Epidemiology of Chronic Kidney Diseases

 

Epidemiology of Chronic Kidney DiseasesIntroduction:

In 2001, chronic terminal renal failure was declared France a major public health priority. This decision is the result of a steady increase in the incidence and prevalence of chronic terminal renal insufficiency.

As a primary outbreak, the kidney is potentially exposed to many attacks. Although renal parenchyma has extraordinary adaptive and regenerative abilities, chronic kidney disease is capable of progressively destroying the functional structures of the kidney: glomeruli, tubes and interstitium, or vessels. Very diverse and multiple by their pathophysiological mechanisms, they have a common functional consequence: chronic renal insufficiency.This may progress inexorably towards the end stage, corresponding to “renal death”. It results in serious consequences for the whole organism, linked to the uremic intoxication, on the one hand, and to the failures of the renal endocrine functions, on the other hand.

The last four decades have witnessed dramatic advances, which have significantly improved the health status of patients. Hemodialysis, peritoneal dialysis, renal transplantation, human recombinant erythropoietin are illustrative illustrations; but there are many others. The task of the clinician with chronic kidney disease is complex. First, it must unravel what is related to the evolution of initial kidney disease and the non-specific progression of chronic renal failure. Then it must take acute events into account. Finally, it manages the consequences of chronic renal insufficiency, particularly cardiovascular, haematological and bone. None of the potential levels of intervention should be neglected.

Epidemiology is a science that has a very broad scope. It starts with the purely descriptive enumeration of the disease, the starting point of understanding its importance. It extends to the evaluation of drug efficacy and therapeutic interventions. Long neglected, chronic kidney disease and chronic kidney failure have recently been the subject of increasingly detailed studies, organized regionally or countrywide. We will first consider the descriptive epidemiology of chronic renal failure. We will insist on the terminal stage; because this is the most visible part of the problem that has the most harmful consequences for the patient and the most burdens in terms of public health. Second, analytic epidemiology, also called etiologic, will allow us to review the set of causes, with emphasis on modifiable factors.

Chronic renal insufficiency: the numbers

The glomerular filtration rate is considered the best marker of renal function. It varies by age, sex and body mass index (BMI), with a normal of 120 to 130 ml / min / 1.73 m 2 in the young adult, with normal value decreasing with age .Chronic renal insufficiency is defined by a decrease in the rate of glomerular filtration, what is in itself the cause (s).Inulin clearance and isotopic methods for measuring the flow rate of glomerular filtration are the most accurate, but their routine application is impossible due to their weight and cost. The clinician must resolve to use more practical, but inaccurate methods: creatinine clearance according to the Cockcroft formula or the Modified of Diet study in Renal Disease, or even measured clearance.

Historically, the vagueness of the definition of chronic renal insufficiency and its severity has undoubtedly led to delays in diagnosis and inadequate medical care. Since 2002, creatinine clearance bounds have been adopted: 15, 30, 60 and 90 ml / min / 1.73 m 2 .

Chronic kidney disease may cause a clearance of less than 90; but chronic renal insufficiency is incontestable below 60.

Chronic terminal renal insufficiency:

Definition:

End-stage renal disease is defined by a glomerular filtration rate of less than 15 ml / min / 1.73 m 2 . Most often it is synonymous with “kidney death” with the vital need to resort to a renal function supplementation technique.

Thus, dialysis and transplantation are the most apparent medical interventions of chronic renal failure, “the tip of the iceberg”. In order to describe the cohort of patients with chronic end-stage renal disease undergoing supportive treatment, account must be taken of demographic and geographic data, historical changes in the management of kidney diseases and substitution treatment. Thus, from the 1960s to the mid-1980s, the development of surrogate techniques dictated the characteristics of dialysis patients. Hemodialysis and then peritoneal dialysis are perfected.The indications for transplantation remain confidential. The description of kidney disease begins. Beginning in 1985, the situation is changing dramatically. With new immunosuppressants, transplantation develops quickly and becomes the therapeutic indication of choice for young or middle-aged patients. Since kidney diseases are better understood, their treatment avoids dialysis.

Incidence of end-stage renal disease treated:

The incidence of a chronic disease is the number of new cases occurring in a population per year. The diagnosis of chronic terminal renal failure is unknown, due to the lack of knowledge of patients not reaching the nephrologist and the existence of patients challenged. The incidence of end-stage renal disease treated (TBRI) exceeds 350 new cases per million inhabitants (pmh) in the United States and 200 pmh in Japan. In 2002, it is between 91.6 pmh (Finland) and 169.8 pmh (French-speaking Belgium) in European countries with a register.

pdf). The incidence of IRTT increased by 57% from 1991 to 2000 in the United States. In Europe, the incidence increased from 79.4 pmh in 1990 to 117.1 pmh in 1998, an increase of 4.8% per year. Until now, the increase was linear in Europe, with the exception of stabilization in the Netherlands.

