Hypokalemic nephropathy

　　1. Etiology

　　This disease is caused by hypokalemic nephropathy due to chronic hypokalemia. The main causes of hypokalemia include insufficient potassium intake; excessive loss (intestinal loss and urinary loss); the use of various diuretics and corticosteroid hormones; chronic kidney diseases such as renal tubular acidosis, Bartter syndrome, Liddle syndrome, renin-secreting tumors, Cushing syndrome, and hypoxanthine oxidase deficiency diseases. Common clinical manifestations of hypokalemia include:

　　1. Non-renal hypokalemia does not increase potassium excretion by the kidneys. An increase in cellular potassium uptake due to various reasons is also one of the common causes of hypokalemia. Hypokalemia caused by increased cellular potassium uptake is often transient and usually does not require special treatment. Hypokalemic periodic paralysis is a rare autosomal dominant genetic disease, in which patients may suddenly develop hypokalemic muscle weakness, with blood potassium levels often below 3 mmol/L. The etiology of the disease is not yet fully understood, and acetazolamide can effectively improve muscle weakness. Some patients with hyperthyroidism may also exhibit clinical manifestations of periodic paralysis, with potassium levels temporarily decreased. However, the etiology may not be completely the same, and acetazolamide is often ineffective, while beta-blockers can significantly improve muscle weakness symptoms. In addition, insufficient potassium uptake or potassium loss due to acute or chronic diarrhea, resulting in intestinal potassium loss, is also a major cause of non-renal hypokalemia.

　　2. Nephrogenic hypokalemia Increased excretion of potassium in urine due to various causes is the main cause of hypokalemia, collectively known as nephrogenic hypokalemia. In addition to the manifestation of hypokalemia, patients often have metabolic acidosis or metabolic alkalosis at the same time. When hypokalemia is accompanied by metabolic acidosis, blood pressure is usually normal, while hypokalemia patients with metabolic alkalosis often have hypertension.

　　(1) Hypokalemia accompanied by acidosis: Due to the compensatory increase in plasma bicarbonate concentration in hypokalemia, most patients tend to have alkalosis; conversely, if hypokalemia patients are accompanied by metabolic acidosis, it is of great help to the diagnosis. Because hypokalemia with acidosis is only seen in tubular acidosis, including proximal and distal tubular acidosis; as well as diabetic ketoacidosis. Diabetic ketoacidosis is promoted by the osmotic diuretic effect of hyperglycemia and the excretion of a large number of negatively charged ketone bodies in urine, which increases the excretion of potassium in urine and promotes a significant decrease in the total potassium content of the body. However, in the early stage of acidosis, due to the redistribution of potassium within and outside the cells, hypokalemia may not be apparent. If potassium is not supplemented when insulin and alkaline drugs are used for treatment, it can cause severe or even fatal hypokalemia.

　　(2) Hypokalemia with normal blood pH or accompanied by metabolic alkalosis:

　　Primary hyperaldosteronism is characterized by elevated serum aldosterone levels, which significantly increases the sodium ions entering the distal tubules, leading to increased potassium excretion in urine due to the sodium-potassium exchange. Patients with this condition, in addition to elevated blood aldosterone levels and hypokalemia, also exhibit clinical manifestations of hypertension and metabolic alkalosis, while the plasma renin activity is usually decreased. Since hypokalemia can feedback inhibit the adrenal cortex from secreting aldosterone, the serum aldosterone levels in patients with severe hypokalemia do not necessarily increase correspondingly. Normal individuals or patients with hypertension due to other causes should have serum aldosterone levels below 110.96 nmol/L (4 ng/dl) after infusion of normal saline or fludrocortisone, and the lack of suppression of serum aldosterone levels is helpful for the diagnosis of this disease. Adrenal tumors, due to higher blood aldosterone levels and more pronounced hypokalemia, must be surgically treated. Adrenal hyperplasia can be initially treated with spironolactone (Anthesterone) for anti-aldosterone therapy, and most patients' hypokalemia and hypertension can be corrected. Some patients with hyperaldosteronism have increased concentrations of 18-hydroxy and 18-oxycortisol in their urine, and a positive dexamethasone suppression test, which is a rare autosomal dominant genetic disorder. These patients can develop extremely severe hypokalemia when taking thiazide diuretics, while taking a low dose of dexamethasone (0.75 mg) can effectively correct hypokalemia and reduce blood aldosterone levels.

