bubble_chart Overview

Chronic renal insufficiency is a clinical syndrome that occurs in the late stage (third stage) of various chronic kidney diseases. It is characterized by persistent decline in renal function, retention of metabolic waste products, and disturbances in water, electrolyte, and acid-base balance.

bubble_chart Etiology

Various primary or secondary renal diseases in the advanced stage can lead to chronic renal insufficiency, but primary renal diseases are more common. Among them, chronic glomerulonephritis accounts for 50–60% of chronic renal insufficiency, chronic interstitial nephritis including chronic pyelonephritis accounts for 15–20%, and other primary renal diseases include polycystic kidney disease, renal subcutaneous nodules, and renal tubular acidosis. Secondary renal diseases and renal toxicity include hypertensive renal arteriolosclerosis, wind-dampness diseases (such as systemic lupus erythematosus, polyarteritis nodosa, etc.), allergic purpura, diabetic nephropathy, hyperuricemia, multiple myeloma, as well as toxicity from analgesics and heavy metals (lead, cadmium, lithium). Urinary tract obstruction caused by prostatic hyperplasia, urinary calculi, urethral strictures, and neurogenic bladder can also lead to chronic renal insufficiency.

The progressive worsening of chronic renal insufficiency is typically explained by the following theories:

1. The intact nephron hypothesis: When renal insufficiency occurs due to various causes, most nephrons lose their function, while the remaining small portion of nephrons with grade I damage still maintain normal function. Micropuncture studies of nephrons show that the afferent arteriolar resistance of intact nephrons decreases, while the efferent arteriolar resistance increases, leading to high pressure, high perfusion, and high filtration within the glomerulus. The single-nephron glomerular filtration rate can be twice the normal level, and the various functions of the renal tubules can also adapt according to compensatory needs. The so-called "three highs" (high pressure, high perfusion, high filtration) cause mechanical injury, damaging the integrity of vascular endothelial cells, leading to glomerular coagulation, changes in basement membrane permeability, proliferation of mesangial cells, and expansion of the mesangial area. The filtration rate in the remaining nephrons increases, filtration volume rises, glomeruli undergo compensatory hypertrophy, and renal tubules dilate compensatorily, ultimately resulting in glomerulosclerosis and loss of function. As the number of intact nephrons gradually decreases, renal function progressively declines. When the GFR falls below 25% of normal, clinical manifestations of renal insufficiency appear, progressing to uremia.
2. The trade-off hypothesis: In chronic renal insufficiency, intact nephrons undergo compensatory adjustments for many substances to achieve a new balance. However, during this adjustment process, new imbalances arise. For example, when GFR declines, urinary phosphate excretion decreases, leading to elevated blood phosphate levels. Phosphate inhibits intestinal calcium absorption, causing hypocalcemia. High phosphate and low calcium stimulate parathyroid hormone (PTH) secretion, which inhibits renal tubular phosphate reabsorption, lowering blood phosphate levels. As nephrons continue to decrease, blood phosphate rises again, further increasing PTH secretion, promoting Ca²⁺ movement from extracellular to intracellular spaces and calcium release from bones into the blood, leading to bone decalcification, renal osteodystrophy, metastatic calcification, and peripheral neuropathy. Another example is sodium retention when GFR declines, stimulating the secretion of natriuretic hormones. On one hand, this reduces renal tubular sodium reabsorption and increases sodium excretion; on the other hand, it inhibits Na-K-ATPase, disrupting sodium transport in many tissue cells, leading to water and sodium retention, hypertension, and cerebral edema.

The symptoms of uremic patients result from the combined effects of multiple pathogenic factors. In addition to water-electrolyte and acid-base imbalances and endocrine dysfunction, the retention of various metabolic products plays a significant role. These metabolic products are collectively referred to as uremic toxins and include:

1. Small-molecular-weight substances: Those with a molecular weight <500 Daltons, mainly urea (nitrogenous metabolites), creatinine (muscle metabolites), guanidines (methylguanidine, guanidinosuccinic acid), amines, and phenols (metabolites of gut bacteria).
2. Middle-molecular-weight substances: Those with a molecular weight of 500–5000 Daltons, such as various hormones, peptides, and conjugated aromatic amino acids.
3. Macromolecular substances: Refers to substances with a molecular weight >5000 Daltons, such as PTH, growth hormone, and adrenocorticotropic hormone.