In France, a register of the IRTT has been developed since 2001. Before this date, the data are fragmented. In 1998, the overall incidence of IRTT was 100 pmh in the Île-de-France region. In 2003, in the seven regions participating in the registry, the average gross incidence rate was 122 pmh. It is much higher in the overseas departments, especially in Reunion.

In Lorraine, the incidence increased from 58 pmh in 1992 to 119 pmh in 1998 and to 144.8 pmh in 2002.

In 2003 and 2004, the incidence seems to stabilize (data from the Lorraine register). In the end, it is estimated that in France, 7,000 people start supplementary treatment each year.

This change in incidence reflects in-depth changes in the causes of TBRI, but also in the provision of care.

The relative frequency of glomerulopathies and interstitial nephropathies decreased by more than half; that of polycystic kidney disease remained stable, whereas vascular and / or diabetic nephropathies had their frequency increase exponentially. For three decades, the distribution of kidney diseases responsible for terminal chronic kidney failure has evolved in a comparable way in Europe.

This situation should be put into perspective with the evolution of incidence by age group. In Lorraine, among those under 65, the incidence is remarkably stable from 1998 to 2003.

On the other hand, between 65 and 74 years, it increased by almost 15%; between the ages of 75 and 84, 65%; over 85 years, by more than 200%. In Europe, the situation is the same.

In 10 years, the incidence has tripled in the over 75 years; that attributable to diabetes or vascular kidney disease has doubled. Since 1990, the secondary incidence of type 2 diabetes has increased by almost 12% per year. The aging of the population and the increase in the incidence of diabetes are the main explanation for the progression of the incidence of prophylaxis, while the other diseases have remained stable.

Changes in incidence between countries, from region to region:

In Greece, Ireland and Finland, the incidence of IRTT is half that of Germany and Luxembourg. In metropolitan France, in 2003, after adjusting for age and sex, standardized rates varied almost twice: Brittany: 85.2 pmh; Limousin: 91.7 pmh; Champagne-Ardenne: 108.9 pmh; Auvergne: 115.2 pmh; Rhône-Alpes: 121.5 pmh; Languedoc-Roussillon: 136.4 pmh; Lorraine: 150.5 pmh. There are four possible explanations:

• genuine differences in the incidence of chronic kidney failure;

• differences in the survival of patients with cardiovascular disease and diabetes;

• Differences in the use and access to substitutes;

• variations in the quality of registers.

The origin of the variations in the incidence of IRTT within a country has been explored in the administrative regions of Austria. These variations are mainly attributable to variations in the incidence of type 2 diabetes. The other explanations have been ruled out. There was no evidence of an under-reporting of kidney disease. The hypothesis of a variation in access to alternative treatment from one region to another is also excluded. Similarly, there were no variations in the density of the means of substitution. Finally, the fifth and last possible explanation is that patients with severe chronic renal failure may die more frequently before dialysis in one region than in another. This hypothesis is excluded; as cardiovascular mortality is lower in the region where the incidence of dialysis-treated renal failure is the lowest.

The least affected region in Austria, Tyrol, is the region with the highest proportion of subjects with a BMI greater than 30 kg / m 2 in Austria and the highest performers. In France, the situation is the same. Unlike Brittany, Lorraine, which has the highest incidence rate after standardization, is one of the regions with the highest prevalence of diabetes and obesity.

Differences between countries are undoubtedly due to differences in the health status of populations, which are in addition to variations in access to care due to differences in health systems. For example, a comparison of incidents in the United States with incidents in Lorraine revealed a respective frequency of diabetes of 53.3% and 32.5%, and of coronary disease of 42.6% and 31.3%.

Moreover, Americans are on average 11 years younger when dialysis than the Lorrainers. As the health status of the Lorraine population is generally worse than that of the rest of France, it is likely that these transatlantic differences are even more important throughout the country.

In conclusion, the health status of a population seems to be the primary determinant of the impact of IRTT within it.

Prevalence of end-stage chronic renal insufficiency treated:

Prevalence is the proportion of patients in a population at a given time. To estimate the prevalence of treated end-stage renal disease (TBRI), consideration should be given not only to patients on hemodialysis and peritoneal dialysis, but also to patients with functional renal grafts. In France, 45,000 live people would be treated by dialysis or would have benefited from a transplant.

In June 2003, the French prevalence of dialysis was estimated at 513 patients per million inhabitants. By comparison, it is 298 pmh in the United Kingdom, 546 pmh in Germany, 1,100 pmh in the United States and almost 1,400 pmh in Japan. In the United Kingdom, there is controversy over access to dialysis in very old subjects, which may explain a lower prevalence. In Germany and Japan, transplantation was less developed, explaining a higher prevalence. Finally, in the United States, despite a large renal transplant activity, the prevalence is twice that of France.

