Nephrology for the Family Physician - O.I. Bakaliuk 2003

Gerontological Aspects of Nephrology

Geriatric nephrology today is one of the most vital fields in gerontology, and addressing its challenges can significantly help fulfill the American Geriatrics Society's motto: «...to add life to years, not more years to life.»

The pathology of old age, characterized by multisystem involvement and severe disease progression, requires moving away from the traditional Classification of diseases into distinct nosological entities and abandoning stereotypical Treatment regimens. Nephrological aspects of age-related pathology are no exception. For instance, according to A.I. Borisov (1990), diabetic glomerulosclerosis is combined with nephroangiosclerosis in 17% of cases, Renal Amyloidosis and renal failure in 4-5%, Chronic Glomerulonephritis and amyloidosis in 4%, and gouty nephropathy and amyloidosis in 3%.

Naturally, the Kidneys—which are endowed with crucial regulatory, incretory, and metabolic Functions as a whole—cannot fail to influence the course of late-life pathology and its outcomes (D. Fliser et al., 1996). Age, in turn, inevitably affects Kidney Structure and function, sometimes in a decisive manner. Therefore, it is essential to determine The impact of renal functional status on the course of comorbid conditions, as well as the reciprocal effect of these conditions on renal function in elderly patients. In doing so, one must account for polypharmacy—the «bane» of modern geriatric medicine—since prescribing 5 or more medications to an elderly patient is far from uncommon. At the same time, it has been proven (I.A. Borisov, 1990) that the simultaneous use of 8 drugs is accompanied by adverse reactions in 20% of cases, and 12 drugs in nearly 100% of cases.

Literature data irrefutably indicate a fatal increase in the incidence of renal lesions with age, a narrowing of the nosological spectrum of these lesions, and a rising frequency of comorbid forms within this spectrum. Thus, an analysis of age-specific mortality rates from kidney diseases (USA, Japan, Great Britain, France) per 100,000 population showed that these rates in individuals aged 65-74 and over 75 exceed those in individuals aged 15-34 by 50-fold and 250-fold (!), respectively (World Health Statistics Annual. - WHO, Geneva, 1995).

Kidney diseases in old age develop against the Background of Structural and functional nephron changes. This leaves a mark on the interpretation of study results, leading either to their underestimation or to the assignment of excessive clinical significance. The above primarily concerns two pathological forms: nephroangiosclerosis, which is diagnosed in 85% of such individuals solely on a pathomorphological basis, and renal failure, which remains undiagnosed in 15-20% of cases altogether.

Involutive Changes in the kidneys can generally be interpreted as a progressive increase in the number of mesangial structures without a clearly established link exclusively to the vascular component. As early as 1926, M. Arataki described structural changes in the kidneys associated with human Aging. They are characterized by Atrophy of the renal parenchyma (a decrease in kidney weight from 280 g in young adults to 200 g in the elderly, a nearly twofold reduction in the number of functioning nephrons, and an increase in mesangial matrix volume from 6.2% to 10.4%).

Age-related glomerular changes (hyalinosis, thickening of the glomerular capillary basement membrane, and an increase in its Collagen content), which progress with tragic inevitability (a 10% decrease in the number of functioning nephrons every 10 years after reaching the age of 40), lead to a reduction in the total area of glomerular capillary loops and, consequently, to a decrease in their filtration surface area (by an average of 40%). Simultaneously, there is an accumulation of structured collagen fibrils in the mesangium, glomerular capillary basement membranes, and podocytes, along with impaired slit Diaphragm function, resulting in decreased effective filtration across the basement membrane.

At the same time, it is recognized that an important role in The Development of these changes is played by mesangial overload, as mesangial Cells lose their highly specialized functions with age (immune complex clearance, osteoclast-like activity) and functionally transform into conventional fibroblasts.

A certain role is also attributed to age-related sclerotic changes in intrarenal arterial vessels, particularly the distal interlobular and afferent glomerular arterioles. The renal fraction of Cardiac Output in the elderly decreases from 25% to 10%, medullary Blood flow by 15%, and cortical blood flow by 40%. Effective renal plasma flow also changes, declining by an average of 10% per decade of human life—respectively from 600 mL/min/1.73 m² at age 20 to 300 mL/min/1.73 m² at age over 80 (I.O. Dudar, 1999, 2000).

Involutive tubular changes involve basement membrane thickening, vacuolar degeneration, and blood granularity relative to platelets. This is accompanied by impaired energy-dependent transport of organic substances and electrolytes in both directions (from the tubular lumen to the mesangium and from the mesangium to the tubular lumen). As involutive changes progress, the length and volume of proximal tubules decrease, and multiple diverticula develop in the distal tubules. The latter is accompanied by impaired urine outflow (stasis) followed by the proliferation of bacterial flora in these regions.