　　② Secondary hyperaldosteronism: This disease often occurs with renal vascular diseases such as renal artery stenosis and renal vasculitis, and can also manifest as hypokalemic alkalosis and hypertension in clinical practice. However, it should be noted that not all secondary hyperaldosteronism has hypokalemia. Renal parenchymal cell tumor (Robertson-Kihara syndrome) is a rare glomerular juxtaglomerular apparatus tumor, which can secrete renin and secondary increase aldosterone, and clinically manifest as hypokalemia and hypertension, with significantly increased renin activity in the ipsilateral renal vein. Certain renal tumors can also cause secondary hyperaldosteronism, but the serum level of non-active renin is mainly increased.

　　③ Congenital hypermineralocorticoid syndrome: Due to the low activity of congenital 11β-hydroxysteroid dehydrogenase (11β-OHSD), the conversion of cortisol in the kidney to inactive hydroxycortisol is blocked, causing a large amount of cortisol to bind to mineralocorticoid receptors and activate them, exerting mineralocorticoid-like effects, and clinically manifesting as increased aldosterone. Licorice, cottonseed phenol, and sodium glycyrrhizinate, among other drugs, also have the effect of inhibiting 11β-OHSD, causing the clinical manifestations of increased mineralocorticoids. There have been reports in the literature of increased mineralocorticoid syndrome caused by the intake of food or drugs containing licorice.

　　④ Liddle's syndrome: It is a familial disease. Clinically, it mainly manifests as hypokalemia, hypertension, and alkalosis. The pathophysiological characteristic of this disease is the significant increase in the reabsorption of sodium in the distal renal tubules, causing volume expansion and further inhibiting the production of renin and aldosterone. Therefore, the level of aldosterone in the blood of patients with this disease is often reduced. Sodium retention is the cause of hypertension, and the increased reabsorption of sodium also leads to increased potassium excretion, causing hypokalemia and alkalosis. The obstacle in the outflow of sodium ions from the red blood cell membrane is also one of the characteristics of this disease. Potassium-sparing diuretics such as triamterene and amiloride (amiloride) can be used for the treatment of this disease. Conversely, spironolactone (spironolactone) is ineffective for this disease and should not be used.

　　⑤ Cushing's syndrome: About 30% of patients with Cushing's syndrome may develop hypokalemia, especially those with secondary Cushing's syndrome due to ectopic adrenal皮质hormone secretion, with a higher incidence of hypokalemia. Since corticosteroids can also produce mineralocorticoid-like effects by binding to mineralocorticoid receptors, causing an increase in potassium excretion by the kidneys. Recently, it has been found in animal experiments that corticosteroids can increase glomerular filtration rate, thereby increasing the amount of fluid passing through the renal tubules, which is the main reason for the increased excretion of urine potassium.

　　⑥ Hypochlorhydria: Hypochloremia is also one of the causes of hypokalemia and metabolic alkalosis, with patients having no hypertension. Hypochloremia often occurs in cases of frequent vomiting or due to the loss of a large amount of chloride ions caused by gastrointestinal decompression. In addition, long-term use of large doses of thiazide or loop diuretics is also an important cause of hypochloremia.