In metropolitan France, there are significant interregional variations in the prevalence of dialysis: from 355 pmh in Pays-de-Loire or 377 pmh in Brittany, up to 602 pmh in Languedoc-Roussillon and 675 pmh in Provence-Alpes-Côte d’Azur. These variations can be explained by differences in population structure. Thus, after adjustment, Nord-Pasde-Calais becomes the region with the highest prevalence.

Prevalence data for transplantation are only available for two French regions.

From 1992 to 2002, total prevalence increased by 74% in 10 years in Limousin, and 88% in Lorraine. Interestingly, the prevalence of functional grafts has doubled in both regions. This demonstrates, first of all, an increase in the cumulative activity of kidney removal, but also in the improvement of the survival of the grafts and the grafts. The prevalence of dialysis increased by 6.2% per year in Limousin, 8.1% per year in Lorraine.

The interpretation of this evolution is tricky. The aging of the population certainly plays a role. However, the Lorraine and Limousine populations are very different, with the Limousin population having the oldest population in Europe, Lorraine having a rate of type 2 diabetes and cardiovascular mortality among the highest in France. As an indication, the increase in the prevalence of dialysis during the same period was 9.7% per year in the United States.

In June 2003, the prevalence of dialysis in Martinique, Guadeloupe and Réunion was much higher than in France, 917, 1,063 and 1,181 patients per million inhabitants respectively. As for Reunion Island, the prevalence has increased little since it was raised to 1,061 pmh in 1996. There may be an excess in dialysis compared to metropolitan France.However, from a public health perspective, the IRTT in this region is a pathology of comparable importance to that of the United States. The same causes have the same effects, but this trend is mainly due to the “explosion” in the incidence of type 2 diabetes and hypertension.

Moderate and pre-terminal chronic renal insufficiency:

Moderate and severe low glomerular filtration rate in the American classification is defined by a glomerular filtration rate of between 30 and 59 and between 15 and 29 ml / min / 1.73m 2 respectively. If chronic end-stage renal disease is the visible part of the iceberg, moderate and pre-terminal chronic renal failure is indeed the immersed part. The absence of functional signs, the determinants of access to care and prevention affect the precise enumeration of this category.

Impact. Prevalence:

Due to the severity of its clinical consequences and the cost of its treatment – 2% of total health care expenditure in France – chronic renal failure is a major public health problem. Despite this, it is surprising to note that in France, no epidemiological studies evaluating the early management of chronic non-terminal renal failure have been carried out in population. In 1991, abnormal serum creatinine was detected (not clearance), among the consultants of the nephrology departments of the Ile-de-France region. The incidence was 92, 264, 523 and 619 pmh respectively for the ages of 20 to 39 years, 40 to 59, 60 to 74 and more than 75. There was a significant sexratio of three men for a woman only beyond that age limit. Given the silent nature of the disease and the variations in access to care, these results are biased.

In Iceland, in a representative sample of 10% of the total population, chronic renal insufficiency is defined as serum creatinine above 150 μmol l -1 and prevalence is 280 pmh in humans, 150 pmh in women . It increases with age. The most original teaching is that, contrary to what is usually considered, the progression of chronic renal insufficiency is not inexorable, since for one patient in three, the slope of decrease of the clearance is zero. In the Southampton population (United Kingdom), the prevalence is considerably higher, with the same diagnostic criterion: 1,070 pmh, with an over-representation of men and elderly subjects. An excess of mortality, particularly cardiovascular mortality, is noted particularly in the lower age classes.

In the United States, estimates of the prevalence of moderate and pre-terminal chronic renal insufficiency prior to dialysis are even higher: 6,600 pmh. One in 16 Americans reported creatinine clearance between 15 and 60 ml / min / 1.73 m 2 . This is consistent with the fact that this country has the highest incidence rate of RTII.

However, a significant proportion of subjects with elevated serum creatinine did not progress to the terminal stage.

There is also suspected a higher cardiovascular mortality in the population of chronic renal insufficiency.

The key question is why some patients do not reach dialysis. First hypothesis: chronic renal failure is not evolutionary.The question then is to determine the criteria for progress. Second hypothesis: these subjects die from cardiovascular causes before dialysis. In this case, increased cardiovascular prevention should lead to an even greater increase in incidence.

Epidemiology of renal insufficiency in the agglomeration of Nancy (EPIRAN):

Given the profound differences between populations in different countries, it is essential to rely on French data. In progress on the territory of the urban community of Nancy, EPIRAN should allow:

• a description of the natural history of chronic renal failure by determining the rate of progression and possible factors of acceleration or decompensation;

• the recognition of health care systems with the respective roles of each physician;

• Assessment of the impact of interventions on morbidity and mortality up to the stage of chronic terminal renal failure and on the conditions of implementation of supplemen- tary treatments, taking into account age and associated diseases.

