Each kidney it is made up of over one million small units called nephrons, with two main structures: the glomerulus and the renal tubule.
The glomerulus it is made up of a dense network of capillaries enveloped by Bowman's capsule, and is the part of the nephron responsible for "filtering the blood". The tubule is home to the reabsorption of almost all the ultrafiltrate produced by the glomeruli (180 liters per day), so as to arrive at about 1 and a half liters of urine produced in 24 hours.
THE tubules, with mechanisms of reabsorption is secretion, allow the recovery of many ultrafiltered substances, useful to the body such as glucose, phosphorus and amino acids and the elimination of other potentially toxic substances. A fundamental role is played by the tubules in the regulation ofhydrosaline and acid base balance, functions of utmost importance for our survival. Finally, the kidneys produce hormones such as erythropoietin and angiotensin II.
Erythropoietin it is an indispensable hormone to stimulate the production of red blood cells (red blood cells) by the bone marrow and therefore, together with the intake of iron with food, avoids anemia, typical in patients with chronic renal failure (CRI), precisely for the reduction of kidney mass and therefore of the kidney's ability to produce Erythropoietin.
Angiotensin II is a hormone capable of maintaining blood pressure, through its vasoconstrictive properties on small arteries. In the presence of kidney disease, angiotensin II is often produced excessively by the ischemic kidney (because it does not receive adequate oxygen from damaged renal arteries), which in turn causes an increase in blood pressure. The increased production of angiotensin II and salt and water retention in chronic renal failure, due to the compromised kidney's difficulty in eliminating salt and water, are the most frequent causes of hypertension in patients with chronic renal failure (CRI).
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Chronic renal failure - CRI
The degree of renal impairment is proportional to the number of nephrons lost. Chronic renal failure is therefore a condition characterized by a reduction in glomerular filtration capacity and by alteration of hormonal renal functions (regulation of blood pressure and production of erythropoietin), a condition that often develops slowly, over many years.
As we said i kidneys are a filter system. Only when about 50% of renal tissue has been damaged does the value of function, which we measure in the clinic with creatinine clearance, begins to decline. The increase in the blood concentration of substances that are normally eliminated by the kidney occurs after a long time, as the remaining nephrons are for a long time sufficient to maintain normal plasma concentrations of uremic toxins and also work more than normal, with a mechanism called hyperfiltration and therefore it is a work in wear that leads to a progressive exhaustion of the function of the nephrons and therefore to the terminal CRI, requiring replacement therapy with dialysis or kidney transplantation.
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Causes of Chronic Renal Failure - CRI
The prevalence ofIRC in the Italian population it is not unlike that of other countries and it can be said that almost 10% of the Italian population presents a certain degree of reduction in renal function. This is also due to the progressive aging of the general population and it is known that elderly people often have a reduction in renal function, without always speaking of chronic kidney disease, especially in the presence of modest reduction without progression factors.
The kidneys can be affected by various diseases. Diabetes mellitus and arterial hypertension are frequent causes of chronic renal failure in people over the age of 50. The other causes of the disease are mainly immunological (primary glomerulonephritis or secondary to systemic diseases such as Lupus), infectious - toxic, also including drugs (pyelonephritis-interstitial nephritis), hypertensive (nephroangiosclerosis) and secondary to diseases such as above all diabetes and obesity, unfortunately in progressive increase also in our Italian population. Finally, there are genetically transmitted diseases such as polycystic kidney, responsible for the 10% of the population entering dialysis and the rarer Alport disease and other hereditary glomerulonephritis.
If renal damage is significant, there is a progressive reduction in renal function, regardless, within certain limits, of the initial cause of renal disease, although the rate of progression of the reduction in renal function can often be very different from case to case. mainly based on the presence or absence of progression factors, especially proteinuria and hypertension. It is also true that in some patients primary renal disease can remain more or less active throughout the course of the CRI and further contribute to the progressive reduction of renal function. However, even in cases where primary renal disease has been successfully treated, if the renal function is too compromised, a progression of the reduction of renal function can still occur, albeit slowed by the therapy in place for CRI. The identification of the mechanisms of progression of renal disease and of the intercurrent factors that can accelerate its progression, constitute the therapeutic cornerstone of the treatment of patients with chronic renal insufficiency to try to remove, even in these progressive patients, the need for replacement therapy
Prevention of Chronic Renal Failure - CRI
How can chronic kidney disease and its progression be prevented? Kidney disease requires a lot of self-care from the patient. To slow down the progression of the disease it is necessary to acquire a correct lifestyle and respect for an appropriate diet.
It is necessary to fight smoking, sedentary life, overweight, hyperglycemia, hypertension, high cholesterol and triglyceride levels, excess alcohol, the abuse of pain-relieving and anti-inflammatory drugs ».
In recent years, cigarette smoking has increasingly become a very important factor in the progression of kidney diseases, in particular diabetic nephropathy. Diabetic smoking patients have a high risk of developing micro albuminuria, up to overt proteinuria and have an accelerated progression of nephropathy towards CRI requiring replacement therapy. But this, it should be emphasized, also applies to a large extent for non-diabetic nephropathies. Therefore, also considering the high cardiovascular risk of patients with CRF, smoking cessation should be considered a priority intervention in the prevention and treatment of progression of CRI.
