Renal medullary necrosis

　　1. Etiology

　　This disease often occurs with severe pyelonephritis, diabetes, urinary tract obstruction, analgesic nephropathy, especially preparations containing phenacetin (Phenacetin) or poisoning, and can also be seen in vascular lesions, transplant renal rejection, sickle cell anemia, hyperuricemia, macroglobulinemia, allergic reactions, shock, excessive use of vasoconstrictive drugs such as norepinephrine, etc. There are also reports that long-term fat-free diet can also lead to renal papillary necrosis. The causes of renal papillary necrosis include:

　　1. Diabetes:Diabetes is the most common disease associated with renal papillary necrosis, accounting for 50% to 60% of RPN cases in large case series. Most cases of recurrent renal papillary necrosis are diabetic patients. A study of intravenous pyelography showed that 25% of insulin-dependent diabetic patients had renal papillary necrosis.

　　2. Obstructive nephropathy:In large case series, obstructive nephropathy accounts for 15% to 40% of the causes of RPN.

　　3. Pyelonephritis:Severe pyelonephritis is one of the common causes of renal papillary necrosis, especially in patients with diabetes or urinary tract obstruction. Since infection can be the cause of renal papillary necrosis, it often occurs concurrently with RPN, and can also be secondary to diabetes, the proportion of infection in the etiology of renal papillary necrosis is difficult to determine.

　　4. Abuse of analgesics:Abuse of analgesics, especially analgesic mixtures containing propyphenazone and the use of large doses of other analgesics, can cause renal papillary necrosis. In the United States, analgesics account for 15% to 20% of the causes of RPN; in countries where analgesic abuse is common, analgesics can account for 70% of the causes of RPN. Children receiving analgesic treatment can also develop renal papillary necrosis.

　　5. Vasculitis

　　(1) Transplant Renal Arteritis: Vasculitis caused by renal rejection can block the blood vessels supplying the papilla, leading to ischemic necrosis of the papilla. In addition, primary diseases such as diabetes and sickle cell hemoglobinopathy can also cause necrosis of the renal papilla in patients.

　　(2) Wegener's granulomatosis.

　　(3) Necrotizing vasculitis: including polyarteritis nodosa, allergic vasculitis, microangiitis, etc.

　　6. Sickle cell hemoglobinopathy.

　　7. Liver disease:

　　Papillary type, also known as complete papillary necrosis, is characterized by the necrosis, demarcation, and separation of the papillae. In the early stage of necrosis, papillary swelling can be seen, the mucosa is normal, and the renal calyx is normal. With progressive necrosis, the mucosa is lost, and the angiography shows irregular papillae with blurred edges. With the separation of the necrotic papillae, sinus formation begins, and renal pelvis angiography shows sinus curvature. When the entire necrotic papilla is separated from the normal tissue, an annular shadow around the necrotic papilla within the sinus can be seen. In a few cases, the necrotic papilla falls into the renal pelvis and can be found in the urine. However, in most cases, the necrotic papilla does not fall off but is absorbed or maintained at a distance, and then the necrotic papilla is calcified or forms the core of a calculus. If the necrotic papilla is absorbed or falls off, an

　　Renal medullary necrosis can be localized to a few papillae or occur in many papillae, and can affect one or both kidneys, with most patients affected by both kidneys. There are reports that in patients with RPN in one kidney, papillary necrosis occurs in the other kidney within 4 years.

　　2. Pathogenesis

　　The main pathogenesis of renal medullary necrosis may be due to insufficient renal medullary blood flow caused by various etiologies, leading to ischemic necrosis. For example, microvascular lesions caused by diabetes or blood flow disorders caused by sickle cell disease.

