Analgesic nephropathy is a tubulointerstitial kidney injury caused by prolonged use of nonsteroidal anti-inflammatory drugs (mainly based on phenacetin, to a lesser extent – ibuprofen, indomethacin, sodium metamizole, acetylsalicylic acid). It is characterized by slowly progressive renal failure against the background of damage to other organs caused by side effects of NSAIDs – stomach pain, weakness, dizziness, pain in the lower back and right hypochondrium. Diagnosis is based on laboratory and instrumental examination of the kidneys (urine tests, ultrasound, CT). Treatment is reduced to discontinuation of analgesics and symptomatic therapy.
N14.0 Nephropathy caused by analgesics
Analgesic nephropathy, or analgesic interstitial nephritis (AIN), is an adverse consequence of taking painkillers from the group of anti-inflammatory drugs. Previously, it was believed that only phenacetin (phenacetin nephropathy) has such a serious side effect, but later it was found that other analgesics of a similar chemical structure can provoke less active damage to the excretory system. The prevalence of pathology depends on the popularity of painkillers – it is mainly found in the countries of Scandinavia, Western Europe, the USA, Australia (in the latter, the proportion of AIN reaches 20% of all nephropathies). On average, women get sick 6-8 times more often than men – this is due to the more frequent consumption of analgesics by female representatives (during menstruation, migraines).
The main reason for the development of analgesic nephropathy in modern urology is considered to be long-term use of medications containing anti-inflammatory drugs of a non-steroidal nature. Using the example of phenacetin, it has been proven that consumption of about 1 gram of the substance per day for 1-3 years is almost guaranteed to lead to damage to the excretory system. There are indications that complex drugs containing several types of NSAIDs or their combination with caffeine and codeine can cause kidney dysfunction even faster. The following causes of nephrotoxic effects of analgesics are assumed:
- Direct nephrotoxic effect. The drugs alter the metabolic processes in the tissues of the cerebral layer of the kidneys and affect the nature of microcirculation in these organs. This leads to atrophy of some nephrons with compensatory hypertrophy of others. At the moment, direct exposure to NSAIDs is considered the leading mechanism for the development of analgesic nephropathy.
- Systemic impact. Abuse of anti-inflammatory drugs leads to disorders of the blood system (anemia), gastrointestinal tract (stomach and duodenal ulcers), liver (analgesic hepatitis). These diseases can increase the load on the excretory system and accelerate the development of kidney pathology.
- Other factors. A different rate of development of manifestations of nephropathy in different patients with the consumption of similar doses of NSAIDs was established. In addition, some experts argue that the more frequent detection of the condition in women cannot be explained only by the constant use of analgesics, which indicates the influence of the sexual factor. Despite the similar level of consumption of painkillers, in the northeastern regions of the United States and Canada, AIN is much less common than in other regions with a similar standard of living of the population.
The prevailing view is that analgesic nephropathy is a multifactorial condition, in the development of which the use of NSAIDs itself plays a major, but far from the only role. The degree of influence of a person’s age, the use of other medicines, climatic and geographical factors is still unknown. But most scientists have no doubt that these circumstances can significantly change the duration of development and severity of symptoms in AIN.
The pathogenesis of direct nephrotoxic effects of phenacetin and similar drugs has been most studied. Being an inhibitor of the enzyme cyclooxygenase-2 (COX-2), it changes the metabolic processes in the epithelial cells of the tubules and interstitial kidney tissue, which leads to a decrease in the formation of prostaglandins and a number of other biologically active substances. Acetylsalicylic acid as part of complex painkillers and antipyretics can accelerate the occurrence of analgesic nephropathy. This is due to its ability to dissociate the processes of oxidative phosphorylation in the mitochondria of tubule cells, which also aggravates the pathology by energy deficiency.