Recent studies have also found that after the loss of a large number of nephrons, the remaining nephrons enter a state of hypermetabolism. Oxygen consumption in the nephrons increases significantly, ATP synthesis accelerates, intracellular inorganic phosphate levels rise, Na/H antiport activity increases, intracellular alkalosis occurs, and lipid peroxidation in the remaining nephrons increases, leading to further renal tissue injury. Lipid metabolism disorders can contribute to glomerular vascular atherosclerosis, coagulation, mesangial cell proliferation, and basement membrane injury, thereby promoting the progression of renal insufficiency.

bubble_chart Pathogen

According to the degree of renal function impairment, it can be divided into four stages:

**Stage of Decreased Renal Reserve Function**: Nephron reduction by 25–50%, endogenous creatinine clearance rate 50–70 ml/min, metabolic balance maintained, normal blood creatinine and urea nitrogen levels, renal excretion and regulatory functions remain adequate, and patients show no symptoms of renal insufficiency.
1. **Stage of Renal Insufficiency**: Nephron reduction by 50–70%, endogenous creatinine clearance rate 25–50 ml/min, blood creatinine 133–221 μmol/L (1.5–2.5 mg/dl), urea nitrogen >7.0 mmol/L (20 mg/dl). The kidneys are insufficient to maintain internal stability, and patients exhibit clinical manifestations such as nocturia, lack of strength, decreased appetite, weight loss, and anemia.
2. **Stage of Renal Failure**: Nephron reduction by 70–90%, endogenous creatinine clearance rate 10–25 ml/min, blood creatinine 221–442 μmol/L (2.5–5 mg/dl), urea nitrogen 17.9–21.4 mmol/L (50–60 mg/dl). Symptoms of renal insufficiency worsen further, accompanied by oliguria, isosthenuria, elevated blood phosphorus, decreased blood calcium, sodium, and potassium, and frequent metabolic acidosis, but without complications.
3. **End-Stage Uremia**: Residual nephrons <10%, endogenous creatinine clearance rate <10 ml/min, blood creatinine >442 μmol/L (5 mg/dl), urea nitrogen >21.4 mmol/L (60 mg/dl). Patients exhibit obvious uremic symptoms, including grade III anemia, nausea, vomiting, systemic toxic symptoms, and even unconsciousness, as well as electrolyte imbalances such as water intoxication and hyperkalemia, along with metabolic acidosis.

4. bubble_chart Clinical Manifestations

   The manifestations of chronic renal insufficiency vary with the degree of severity, and can be summarized as follows:

   1. Manifestations of water, electrolyte, and acid-base imbalances

   1. **Dehydration and Edema**: Patients have poor adaptability and regulatory capacity for water. Consuming a large amount of water at once cannot be excreted in a short time, leading to edema. Due to impaired renal concentrating function, when vomiting, diarrhea, or insufficient intake occurs, the kidneys cannot reduce water excretion accordingly, making dehydration likely and worsening the condition. When GFR drops to 40–30 ml/min, polyuria and nocturia appear, with urine specific gravity often below 1.016. When GFR falls to 10–5 ml/min, 24-hour urine output is usually less than 1000 ml. In advanced stages, when GFR is extremely low, oliguria or anuria occurs.
   2. **Hyponatremia and Hypernatremia**: When GFR is below 25 ml/min, the kidneys' ability to regulate sodium is impaired, leading to sodium balance disorders. Vomiting, diarrhea, and reduced sodium reabsorption in the renal tubules cause excessive sodium loss, resulting in hyponatremia, manifested as weakness, apathy, anorexia, etc. In severe cases, hypotension or even unconsciousness may occur. A sudden increase in sodium intake cannot be quickly excreted by the kidneys, leading to extracellular sodium accumulation, water and sodium retention, and resulting in edema, hypertension, or heart failure.
   3. **Hypokalemia and Hyperkalemia**: Potassium metabolism in patients is generally balanced. However, when GFR falls below 10 ml/min, hyperkalemia is more likely to occur, mainly due to reduced potassium excretion from oliguria, metabolic acidosis causing K+ to shift from intracellular to extracellular spaces, increased catabolism, excessive intake, or the use of potassium-sparing diuretics. Hyperkalemia manifests as drowsiness and bradycardia. When serum potassium exceeds 6.5 mmol/L, arrhythmias or cardiac arrest may occur. If intake is low due to nausea, vomiting, diarrhea, or long-term use of potassium-wasting diuretics, potassium loss increases, leading to hypokalemia, which presents as weakness, abdominal distension and fullness, muscle weakness, loss of tendon reflexes, limb paralysis, and in severe cases, respiratory muscle paralysis and arrhythmias.
   4. **Hypocalcemia and Hyperphosphatemia**: These are very common in such patients. When GFR drops to 20–25 ml/min, phosphorus excretion decreases, leading to hyperphosphatemia. Phosphorus binds with calcium in the intestines and is excreted, limiting calcium absorption. Reduced production of 1,25-dihydroxycholecalciferol also decreases intestinal calcium absorption. Hypocalcemia increases PTH secretion, promoting calcium and phosphorus release from bones into extracellular fluid. If the calcium-phosphorus product is too high (>70), renal osteodystrophy or metastatic calcification may occur. Hypocalcemia usually does not cause clinical symptoms, but correcting acidosis with sodium bicarbonate may lower free calcium levels, leading to hand-foot convulsions.
   5. **Metabolic Acidosis**: Acidosis is a common manifestation of chronic renal insufficiency, with severity roughly paralleling the degree of renal dysfunction. In advanced stages, the CO2 combining power is <4.5 mmol/L (10 vol/dl). This is due to:
      1. - Retention of acidic metabolites due to reduced excretion;
      2. - Impaired renal tubular ammonia synthesis and hydrogen excretion;
      3. - Decreased renal tubular reabsorption of bicarbonate;
      4. - Loss of alkaline intestinal fluid due to diarrhea. Severe acidosis causes a significant drop in blood pH, with normal or low chloride levels. Retention of acidic metabolites increases the anion gap significantly above normal. Patients may experience fatigue, anorexia, nausea, vomiting, drowsiness, deep breathing, and may gradually progress to unconsciousness, shock, and cardiac arrest.

   2. Systemic symptoms caused by uremic toxins

   1. Gastrointestinal manifestations are the earliest and most prominent symptoms in patients, which worsen as the disease progresses. This is mainly due to the breakdown of urea into ammonia and ammonium carbonate by bacteria in the gastrointestinal tract, which irritates the mucous membrane. Symptoms include loss of appetite, nausea and vomiting, hiccups, abdominal distension and fullness. In advanced stages, patients may have an ammonia-like odor in the mouth, accompanied by erosion and ulcers of the oral mucous membrane, as well as massive gastrointestinal bleeding.
   2. Early manifestations of mental and neurological symptoms include dizziness, fatigue, memory decline, difficulty concentrating, insomnia, forgetfulness, etc. Gradually, emotional and personality changes emerge, such as apathy, lack of desire, reticence, and mental lethargy. In the advanced stage, symptoms like drowsiness, hallucinations, delirious speech, and urinary incontinence may occur until unconsciousness sets in. Peripheral neuropathy often presents as sensory abnormalities, with patients experiencing limb numbness, a burning sensation in the skin, and, in some cases, unbearable leg pain that forces them to constantly move their lower limbs. The mechanism behind these symptoms involves a combination of uremic toxins, water-electrolyte imbalances, and acid-base disturbances.
   3. Hematopoietic system manifestations typically include normocytic, normochromic anemia, with the severity matching the degree of renal dysfunction. The causes of anemia include reduced erythropoietin secretion by the kidneys, shortened red blood cell lifespan, the presence of substances inhibiting erythropoiesis, and deficiencies in hematopoietic materials. Bleeding is also very common, presenting as epistaxis, skin ecchymosis, and gastrointestinal bleeding, which are related to decreased platelet count, poor platelet function, and abnormalities in various clotting factors.
   4. Cardiovascular system manifestations in the advanced stage of chronic renal insufficiency include hypertension in about 71% of patients, with blood pressure typically ranging from 21–27/13–16 kPa (150–200/90–120 mmHg). This is due to factors such as decreased GFR, water and sodium retention, increased blood volume, heightened activity of the renin-angiotensin-aldosterone system, reduced secretion of antihypertensive substances by the kidneys, and increased peripheral vascular resistance. Long-term hypertension can lead to cardiac enlargement, arrhythmias, and, in severe cases, hypertensive encephalopathy. Fundoscopic examination may reveal retinal arteriosclerosis, exudation, and hemorrhage. In the advanced stage, uremic cardiomyopathy, heart failure, and fibrinous pericarditis may develop, potentially complicated by pericardial effusion and cardiac tamponade.
   5. Respiratory system manifestations in uremic patients include a heightened susceptibility to respiratory infections due to compromised immune function. Interstitial pneumonia is relatively common, with X-rays showing a butterfly-shaped shadow around the hilum, referred to as "uremic lung." In cases of grade III acidosis, deep and labored breathing may occur, and some patients may develop pleuritis or pleural effusion.
   6. Skin manifestations include a pale and sallow complexion, hyperpigmentation, dry and dull skin with poor elasticity. Urea excreted through sweat may deposit on the skin, forming urea frost, or secondary hyperparathyroidism may lead to calcium deposition in the skin, causing intractable itching.