Serum creatinine concentrations greater than 150 μmol l -1 (17 mg l -1 ) in adults, 133 μmol l -1 in children over 7 years and 100 μmol l -1 in children under 7 years are recorded prospectively in all laboratories of medical biology of the Nancy agglomeration. Each case is studied systematically to identify its chronic (persistent more than 3 months) incidences or prevalent. The cohort consists of incidents, which are monitored over a 2-year period. The preliminary results (period from 1 January 2004 to 30 June 2004) are original.

Screening:

The frequency of chronic renal insufficiency, the severity of its complications and the existence of effective nephroprotection measures applicable in clinical practice may justify systematic screening of clinically silent urinary abnormalities in the general population. For example, in the United States, only 10% of patients with early stages of chronic renal failure are aware of the abnormalities presented. In population, to identify a case of proteinuria, three diabetics or seven non-diabetic hypertensive patients or six people over 60 years of age must be tested.

However, proteinuria is associated with renal insufficiency. For example, only one-third of the over-60s with clearance  30 ml / min / 1.73 m 2 have proteinuria.

In addition, a cost-effectiveness study was negative for the US population. Systematic screening by urine strip is acceptable only in a targeted population: elderly and / or hypertensive subjects. In Europe, it is interesting to note that the consensus on the systematic detection of chronic renal insufficiency concerns the same populations: hypertensive subjects, diabetics, over 60 years old, a family history of kidney disease, repeated urinary infections, some toxic.

Medical care:

Today, in our country, patients with chronic renal insufficiency are treated late by the nephrologist. About 40% of those on dialysis were seen less than 6 months before by a nephrologist. In some subgroups, late implementation of dialysis has dramatic consequences: excess early mortality in the order of 25% in diabetics and severe degradation of quality of life in elderly patients.

In 1998, a national survey showed that the first symptom of kidney disease appeared on average more than 5 years before the use of substitutes. Patients were referred to the nephrologist by their general practitioner in 47% of cases, by a cardiologist in 12%, by a diabetologist in 7%, by a urologist in 5%. From 1998 to 2003, the incidence of associated diseases during dialysis increased from 21% to 27% for type 2 diabetes, from 17% to 23.3% for heart failure, and remained stable at 7% for type 1 diabetes, 19% for coronary heart disease, and 8% for stroke.

If the chronic end-stage renal disease threshold is set at 15 ml / min / 1.73 m 2 creatinine clearance, there are in practice large variations in the values ​​observed at the onset of supplementation. In the 1998 national survey, it was less than 5 ml / min / 1.73 m 2 in 7% of cases, between 5 and 10 in 62%, between 10 and 15 in 21%, between 15 and 20 in 2 %, and greater than 20 in 8%. In 1998, in Ile-de-France, it averaged 8 ml / min / 1.73m 2 . This is comparable to what is found in the United States. Observational epidemiological studies have established therapeutic thresholds associated with a better clinical condition.

The EPIREL (epidemiology of chronic end-stage insufficiency in Lorraine) demonstrated a statistically significant association between the nephrologist’s intervention and the application of recommendations of good practice with the attainment of therapeutic targets (Thilly N, et al., Early nephrology referral: what does it mean? The sooner the nephrologist sees the nephrologist, the higher the hemoglobin concentration, the higher the blood pressure and phosphocalcic metabolism will be, the more likely it is to benefit from nephroprotective therapy. The central issue is the optimization of care for chronic renal insufficiency, in a demographic context where the proportion of nephrologists per million inhabitants will decline sharply.

It can (must) be an effective collaboration between the nephrologist and the general practitioner. Networks of care are an appropriate solution for implementing therapeutic interventions. A remote telemedicine consulting activity could limit the number of consultations with the nephrologist and facilitate the interventions of the general practitioner to meet the growing needs in this field.

When to start dialysis?

There are no precise and indisputable biological criteria for setting up substitutes. According to a prospective Canadian study, it is not possible to develop a decision algorithm to discern patients for whom dialysis is contraindicated. The decision must therefore be based on a range of clinical and biological criteria.

The installation of the symptoms of chronic renal insufficiency is sneaky, the appearance of functional or clinical signs is delayed, which suggests a rapid implementation of dialysis. In addition to the hydrosodic overload, which must be systematically sought and corrected, the digestive symptoms are delayed by undernutrition, which is subsequently responsible for an increased risk of mortality, especially in the elderly. The clinician overestimates residual renal function, due to an overestimation of lean mass. Finally, a clinical situation, even very stable, can be decompensated very quickly, and this especially since there are associated diseases that weaken the clinical equilibrium.

One of the highlights of the planned dialysis is the active participation of the patient in his management. Self-evaluation of the impact of chronic kidney failure may facilitate decision-making, but the patient’s fears about future dialysis should never be underestimated and may even lead to unnecessary delay in dialysis. start-up. Careful preparation of the dialysis leads to satisfactory results in terms of survival and rehabilitation, without, however, starting to start.

