Albuminuria

ALBUMINURIA, the excretion of coagulable proteins in the urine, was until relatively recently considered a symptom pathognomonic for kidney diseases, and it was thought possible to judge the severity of the disease by its degree. However, over time it became clear that albuminuria is often encountered in people with perfectly healthy kidneys and may be absent or minimal in the most severe kidney lesions. Protein bodies of urine. The main mass of proteins found in urine consists of blood proteins—albumins and globulins, which can be separated from one another, albeit without great precision, by salting out (saturating urine with magnesium sulfate or half-saturating with ammonium sulfate and sodium sulfate) or by passing CO₂ through the urine: performed in previously neutralized urine, these reactions entail the precipitation of coarsely dispersed globulins, which carry with them a certain portion of albumins, and make it possible to establish the approximate ratio between both fractions. This ratio is called the protein coefficient (a name introduced by Hoffmann) and fluctuates within wide limits between 1 and 10, but most often is found between 5 and 10 (in blood it is equal to 1.5–2). Opinions of various authors differ greatly regarding the significance of this coefficient: some of them found a definite connection between its magnitude and the nature of the disease (high coefficient in chronic nephritis, low in acute nephritis, renal amyloidosis, lipoid nephrosis, and functional albuminuria), others do not recognize this connection, but make the coefficient dependent on the severity of the disease (low in severe forms, high in mild ones, a decrease during worsening of the disease, an increase during improvement), and others, finally, do not attach any significance to it. The protein coefficient also plays a role in some hypotheses explaining the mechanism of albuminuria (see below). Besides these blood proteins, another type of protein is often found in the urine, to which Lichtwitz and Strauss attach particularly great importance: this is the so-called acetic-protein body, which precipitates even upon slight acidification of diluted urine, but is also detectable in native urine in the form of a "cloud" (nubecula). It was previously viewed as nucleoalbumin; at the present time, however, it is regarded as a product of the action on protein of chondroitinsulfuric, nucleic, and bile acids excreted in the urine. These acids can enter the urine as a result of disorders of intermediate metabolism caused by various diseases (e.g., in liver diseases). In other cases, their origin is attributed to the renal epithelium. Strauss and Lichtwitz see in them a "most sensitive reagent for damage in the region of the tubules." Contrary to this opinion, many authors do not consider it necessary to even mention this body. Hemoglobin, albumoses, and the Bence-Jones protein body, which are sometimes encountered in the urine, do not fall within the concept of albuminuria and are subject to separate consideration (see Albumosuria, Hemoglobinuria, Bence-Jones protein body). Origin of albuminuria. Despite numerous works devoted to this question, it has not yet received a proper resolution, and a whole series of theories compete with each other in explaining albuminuria. The filtration theory represents the process such that the cells of the renal epithelium form a kind of semipermeable membrane, which under normal conditions allows only crystalloids to pass, but upon disease becomes permeable to large colloidal molecules as well. Since serum albumins differ from globulins by the smaller size of their molecules, in milder diseases it is primarily the former that pass through the kidneys, while globulins appear in more significant quantities only in severe kidney damage. Proponents of this theory rely on the aforementioned changes in the protein coefficient, on its difference in urine and blood, and on the fact that in kidney diseases a significant decrease in albumin in the blood serum is observed, which in severe cases extends to globulins. Lichtwitz puts forward against this theory an indication of the contradiction between the admitted permeability for large molecules and the simultaneously observed retention of much smaller salt molecules, but proponents of the filtration theory explain this by saying that the retention of salts is caused not by the impermeability of the kidneys to them, but by the increased affinity of tissues for water and salts (Kollert and Starlinger). The theory of the renal origin of urinary proteins was developed by M. H. Fischer. According to this theory, in kidney diseases, there is an accumulation of acids in the renal epithelium, swelling and precipitation of cellular colloids (cloudy swelling) with their subsequent dissolution and excretion into the renal tubules. Recently, this theory has also been put forward by Munk, who found that the accumulation of positively charged ions caused experimentally by an electric current is capable of carrying with it negatively charged protein particles from lymph and epithelial cells. Along with this, however, he also puts forward a theory about a change in the colloidal state of proteins occurring in the blood, entailing the precipitation of euglobulin, which is then excreted by the kidneys like a foreign body. Thereby, he partly joins the proponents of the secretory theory, who see in albuminuria the consequence of a pathological change in the function of epithelial cells, which begin to excrete protein substances of the blood. Despite the big names of the proponents of this theory (Lichtwitz, Strauss, Volhard), sufficient evidence for it has not been presented. It is quite possible that in different cases there is a predominance of one or the other of the listed methods of the origin of albuminuria (Yanovsky). False Albuminuria (A. spuria). Upon detecting protein in the urine, it is always necessary to check whether its appearance is caused by an admixture of pus, blood, or secretions from the urinary tract (tumors, stones, pyelitis, cystitis) or from the genital organs (menstruation, leukorrhea). In women, it is therefore necessary in every slightly doubtful case to perform washing of the external genitalia, douching, and in some cases to resort to the help of a catheter. In the presence of pus or red blood cells in the urine, it is necessary to take into account that 30,000 erythrocytes or 100,000 white blood cells in 1 cubic mm of urine yield about 1‰ protein. Physiological Albuminuria. Protein can appear in the urine not only with perfectly healthy kidneys but also in the absence of any pathological changes in the organism at all; moreover, with sufficiently sensitive reagents, it is possible to detect protein in the urine of almost every person. More significant quantities of protein, determined already by ordinary reagents, are encountered not infrequently during menstruation and immediately after childbirth, during nervous shocks or excitement, after abundant and protein-rich food, during constipation (together with casts!), after palpation of the kidneys, after cold baths (regardless of whether a person is accustomed to them or not). Of particular interest is the appearance of protein in the urine after muscular work, observed by some authors in 80% of all examined and capable of reaching up to 4‰ (Lichtwitz). After light exercises, only the acetic-protein body may appear, while after heavy work, both albumins and globulins, and even casts and red blood cells appear, with this albuminuria being encountered less frequently in accustomed and trained people than in novices. But even in the case when it is constant, such albuminuria does not have a harmful effect on the kidneys (Lichtwitz). To this same group, apparently, should be assigned the albuminuria of newborns, which is encountered in the first 2 weeks of life in almost all children and the cause of which is considered, mainly, the incomplete development of the Malpighian corpuscles, which consequently allow protein to pass; along with this, a whole series of factors may play a role, such as trauma (difficult labor), insufficient supply of fluid to the kidneys in the first days of life, with which is connected the incomplete development of the function of the renal epithelium (cf. albuminuria during starvation in small children), possibly the presence of uric acid infarct, as well as toxic substances acting both from the side of the mother's organism and from the side of the child with his metabolism still not established in the first days. As for the dimensions of albuminuria, within the limits of which it can be considered physiological, some consider its limit to be the appearance of a ring in the Heller test, others 0.4–0.5‰; after cold baths, albuminuria can reach 1‰! after heavy work—4‰! so that here, obviously, the main role is played not by the quantity of protein, but by the accompanying phenomena; it goes without saying, however, that the more protein, the more cautiously one should speak about physiological albuminuria, and the more thoroughly the carrier of it must be examined. Functional albuminuria, in contrast to physiological, can be called that which is observed with anatomically healthy kidneys but is accompanied at the same time by various other pathological phenomena in the organism or is caused by them. This includes, first and foremost, orthostatic (lordotic, juvenile, cyclic) albuminuria, the distinctive feature of which is the dependence of the appearance of protein in the urine on the position of the body; it appears when the patient is standing upright or with arms raised, and disappears when lying down.

Orthostatic albuminuria is observed in children and adolescents (from 8 to 14-18 years of age); it is often a familial and hereditary phenomenon, accompanied by other signs of constitutional insufficiency. These are, for the most part, weak children with a labile cardiovascular system, with a drop heart, with a frequent, unstable pulse and blood pressure, pale, with acrocyanosis and cyanotic spots on the extremities, with reduced tone of the entire musculature, leading to sluggishness of movements, rapid fatigue, stooping and curvature of the spine, suffering from headaches, dizziness, fainting, constipation, and achylia. Against the background of this general asthenia, it is also quite natural to consider orthostatic albuminuria as a manifestation of a certain constitutional weakness of the renal apparatus and, in particular, the nervous apparatus of the kidneys. Regarding the mechanism of orthostatic albuminuria, the prevailing theory at the present time is that of Fehle, according to which the moment causing albuminuria is the lordotic curvature of the lumbar part of the spine, which occurs during standing. That the issue here is precisely lordosis, and not the vertical position itself, is proven by the fact that protein disappears not only when lying down, but also when standing, if the lordosis is corrected in one way or another (when climbing a mountain, when bending over, if one foot is placed on a chair, when pulling in the stomach, etc.). On the other hand, protein appears even when lying down if lordosis is induced with the help of a pillow placed under the back, while swimming, etc. However, the question of how lordosis leads to albuminuria remains unclear. Fehle himself sees it as a consequence of venous stasis caused by the kinking or stretching of the renal veins (or compression of the vena cava by the diaphragm, which is in an abnormal position—a much rarer phenomenon), and this point of view finds confirmation in the studies of Sonne: proceeding from the differences in the position of the renal veins, he suggested that in