　　⑦ Bartter syndrome: This is a rare genetic disease, 80% of patients develop the disease before the age of 15, and most patients are accompanied by growth and development delay. It is extremely rare for patients to develop the disease after the age of 50. The pathological feature of this disease is the hyperplasia of the juxtaglomerular apparatus, and patients may present with hyperreninemia and hyperaldosteronism, so hypokalemia is also an outstanding clinical symptom. Due to the significant increase in the production of prostaglandins and kinins in patients, they develop resistance to the effects of angiotensin II and norepinephrine, so they do not have hypertension. Studies have found that the hypokalemia in this disease is not entirely due to increased aldosterone, as restricting sodium salt intake, taking spironolactone (spironolactone), aminoglutethimide, or removing the adrenal glands can effectively reduce the excretion of urinary potassium in patients with increased aldosterone, but these methods cannot correct the hypokalemia in Bartter syndrome. On the contrary, drugs such as indomethacin (analgin) that inhibit prostaglandin production can correct all the metabolic disorders and abnormalities in this disease, suggesting that excessive prostaglandin production may be the main cause of this disease. The treatment of this disease should include the use of prostaglandin inhibitors, and potassium supplementation should be timely. For patients with increased urinary potassium excretion, potassium-sparing diuretics should also be administered, among which amiloride (amiloride) is the most effective.

　　⑧ Magnesium deficiency: Magnesium deficiency can also lead to increased urinary potassium excretion and hypokalemia, the cause of which is not yet clear. For some patients, the excretion of urinary potassium can be reduced after supplementing an adequate amount of magnesium. The clinical manifestations of hypomagnesemia are similar to those of hypocalcemia, mainly manifested as increased neuromuscular irritability, such as muscle tremors, irritability, photophobia, and mental disorders, and in severe cases, delirium and convulsions may occur.

　　⑨ Diuretics: Thiazides, acetazolamide, mercury diuretics, and furosemide and etacrynic acid and other diuretics can increase urinary potassium excretion and lead to hypokalemia. The main reason is that these drugs inhibit the reabsorption of sodium and water in the renal tubules, resulting in a significant increase in sodium and water reaching the distal tubules, which increases the Na-K exchange and increases urinary potassium excretion. In addition, these diuretics (except for acetazolamide) can also cause metabolic alkalosis, further increasing urinary potassium excretion. In addition to diuretics, many other drugs also cause hypokalemia, and the mechanisms by which they cause hypokalemia are not entirely the same. The following table lists some commonly used drugs that can cause hypokalemia and their principles of causing hypokalemia.

　　Second, Pathogenesis

　　The understanding of the possible pathogenesis of hypokalemia nephropathy comes from the study of experimental hypokalemia in rats. The main cause of renal damage in this disease may be the abnormal production of ammonia during hypokalemia. Experimental results show that hypokalemia stimulates ammonia production, the mechanism of which is intracellular acidosis during hypokalemia, resulting in the activation of the complement alternative pathway, followed by the infiltration of immune cells into the stroma, leading to progressive tubulointerstitial damage. In rats with hypokalemia, the administration of sodium bicarbonate to inhibit ammonia production results in a reduction in tubulointerstitial lesions.

　　The reversible changes in tubular structure and function accompanying potassium loss show reversibility. These lesions may not necessarily develop into chronic tubulointerstitial nephropathy and lead to persistent renal insufficiency, but they are related to the duration of hypokalemia. There have been reports of a familial type of hypokalemic tubulointerstitial nephropathy that shows progressive renal failure. The results of rat experimental hypokalemia show that after hypokalemia persists for several months, irreversible interstitial fibrosis may occur. However, the tubulointerstitial lesions in rats with hypokalemia are more severe than in humans, and these lesions may be caused by the susceptibility of hypokalemic rats to chronic pyelonephritis.

　　This disease is prone to complications of pyelonephritis and systemic hypokalemia symptoms; in severe cases, chronic renal insufficiency may gradually appear with the progression of the disease.

　　1. Pyelonephritis (pyelonephritis) refers to inflammation of the renal pelvis, mostly caused by bacterial infection, usually accompanied by inflammation of the lower urinary tract. It is difficult to distinguish strictly in clinical practice. According to the clinical course and disease, pyelonephritis can be divided into acute and chronic stages. Chronic pyelonephritis is an important cause of chronic renal insufficiency.