　　The occurrence of this disease is related to the anatomical and physiological characteristics of the renal medullary pyramid blood supply, as well as renal ischemia, medullary papillary vascular lesions and infection. The blood flow of the kidney accounts for 85% to 90% in the cortex, while the medulla only accounts for 10% to 15%. The blood supply near the renal papilla is less, and all of them come from the efferent arterioles of the perimedullary renal units through straight blood vessels. Affected by the solute concentration and osmotic pressure gradient in the medulla, the blood viscosity gradually increases, the blood flow slows down, which is a common site of ischemic necrosis. Concurrent basic diseases such as diabetes, analgesic nephropathy, hyperuricemia, etc., can itself cause chronic interstitial nephritis and renal small vessel lesions. Analgesic nephropathy, sickle cell anemia, macroglobulinemia, etc., can cause the papillary area to be stimulated by high concentration of acidic substances and abnormally high blood viscosity. When there is urinary tract obstruction, the pressure in the renal pelvis, renal calyx, and renal tubules increases, all these factors can lead to severe ischemia and necrosis of the medullary papilla. In addition, the patient's increased susceptibility to bacterial invasion, both locally and globally, can easily lead to kidney and urinary tract infections, further aggravating the blood supply disorder of the renal pyramid and tissue necrosis. Clinically, more than half of the cases of renal papillary necrosis have two or more pathogenic factors (such as diabetes complicated with urinary tract infection), and the more pathogenic factors, the higher the incidence rate.

　　Complications of renal medullary necrosis can cause progressive renal function decline, leading to chronic renal failure and uremia. In severe bilateral extensive renal medullary necrosis, acute renal failure may occur.

　　According to the urgency of onset, it can be divided into acute, subacute, and chronic types. According to the pathological location, it can be divided into renal medullary type and renal papillary type. Patients are mostly over 40 years old, with more females than males, and chronic renal medullary necrosis in children is rare, but there are reports of acute renal medullary necrosis caused by hypoxemia, dehydration, or sepsis. The clinical manifestations depend on the extent of necrosis, the number of involved papillae, and the speed of necrotic development. Acute renal medullary necrosis often occurs suddenly on the basis of the above chronic diseases, with chills, high fever, gross hematuria or varying degrees of hematuria and pyuria, often accompanied by urinary tract irritation signs and lumbar pain, as in acute pyelonephritis. If the necrotic tissue of the renal papilla falls off or blood clots block the ureter, it can cause colic and oliguria, even anuria. In severe bilateral extensive cases, renal medullary necrosis can lead to acute renal failure, with rapid progression and poor prognosis, with patients often dying of sepsis or complications of acute renal failure.

　　This type of patient often has local symptoms that are not prominent due to severe systemic conditions, especially when the patient has diabetes, urinary tract obstruction, and cardiovascular lesions, making it difficult to diagnose in a timely manner. Clinically, this type is more common; subacute cases are less severe or rapid than the former, with a longer course that can last for several weeks or months. The detachment of necrotic papillae can cause urinary tract obstruction, with more common symptoms of renal colic and difficulty in urination due to renal tissue necrosis, detachment, and symptoms along the urinary tract, as well as oliguria and progressive renal insufficiency; chronic type often occurs on the basis of chronic interstitial nephritis, with a stealthy onset and a course that can last for several years. Clinically, it presents similar to chronic interstitial nephritis or recurrent chronic pyelonephritis, with the appearance of tubular dysfunction, such as polyuria, nocturia, reduced urine concentration function, and decreased phenol red excretion rate, dysfunction of acidification, leading to tubular acidosis, etc. There may be persistent microscopic hematuria and pyuria, as well as progressive renal function decline, ultimately leading to chronic renal failure and uremia; it may also be asymptomatic, often discovered incidentally during excretory urography or at post-mortem autopsy, with some cases commonly accompanied by urinary tract epithelial tumors.

　　The main treatment is to actively seek the primary disease and provide effective treatment in a timely manner. Strive to restore renal function as soon as possible to prevent the disease from progressing to the stage of renal papillary necrosis. Patients with clear diagnosis should rest fully and grasp the integrated traditional Chinese and Western medicine treatment to delay the deterioration of renal function. The main treatment principle of this disease is to treat the primary disease according to the cause, eliminate the triggering factors, improve renal blood supply, alleviate discomfort, and promote renal repair. The treatment plan includes finding the underlying disease as much as possible, controlling the development of the underlying disease, eliminating the triggers; promoting blood circulation and removing blood stasis, dredging the renal circulation, increasing renal blood flow, and improving medullary blood supply; antispasmodic, analgesic, hemostatic and other symptomatic treatment; hemodialysis treatment for renal insufficiency.

