bubble_chart Overview

Chronic renal failure, also known as chronic kidney failure, occurs when the destruction and reduction of nephrons severely impair the kidneys' excretory, regulatory, and endocrine metabolic functions, leading to a series of symptoms, signs, and complications caused by water-electrolyte and acid-base imbalances. The causes of chronic kidney failure in children are closely related to the child's age at the time of the first detection of renal failure. In children under 5 years old, chronic kidney failure is often the result of anatomical abnormalities, such as renal hypoplasia, renal dysplasia, urinary tract obstruction, and other congenital malformations. In children over 5 years old, chronic kidney failure is primarily caused by acquired glomerular diseases like glomerulonephritis or hemolytic uremic syndrome, or hereditary disorders such as Alport syndrome and polycystic kidney disease.

bubble_chart Pathogenesis

Regardless of the cause of kidney damage, once renal function impairment reaches a dangerous level, progression to end-stage renal failure becomes difficult to avoid. Although the progression to renal impairment is not fully understood, it is associated with the following key factors, including progressive immune-mediated damage, hyperfiltration in surviving glomeruli influenced by hemodynamics, dietary intake of protein, phosphorus, and common bletilla tuber, persistent proteinuria, and hypertension.

If immune complexes or anti-GBM antibodies continue to deposit in the glomeruli, it can lead to glomerular inflammation and eventual scar formation.

Regardless of the initial mechanism causing kidney damage, hyperfiltration injury may be a common process leading to eventual glomerular destruction. The loss of nephrons due to any cause can lead to functional and structural hypertrophy of the remaining nephrons, with at least partial increases in glomerular blood flow. Increased blood flow raises the glomerular filtration force within the nephrons. The hyperfiltration in surviving glomeruli may help maintain renal function, but the mechanism by which it also damages these glomeruli remains unclear. Potential mechanisms of damage include elevated hydrostatic pressure directly affecting capillary integrity, leading to increased protein leakage through capillaries or a combination of both. Ultimately, this results in changes to the glomerular basement membrane and epithelial cells, leading to glomerulosclerosis. As sclerosis progresses, the remaining nephrons bear an increased excretory burden, creating a vicious cycle of increased glomerular blood flow and hyperfiltration. Inhibiting angiotensin-converting enzyme to reduce hyperfiltration may slow the progression of renal failure.

Animal models of chronic kidney failure show that high-protein diets accelerate renal failure, possibly due to afferent arteriole dilation and hyperfiltration injury. Conversely, low-protein diets slow the rate of renal function impairment. Studies in humans also confirm that glomerular filtration rate in healthy individuals is directly related to protein intake, suggesting that restricting dietary protein can slow the progression of renal impairment in patients with chronic renal insufficiency.

Some studies in animal models indicate that restricting dietary phosphorus intake in chronic renal insufficiency may protect renal function. Whether this is due to preventing calcium-phosphate salt deposition in blood vessels and tissues or suppressing parathyroid hormone secretion—a potential renal toxin—remains unclear.

Persistent proteinuria or hypertension can directly damage the glomerular capillary walls, leading to glomerulosclerosis and hyperfiltration injury.

When renal function begins to deteriorate, the remaining nephrons compensate to maintain normal homeostasis. If the glomerular filtration rate drops to about 20% of normal, patients develop clinical symptoms of uremia, along with alterations in generation and transformation and metabolic abnormalities. The pathophysiological manifestations of uremia are as follows:

(1) Azotemia: Caused by decreased glomerular filtration.

(2) Sodium depletion or retention: The kidneys lose the ability to regulate sodium and water. In patients on long-term salt restriction or diuretics, hyponatremia is likely. In conditions like nephrotic syndrome, congestive heart failure, anuria, or excessive salt intake, sodium retention occurs.

(3) Acidosis: Due to reduced renal excretion of hydrogen and ammonium ions, large amounts of sodium and bicarbonate ions are excreted in the urine, coupled with the retention of acidic metabolites, leading to acidosis. However, patients tolerate acidosis relatively well, so even with grade II acidosis, clinical symptoms may not appear.

(4) Hyperkalemia: Causes include reduced glomerular filtration, metabolic acidosis, intake of potassium-rich foods like fruits, or the use of drugs such as spironolactone and triamterene, which inhibit aldosterone secretion and reduce renal tubular potassium secretion.