   III. Metabolic, Endocrine Disorders, and Immune Dysfunction

   Patients exhibit decreased plasma albumin levels, deficiencies in essential amino acids, and a negative nitrogen balance. Blood triglyceride levels rise, while glucose tolerance tests show reduced results. Fasting blood insulin levels are elevated. Excessive secretion of renin-angiotensin, prolactin, and gastrin occurs, while levels of thyroid-stimulating hormone, testosterone, and cortisol are lower than normal. Hypothyroidism and hypogonadism may lead to growth and developmental disorders. Peripheral lymphocyte counts decrease, lymphocyte transformation rates decline, and various immunoglobulin levels are reduced, weakening the body's resistance and increasing susceptibility to respiratory, urinary, and skin infections.

   bubble_chart Auxiliary Examination

   1. Blood routine examination shows hemoglobin below 80g/L, with severe cases ranging only 40-60g/L, presenting as normocytic normochromic anemia. Platelets are normal or slightly low, while white blood cells may increase during infection or severe acidosis. The erythrocyte sedimentation rate is often accelerated.
   2. Urinalysis typically reveals proteinuria ranging from + to +++, but in advanced stages with very low GFR, proteinuria may decrease. Microscopic examination of urine sediment shows varying degrees of hematuria and cylindruria, with broad waxy casts being particularly helpful for diagnosis. Morning urine osmolality is mostly below 450 mOsm/kg·L water, and specific gravity is usually below 1.018. Concentration-dilution tests show increased nocturia with small specific gravity differences. In advanced stages, urine specific gravity becomes fixed between 1.010-1.020, and anuria occurs when GFR drops to 1-2 ml/min.
   3. Renal function tests reveal the stages of chronic renal insufficiency.
   4. Blood generation and transformation tests show total plasma protein <60g/L, albumin <30g/L, blood calcium often below 2mmol/L (8mg/dl), blood phosphorus mostly >1.7mmol/L (5mg/dl), while blood potassium and sodium levels depend on the clinical condition.
   5. Other examinations: Abdominal X-ray plain films can observe kidney size, morphology, and the presence of urinary tract obstruction or stones. Radionuclide renal scanning and renography can assess kidney size, blood flow, and secretion/excretion functions. B-mode ultrasound or X-ray computed tomography (CT) is valuable for determining kidney position, morphology, and internal structural changes. The characteristic change of this disease in advanced stages (except for polycystic kidney disease) is reduced kidney volume as shown by these examinations.