Age-related changes in the juxtaglomerular apparatus are also noted, correlating with afferent arteriole hyalinosis and excessive accumulation of Connective Tissue elements in the functional Cell zone of this apparatus.

The morphological changes described above are accompanied by a decline in renal functional capacities. Thus, the GFR decreases from 120 mL/min in young individuals to 60-80 mL/min in the elderly, with a simultaneous increase in renal vascular resistance. Due to the reduction in Muscle tissue mass—and consequently, the primary source of creatinine production—we present the formula by D. Cockcroft et al. (1976) to determine the age-adjusted normal GFR value accounting for this factor:

The formula given above applies to men; for women, the calculated GFR values should be additionally multiplied by 0.85.

Impairments in the clearance of creatinine, electrolytes, free Water, tubular transport mechanisms for various substances, and JGA activity (renin-depleting type) are accompanied by a sluggish renal response to loads, particularly sodium.

Particular difficulties arise when evaluating subtle clinical and laboratory signs of renal pathology, such as proteinuria, which is a frequent (20-70%) finding in the elderly.

Recent data allow us to almost entirely rule out The Link Between proteinuria and involutive renal changes, unambiguously classifying it as a sign of pathology. Even though its severity can be influenced by various factors (orthostatism, infections at other sites with a hyperthermic reaction, Heart Failure, etc.), it must be acknowledged that proteinuria of aging is a characteristic feature of nephroangiosclerosis, whereas proteinuria exceeding 1 g/day, especially when combined with Nephrotic Syndrome, is an absolute and reliable sign of primary renal involvement (ranging from renal amyloidosis, acute glomerulonephritis, and renal vein thrombosis to paraneoplastic syndrome).

Clinicians quite frequently have to evaluate so-called «asymptomatic» bacteriuria. Among the adult population aged 26-65 years, asymptomatic bacteriuria is observed in 0.5-4%, whereas in those aged 65-80 years, it occurs in 20-35% of cases. This figure rises to 100% in patients who undergo frequent Urinary Bladder catheterization due to various circumstances. The flora is most commonly represented by Escherichia coli (80%).

Long-term observations and detailed studies of renal function in elderly patients with such bacteriuria have revealed signs of diminished renal functional capacity or allowed for the Diagnosis of asymptomatic Pyelonephritis. Therefore, true «asymptomatic» bacteriuria of this kind (especially persistent bacteriuria) is better viewed as a manifestation of latently progressing pyelonephritis, which in turn requires special attention and, potentially, medical intervention.

Hematuria, usually microhematuria, is detected in 50% of elderly patients. Interpreting it is always challenging given the necessity of establishing THE ORIGIN OF hematuria by first ruling out tumors of various locations, which account for 4% to 6% of hematuria cases.

Persistent leukocyturia in individuals of this age bracket generally has a fairly specific cause—senile pyelonephritis.

Hypertension syndrome is identified in 50-60%, and isolated systolic hypertension in 7-10% of individuals in this age group.

The Pathogenesis of senile hypertension, especially when combined with isolated urinary syndrome, is more commonly associated with atherosclerotic and, less frequently, hypertensive nephroangiosclerosis—the leading forms of renal pathology (60-70% of cases). To diagnose them, clinical data must be interpreted correctly. Pronounced hypercholesterolemia, dyslipidemia, signs of involvement in other vascular beds, relative stability of blood pressure without extremely high readings, and signs of slowly progressive renal failure predominantly point toward atherogenic nephroangiosclerosis, whereas terminal renal failure develops more rapidly in hypertensive nephroangiosclerosis. It should also be borne in mind that hypertension may be the sole manifestation of Chronic Pyelonephritis in 33-63% of cases, and in 20% of these, it acquires malignant features, which is associated with the development of hypervolemia, altered activity of the renin-angiotensin-aldosterone system, and the renal depressor system. However, chronic pyelonephritis is perhaps the only parenchymal kidney disease in which the prevalence of hypertension does not increase in parallel with the decline in GFR.

Regarding specific forms of renal pathology in the elderly, let us emphasize once again that kidney diseases frequently coexist with one another, as well as with pathologies or functional failures of other Organs and systems, constituting METABOLISM/2.html">THE CONCEPT OF polypathology.

The most common combinations are: diabetic nephropathy + nephroangiosclerosis + pyelonephritis (17% of cases), diabetic nephropathy + amyloidosis + pyelonephritis (7% of cases), chronic glomerulonephritis + amyloidosis (4% of cases (I. Dudar, 2001)).

