Analgetic nephropathy – the damage of kidneys of tubulointerstitsialny character caused by long reception of nonsteroid resolvents (mainly on the basis of a fenatsetin, to a lesser extent – an ibuprofen, indometacin, metamizol of sodium, acetilsalicylic acid). It is characterized by slowly progressing renal failure against the background of the damage to other bodies caused by side effects of NPVS – stomach pains, weakness, dizzinesses, pains in a waist and the right podreberye. Diagnostics is based on a laboratory and tool research of kidneys (analyses of urine, ultrasonography, KT). Treatment comes down to the termination of reception of analgetics and symptomatic therapy.
The analgetic nephropathy, or the analgetic interstitsialny nephrite (AIN), is an adverse effect of reception of the anesthetizing medicines from group of resolvents. Earlier was considered that has such serious side effect only (a fenatsetinovy nephropathy), however it was established later that less actively also other analgetics of similar chemical structure can provoke defeat of secretory system. Prevalence of pathology depends on popularity of anesthetics – generally it meets in the countries of Scandinavia, Western Europe, the USA, Australia (in the last the share of AIN reaches 20% of all nefropatiya). Women on average are ill 6-8 times more often than men – it is caused by more frequent consumption of analgetics by female representatives (in the period of periods, migraines).
Reasons of an analgetic nephropathy
Long reception of the medicines containing resolvents of nonsteroid character is considered the main reason of development of a nephropathy. On the example of a fenatsetin it is proved that consumption practically with guarantee leads about 1 gram of substance a day for 1-3 years to defeat of secretory system. There are instructions that the complex medicines containing several NPVS types or their combination to caffeine and codeine are capable to cause dysfunction of kidneys even quicker. The following reasons of nefrotoksichesky influence of analgetic means are assumed:
- Direct nefrotoksichesky action. Medicines change processes of metabolism in fabrics of a brain layer of kidneys and influence the nature of microcirculation in these bodies. It leads to an atrophy of one nefron with a compensatory hypertrophy of others. For today direct influence of NPVS is considered the leading mechanism of development of an analgetic nephropathy.
- System influence. Abuse of resolvents leads to violations from system of blood (anemia), digestive tract (stomach ulcer and a duodenum), a liver (analgetic hepatitis). These diseases can increase load of secretory system and accelerate development of pathology of kidneys.
- Other factors. Various speed of development of manifestations of a nephropathy in different patients at consumption of similar doses of NPVS is established. Besides, some experts claim that more frequent identification of a state at women cannot be explained only with constant reception of analgetics that it speaks about influence of a sexual factor. Despite consumption of anesthetics, similar on level, in northeast regions to the USA and Canada AIN meets much more less than in other regions with the similar standard of living of the population.
The point of view prevails that the analgetic nephropathy is a multifactorial state in which development use actually NPVS plays the main, but not the only role. So far degree in liyaniye of age of the person, use of other medicines, climatic and geographical factors is unknown. But most of scientists do not doubt that these circumstances are capable to change significantly duration of development and expressiveness of symptoms at AIN.
The pathogenesis of direct nefrotoksichesky influence of a fenatsetin and medicines, similar to it, is most studied. Being enzyme inhibitor tsiklooksigenaza-2 (TsOG-2), it changes processes of a metabolism in cages of an epithelium of tubules and interstitsialny tissue of kidneys that leads to reduction of formation of prostaglandins and a number of other biologically active agents. Acetilsalicylic acid as a part of complex anesthetics and febrifuges can accelerate emergence of an analgetic nephropathy. It is caused by its ability to separate processes of oxidizing phosphorylation in mitochondrions of cages of tubules that aggravates pathology also deficiency of energy.
Decrease in amount of prostaglandins in interstitsialny fabric leads to the ischemic phenomena – to insufficient blood supply of deep layers of brain substance of kidneys. There is a necrosis and calcification of nipples to death and a slushchivaniye of an epithelium of loops of Genle. Finally it leads to dying off of separate nefron and a gialinoz of their balls. The listed processes are aggravated with influence of system factors – anemia, damage of a GIT, liver, a metabolic disorder. Duration of development of a nephropathy depends on a huge number of circumstances – dosages of NPVS, the drinking mode, character of food and some others.
There is no division of an analgetic nephropathy according to such sign as use of any concrete medicine. Modern classification is constructed at clinical stages of a pathological state as it has the progressing character (at continuation of use of anti-inflammatory medicines). Duration of each stage differs at different patients, depends on type and a dosage of analgetic means, associated diseases and other factors. In most cases during AIN the following stages are defined:
- Compensation stage. Proceeds from the beginning of reception of NPVS before emergence of the first laboratory signs of damage of kidneys. During this period damage of nefron is completely compensated, no signs of nefrotoksichesky action are observed, duration of a stage fluctuates from several months to 2-3 years. Some researchers deny need of allocation of this stage of pathology.
- Stage of damage of kidneys. It is characterized by the first changes of urine revealed by means of laboratory analyses. Arises in several months or years since the beginning of the use of analgetics, any subjective symptoms or complaints from secretory system are not observed. Often other signs of abuse of anesthetics are registered: anemia, stomach pains, duodenum ulcer, early atherosclerosis.
- Stage of a renal failure. Develops in 7-15 years after the beginning of regular reception of nonsteroid analgetics. Manifestations are typical for a chronic renal failure: pallor of integuments, weakness, frustration of a diuresis (nikturiya, oliguriya), headaches. Slow progressing of HPN therefore duration of this stage can make many years is characteristic of an analgetic nephropathy.
- Stage of an additional infection. Arises at accession of a bacterial infection of urinary ways and kidneys against the background of a chronic renal failure. It is clinically characterized by severe fever, waist pains, brown color of urine. The infection has recidivous character, in 2-3 years after the first attack the total renal failure comes to light.