(5) Impaired urine concentration: Results from nephron loss, diuretic use, or increased medullary blood flow.

(6) Renal osteodystrophy: ① When renal function is impaired, phosphate cannot be excreted through the kidneys and is instead excreted through feces. In the intestines, phosphorus combines with calcium to form insoluble complexes, leading to poor calcium absorption, resulting in hypocalcemia, osteoporosis, and deformities. ② Due to high blood phosphorus and low blood calcium, hyperparathyroidism occurs, causing bone changes. ③ When renal function is insufficient, the synthesis of 1,25-(OH)₂D₃ is impaired.

(7) Anemia: Due to ① decreased erythropoietin production; ② hemolysis; ③ loss of blood; ④ shortened red blood cell lifespan; ⑤ insufficient intake of iron and folic acid; ⑥ accumulation of metabolic products (such as erythropoietin inhibitory factors) can inhibit the activity of erythropoietin.

(8) Growth retardation: Due to insufficient calorie intake, bone dystrophy, acidosis, anemia, and other unknown causes.

(9) Bleeding tendency: Due to thrombocytopenia and poor platelet function.

(10) Infection: Poor granulocyte function and weakened immune response make secondary infections more likely, which is a major factor in the exacerbation of chronic kidney failure.

(11) Neurological symptoms: Fatigue, decreased concentration, headache, drowsiness, memory impairment, slurred speech, increased neuromuscular excitability, convulsions and spasms, unconsciousness, and peripheral neuropathy are caused by uremia and aluminum toxicity.

(12) Gastrointestinal ulcers: Due to excessive gastric acid secretion.

(13) Hypertension is caused by water and sodium retention and excessive renin production.

(14) Hypertriglyceridemia is due to plasma lipoprotein lipase deficiency.

(15) The causes of pericarditis and cardiomyopathy remain unclear.

(16) Glucose intolerance: Due to tissue insulin resistance.

bubble_chart Clinical Manifestations

Before patients progress to renal insufficiency, they are often diagnosed with kidney diseases such as glomerular or hereditary sexually transmitted diseases. The condition may gradually develop into renal failure. Despite anatomical abnormalities, patients may exhibit nonspecific symptoms like headaches, fatigue, drowsiness, anorexia, vomiting, excessive thirst, polyuria, and growth retardation. Physical examinations occasionally reveal significant abnormalities, but the vast majority of renal failure patients present with pallor, weakness, and hypertension, and may also show growth retardation and rickets.

bubble_chart Treatment Measures

The management of pediatric chronic kidney failure requires monitoring of the child's clinical condition (physical examination and blood pressure) and laboratory tests, including hemoglobin, electrolytes (hyponatremia, hyperkalemia, acidosis), blood urea nitrogen and creatinine levels, calcium and phosphorus levels, and alkaline phosphatase activity. Regular checks of parathyroid hormone levels and bone X-rays are necessary for early detection of bone dystrophy. Chest X-rays and echocardiography may help assess cardiac function. Nutritional status can be monitored by regularly checking serum albumin, zinc, transferrin, folate, and iron levels.

1. Diet for chronic kidney failure When a child's glomerular filtration rate falls below 50% of normal, growth rate declines, primarily due to insufficient caloric intake. Although the optimal caloric intake for renal insufficiency is unclear, efforts should be made to ensure caloric intake meets or exceeds the recommended levels for the child's age group. Unrestricted carbohydrates (e.g., sugar, jam, honey, glucose polymers) and fats (e.g., medium-chain triglycerides) can be used to increase dietary caloric intake, provided the child tolerates them.

When blood urea nitrogen exceeds 30 mmol/L (80 mg/dL), the child may experience nausea, vomiting, and anorexia, which can be alleviated by limiting protein intake. However, children with renal failure still require a certain amount of protein for growth. A protein intake of 1.5 g/(kg·d) is recommended, prioritizing high-quality proteins rich in essential amino acids (e.g., eggs, lean meat, milk, followed by meat, fish, chicken, and poultry). Milk contains high phosphorus and should be used sparingly. Glucose and peanut oil can supplement calories.

Due to inadequate intake or dialysis losses, children with renal insufficiency may develop deficiencies in water-soluble vitamins, which should be routinely supplemented. Trace elements such as iron and zinc should also be supplemented if deficient. Fat-soluble vitamins (A, E, K) do not require supplementation.