Among kidney diseases in the elderly, pyelonephritis rightfully occupies first place. This age bracket accounts for the third peak in pyelonephritis incidence, predominantly affecting males. This is due to The Influence of multiple factors—both specific and nonspecific. Among the specific ones, we note a decrease in the functional activity of the Prostate Gland, local secretion of Lysozyme and a thermostable bacterial factor, and an increased frequency of hypertrophic and neoplastic processes. Other factors include:

- development of involutional changes in the Urinary System accompanied by impaired urodynamics;

- age-related decline in The activity of the immune defense system at the cellular and humoral levels, which is potentiated by the frequent use of Antibiotics, Hormones, immunosuppressants, and NSAIDs for the treatment of other conditions;

- increased susceptibility to infection with hospital strains of microorganisms, along with a growing role of opportunistic microflora;

- presence of comorbid conditions affecting the body's major homeostatic systems, namely The Cardiovascular system (atherosclerosis, coronary artery disease, hypertension), Respiratory system (Chronic Bronchitis, pulmonary sclerosis), and Digestive System (chronic hepatitis, pancreatitis, colitis), accompanied by functional insufficiency and metabolic disturbances (hypercholesterolemia, hyperglycemia, hyperuricemia, hypoxemia, metabolic acidosis).

Diabetes Mellitus, involutional Osteoporosis with hyperkalemia, Gout, blood disorders, hypovitaminosis, and other renal diseases accompanied by functional or organic urodynamic disorders, toxic renal damage, and inflammatory processes in other organs are also identified as risk factors for Urinary Tract infection (UTI).

The prevalence of clinically manifest UTI in men aged 70–79 years is 25–30%, in women 21–25%, and over 80 years old it is 36–40% and 29–35%, respectively. Discrepancies between clinical and postmortem diagnoses of UTI are often observed, with overdiagnosis occurring in 10% and underdiagnosis in 13–20% of cases. Such UTIs are most frequently caused by Escherichia coli (60%), and less commonly by Pseudomonas aeruginosa (17%), Enterococcus (17%), and Proteus (7%) (I.A. Borisov, 1995).

The Clinical presentation of acute UTI or an acute Exacerbation of chronic UTI in elderly individuals, aside from typical signs of varying severity (fever, dysuria, lumbar pain), is frequently characterized by oligosymptomatic or monosymptomatic courses, such as endogenous Intoxication syndrome, prolonged low-grade fever, anemia, and arterial hypertension; an adequate renal response to infection is relatively rare. Acute purulent UTI may also present atypically (cerebral, meningeal, or typhoid-like forms, Sepsis-like presentation, disease progression with normal BODY Temperature AND no obvious signs of renal involvement, fever syndrome without urinalysis changes, or intermittent gross hematuria). In the clinical picture of chronic UTI, some authors distinguish specific forms—latent, recurrent, hypertensive, anemic, and azotemic—justifying this classification by purely practical aspects and the predominance of monosymptomatology (S.I. Ryabov, 2000).

UTI caused by Escherichia coli is one of the most frequent causes of septicemia and bacterial Shock, subsequently leading to ACUTE RENAL FAILURE (ARF); the onset of acute acid-base balance disorders, specifically acidosis, further aggravates the clinical course. The urinary syndrome in UTI is characterized by proteinuria, which typically does not exceed 1 g/day, pyuria, and bacteriuria.

A notable feature of UTI in elderly patients is its frequent occurrence in the background of phosphate stones. An explanation for this phenomenon has only recently emerged. As discovered by N.Z. Kajander (1998), calcium phosphate precipitates in various internal organ diseases. The cause of this phenomenon is a single-celled Organism, nanobacterium, recently discovered via ultramicroscopy, which is present in virtually 100% of elderly individuals. Using energy-dispersive X-ray spectroscopy, it was proven that nanobacteria produce a mineral identified as apatite carbonate in all phases of their development. In fibroblasts infected with nanobacteria, Electron Microscopy identified intracellular and extracellular crystal deposits analogous to phosphate stones.

Until recently, all models of renal phosphate stone formation were based on the hypothesis that elevated urine pH, combined with altered urease and/or alkaline phosphatase activity, served as the primary lithogenic factors. Research by N.Z. Kajander (1998) proved that phosphate stones can form at a urine pH of 7.4 and physiological blood concentrations of phosphates and calcium.