A decrease in the amount of prostaglandins in interstitial tissue leads to ischemic phenomena – insufficient blood supply to the deep layers of the medulla of the kidneys. Necrosis and calcification of the papillae occurs with the death and peeling of the epithelium of the Henle loops. Ultimately, this leads to the death of individual nephrons and hyalinosis of their glomeruli. These processes are aggravated by the influence of systemic factors – anemia, gastrointestinal tract, liver, metabolic disorders. The duration of the development of nephropathy depends on a huge number of circumstances – the dosage of NSAIDs, drinking regime, the nature of nutrition and a number of others.
Classification of analgesic nephropathy
There is no separation of analgesic nephropathy on such a basis as the use of any particular drug. The modern classification is based on the clinical stages of the pathological condition, since it has a progressive character (with continued use of anti-inflammatory drugs). The duration of each stage varies from patient to patient, depending on the type and dosage of the analgesic, concomitant diseases and other factors. In most cases , the following stages are determined during the AI:
- Stage 1 of compensation. It continues from the start of taking NSAIDs until the first laboratory signs of kidney damage appear. During this period, damage to the nephrons is fully compensated, no signs of nephrotoxic action are observed, the duration of the stage ranges from several months to 2-3 years. Some researchers deny the need to isolate this stage of pathology.
- Stage 2 kidney damage. It is characterized by the first changes in urine detected by laboratory tests. Occurs after several months or years from the beginning of the use of analgesics, there are no subjective symptoms or complaints from the excretory system. Other signs of abuse of painkillers are often recorded: anemia, stomach pain, duodenal ulcers, early atherosclerosis.
- Stage 3 of renal failure. Develops 7-15 years after the start of regular use of nonsteroidal analgesics. The manifestations are typical for chronic renal failure: pallor of the skin, weakness, diuresis disorders (nocturia, oliguria), headaches. Analgesic nephropathy is characterized by slow progression of CRF, so the duration of this stage can be many years.
- Stage 4 of an additional infection. It occurs when bacterial infection of the urinary tract and kidneys is attached against the background of chronic renal failure. Clinically characterized by severe fever, lower back pain, brown urine. The infection has a recurrent character, 2-3 years after the first attack, total renal failure is detected.
There are disagreements about the last stage of pathology in the scientific community – some consider an additional infection to be a natural and almost inevitable result of the development of AIN, while others perceive it as a complication of nephropathy. At the moment, there are no reliable and generally accepted confirmations of the correctness of the supporters of the first or second opinion.
Symptoms of analgesic nephropathy
For a long time there are no clinical manifestations – at the stage of kidney damage, changes are detected only by laboratory examination of urine. At this stage, extrarenal symptoms of NSAID abuse are more indicative: abdominal pain, weakness, pale skin and palpitations due to anemia. The actual renal signs of pathology begin to manifest themselves at the beginning of the stage of insufficiency – there are violations of diuresis (polyuria, nocturia), muscle weakness or convulsions caused by electrolyte disorders. Symptoms are progressing, metabolic acidosis and osteodystrophy develop at the terminal stages.
In a third of patients, the manifestation of nephropathy is accompanied by a sharp increase in temperature, the appearance of visible blood in the urine (macrohematuria), hypertensive crises, renal colic with signs of transient acute renal failure. Renal disorders are combined with inflammation of the joints as a result of deposits of uric acid crystals – small joints of the toes and hands are deformed, become painful, the skin above them turns red. Secondary infection is often observed, pyelonephritis, cystitis and other lesions of the urinary tract occur. Pathology is aggravated by the development of urolithiasis due to hyperuratemia.
The most common complication of analgesic nephropathy is the addition of bacterial infection with severe fever, hematuria, pyelonephritis. Some researchers consider this process to be one of the options for the outcome of the disease. Another serious long-term consequence of the pathology is transitional cell carcinoma of the renal pelvis – the risk of developing this cancer in people who abuse analgesics is 20 times higher than in the population.