　　2. When the concentration of potassium ions in human plasma is less than 3.5mEq/L, it is called hypokalemia. Common causes include decreased intake, excessive loss, such as diarrhea, vomiting, and the transfer of potassium ions from extracellular fluid to intracellular fluid. When hypokalemia occurs in the human body, it will affect the cardiovascular system, central nervous system, digestive system, urinary system, and muscle system.

　　Prevention: Actively diagnose and treat the primary disease, eliminate various predisposing factors for hypokalemia, strive to correct hypokalemia, and prevent the progression and aggravation of the disease.

　　1. Shenling Baizhu Powder:6g, twice a day, for those with deficiency-cold of the spleen and stomach.

　　2. Jianbu Huqian Wan:Take one pill each time, three times a day, for those with deficiency of the liver and kidney.

　　3. Tianwang Buxin Dan or Zhusha Anshen Wan:Take one pill each time, three times a day, for those with evil toxins attacking the heart.

　　Actively diagnose and treat the primary disease, eliminate various predisposing factors for hypokalemia, strive to correct hypokalemia, and prevent the progression and aggravation of the disease.

　　1. Urinalysis:Visible proteinuria and casts, with more white blood cells present in cases of concurrent infection. Urine concentration and dilution tests show reduced concentrating function, decreased urine specific gravity (reduced excretion rate of phenol red and para-aminobenzoic acid), and increased prostaglandin E in urine.

　　2, Blood test:The blood BUN and Scr may be normal in the early stage of the disease; as the disease progresses and renal failure occurs, the levels of blood creatinine and urea nitrogen increase, and the characteristic change is the decrease in blood potassium, and the increase in renin and aldosterone.

　　The pathological change of this disease is tubulointerstitial nephritis, accompanied by progressive renal failure. The appearance of vacuoles in the proximal tubules is the pathological feature of hereditary or acquired hypokalemia nephropathy, that is, there are many vacuoles in the renal tubular epithelial cells, especially prominent in the proximal tubular lesions. The vacuoles do not contain fat or glycogen. The glomeruli and renal vessels are generally not damaged. Long-term hypokalemia causes tubulointerstitial fibrosis, forming scars, kidney atrophy. The pathophysiological changes are various renal function abnormalities, accompanied by potassium loss, the characteristics are vasopressin-resistant urine concentration dysfunction, increased ammonia generation, decreased glomerular filtration rate. In the human body, the characteristic structural change accompanying potassium loss is the appearance of vacuoles in the tubular epithelium, which is due to the expansion of the cistern of the endoplasmic reticulum. This damage is mainly limited to the proximal tubules, and only focal changes in the distal tubules. Routine renal biopsy and imaging examination can see the above characteristic changes.

　　I. Treatment for hypokalemia nephropathy (the following information is for reference only, detailed information needs to be consulted with a doctor)

　　1, Astragalus and粳米 porridge

　　[Ingredients]: Take 60 grams of astragalus, 50 grams of粳米, a little brown sugar.

　　[Preparation]: First decoct astragalus in water for 40 minutes, then take the decoction and cook with粳米 to make porridge, add a little brown sugar and melt it before eating, take twice a day, once in the morning and once in the evening.

　　[Function]: It has the effects of tonifying the spleen and stomach.

　　2, Poria and粳米 porridge

　　[Ingredients]: Take 15 grams of white poria (ground into fine powder), 50 grams of粳米.

　　[Preparation]: Cook the two into porridge and eat, one dose a day.

　　[Function]: It has the effects of benefiting the heart and spleen, promoting diuresis, and reinforcing the healthy and eliminating the pathogenic.

　　3, Euryale porridge

　　[Ingredients]: 30 grams of euryale, 30 grams of glutinous rice, 10 white fruits.

　　[Preparation]: First peel and remove the kernel of white fruit, then cook the white fruit with euryale and glutinous rice to make porridge. Take once a day, and 10 days as one course of treatment.