The diagnosis of UTI is based on General Principles: Nechiporenko urine test, prednisolone test, urine culture for flora and antibiotic sensitivity, microbial colony count, study of active leukocytes and Sternheimer-Malbin cells, renal ultrasound, excretory urography, isotope renography, and computed tomography. Immunological studies are also informative (elevated antibody titers to the O-A2 strain of Escherichia coli, suppression of cellular immune reactivity).

From a practical standpoint, it should be noted that in a subset of patients (30–35%) with UTI, a low degree of bacteriuria (up to 20,000 Bacteria per 1 ml of urine) is detected. This is attributed to numerous factors, including the CHARACTERISTICS OF THE culture medium, the ability of microorganisms to proliferate outside the organ, the Location and size of the inflammatory focus, etc. In such cases, management should be guided not by the degree of bacteriuria, but by the clinical picture (progressive course, microbial virulence, persistence of isolation upon repeated testing).

The treatment of UTI in these age groups follows general principles. At the same time, we emphasize the need to adhere to geriatric dietary requirements, recommend adequate fluid intake for renal "flushing" and parenteral administration of solutions (provided there are no contraindications), and closely monitor urine passage and partial renal functions. Treatment is carried out in 1.5–2-week courses; criteria for efficacy include the absence of bacteriuria and leukocyturia 12 days after antibiotic discontinuation, improvement of partial renal functions, and resolution of extrarenal manifestations.

The development of acute glomerulonephritis (GN) in elderly and senile individuals is not as rare as previously believed (in the 1950s, E.M. Tareyev described only isolated cases).

While O.P. Kuznetsova et al. reported in 1985 that this disease occurred in individuals over 60 years of age with a frequency of 0.62–1.49% of all acute GN cases, this figure rose to 4% by the early 1990s. This likely reflects improvements in diagnostic accuracy rather than a true increase in the incidence of GN in this age group. Indeed, according to I.A. Borisov et al. (1995), based on a population study of 25,380 individuals, no statistically significant difference was found in the detection rate of GN between individuals older and younger than 60 years (0.4% and 0.3%, respectively).

Special features of GN in the elderly include its malignancy, a presentation dominated by hypertensive syndrome with acute or progressive chronic heart failure, and a significant decline in renal function during the acute phase. Another characteristic feature of GN in this age group is its frequent occurrence against the background of one or more pre-existing conditions, such as coronary artery disease, hypertension, diabetes mellitus, or urinary tract infections.

According to H. Arieff et al. (1997), the most frequent causes of acute GN in this age group are periarteritis nodosa, hemorrhagic capillarotoxicosis, Goodpasture syndrome, Wegener's granulomatosis, and hemolytic-uremic syndrome. In 50–75% of cases, renal involvement proceeds as rapidly progressive GN and less frequently as acute poststreptococcal GN.

The development of acute GN in the elderly, accompanied by hypervolemia and left ventricular failure, severely complicates the accurate interpretation of renal symptoms against the background of existing cardiac decompensation or hypertension. However, it should be noted that the onset of acute GN in this situation, unlike UTI, is accompanied by more pronounced clinical symptoms, dominated by edema combined with typical GN urinary syndrome or the development of acute renal failure. Occasionally, a septic variant of GN is observed, requiring Differential diagnosis with sepsis, or an autoimmune variant manifesting as vasculitis of varying severity and distribution (I.A. Borisov et al., 1995).

Chronic GN in elderly individuals is encountered much less frequently than acute GN for understandable reasons (mortality from chronic renal failure at a younger age).

The treatment of GN in elderly and senile individuals has specific characteristics. First and foremost, we note The Use of the most sparing pathogenetic regimens, maximal utilization of symptomatic therapy, more frequent use of antibacterial agents, and high-quality follow-up care.

There are no absolute contraindications for the use of glucocorticoids in elderly patients; however, paraneoplastic nephrotic syndrome, diabetic nephropathy, and amyloidosis must be ruled out. Relative contraindications include pronounced hypertension, chronic renal failure, tuberculosis, chronic infectious processes, severe coronary artery disease, and heart failure. The optimal approach is considered to be the administration of low (30 mg/day) and moderate (30–60 mg/day) doses of prednisolone with a gradual reduction in the daily dose, preferably on an alternate-day schedule. Pulse therapy and maintenance therapy are not practiced in these cases.

Cytostatics are strictly contraindicated in the presence of an infectious focus, which is precisely why they are almost never used to treat GN in this age group (administration of minimal doses of cyclophosphamide (50–100 mg/day) for a short period is permissible; pulse therapy with cyclophosphamide is also not practiced).