Natural History of Chronic Kidney Disease:

The classification published in 2002 in the United States uses the term chronic kidney disease, which describes any irreversible renal destruction, regardless of cause (single or multiple). This expression refers the French-speaking physician to an area where initiation factors, mainly the physiopathology of renal diseases, are at the forefront, while chronic renal failure focuses attention on the functional consequences of nephron reduction and its pejorative progression factors for the patient. The decrease in glomerular filtration rate, as evidenced by the decrease in creatinine clearance, is the most common reason for the use of nephrologists.

It should not be forgotten that early intervention on the risk factors for chronic kidney failure can be very beneficial.

Different factors of initiation: renal diseases

In 1966, Jean Hamburger wrote: “Renal diseases are precarious, moving, often arbitrarily defined entities according to historical hazards and not according to the requirements of the scientific method.” This remark remains today partly correct. Indeed, nosological inaccuracies persist in the description of kidney disease. Some of them are perfectly described: diabetic nephropathy, polycystic kidney disease, etc. At the same time, others remain of undetermined origin, in particular because of the physiopathological uncertainties.

Glomerular nephropathies:

Glomerulonephritis is the best known kidney disease. They are the archetype of diseases whose diagnosis depends on the indication of further examination. Indeed, the incidence of glomerular diseases varies from one region to another, from one country to another, depending on the policy of renal biopsy, especially in subjects older than 60 years.

Among the renal diseases responsible for end-stage renal disease treated, the proportion of glomerulonephritis has decreased steadily over the last 30 years, from more than 50% to 13%. In fact, this decrease is relative because the incidence of vascular and diabetic nephropathies has increased markedly. In addition, glomerulonephritis affects mostly the young adult, the age group where the incidence of dialysis is stable.

The most common chronic glomerulonephritis leading to chronic terminal renal failure is immunoglobulin A (IgA) nephropathy. Indeed, one in two patients on average, or even three patients out of four according to the age groups (40-60 years) reaching the stage of the chronic end-stage renal failure due to a glomerular disease are carriers of a nephropathy to IgA. The nephrotic syndrome with minimal glomerular lesions evolves exceptionally towards the indication of a renal supplement. Extramembraneous glomerulonephritis has a low evolving potential.

Longitudinal monitoring of glomerular renal disease in the Côtes-d’Armor department revealed significant incidence variations.

Over a period of 27 years, there was a significant decrease in the frequency of membranoproliferative glomerulonephritis.

This development appears to be directly linked to the evolution of bacterial infectious diseases, in particular streptococci. The incidence of extramembrane glomerulonephritis also decreases, while that of IgA nephropathy is marked by high stability. Glomerular nephropathies are models of complex multifactorial diseases, induced by a combination of genetic and environmental factors that vary from one individual to another.

The rapidly progressive glomerulonephritis, also called glomerulonephritis with extracapillary proliferation, should be considered separately. It is distinguished from other glomerular nephropathies by its rapidity of evolution. Despite intensive treatment, it most often leaves permanent sequelae responsible for chronic kidney failure. It is primary or secondary, associated with high mortality, 50% to 5 years in the case of Goodpasture’s syndrome or Wegener’s disease. It appears to be more frequent in elderly subjects, subject to significant seasonal variations with frequency peaks in spring and autumn. This refers to the predominant impact of environmental factors and a possible link with infections.

Chronic interstitial nephropathy:

Primary forms of chronic tubulointerstitial nephropathy constitute today a small proportion, less than 5%, of diseases leading to chronic terminal renal failure. In nephrology, they represent only 7.5% of kidney disease.

It is possible that variations in the diagnostic criteria are responsible for this low incidence. Similarly, renal alteration mechanisms remain obscure. Toxic exposure is probably more frequent than expected: use of nonsteroidal anti-inflammatory drugs, exposure to lead, cadmium, etc. Some hereditary interstitial nephropathies have recently been described, such as autosomal dominant nephropathy with early hyperuricemia.

Vascular nephropathies:

Although these pathologies suffer from a major nosological imprecision, the prevalence of vascular nephropathies among newly dialysed patients has been multiplied by a factor of 4 over the past 30 years. Theoretically, the size of the damaged renal vessels determines three categories of vascular nephropathy.

Atheromatous stenoses of renal arteries:

Atherosclerotic stenoses of renal arteries, secondary to atherosclerosis, are present in 15% of subjects affected by diffuse atheromatous disease. Classically, they cause severe arterial hypertension, but their main risk is dialysis due to bilateral involvement with parenchymal hypoperfusion. Angioplasty of the renal arteries is aimed both at the nephronic protection and the control of the hypertension. After 60 years, this indication concerns 25 new patients per 100,000 inhabitants each year. Cholesterol embolisms are also secondary to atherosclerosis. They are favored by endoluminal vascular interventions and anticoagulation.