   bubble_chart Diagnosis

   1. The degree of chronic renal insufficiency can be staged according to the medical history, symptoms, and signs, referencing the staging criteria for chronic renal insufficiency.
   2. The diagnosis of the primary disease is often based on a clear history of kidney disease combined with clinical manifestations. However, in advanced-stage patients, uremia is the predominant presentation, and the primary disease may be concealed and difficult to identify. In such cases, uremia should be addressed first as an emergency, and further examinations can be conducted to confirm the primary disease once the condition improves.
   3. Factors that exacerbate renal insufficiency, also known as reversible factors of uremia, commonly include:
      1. Infections: primarily respiratory, urinary tract, and skin infections;
      2. Effective hypovolemia;
      3. Use of nephrotoxic drugs such as aminoglycoside antibiotics, polymyxins, antipyretics and analgesics, sulfonamides, and contrast agents;
      4. Congestive heart failure or cardiac tamponade;
      5. Severe hypertension;
      6. High-protein diet, among others.

   bubble_chart Treatment Measures

   The treatment approaches vary depending on the severity of chronic renal insufficiency. During the renal reserve function decline stage, active treatment of the primary disease is essential to prevent further deterioration of renal function. In the renal insufficiency stage, in addition to treating the primary disease, it is crucial to prevent or eliminate aggravating factors and protect the remaining renal function. During the renal failure stage, protein intake should be restricted, and measures should be taken to correct {|###|}typical edema, electrolyte and acid-base imbalances, along with symptomatic management. End-stage uremia requires dialysis or kidney transplantation.

   ### I. General Treatment

   Patients with compensated renal function and no uremic symptoms may engage in light work but should avoid overexertion, exposure to cold, and infections. Nephrotoxic drugs should be avoided, and regular monitoring of renal function and urine tests should be conducted. Patients with decompensated renal function and uremic symptoms should rest and receive treatment. Some primary diseases, such as lupus nephritis treated with hormones and immunosuppressants, active pyelonephritis treated with antibiotics, or obstructive nephropathy with obstruction removal, can often improve renal function. If factors exacerbating renal insufficiency exist, efforts should be made to eliminate them.

   ### II. Correction of {|###|}Typical Edema and Electrolyte-Acid-Base Imbalances

   1. **Water and Sodium Balance:** Sodium and water retention due to oliguria is common. Water and sodium intake should be restricted. The recommended fluid intake is the previous day's urine output plus 500–1000 ml, with sodium salt limited to 2–3 g/day. Grade I dehydration can be managed with oral rehydration, while Grade III dehydration requires intravenous fluids, avoiding excess. Hypernatremia is often caused by dehydration and should be treated primarily with fluid replenishment, such as normal saline. For Grade I hyponatremia, salt intake can be increased (4–6 g/day). If serum sodium is <120 mmol/L, 200 ml of 3% sodium chloride can be administered intravenously, with subsequent adjustments based on serum sodium levels.
   2. **Hypokalemia and Hyperkalemia:** For Grade I hypokalemia, oral potassium salts or potassium-rich foods are sufficient. Severe hypokalemia requires intravenous potassium supplementation, with the concentration not exceeding 0.3%. For hyperkalemia, in addition to restricting potassium intake, diuretics or laxatives can be used to accelerate potassium excretion. If serum potassium exceeds 6.5 mmol/L, emergency measures are needed, such as intravenous injection of 10 ml of 10% calcium gluconate or infusion of sodium bicarbonate or sodium lactate as antagonists. Alternatively, insulin and glucose can be infused intravenously at a ratio of 1 unit:3–5 g. These methods temporarily shift potassium into cells for 6–8 hours, and dialysis should be prepared.
   3. **Hyperphosphatemia and Hypocalcemia:** In addition to limiting high-phosphorus foods, 10–15 ml of aluminum hydroxide gel can be taken orally three times daily to increase phosphorus excretion through the intestines. Long-term use may cause hyperaluminemia and should be monitored. For Grade I hypocalcemia, oral calcium carbonate or calcium lactate (3–6 g/day, divided into 2–3 doses) can be given. For hypocalcemic convulsions, 10–30 ml of 10% calcium gluconate can be slowly injected. Adjusting oral 1,25-dihydroxycholecalciferol (calcitriol) can effectively increase serum calcium and prevent renal osteodystrophy.
   4. **Metabolic Acidosis Management:** Grade I acidosis is often asymptomatic and can be managed with oral sodium bicarbonate or citrate mixture. If the CO₂ combining power is <13.5 mmol/L (30 vol/dl) with acidosis symptoms, intravenous alkali therapy is required. The dose is calculated as 0.5 ml of 5% sodium bicarbonate or 0.3 ml of 11.2% sodium lactate per kg of body weight to raise the CO₂ combining power by 0.449 mmol/L. Initially, two-thirds of the required amount is given, with further adjustments based on CO₂ combining power results, aiming for 17.96 mmol/L (40 vol/dl). Correction of acidosis may lead to hypocalcemia, so calcium supplementation should be considered.