　　1. Urinalysis

　　There is hematuria, gross hematuria accounts for 20%, and microscopic hematuria is 20% to 40%; if there is a large amount of hematuria combined with hemorrhagic anemia, a nephrectomy operation is needed, 50% to 60% of patients have leukocyturia; 80% of patients have moderate proteinuria, and urinary tract infection can occur in patients with bacteriuria, which is positive, and necrotic tissue of sloughed renal papillae is found in the urine.

　　2. Ultrasound examination

　　Its value in examination is limited, unless in obstructive nephropathy, it can cause papillary necrosis or residual necrotic papillae in the renal pelvis.

　　3. X-ray examination

　　1. KUB plain film:1. Early radiological examination may be negative. Venous pyelography shows that the contrast agent enters the area around the renal papillae that have not completely sloughed off, and (or) there are club-shaped or spotted filling points in the renal papillary area. The contrast agent enters the cavity after the papillae have sloughed off, and (or) there are 'corrosive' changes at the edge of the minor renal calices.

　　2. X-ray examination shows:

　　(1) Papillary necrosis type: Initially, the renal pelvis dome is somewhat blurred, and then, due to the formation of blind tubes in the renal pelvis dome, the two blind tubes gradually merge, and the contrast study shows an 'arc-shaped' or 'ring-shaped' image; the necrotic renal papillae fall into the renal pelvis, causing a filling defect, and the papillae appear as rod-shaped cavities. Necrotic papillae produce filling defects and proximal dilatation in the ureter, and when there is calcification around the necrotic papillae, a ring-shaped calcification shadow can be seen on the plain film.

　　(2) Medullary necrosis type: When the necrotic tissue is deep within the pyramids and has not communicated with the renal pelvis, there is no change in the contrast study, but the above phenomenon appears only after a fistula is formed and communicates with the renal pelvis.

　　3. IVP is the most valuable diagnostic method for this disease.

　　(1) There is a circular shadow or defect in the renal papillary location.

　　(2) Medullary or papillary calcification shadow.

　　(3) Renal shadow shrinkage and irregular contour.

　　Patients with renal medullary necrosis should eat

　　Eat more pork kidneys, chives, walnuts, and other nuts, drink more water, drink less alcohol, do appropriate exercise, and can do some massage on the waist.

　　中医认为本病主要是由于湿热所伤而致脾肾虚损、气滞血淤而发病，故治疗首先应以清利湿热为主，继之调理脾肾，佐以理气化瘀。肾乳头坏死的中医辨证治疗：

　　1. Damp-heat蕴蒸型:Frequent urination, burning and stinging pain, dripping不畅, yellowish urine, distension in the lower abdomen or back pain that resists pressing, or accompanied by fever and chills, bitter taste and nausea, or constipation, red tongue with yellow greasy fur, and slippery and rapid pulse.

　　治疗方法：清热解毒，利湿通淋。

　　Basic medicine: Modified Er Miao San: The formula uses Phellodendron amurense, Atractylodes macrocephala, Coptis chinensis, Plantago asiatica, Polygonum cuspidatum, Angelica sinensis, Achyranthes bidentata, and Taraxacum mongolicum.

　　2. Deficiency of both spleen and kidney:Frequent urination, hematuria, loss of appetite, loose stools or accompanied by nausea and vomiting, abdominal distension, fatigue, pale complexion, soreness in the waist and knees, or clear night urination, pale tongue, and weak pulse.

　　治疗方法：健脾益气，补肾固摄。

　　基本方药：四君子汤合无比山药丸加减：方用人参、黄芪、白术、茯苓、山药、苁蓉、生地、山萸肉、菟丝子、巴戟天、紫珠草、白茅根、陈皮。

　　3. Blood stasis obstruction type:The pain in the lower back is fixed and not easy to move, mild cases may cause difficulty in bending forward and backward, and severe cases may not be able to turn due to severe pain, the pain is like a needle, the pain spot resists pressing, hematuria, or small blood clots in the urine, purple tongue with ecchymosis or petechiae, and fine and涩脉.

　　Treatment Method: Promote blood circulation and remove blood stasis, regulate qi and relieve pain.