Nephrochiosclerosis:

The second type of vascular nephropathy is nephroangiosclerosis.

This term is defined by the arteriosclerosis observed on a histological fragment obtained by renal biopsy. It affects the arteries of medium and small caliber to the interlobar arteries. However, the term “nephroangiosclerosis” is frequently used to refer to any unlabeled renal disease, which is responsible for chronic renal failure, particularly in elderly hypertensive patients.

Vascular nephropathy following arteriosclerosis:

The third and last type of vascular nephropathy is consecutive to the arteriosclerosis that affects the glomerular arterioles.

As noted by Meyrier, hypertension explains only part of this lesion. It may be histologically associated with all renal diseases, from glomerulonephritis to polycystic disease, even when optimal blood pressure control. This suggests the involvement of other mechanisms, possibly genetic, hormonal and inflammatory. Finally, since there is a striking parallelism between the histological lesions of the elderly kidney and those of vascular nephropathy, vascular “aging” could be a determining factor.

Hemolytic uremic syndrome:

Although it is responsible for vascular renal disease, hemolytic uremic syndrome should be considered separately;because it appears suddenly and responds to specific pathophysiological mechanisms. A meta-analysis of 44 studies showed that it left sequelae in one case in four: clearance less than 80 ml min -1 , hypertension, proteinuria.

It is an exceptional cause of reliance on substitutes.

Diabetic nephropathy:

All diabetics do not develop diabetic nephropathy, characterized by proteinuria of increasing intensity. In a representative sample of French general practitioners, a micro- or macroalbuminuria was present in 18.6% of type 1 diabetics, 11.2% of insulin-treated type 2 diabetics, 9.5% type 2 diabetes without insulin. In the United Kingdom, after 15 years of evolution, type 2 diabetes is accompanied by microalbuminuria in 28% of cases, massive proteinuria in 7.1%, renal insufficiency in 2.3 %. In Turin, at the time of management in nephrology, one in two diabetics has an abnormal creatinine, one in five significant proteinuria.

Ultimately, the histological diagnosis of diabetic nephropathy is often hypothetical. Registers from the early 1980s to the mid-1990s showed prevalence of diabetic nephropathy in the United States at 31.8%. This trend now reaches France.

Although not always directly responsible for chronic renal failure, diabetes is primarily a disease associated with it, which is responsible for vascular complications.

Today, in the United States, patients on dialysis have type 2 diabetes in more than 50% of cases, more than 30% in some parts of Europe. The mortality of diabetics with significant proteinuria and / or renal failure is very high before and after the start of the supplement.

Polykystosis:

It is often forgotten that polycystic disease is the most frequent hereditary disease, since it affects 1,000 births. It is characterized by two distinct phenotypes. The first is characterized by a rapid evolution and requires the use of substitution around 40 years; in the second, of a slower evolution, the substitution is instituted only beyond 60 years. In France as in Europe, its frequency among the causes of dialysis (around 10%) has remained remarkably stable. Given the steady increase in incidence, the number of patients put on dialysis for polycystic disease has therefore increased over the past 30 years. This probably reflects increased management of elderly patients with the slow phenotype.

To date, no etiopathogenic treatment can slow the growth of cysts and prevent the lesions they cause. On the other hand, the progression from polycystic disease to dialysis was significantly slower in the period 1992-2001 than in the period 1985-1992, the average age at dialysis being 63 years compared with 53 years previously. This, as with other nephropathies, testifies to the efficacy of conservative treatments. This helps to increase dialysis in elderly patients with polycystic disease.

Other kidney diseases:

The other kidney diseases responsible for end-stage renal disease treated account for 10 to 20% of the cases.

They are very diverse. However, whether they are related to hemopathy, lithiasis, sequelae of severe acute pyelonephritis or ciclosporin toxicity after cardiac transplantation, their frequency as dialysis-causing diseases is relatively anecdotal. Over time, some causes of chronic renal failure have simply disappeared, for example, chronic kidney failure after obstetric complications.

Factors of progression of chronic renal insufficiency:

It is striking that a significant proportion, of the order of 20%, of patients reaching the stage of end-stage renal disease treated do not have clearly identified causative renal disease! This is only an illustration of the uncertainties regarding the pathophysiology of kidney disease.

In contrast, the factors responsible for the development and progression of chronic renal insufficiency are better known. They can be divided into three categories:

• the first includes non-modifiable factors such as age, gender, genetic and ethnic factors;

• the second includes intrinsic progression factors such as immunological and inflammatory abnormalities present in glomerulonephritis, haemodynamic changes following arterial hypertension, or metabolic changes in diabetes and dyslipidemias;

• finally, the third consists of general modifiable factors that can be influenced to limit the progression of renal insufficiency: blood pressure, proteinuria, hyperglycemia, dyslipidemia, smoking.