   ### III. Maintaining Positive Nitrogen Balance and Reducing Azotemia

   1. A low-protein diet and essential amino acid therapy are suitable for patients before the onset of end-stage uremia. For patients with increased protein metabolites (such as blood urea nitrogen), deficiency of essential amino acids, and elevated non-essential amino acids, to meet the body's basic metabolic needs without exacerbating azotemia, a daily caloric intake of 146.3 J (35 cal)/kg and high-quality protein of 0.3–0.5 g/kg should be provided. This includes foods rich in essential amino acids, such as eggs, milk, lean meat, and fish, while reducing intake of foods high in non-essential amino acids, such as plant proteins like rice, flour, and legumes. Alternatives like wheat starch and vegetables (e.g., cabbage, sweet potatoes, pumpkin) can be used to satisfy hunger. Vegetable oil, sugar, and fruits are generally not strictly restricted. A daily supplement of an essential amino acid mixture, along with sufficient caloric intake and protein consumption limited to <20 g/d, can promote nitrogen balance and alleviate azotemia. Alternatively, oral α-keto acid preparations (e.g., Ketosteril) can be used to replace essential amino acid injections, achieving the same therapeutic effect.
   2. Gastrointestinal Adsorption Therapy Oxidized starch is a compound of starch and sodium periodate. When taken orally, it binds with urea nitrogen in the intestinal lumen and is excreted in feces, thereby reducing azotemia. Currently, the common dosage is 5–10g of coated aldehyde-oxidized starch taken orally 2–3 times daily. Note that it should not be combined with alkaline drugs to avoid reducing its efficacy. Chinese medicinals such as Rhubarb Rhizoma decoction, taken orally or administered as an enema, can increase fecal nitrogen excretion. Alternatively, a decoction of Rhubarb Rhizoma 30g, calcined oyster shell 30g, and Dandelion 20g in 600–800ml of warm water can be used for retention enema once nightly, yielding certain therapeutic effects.
   3. Increasing Protein Synthesis Injecting anabolic steroids can enhance protein synthesis, alleviate azotemia, and improve anemia. Commonly used agents include nandrolone phenylpropionate or testosterone propionate at 25–50mg, administered intramuscularly every 2–3 days. Alternatively, nandrolone decanoate 25mg can be injected intramuscularly every two weeks.