　　[Function]: It is suitable for calming the liver and subduing the yang, mainly to strengthen the kidney.

　　4, Poria and adzuki bean porridge

　　25 grams of poria, 30 grams of adzuki bean, 10 dates, 100 grams of粳米.

　　First soak adzuki bean in cold water for half a day, then cook with poria, jujube, and粳米 into porridge. Take warm porridge for breakfast and dinner.

　　5, Grass root and bean porridge

　　200 grams of fresh grass root, 200 grams of粳米, 200 grams of red bean.

　　Add fresh grass root to an appropriate amount of water, decoct the juice and remove the dregs, then add粳米 and red bean, and cook into porridge. Take 3-4 times a day.

　　6, Corn bean jujube porridge

　　50 grams of corn, 25 grams of mung bean, 50 grams of jujube.

　　Boil the above three ingredients into porridge, and eat once a day.

　　7, Amaranthus and crucian carp porridge

　　5-8 bundles of amaranthus, 1-2 crucian carps, 30 grams of white rice.

　　Remove the scales and internal organs of crucian carp, wrap it in gauze, and cook with amaranthus and white flowers to make porridge. Take 2-4 times consecutively.

　　Second, what foods are good for kidney disease with hypokalemia?

　　1. It is advisable to eat light and easy-to-digest foods.

　　2. It is advisable to eat fresh vegetables and a moderate amount of fruit, and drink an appropriate amount of water.

　　3. It is appropriate to eat high-potassium foods such as bananas, oranges, potatoes, tomatoes, pumpkins, tea, soy sauce, monosodium glutamate, etc.

　　Third, what foods should kidney disease with hypokalemia avoid?

　　1. Avoid seafood, beef, mutton, spicy刺激性 foods, alcohol, and all kinds of heat-inducing foods such as five-spice powder, coffee, coriander, etc.

　　2. Avoid all tonics, tonics, and easy-to-heat foods such as chili, lychee, chocolate, etc.

　　3. Those with high blood uric acid levels should especially avoid eating animal internal organs, fish, shrimp, crabs, clams, beer, mushrooms, beans, spinach, etc.

　　4. It is advisable to drink less alcohol and eat fewer spicy foods such as chili and pepper.

　　Medication Treatment:

　　1. This disease is caused by hypokalemia, so the treatment for hypokalemia is the most fundamental treatment. Since the consequences of hypokalemia can be severe if not corrected in a timely manner, it is necessary to master the general treatment principles, that is, to remove the causes of hypokalemia. Hypokalemia caused by the redistribution of potassium ions inside and outside the cells due to various reasons is generally transient and mild, and may not require treatment. However, if hypokalemia is severe, potassium supplementation is necessary. For mild hypokalemia, oral potassium chloride can generally be given, 3-6g per day, taken in divided doses. If the patient has been supplementing potassium for a long time, a sustained-release formulation of potassium chloride, such as potassium chloride sustained-release tablets (Pudashou), can be given to reduce gastrointestinal irritation and fluctuations in blood potassium levels.

　　For those who cannot take oral medication due to severe potassium deficiency or fasting and other reasons, intravenous potassium supplementation should be given, with potassium chloride being the most commonly used. Potassium chloride is strictly prohibited from being administered intravenously and should be diluted in normal saline or glucose solution for infusion, with no more than 1g per hour being recommended. For patients with hypochloremic acidosis and low blood potassium levels, if there are obvious symptoms of renal tubular acidosis, potassium chloride supplementation is not advisable, unless in an emergency situation, potassium salts without chloride, such as potassium citrate, are generally recommended. For patients with oliguria, especially those who are also taking potassium-sparing diuretics, be careful not to overcorrect and cause hyperkalemia when supplementing potassium. Conversely, for patients with metabolic acidosis, correcting acidosis can further exacerbate hypokalemia, so the amount and speed of potassium supplementation should be appropriately increased.