Age Factors:

In France, the majority of nephrologists consider that the care of the elderly in dialysis characterizes the recent evolution of their activity. In the 1970s, patients retained for the start of supplemental therapy were young with no associated pathology. Gradually, clinical experience has resulted in good results in older patients. In 1982, less than 4% of French dialysis patients, or 360 people, were over 75 years of age. In some age groups, chronic terminal renal failure (CRFI) was still purely and simply a death sentence.

For 20 years, thanks to prevention actions, there has been a decline in the age of onset of cardiovascular disease – “compression phenomenon” of morbidity in the most advanced ages. At the same time, the increase in the life expectancy of the general population, and of type 2 diabetics in particular, increases with associated diseases and disabilities.

In 1991, the over 80 years represented approximately 1,000 people, or 5.5% of the total dialysis. In Rhône-Alpes, since 1993, the annual prevalence has increased by 6.7% per year for the 65-74 years and by 13.7% per year for the 75-84 year olds.

Aging, diabetes and vascular nephropathy induce a constant increase in the number of dialysis patients. However, the dogma of the inexorable aging of the kidney could be called into question. The decrease in clearance is present only in two thirds of the elderly and appears to be predominantly due to a disease.

Gender-related factors:

In the United States, the role of sex as a factor in promoting chronic renal failure has been considered modest.However, in France as in Europe, the sex ratio is 1.5 in all age groups.

Genetic and hereditary factors:

Apart from renal diseases fully explained by genetic factors, such as polycystic disease, the existence of hereditary factors favoring the occurrence of different kidney diseases in the same family is known. Americans of African descent have a higher mean serum creatinine than Americans of other origin with a risk of terminal chronic renal failure multiplied by four compared to Americans of European origin (2003 USRDS report). However, this risk decreases very significantly after adjustment to medical factors of chronic renal insufficiency. In the Framingham cohort, a genetic susceptibility appears to be associated with the development of chronic renal failure. All this suggests a higher concentration and intensity of risk factors in some populations.

Hypertension:

Even if the medical profession is not always aware of this, the link between hypertension and kidney failure is narrow.Thus, a study of a representative sample of French cardiologists showed that they consider the renal function of their hypertensive patients to be normal in 71% of the cases, whereas in reality, chronic renal insufficiency is present in 61% of patients 7% with a creatinine clearance of less than 30 ml min -3 . In a cohort of nearly 5,000 hypertensive patients enrolled in Ile-de-France through 1,429 general practitioners, patients with a cardiovascular event in their development had more frequent chronic renal insufficiency at baseline.

The prevalence of hypertension varies according to conventional thresholds. However, the cardiovascular risk associated with hypertension appears above 115/75 mmHg and doubles at each step of 20/10 mmHg. In the United States, if the threshold is set at 140/90 mmHg, the prevalence among men aged 18-74 is 22.8%. In France, the prevalence of hypertension in a cohort of nearly 30,000 active subjects is 16.2% for men and 9.4% for women.Therapeutic control of hypertension is generally insufficient. There is a risk of renal failure, which patients are unaware of.

Proteinuria:

With the exception of the selective and massive proteinuria of nephrotic syndrome with minimal glomerular lesions, regardless of nephropathy, proteinuria is one of the most sensitive markers of the risk of progression to chronic renal insufficiency. The lower the rate, the more the dialysis deadline falls. The efficacy of therapeutic strategies to reduce proteinuria has been proven by randomized trials.

They include strict control of blood pressure, use of an inhibitory treatment of the renin-angiotensin system, protein restriction, a decrease in total cholesterol, and so on.

Obesity and metabolic factors:

In a US population of healthy subjects, a BMI greater than 30 kg / m 2 increases the risk of developing chronic renal insufficiency by 23% within 20 years. This result was obtained by taking into account the other risk factors. In Japan, in healthy subjects with normal function without proteinuria, the risk of a proteinuria on the strip within two years is 54% in the case of obesity. This trend, correlated with the intensity of obesity, remains statistically significant in humans after adjustment.

An association between obesity and the severity of chronic kidney disease has also been demonstrated. Thus, during IgA nephropathy, a BMI greater than 25 kg / m 2 at the time of the biopsy was associated with more severe histological lesions, as well as a more rapid progression from chronic renal failure to supplementation .

In young people, obesity would be associated with a higher incidence of diseases, as well as higher mortality. In the case of chronic renal insufficiency, this impact appears to be mixed. Thus, in dialysis patients, a BMI greater than 25 kg / m 2 is associated with superior survival. High BMI may be associated with higher nutritional status as well as lower inflammatory status.

Today, patients with end-stage renal disease treated have very high morbidity associated with atherosclerosis and cardiovascular mortality. At earlier stages, Jungers found a risk of myocardial infarction three times higher in renal insufficiency than in the general population. Cardiovascular risk increases when creatinine clearance becomes less than 60 ml min -1 .