Other agents (heparin, low-molecular-weight heparins, antiplatelet agents, fresh frozen plasma) are used more widely than glucocorticoids and immunosuppressants. NSAIDs are prescribed with caution, taking into account their side effects, negative impact on intrarenal hemodynamics, and prostaglandin synthesis.

Among Instrumental Methods of GN treatment, plasmapheresis is used most frequently.

Acute renal failure is a frequent companion of various pathological conditions in elderly patients.

The most frequent causes of its development include postoperative states (25–45%), acute inflammatory processes (purulent or non-Purulent Pyelonephritis, sepsis, Croupous Pneumonia, viral infections (15–30%), acute coronary and arrhythmic syndromes (15–25%), Diseases of the choledochopancreatoduodenal zone (5–10%), acute cerebrovascular accidents, thromboses of other localizations (Nygard-Brown syndrome) (2–5%), polytraumas (2–3%), and various types of hemorrhages (2%).

A distinctive feature in the development of such forms of ARF is the early impairment of electrolyte Homeostasis, primarily sodium balance.

Symptoms of electrolyte disorders are predominantly neurological, caused either by cerebral edema due to hyponatremia or Brain dehydration in hypernatremia. This quite frequently leads to the misinterpretation of the patient's condition when neurological symptoms are already present. Somnolence, clouded consciousness, headache, convulsions, muscle spasms, hemiparesis, and coma in cases of hyponatremia, as well as apathy, irritability, progressive muscle rigidity, tremor, hyperreflexia, ataxia, seizures, and coma in hypernatremia, primarily require the exclusion of a vascular genesis for these disorders.

Sodium imbalance resulting from the pathology of other organs or the administration of medications (e.g., active diuretic therapy) is accompanied by the development of hyperosmolar syndrome and azotemia, which, in turn, are often interpreted as an indication for intensifying dehydration therapy. Therefore, an adequate assessment of water-electrolyte homeostasis in this situation is extremely important to prevent dehydration.

Thus, the main indicators whose changes should be taken into account when treating ARF in such patients, In addition to the dynamics of diuresis and blood creatinine and urea levels, must also include natremia, natriuresis, and blood osmolality. Furthermore, a decrease in renal sodium excretion should not be interpreted as a manifestation of renal failure, but rather as an indicator of the preservation of a certain level of Tubular Function in the kidneys.

The functional state of the tubules can be inferred by analyzing the osmolality coefficient (K):

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This parameter indicates how many times higher the osmotic concentration of urine is compared to that of plasma, and its normal value ranges from 3.0 to 5.1. An index value of 2.7 or lower indicates a significant reduction in the urine-concentrating function.

In the development of acute RF in elderly patients, due credit is also given to disseminated intravascular coagulation syndrome, the development of which is characteristic of diseases caused by gram-negative flora, all types of shock, malignant neoplasms, blood disorders, trauma, and surgical interventions. The decisive factor in its development in these cases is the activation of the Blood Coagulation SYSTEM by endogenous activators—tissue proteases and tissue thromboplastin—as well as hyperaggregation of Blood Cells with an increase in blood viscosity.

It must be emphasized that acute RF, regardless of its genesis, in such patients, even with a favorable course, is complicated in practically 100% of cases by the onset of infection (pyelonephritis). The latter is characterized by relentless progression with the rapid development of CRF.

Determining the Etiology of chronic renal failure as the leading clinical syndrome in the elderly is a challenging task due to the simultaneous coexistence of renal processes with different pathogenesis and age-related impairments in other systems (hemodynamics, The Immune System, and metabolism).

According to I.A. Borisov et al. (1988), the leading causes of CRF in this age group are chronic pyelonephritis (63.8%) and nephroangiosclerosis (21.1%), and less frequently, diabetic glomerulosclerosis (7.2%). These figures are consistent with the findings of other researchers (A. Wing et al., 1992). The clinical course is severe, with cachectic, anemic, and dyspeptic syndromes predominating in the clinical picture.

Considering the characteristics of senescence-related Immunity, the impact of tumors on renal status in this age group deserves another mention. While the primary problem of geriatrics—chronic pyelonephritis—is only affected by Prostatic Adenoma and prostate Cancer, the indirect impact of neoplasms on the functional state of the kidneys is extremely complex (paraneoplastic manifestations of renal lesions), as mentioned above.

A frequent companion of old age is also postmenopausal osteoporosis, which is associated with hypercalciuria, urolithiasis, gout, gouty nephropathy, and pseudogout characterized by the deposition of calcium pyrophosphate in the joints.

Thus, the material presented above demonstrates the entire complexity of The problem of kidney disease in elderly patients, and many issues regarding their Diagnosis and treatment still await resolution today.