blood in the vomit or in stools • decreased alertness, lethargy, coma, muscle twitching or cramps, seizures • increased skin pigmentation--skin may appear yellow or brown • uremic frost--deposits of white crystals in and on the skin • decreased sensation in the hands, feet, or other areas
Signs Blood pressure may be high, with mild to severe hypertension. A neurologic examination may show polyneuropathy. Abnormal heart or lung sounds may be heard with a stethoscope. Skin, abnormally dark or light paleness
Tests A urinalysis may show protein or other abnormalities. An abnormal urinalysis may occur 6 months to 10 or more years before symptoms appear. Creatinine levels progressively increase. BUN progressively increases. Creatinine clearance progressively decreases. Creatinine clearance rate(CCr, ml/min) =Ucr(μmol/L)*urine volume(24 hours, ml) / [Scr(μmol/L)*1440(min)]
Potassium test may show elevated levels. Arterial blood gas and blood chemistry analysis may show metabolic acidosis. Changes that indicate chronic renal failure, including both kidneys being smaller than normal, may be seen on: renal or abdominal X-ray; abdominal CT scan; abdominal MRI; abdominal ultrasound.
The Uremic Syndrome Patients with renal insufficiency usually become symptomatic when GFR is < 10 ml/min. Diabetics with renal insufficiency usually demonstrate symptoms at a higher GFR. Uremia is a syndrome that affects every organ system. Uremia is likely the consequence of combined effects of several retained molecules and the deficiency of important hormones and factors, rather than the effect of a single uremic toxin .
Urea, in addition to being the most commonly used measure of renal failure and adequacy of dialysis, can cause symptoms of fatigue, nausea, vomiting, and headaches.
Guanidines, by-products of exogenous or indigenous protein metabolism, are increased in renal failure. They could inhibit l-alpha hydroxylase activity within the kidney, leading to deficient calcitriol production and secondary hyperparathyroidism. High parathyroid hormone level has been implicated in various manifestations of uremia, especially in cardiomyopathy and metastatic calcifications. Beta-2 microglobulin accumulation in patients with renal failure has been associated with neuropathy, carpal tunnel syndrome, and amyloid infiltration of the joints.
Specific Manifestations of Uremia • GASTROINTESTINAL DISEASE • HEMATOLOGIC EFFECTS • CARDIOVASCULAR EFFECTS • NEUROLOGIC MANIFESTATIONS • DERMATOLOGIC MANIFESTATIONS • MUSCULOSKELETAL MANIFESTATIONS • ENDOCRINE ABNORMALITIES • METABOLIC DISORDERS • HYPERKALEMIA • ACID-BASE DISORDERS
GASTROINTESTINAL DISEASE • Gastrointestinal disturbances are among the earliest and most common signs of the uremic syndrome. • Patients with renal failure usually describe a metallic taste and loss of appetite. Later, nausea and voltting become intractable and improve after starting dialysis
HEMATOLOGIC EFFECTS. Erythropoietin(EPO), a hormone produced by the kidney that regulates the production of erythrocytes by the bone marrow becomes progressively deficient as renal mass declines. This is the most common cause of anemia in chronic renal failure. Routine administration of erythropoietin to patients with ESRD results in correction of anemia, improved quality of life, and decreased dependence on blood transfusions.Bleeding disorders are common in uremia.
CARDIOVASCULAR EFFECTS. • Mortality from cardiovascular disease in renal failure patients is three and a half times that of an age-matched population. Hypertension is common in renal failure and is usually aggravated by fluid retention. More than 60% of patients starting dialysis have echocardiographic(UCG) manifestations of left ventricular hypertrophy, dilation, and systolic or diastolic dysfunction. Pericarditis can occur in uremic patients before initiating dialysis and in patients already on dialysis.
NEUROLOGIC MANIFESTATIONS. • subtle changes in cognitive function, and memory and sleep disorders. Lethargy, asterixis, and, seizures, these are usually avoided by early start of dialysis therapy. • Peripheral neurologic manifestations present as a symmetric sensory neuropathy in a glove and stocking distribution.
DERMATOLOGIC MANIFESTATIONS. Pruritus is a common complaint of patients with renal failure, and the exact etiology is not certain.It usually responds to dialysis, control of hyperparathyroidism, improved calcium and phosphate balance
MUSCULOSKELETAL MANIFESTATIONS. Alterations in calcium and phosphate homeostasis and renal osteodystrophy are common manifestations of uremia. hyperparathyroidism are the result of phosphate retention and lack of l-alpha hydroxylase activity in the failing kidney, which results in deficiency of the most active form of vitamin D.
Control of hyperparathyroidism with phosphate binders, calcium supplementation, and 1, 25 Vitamin D together with dialysis therapy is now achievable.
ENDOCRINE ABNORMALITIES Symptoms of hypothyroidism and the uremic syndrome may overlap. Deranged pituitary gonadal axis can result in impotence, amenorrhea, sterility, and uterine bleeding.
METABOLIC DISORDERS As renal function diminishes, many diabetic patients have a decrease in their insulin requirements. This is partly due to the increased half-life of exogenously administered insulin. increase in plasma triglycerides and less of an increase in total cholesterol.
HYPERKALEMIA Low-salt diets with ingestion of salt substitutes (which contain potassium chloride)and administration of drugs that either interfere with renal potassium excretion (triamterene, amiloride, spironolactone, ACE inhibitors, NSAIDs) or block cellular potassium uptake (beta-blockers) can produce hyperkalemia at higher levels of GFR.
ACID-BASE DISORDERS. Most metabolic acidosis in renal failure is due to inability of damaged kidneys to excrete the 1 mEq/kg/d of acid generated by metabolism of dietary proteins.Though patients with chronic renal failure are in positive hydrogen ion balance, the arterial blood pH is maintained at 7.25-7.35 and the serum bicarbonate concentration rarely falls below 15mEq/L.
When patients present with elevated serum creatinine, acute renal failure(ARF) must be differentiated from chronic renal failure, as discussed in the Chapter of ARF.
Diagnosis of the underlying etiology • Biopsy is the most specific tool to reach definitive diagnosis. This allows specific treatment of the underlying etiology, assessment of the prognosis, and suitability of kidney transplantation. If the biopsy is not performed because of small kidney size,
diagnosis is made based on present, past, and family history, serologic evaluation, examination of the urine sediment, and ultrasound evaluation.
Although most chronic kidney diseases are associated with progressive decrease in kidney size, few systemic diseases are characterized by presentation of normal kidney size despite advanced renal failure. These are diabetes mellitus, multiple myeloma, polycystic kidney disease, and amyloidosis.
2. Seeking the causes of deterioration of renal function Table The Common Causes of Acute Deterioration of Renal Function
Treatment of the underlying disorders may help prevent or delay development of chronic renal failure. Diabetics should control blood sugar and blood pressure closely and should refrain from smoking.
Treatment focuses on controlling the symptoms, minimizing complications, and slowing the progression of the disease.
1. The treatment of underlying diseases and causes of deterioration of renal function Associated diseases that cause or result from chronic renal failure must be controlled. Hypertension, congestive heart failure, urinary tract infections, kidney stones, obstructions of the urinary tract, glomerulonephritis, and other disorders should be treated as appropriate.