　　Basic Prescription: Modified Shentong Huyu Decoction: Ingredients include peach kernel, safflower, angelica sinensis, five spirit resins, prepared cyperus rotundus, astragalus membranaceus, earthworm, salvia miltiorrhiza, panax notoginseng powder, chuanxiong.

　　First, treatment

　　1. Indications for the treatment of this disease:Including various primary diseases such as diabetes, vasculitis, obstructive nephropathy, alcoholic liver disease, analgesic nephropathy, sickle cell disease, macroglobulinemia, renal tuberculosis, epidemic hemorrhagic fever, pyelonephritis, or venous thrombosis, as well as hematuria, back pain, renal colic, oliguria, nitrogen retention, and renal failure caused by renal papillary necrosis and shedding.

　　2. The treatment principles of this disease:Primarily aimed at treating the underlying cause, eliminating the triggering factors, improving renal blood supply, alleviating discomfort symptoms, and promoting renal repair. The treatment plan includes finding the underlying disease as much as possible, controlling the development of the underlying disease, eliminating the triggering factors; promoting blood circulation and removing blood stasis, dredging the renal intracirculation, increasing renal blood flow, and improving medullary blood supply; antispasmodic, analgesic, hemostatic, and other symptomatic treatments; for renal insufficiency, hemodialysis treatment is adopted.

　　3. Treatment plan

　　(1) Active treatment of underlying diseases: If there is diabetes, actively control blood sugar, blood lipids, and blood pressure; remove urinary tract obstruction as soon as possible if there is urinary tract obstruction; stop using analgesics as soon as possible for those taking analgesics; for sickle cell disease or macroglobulinemia, treat the primary disease, dilute the blood, and reduce blood viscosity.

　　(2) Active control of infection: Whether it is the underlying disease of chronic pyelonephritis or new-onset pyelonephritis on the basis of other diseases, strong antibiotics should be used to actively control infection. Complex factors should be eliminated as soon as possible, such as urinary tract obstruction caused by stones, blood clots, and necrotic tissue blocks, as well as indwelling catheters. Refer to the drug sensitivity results if available, and select third-generation cephalosporin antibiotics with good efficacy against Gram-negative bacilli and relatively low nephrotoxicity if there are no drug sensitivity results. If renal function is still good, third-generation quinolone antibiotics can also be selected.

　　(3) Increase renal blood flow: The pathological basis of renal papillary necrosis is the disturbance of renal medullary blood flow and ischemia centered on the renal papilla, therefore, it should be treated by promoting blood circulation and removing blood stasis, unblocking the intrarenal circulation, increasing renal blood flow, improving medullary blood supply, and reducing renal damage. Low molecular weight dextran and compound Danshen injection can be administered intravenously, and appropriate heparin or urokinase can be used intravenously, as well as small doses of dopamine, dipyridamole, vitamin E, and others. The specific usage and dosage can be determined according to hemorheological indicators such as blood viscosity and vascular elasticity. In the early stage, local treatment such as renal area diathermy, perirenal closure, and intramuscular or subcutaneous injection of dihydroergotamine 0.3-0.6mg, once a day or every other day, can be used to improve renal papillary blood supply. These methods should not be used temporarily when hematuria is obvious. Non-steroidal anti-inflammatory drugs should be avoided, as these drugs can inhibit the synthesis of prostacyclin, reducing renal blood flow.

　　(4) Antispasmodic, analgesic, and hemostatic treatment: When the necrotic tissue of the renal papillae falls off, hematuria often occurs; when bleeding is obvious, hemostatic treatment should be administered; when massive bleeding occurs, fresh blood or concentrated red blood cells should be transfused; when necrotic tissue and blood clots block the ureter, renal colic may occur, and antispasmodics and analgesics such as atropine and pethidine can be administered; it is also possible to insert a ureteral catheter to flush the renal pelvis with urokinase or to place a drain, and antibiotics can be injected through this; if there is no water and sodium retention, encourage the patient to drink more water, strengthen fluid infusion, and promote the excretion of necrotic tissue or blood clots.