   IV. Symptomatic Treatment

   1. Nausea and Vomiting In addition to correcting acidosis, metoclopramide 10mg can be administered intramuscularly, or domperidone 10mg can be taken orally three times daily. Severe cases may require intramuscular diazepam or chlorpromazine for antiemesis. For upper gastrointestinal bleeding, cimetidine 0.4–0.6g can be dissolved in glucose solution for intravenous drip, alongside hemostatic agents.
   2. Hypertension Management Antihypertensive therapy should follow a stepwise approach to avoid sudden blood pressure drops, which may impair renal blood flow and accelerate renal dysfunction. Beta-blockers should be avoided as they constrict renal vessels, reduce renal blood flow, and decrease GFR. The following medications can be used sequentially:
      1. Diuretics: Commonly used is furosemide 40–80mg/d, divided into 2–3 oral doses.
      2. Calcium Channel Blockers: Nifedipine 15–60mg/d, divided into three oral doses, or alternatives like nimodipine.
      3. Vasodilators: Prazosin 0.5–1mg, taken orally three times daily, or methyldopa 0.25–0.5g, taken orally 2–3 times daily.
      4. Angiotensin-Converting Enzyme Inhibitors: Such as captopril 12.5–25mg, taken orally 2–3 times daily, or enalapril 2.5–10mg, taken orally twice daily.
   3. Diuresis Diuresis can alleviate edema, enhance toxin excretion, and reduce azotemia. For an endogenous creatinine clearance rate (Ccr) >25ml/min, thiazide diuretics are effective. For Ccr <25ml/min, loop diuretics like furosemide are required. Start with a low dose, with a maximum daily dose of 600mg. High doses are best administered intravenously in glucose solution. Monitor for side effects like deafness, hematuria, and elevated uric acid. If Ccr <5ml/min, diuretics are less effective; oral administration of 20% mannitol 100ml, warmed, 2–4 times daily may be used while preparing for dialysis.
   4. Other Symptoms For grade I anemia, supplement with iron and folic acid. For grade III anemia with significant hypoxia, transfuse small amounts of fresh blood or red cells, though the effect is temporary. If available, intramuscular erythropoietin is highly effective. Use hemostatics for skin or mucosal bleeding. For infections, choose antibiotics non-toxic to the kidneys. For heart failure, besides diuretics, use phentolamine to reduce cardiac load and small doses of cedilanid for cardiac support. For pruritus, apply calamine lotion and take antihistamines orally. For restlessness, use sedatives.

   V. Blood Purification Therapy

   This involves artificial methods to replace renal excretory function, purifying the blood to help reversible uremia survive critical periods, sustain life in end-stage uremia, or prepare for kidney transplantation. Indications include end-stage uremia, refractory hypervolemia, edema, heart failure, hyperkalemia, or severe metabolic acidosis. Common blood purification methods include:

   1. Hemodialysis (HD): The patient's blood and dialysate are continuously and simultaneously introduced into the dialyzer, flowing in opposite directions on either side of the dialysis membrane. The dialysis membrane is an artificial semipermeable membrane. According to the principle of membrane equilibrium, solutes in the liquids on either side of the semipermeable membrane move from the side with higher concentration to the side with lower concentration (diffusion), while water permeates from the side with lower osmotic pressure to the side with higher osmotic pressure (osmosis), ultimately achieving dynamic equilibrium. Uremic toxins such as urea, creatinine, guanidine compounds, and middle-molecular-weight substances, as well as excess water and electrolytes in the patient's blood, diffuse and permeate into the dialysate for removal. Meanwhile, large-molecular-weight substances like proteins, blood cells, and bacteria cannot pass through the semipermeable membrane. Substances needed by the patient, such as bicarbonate and lactate, diffuse into the blood for replenishment, thereby achieving the purpose of an "artificial kidney." Hemodialysis requires a dialysis machine (dialysate supply device and monitoring system), dialysate (with main components similar to plasma), a dialyzer, and vascular access (Figure 5-5-1). The dialyzer is made from raw materials such as cellophane, cuprophane, or polyacrylonitrile membranes, forming 8,000 to 10,000 semipermeable hollow fibers housed in a cylindrical structure with a diameter of 5–10 cm and a length of 20–25 cm. The dialysis surface area is 1.0–1.5 m², with a priming volume of approximately 75–95 ml. Blood flows inside the hollow fibers, while the dialysate flows outside them. For long-term hemodialysis, subcutaneous arteriovenous anastomosis (internal fistula) in the limbs is commonly used as the pathway for blood drainage and return. The frequency of dialysis per week is determined based on the degree of renal failure, with the goal of adequate dialysis. Generally, dialysis is performed 2–3 times per week, with each session lasting 4–5 hours.
   2. Peritoneal dialysis (PD): The peritoneal membrane is a natural semipermeable membrane, with an area of 2.2m² in adults. It functions in diffusion and ultrafiltration, capable of removing uremic toxins from the blood and regulating water and electrolyte balance. Typically, a peritoneal dialysis catheter is surgically placed in the rectovesical (or rectouterine) pouch to drain the dialysate. The dialysate is introduced into the peritoneal cavity, where it fully exchanges with the patient's blood through the peritoneal membrane. Once the electrolytes and metabolic products in the dialysate reach near equilibrium with those in the blood, the dialysate is drained from the peritoneal cavity. This process is repeated to achieve dialysis. There are two types of peritoneal dialysis: intermittent peritoneal dialysis (IPD) and continuous ambulatory peritoneal dialysis (CAPD). Initially, IPD is performed with 1000ml of dialysate per infusion, administered 10 times a day at intervals of 30 minutes to 1 hour. Once the patient's condition stabilizes, CAPD is initiated, with 2000ml of dialysate per infusion, administered 4 times a day at 4-hour intervals. Peritoneal dialysis does not require a machine, is simple to operate, and offers good cardiovascular stability. It is superior to hemodialysis in clearing middle-molecular-weight substances. However, its drawbacks include a higher risk of peritonitis and protein loss.
   3. Other blood purification therapies: These include hemofiltration, hemoperfusion, and gastrointestinal dialysis. Hemofiltration has fewer side effects than hemodialysis and allows precise and rapid dehydration, making it suitable for patients with hypervolemic heart failure or poor cardiovascular stability. Hemoperfusion involves directing the patient's pulsatile blood flow into a container filled with adsorbent material to remove toxins from the blood before returning it to the body. Since it cannot eliminate excess water, it is only applicable for certain poisonings and immune-related diseases. Gastrointestinal dialysis involves orally ingesting several liters of dialysate to remove toxins through diarrhea. Due to its poor efficacy and low patient acceptance, it is rarely used nowadays.