Against the background of uncontrolled administration of NSAIDs, the formation of severe stomach ulcers, duodenal ulcers with bleeding is possible. The cardiovascular system suffers, because painkillers can cause atherosclerosis, and nephropathy provokes an increase in blood pressure. This increases the risk of heart attacks and strokes in the future.
It is possible to prove the presence of analgesic nephropathy only with close cooperation of a nephrologist and a patient – the latter must honestly inform the specialist about the causes, timing of use and approximate dosage of anti-inflammatory drugs taken. A number of laboratory and instrumental research methods are also used to assess the degree of kidney damage, the presence or absence of other disorders caused by NSAIDs. The diagnostic algorithm includes the following steps:
- Collecting anamnesis of the patient’s life. Particular attention is paid to the number of analgesic drugs taken and the reasons for their use. It is possible to suspect the presence of pathology in the case of long-term systematic administration of NSAIDs.
- Laboratory tests. A general urine analysis at the latent stage reveals microhematuria, abacterial leukocyturia and insignificant (up to 1 g / day) excretion of protein in the urine – an increase in the latter indicator is a poor prognostic sign. A blood test detects anemia, and its degree exceeds the level of kidney damage, which is characteristic of this nephropathy.
- Functional tests. An early functional sign of pathology is a decrease in urine density and changes in diuresis – hypostenuria and nocturia. The Rehberg test reveals a decrease in the glomerular filtration rate, the degree of decrease depends on the severity of renal tissue damage.
- Ultrasound examination. On ultrasound of the kidneys in the stages of lesion or insufficiency, there is a noticeable decrease in the size of the organ and the compaction of the cerebral layer, calcified papillae in the pelvis are determined. Dopplerography (ultrasound of kidney vessels) confirms a decrease in blood flow activity. At the final stages, concretions can be determined in the pelvis or ureters.
- Radiopaque studies. Urography reveals a decrease in the filtration capacity of the excretory system, deformation of the cups, ring-shaped shadows in the pelvis (necrotic papillae surrounded by contrast). Excretory urography should be prescribed for analgesic nephropathy with caution, taking into account the functional capabilities of the kidneys and the degree of their damage.
Differential diagnosis is performed with other types of nephropathies. The determining factor in favor of the analgesic form will be long-term long-term abuse of NSAIDs.
Treatment of analgesic nephropathy
Treatment consists in the complete abolition of taking any non-steroidal anti-inflammatory drugs – at the initial stages of kidney damage, this may be enough to restore the excretory system. In the presence of concomitant disorders, symptomatic therapy is carried out, most often including the following components:
- Elimination of hypertension. ACE inhibitors, beta-blockers, angiotensin 2 receptor blockers are used to reduce blood pressure.
- Elimination of anemic manifestations. Anemia in this pathology has an iron deficiency character, therefore, iron preparations and mineral-vitamin complexes are used to restore the normal blood picture.
- Correction of the electrolyte balance. The loss of electrolytes in the urine greatly complicates the course of nephropathy. To correct the ion balance, infusion therapy is used, after which it is recommended to maintain an optimal water regime.
- Removal of exchange products. In the advanced stages of the disease with the development of CRF, the use of hemodialysis is indicated to reduce the load on the kidneys.
According to the indications, the treatment of diseases of other organs caused by prolonged systematic intake of NSAIDs – stomach, heart, liver. Treatment tactics are determined taking into account the revealed pathological changes.
Prognosis and prevention
If analgesic nephropathy is detected at the stage of the asymptomatic period, the prognosis of pathology is unambiguously favorable – a simple withdrawal of anti-inflammatory drugs will be enough to improve the condition of the kidneys. If signs of CRF or an additional infection occur, the prognosis worsens somewhat, however, with properly constructed therapy and competent correction, the survival rate of patients is very high. After diagnosis, you should be regularly examined by a nephrologist for the development of long-term complications – primarily kidney cancer. Early detection of the malignant process provides a higher efficiency of its treatment.