Concerning the last stage of pathology in the scientific environment there are disagreements – one consider an additional infection natural and almost inevitable result of development of AIN whereas others perceive it as a nephropathy complication. At the moment there are no reliable and conventional confirmations of correctness of supporters of the first or second opinion.
Symptoms of an analgetic nephropathy
Long time clinical manifestations are absent – at a stage of damage of kidneys of change come to light only at a laboratory research of urine. At this stage ekstrarenalny symptoms of abuse of NPVS are more indicative: belly-aches, weakness, pallor of skin and heartbeat owing to anemia. Actually kidney symptoms of pathology begin to be shown at the beginning of an insufficiency stage – there are violations of a diuresis (a polyuria, a nikturiya), the weakness of muscles or spasms caused by electrolytic violations. The symptomatology progresses, at terminal stages metabolic acidosis and osteodystrophy develops.
At a third of patients the demonstration of a nephropathy is followed by sharp temperature increase, emergence of visible blood in urine (makrogematuriya), hypertensive crises, renal gripes with symptoms of a passing sharp renal failure. Kidney violations are combined with inflammations of joints as a result of deposits of crystals of uric acid – small joints of toes and hands are deformed, become painful, skin over them reddens. Accession of a secondary infection is often observed, there are pyelonephritises, cystitis and other defeats of urinary ways. Pathology is made heavier by development of an urolithic disease owing to a giperuratemiya.
The most frequent complication of an analgetic nephropathy is accession of a bacterial infection with heavy fever, a gematuriya, pyelonephritis. Some researchers consider this process one of disease outcome options. Other serious remote consequence of pathology is perekhodnokletochny cancer of a lokhanka of a kidney – the risk of development of this oncological disease in the people abusing analgetics is 20 times higher, than in population. Against the background of uncontrolled reception of NPVS formation of heavy stomach ulcers, a duodenum with bleeding is possible. The cardiovascular system as anesthetics are capable to cause atherosclerosis suffers, and the nephropathy provokes increase in pressure of blood. It increases risk of heart attacks and strokes further.
It is possible to prove existence of an analgetic nephropathy only at close cooperation of the doctor-nephrologist and patient – the last has to report to the expert about the reasons, terms of the use and an approximate dosage of the accepted anti-inflammatory medicines honestly. Use also a number of laboratory and tool methods of a research for assessment of a damage rate of kidneys, existence or lack of other violations caused by NPVS. The algorithm of diagnostics includes the following stages:
- Collecting anamnesis of life of the patient. Special attention is paid to amount of the accepted analgetic medicines and the reasons of their use. It is possible to suspect existence of pathology in case of long-term systematic reception of NPVS.
- Laboratory researches. The general analysis of urine at a latent stage reveals a mikrogematuriya, an abacterial leykotsituriya and insignificant (to 1 g/days) allocation with protein urine – increase in the last indicator is a bad predictive sign. Blood test finds anemia, and its degree exceeds the level of damage of kidneys that is characteristic of this nephropathy.
- Functional tests. An early functional symptom of pathology is decrease in density of urine and change of a diuresis – a gipostenuriya and a nikturiya. Reberg's test reveals reduction of speed of a glomerular filtration, extent of decrease depends on expressiveness of defeat of renal fabric.
- Ultrasonography. On ultrasonography of kidneys in stages of defeat or insufficiency reduction of the sizes of body and consolidation of a brain layer is noticeable, calciphied nipples at a lokhanka are defined. Doppler sonography (UZDG of vessels of kidneys) confirms decrease of the activity of a blood-groove. At final stages in a lokhanka or mochetochnik concrements can be defined.
- X-ray contrast researches. The urography finds reduction of filtrational ability of secretory system, deformation of cups, ring-shaped shadows in lokhanka (the nekrotizirovanny nipples surrounded with contrast). It is necessary to appoint excretory urography at an analgetic nephropathy with care, considering functionality of kidneys and extent of their defeat.
The differential diagnosis is carried out with other types of nefropatiya. Long long-term abuse of NPVS will be the defining factor in favor of an analgetic form.
Treatment of an analgetic nephropathy
Treatment consists in full cancellation of reception of any nonsteroid anti-inflammatory medicines – at initial stages of damage of kidneys of it can be enough for recovery of work of secretory system. In the presence of the accompanying violations carry out the symptomatic therapy most often including the following components:
- Elimination of hypertensia. For a lowering of arterial pressure use APF inhibitors, beta , blockers of receptors to angiotensin 2.
- Elimination of anemichesky manifestations. The anemia at this pathology has iron deficiency character therefore for restoration of a normal picture of blood use medicines of iron and mineral and vitamin complexes.
- Correction of electrolytic balance. Loss of electrolytes with urine strongly complicates a current of a nephropathy. Apply infusional therapy after which recommend to support the optimum water mode to correction of balance of ions.
- Removal of products of exchange. In far come disease stages with development of HPN for decrease in load of kidneys application of a hemodialysis is shown.
According to indications carry out therapy of diseases of other bodies caused by long systematic reception of NPVS – a stomach, heart, a liver. Tactics of treatment is defined taking into account the revealed pathological changes.
Forecast and prevention
At identification of an analgetic nephropathy at a stage of the asymptomatic period the forecast of pathology unambiguously favorable – idle time of cancellation of anti-inflammatory medicines will be enough for improvement of a condition of kidneys. At emergence of signs of HPN or an additional infection the forecast worsens a little, however at correctly constructed therapy and competent correction survival of patients is very high. After diagnosis it is regularly necessary to be examined by the doctor-nephrologist regarding development of the remote complications – first of all kidney cancer. Early identification of malignant process provides higher efficiency of its treatment.