orthostatic albuminuria, the left kidney should play the main role. He showed that during catheterization of the ureters, protein appears, indeed, only in the urine from the left kidney. Nevertheless, Lichtwitz believes that a combination of slight venous stasis and constitutional weakness of the kidneys alone is insufficient to explain orthostatic albuminuria, and attributes some significance to the mechanical irritation of the renal nerves accompanying the veins, similar to how irritation of the sympathetic nerve causes the salivary glands to secrete more viscous and thick, i.e., protein-rich, saliva. In view of the fact that orthostatic albuminuria is encountered in almost 50% of school-age children and that its false interpretation can cause great harm to an adolescent (when applying a dietary and daily regimen associated with true kidney disease), and, on the other hand, the opposite error can have fatal consequences, the recognition of orthostatic albuminuria acquires very important significance. The main role here is played, of course, by the identification of changes associated with a change in position. After the awakened patient has passed urine, he is left for an hour in bed in a strictly horizontal position; the urine collected after this should not contain any protein at all; then the patient stands vertically, while placing one leg, bent at the knee, on a chair; the urine excreted after 15 minutes of such standing should also be free of protein; finally, the patient is placed in a strictly upright position, and in about 15 minutes, protein is already detected in the urine. The amount of protein in the urine in orthostatic albuminuria can reach 3-4‰, which has no special diagnostic significance; however, it is important to know that the excreted protein consists largely of an acetic-protein body and that, besides it, significant sediments of oxalates, phosphates, and urates are observed in the urine, especially the former. Finally, it is necessary to pay attention to the aforementioned constitutional features and to the anamnesis, since intermittent albuminuria is also often observed during the recovery period from acute kidney diseases: here, the presence of at least traces of protein in the night urine, casts, and red blood cells acquires special significance. In the case where orthostatic albuminuria is precisely established, one should not only not prescribe any restrictions in diet and movement, but, on the contrary, one should convince the patient that he is healthy and take measures to strengthen his muscular and nervous system as much as possible with the help of physical exercises, sports, tourism, and reasonable pedagogical measures. Congestive albuminuria belongs to the same group and is associated with the weakening of cardiac activity in various heart ailments. The kidneys retain the ability to excrete nitrogenous waste. Functional albuminuria further includes: albuminuria in pernicious anemia and leukemia, in jaundice, diabetes, scurvy, and other similar diseases; albuminuria in allergic diseases and conditions; finally, albuminuria in diseases of the nervous system, starting from migraine and up to psychoses, epilepsy, delirium tremens, etc., the mechanism of which is unknown, but is perhaps connected with disturbances of blood circulation in the kidneys. Finally, the last group consists of true nephropathic albuminurias, for which their duration and persistence are typical. The amount of protein can vary from negligible traces to 50‰ depending on the nature and degree of the disease. In acute nephritis, it is usually small, does not exceed 3-5‰, and falls as the process subsides. By the changes in this amount, one can to some extent judge the course of the disease in connection, of course, with other symptoms. In chronic nephritis, protein usually does not exceed 1‰, and often falls to traces and is even completely absent, and this circumstance does not in the least prevent the onset of hypertension, uremia, etc. The situation is exactly the same in the extreme stages of nephritic contracted kidney and in arteriosclerotic contracted kidney. In nephrosis, the amount of protein is usually quite significant, especially in cases of poisoning with mercuric chloride and in syphilitic nephrosis, when its amount can reach up to 40‰. Although here, too, with the improvement of the disease, the protein in the urine falls and allows one to judge its course, a single examination does not give the right to conclude about the severity of the disease, since even the most favorable forms can be accompanied by the excretion of significant masses of protein. In various kidney diseases, albuminuria does not have the significance of a decisive symptom. It acquires it only when considering the overall picture of the disease. A special place is occupied by albuminuria in pregnant women and women in labor. It is encountered in the last months of pregnancy in 15-20% of cases, and within the limits of up to 0.5-1‰ of protein, it is considered by some to be a physiological phenomenon. Albuminuria depends on mechanical causes—difficult outflow of urine, circulatory disorders in the kidneys, etc. The cause of the arising albuminuria can also be the effect on the renal parenchyma of toxins coming from the fetal egg. Albuminuria is a pathological phenomenon in cases of greater kidney damage (nephrosis, nephritis of pregnancy) and a greater protein content in the urine, and in cases where it is a concomitant moment in the course of other toxicoses. Albuminuria in the first months of pregnancy is almost always a pathological phenomenon and indicates a chronic process in the kidneys that existed before pregnancy. Timely recognition of albuminuria in pregnant women is of great importance in diagnostic and prognostic respects, and also plays a large role in the prevention of eclampsism and eclampsia.