For some, the combination of all conventional cardiovascular risk factors, such as tobacco, hypercholesterolemia or innate factors, such as family history, age, sex, would be sufficient to explain the increased incidence of cardiovascular disease . For others, chronic renal insufficiency generates specific cardiovascular risk factors: oxidative stress, hyperhomocysteinemia, inflammation. In the dialysis, hyperphosphatemia, elevation of the phosphocalcic product and hyperparathyroidism also seem to play a major role in the pathophysiology of vascular and tissue calcifications.

Medicinal plants:

Epidemiological data on renal risks related to the use of medicinal plants are non-existent.

However, a number of substances have been clearly identified as possibly causing chronic interstitial nephropathies, lithiasis, urothelial tumors.

Following the occurrence of kidney complications after consumption of Chinese herbs, four mechanisms of toxicity were mentioned:

• medicinal plants that are well identified but whose effect is uncertain or underestimated;

• medicinal plants contaminated with a drug, hormones or heavy metals;

• poorly identified medicinal plants;

• medicinal plants responsible for interaction with medicines.

Tobacco:

Tobacco use undoubtedly aggravates the progression of chronic renal insufficiency. This effect appears to be independent of the initiation factors of renal diseases. Thus, it is identical in patients with IgA nephropathy or extramembrane glomerulonephritis or segmental and focal hyalinosis. There would be an interaction between tobacco use and sex, men, especially when they are elderly and hypertensive, at a much higher risk than women. Similarly, an interaction between tobacco and ACE inhibitors would exist, the latter appearing to “protect” the kidney from the harmful effects of tobacco.

Illegal Drugs:

In a population where illicit drug use has been accurately measured, it is significantly associated with the risk of terminal chronic renal failure.

After adjusting for age, sex, ethnicity, socio-economic factors, hypertension and diabetes, a heroin addict or a cocaine and crack cocaine consumer is at risk of dialysis multiplied by 20 and 3.2 .

This association is linked to malignant hypertension and / or to genuine kidney damage. The exact frequency of renal failure secondary to this exposure is difficult to determine because, in the registers, nephrologists do not declare this cause to protect their patients. However, it would reach 5% in some urban areas.

Determinants of access to care:

Socio-economic factors:

Despite the individualization of the main risk factors for chronic renal failure, despite the demonstration of the benefits of their modification, the incidence of chronic terminal renal insufficiency continues to increase. Socio-economic factors have long been recognized as major determinants of health status. In addition to proven risk factors for chronic kidney failure, they could play a role. Data on this issue are scarce. In the United States, individuals with the lowest incomes had a higher risk of impairment of renal function than those with higher incomes. Furthermore, the appearance of chronic renal failure is significantly correlated with the level of education. In Sweden, the risk of chronic renal insufficiency is increased by 40% in patients who have not studied compared to those with the longest studies. This risk persists after adjusting for age, sex, BMI, smoking, alcohol and analgesic use.

Factors correlated with socioeconomic status explaining the onset of chronic renal insufficiency are numerous: exposure to heavy metals (lead, mercury, cadmium), determinants of access to care, dietary factors, smoking, alcohol or drug.

In order to improve the health status of these populations at risk, for example, screening of hypertensive patients in occupational medicine, hypertension, for example, would make it possible to identify hypertensive patients in the least-favored socio-occupational categories in the stage of complicated arterial hypertension.

Medical Decisions:

In the more than 75/80 years, a stable clinical condition with a satisfactory quality of life is often noted despite severe renal insufficiency. Since chronic renal insufficiency is a silent pathology, a patient may die from complications of uremic syndrome or an associated disease without access to nephrological structures.

The use of the nephrologist depends on the decision of the physicians who demonstrate the decrease of the glomerular filtration rate. Within a network of care, the collaboration between the nephrologist and the general practitioner can help to maintain a favorable clinical balance.

A medical follow-up, at least monthly, will allow the general practitioner to decide, in agreement with the patient, whether the substitute should be started or not.

Conclusion:

Chronic renal insufficiency is a likely organ failure in the population. Its discovery justifies a diagnostic approach. The frequency of certain etiologies decreases: chronic glomerulonephritis, malformative uropathies, type 1 diabetes. Today, the main causes are type 2 diabetes and age-related vascular diseases. Chronic renal insufficiency does not always progress towards the terminal stage. Many people normally live without symptoms despite decreased clearance.

Whether to consider them sick or as a risk factor is debated.

Therapeutic interventions include early nephroprotection measures, combined with prevention of aggravating factors and cardiovascular risk factors.

When chronic renal failure is severe (creatinine clearance  30 ml min -1 ), complications should be managed. Dialysis and / or transplantation should be scheduled. The improvement of epidemiological knowledge, thanks to the registers, is essential to adapt the supply of care to the increasing demand.

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