　　(5) Hemodialysis treatment: In cases of bilateral extensive renal papillary necrosis with acute renal failure, treatment should be given according to acute renal failure, and hemodialysis treatment should be performed when necessary.

　　(6) Other treatments: The shed renal papillae often can be automatically excreted, and occasionally surgical intervention is required. For individual severe cases with persistent massive hematuria, nephrectomy treatment is needed.

　　① For unilateral acute renal papillary necrosis, if it presents as an explosive infection, or there is massive hematuria without ceasing due to papillary necrosis, or severe obstruction is caused, nephrectomy of the affected kidney can be performed.

　　② For those with allergic reactions, adrenal cortical hormones can be administered for treatment.

　　③ In cases of electrolyte and acid-base balance disorders, and hypertension, actively correct the disorders and control blood pressure.

　　(7) Traditional Chinese Medicine Treatment: Traditional Chinese medicine categorizes renal papillary necrosis under the scope of diseases such as hematuria, stranguria, and lumbar pain. It is believed that the occurrence of renal papillary necrosis is due to irregular diet, excessive consumption of spicy, greasy, and rich foods, food retention, internal damp-heat, leading to spleen deficiency and damp obstruction, or improper lifestyle, exposure to damp-heat, damp-heat pathogenic factors accumulating in the bladder, loss of proper Qi transformation, and obstruction of the waterway, resulting in burning and pricking pain during urination. If the bladder heat is severe, it may injure the Yin collaterals, forcing blood to flow recklessly, resulting in hematuria. Or due to prolonged illness without relief, the spleen and kidney deficiencies become more severe over time, leading to weakened adhesion and exacerbation of the condition. Due to spleen and kidney deficiencies and damp-heat obstruction, it can often cause collateral stasis, such as lumbar pain due to renal collateral obstruction, stasis blood blocking the new blood from returning to the meridians, and the blood following urine, manifested as hematuria. If Qi and blood circulation is not smooth, and there is no way for blood to flow, blood stasis occurs, leading to persistent and difficult-to-heal illness.

　　中医认为本病主要是由于湿热所伤而致脾肾虚损、气滞血淤而发病，故治疗首先应以清利湿热为主，继之调理脾肾，佐以理气化瘀。肾乳头坏死的中医辨证治疗：

　　①湿热蕴蒸型：小便频数，灼热刺痛，淋沥不畅，点滴而下，尿色黄浊，小腹坠胀或有腰痛拒按，或伴发热寒战，口苦恶呕，或大便秘结，舌质红，苔黄腻，脉滑数。

　　治疗方法：清热解毒，利湿通淋。

　　基本方药：加味二妙散加减：方用黄柏、苍术、通草、车前子、萆粟、当归、怀牛膝、蒲公英。

　　②脾肾两亏型：小便频数，尿血，不思饮食，便溏或伴恶心呕吐，腹胀，精神困惫，面色萎黄，腰膝酸痛，或夜尿清长，舌质淡，脉虚弱。

　　治疗方法：健脾益气，补肾固摄。

　　基本方药：四君子汤合无比山药丸加减：方用人参、黄芪、白术、茯苓、山药、苁蓉、生地、山萸肉、菟丝子、巴戟天、紫珠草、白茅根、陈皮。

　　③ Blood stasis obstruction type: Fixed and shifting back pain, mild cases may cause difficulty in bending and extending, severe cases may not be able to turn due to severe pain, pain like a needle, pain location is resistant to pressing, hematuria, or small blood clots in urine, purple or ecchymotic tongue, fine and涩脉.

　　Treatment Method: Promote blood circulation and remove blood stasis, regulate qi and relieve pain.

　　Basic Prescription: Modified Shentong Huyu Decoction: Ingredients include peach kernel, safflower, angelica sinensis, five spirit resins, prepared cyperus rotundus, astragalus membranaceus, earthworm, salvia miltiorrhiza, panax notoginseng powder, chuanxiong.

　　II. Prognosis

　　Since the renal papilla cannot regenerate, the prognosis of this disease mainly depends on the severity of renal papilla damage at the time of onset. Whether the primary etiology that causes renal medullary necrosis can be removed also determines the prognosis of renal medullary necrosis. Effective treatment of infection and obstruction can prevent the progression of this disease.