   VI. Kidney Transplantation

   Transplanting a healthy kidney into a uremic patient is an effective treatment for uremia. Since its inception in the 1950s, significant progress has been made, particularly with the clinical application of potent anti-rejection drugs (e.g., cyclosporine A) in the 1970s and advancements in tissue matching techniques. These developments have markedly improved kidney transplant survival rates, with a 2-year survival rate of 90% for kidneys from living relatives and around 70% for cadaveric kidneys. The number of transplants has been increasing annually. However, challenges remain, such as limited kidney availability, imperfect tissue matching, and unresolved side effects of anti-rejection drugs, resulting in relatively low 10-year survival rates for transplant recipients. It is believed that as organ transplantation techniques continue to improve, kidney transplantation will become more widely applied. Indications for kidney transplantation include: chronic renal insufficiency with an endogenous creatinine clearance rate <10ml/min; a creatinine clearance rate >10ml/min but accompanied by refractory hypertension, secondary hyperparathyroidism, or polyneuropathy; age under 50 with no significant pathologies in other major organs such as the heart, brain, liver, lungs, or lower urinary tract; and uremia caused by primary renal disease rather than systemic conditions.

bubble_chart Differentiation

1. Acute renal failure: Some patients with renal disease have an insidious course. When faced with stressful conditions (trauma, infection, vomiting and diarrhea, fever, dehydration, heart failure, food poisoning), chronic renal insufficiency may suddenly worsen, necessitating differentiation from acute renal failure. Acute renal failure is characterized by a short medical history, an acute clinical course, absence of significant anemia and hypoalbuminemia, and no reduction in kidney size as seen on X-ray or B-ultrasound.
2. Symptoms of primary systemic diseases: The systemic symptoms of chronic renal insufficiency are not characteristic. When there is no history of kidney disease and the prominent manifestation is damage to a particular system, it is easy to confine the diagnosis to a primary disease of that system, such as anemia, hypertension, pleural or pericardial inflammation, upper consumptive thirst, gastrointestinal bleeding, and gastroenteritis.
3. Diabetic ketoacidosis: This condition involves water and electrolyte imbalances and metabolic acidosis, with manifestations such as nausea, vomiting, drowsiness, and unconsciousness. It can be differentiated based on medical history, urine glucose, blood sugar, ketone bodies, and renal function tests.