2. Management of water and electrolytes Children with renal insufficiency rarely require fluid restriction, as the brain's thirst center regulates intake unless end-stage renal failure develops, necessitating dialysis. Most children with renal insufficiency can maintain normal sodium balance with an appropriate diet. Some patients with anatomical abnormalities leading to renal insufficiency may lose excessive sodium in urine, requiring dietary sodium supplementation. Conversely, patients with hypertension, edema, or congestive heart failure require sodium restriction, sometimes combined with furosemide (1–4 mg/(kg·24h)).

Hyperkalemia may occur due to excessive dietary potassium intake, severe acidosis, or aldosterone deficiency (damage to the juxtaglomerular apparatus), even with grade II renal insufficiency. However, most children with renal insufficiency can maintain potassium balance. If renal function worsens, dialysis may be necessary. Hyperkalemia can initially be managed by restricting dietary potassium intake, administering oral alkali, or using potassium-lowering resins (sodium polystyrene sulfonate, Kayexalate).

Almost all children with renal insufficiency have acidosis, which generally does not require treatment unless serum bicarbonate falls below 20 mmol/L, in which case sodium bicarbonate should be used for correction.

3. Renal osteodystrophy Renal osteodystrophy often occurs with hyperphosphatemia, hypocalcemia, elevated parathyroid hormone levels, and increased serum alkaline phosphatase activity. When the glomerular filtration rate falls below 30% of normal, serum phosphorus levels rise, serum calcium declines, and secondary hyperparathyroidism develops. Hyperphosphatemia can be managed with a low-phosphorus diet or oral calcium carbonate/antacids to promote phosphorus excretion via the gut. Children should also be monitored for aluminum toxicity, with regular serum aluminum level checks.

Severe renal insufficiency may lead to vitamin D deficiency. Vitamin D should be used for persistent hypocalcemia, radiographic evidence of rickets, or elevated serum alkaline phosphatase activity.

4.Anemia Most patients maintain stable hemoglobin levels between 60-90g/L (6-9g/dl) and do not require blood transfusion. If hemoglobin falls below 60g/L, carefully administer 10ml/kg of red blood cells (small amounts reduce the risk of circulatory overload).

5. Hypertension For hypertensive emergencies, nifedipine can be administered sublingually or diazoxide (5mg/kg, maximum 300mg, injected intravenously within 10 seconds). In cases of severe hypertension complicated by circulatory overload, furosemide (2–4mg/kg at a rate of 4mg/min) can be administered. In renal insufficiency, sodium nitroprusside should be used with caution due to the potential toxicity of thiocyanate abdominal mass.

For persistent hypertension, a combination of dietary sodium restriction (2–3g/d), furosemide [1–4mg/(kg·d)], propranolol [1–4mg/(kg·d)], hydralazine (1–5mg/kg), minoxidil, and captopril may be used.

In summary, early diagnosis and removal of the disease cause should be prioritized. If detected too late, even after removing the disease cause, renal tissue damage may be irreversible. If the disease cause is urinary tract obstruction, appropriate surgical intervention should be performed. However, since the child often has compromised renal function and cannot tolerate major surgery, initial procedures such as nephrostomy or suprapubic bladder drainage may be performed to facilitate drainage. If persistent or intermittent pyuria is present, active infection control and follow-up monitoring are essential. For end-stage renal disease or irreversible renal failure, chronic hemodialysis (artificial kidney, also known as long-term intermittent hemodialysis) has been increasingly used in recent years, enabling many patients to survive or return to normal life. Current long-term regular dialysis typically involves 2–3 sessions per week and can be performed during nighttime sleep. In children undergoing chronic dialysis, the development of secondary sexual characteristics and weight gain are generally unaffected, though height may be slightly impacted. In recent years, chronic hemodialysis abroad has shifted from hospitals to patients' homes, with some children undergoing dialysis for as long as 4–5 years. Peritoneal dialysis has also been applied to chronic kidney failure, primarily involving the long-term placement of an indwelling catheter in the peritoneal cavity for scheduled daily dialysis, which can also be performed at home under medical guidance.

The ultimate goal in treating pediatric end-stage renal failure is kidney transplantation. Abroad, the success rate of kidney transplantation in children over 5 years old is comparable to that in adults. Before transplantation (to sustain the child’s life while awaiting a suitable donor kidney) or after transplantation if rejection occurs, effective chronic hemodialysis remains essential.