Chronic renal failure therapy - IRC
Effective antihypertensive therapy is currently the mainstay treatment of chronic renal failure. Some classes of antihypertensive drugs and in particular those capable of blocking the renin-angiotensin-aldosterone system, slow down the progression of chronic proteinuric nephropathies. ACE inhibitor and sartanic drugs (angotensin II receptor antagonists), are in fact considered of first choice in the presence of proteinuria, while anti-aldosterones, although very effective in reducing proteinuria and therefore probably in slowing the progression of CRI and in improving the cardiac situation, they are used with caution, especially in the fairly advanced forms of CRI, due to the serious risk of causing hyperkalaemia, which can even be fatal if not carefully monitored
However, a combination therapy with different antihypertensive agents is often necessary to achieve adequate blood pressure control (ideally 120/80 mmHg, especially if there is significant proteinuria), which is more difficult in the presence of CRF and using greater caution in elderly patients. frail with generalized arteriosclerosis and in the absence of significant proteinuria. In this elderly and frail population, higher blood pressure values can also be accepted (although the very recent study SPRINT, albeit with important limitations of applicability on the general population, it does not seem on the same line of thought), but lower than 150/90 mmHg. However, blood pressure must be measured both in supine and standing position, to prevent the risk of orthostatic hypotension and consequent falls, with the risk of fractures, especially of the femur, a very fearful complication in the elderly.
Prevention of cardiovascular disease
The prevention of the progression of CRI must be accompanied by the prevention of the progression of cardiovascular disease, because it is known that even a modest reduction in renal function and even a modest loss of albumin in the urine (microalbuminuria), even in the presence of preserved renal function, they are associated with an important increase in the risk of cardiovascular disease. Hence the need to implement early all interventions capable not only of preventing or slowing the progression of CRI, but also those capable of preventing cardiovascular complications. These interventions consist of adequate antihypertensive therapy, in the partial correction of anemia, in the correction of hydro-salt overload, limiting the sodium intake in foods and avoiding foods rich in salts or preserved with the salting system. Furthermore, the control of calcium-phosphorus metabolism is increasingly important, limiting the supply of phosphorus with food, but especially the phosphorus contained in food as a preservative and that contained in beverages defined as "soft drinks". Finally, the prevention of dyslipidemia is necessary, with dietary advice and possibly specific drugs such as statins.
For more than 50 years it has been suggested that reducing protein intake can slow down the progression of CRI by reducing the pressure within the glomeruli, which is also done by the low-sodium diet. Opinions that reducing protein intake can slow down the progression of CRI are highly controversial and the notion that in symptomatic patients (poorly tolerant to the accumulation of nitrogenous substances in the blood), reduce the intake of substances tends to prevail nitrogen in the diet may make patients more tolerant of their uremia situation, also avoiding malnutrition and thus delaying the need for dialysis. In fact, much has been done to improve the nutritional status and symptoms of CRI patients, especially by recommending an adequate protein intake according to the stage of CRI. In the initial stage of CRI, a protein intake of 0.8 - 1 g / kg of ideal body weight is adequate. This protein intake (0.8 / kg of ideal weight), without resorting to protein-free products, can be adequate even in the presence of a more advanced CRI, possibly correcting metabolic acidosis with sodium bicarbonate, controlling salt and water retention with sodium restriction and possibly using loop diuretics and treating anemia with erythropoietin.
All this has allowed, in many patients, to remove the need for dialysis, even without improving kidney function. Obviously, if the patient is still symptomatic, despite a moderate residual renal function, the protein intake should be reduced to 0.6 gr / kg of ideal weight, favoring noble proteins, using protein-free products, but obligatorily guaranteeing a caloric intake of 40 Kcal / Kg of ideal body weight, even more so if, in the most motivated patients, it was decided to further reduce the protein intake to 0.3gr / Kg of ideal weight, supplemented with Ketoanalogues (14 tablets per day).
In conclusion, all patients with conservative CRF, especially if with moderate to severe chronic renal failure, should receive dietary recommendations aimed at ensuring an adequate caloric intake, a reduced intake of sodium and phosphorus and a controlled protein content proportionate to the degree. of CRI, being the nutritional aspect important to remove the need for dialysis, maintain a good nutritional status and thus prevent complications. In this regard, the control of hyperphosphorus is increasingly important, to prevent secondary hyperparathyroidism, with the consequent reductions in the calcium content of the bones, the phospho-calcium precipitations in the noble parenchyma and soft tissues and cardiovascular calcifications
Treatment of arterial hypertension and reduction of proteinuria
The treatment of arterial hypertension and the reduction of proteinuria, in addition to the targeted therapy of the underlying nephropathy, are the main therapeutic interventions to slow the progression of CRI. It is known that patients with higher levels of proteinuria have a greater rate of progression of the CRI, but benefit more from the tight control of blood pressure values. Therefore it is important to consider the levels of proteinuria when defining the blood pressure target to be achieved in the individual patient, trying to obtain lower levels in proteinuric patients.
In addition to the ability to reduce blood pressure. some drugs have renal protective properties, partially independent of pressure control alone.
In fact, some classes of antihypertensive drugs, in particular those capable of blocking the renin-angiotensin system, slow down the progression of chronic proteinuric nephropathies. ACE inhibitors and sartanic drugs (angotensin II receptor antagonists) are therefore considered first choice drugs in the presence of proteinuria.
This category of drugs would also have an important cardiac action in reducing left ventricular hypertrophy and would improve cardio-circulatory compensation.
However, combination therapy with various antihypertensive agents is often necessary to achieve adequate blood pressure control.
Correction of anemia
Anemia, very frequently present in the patient with CRF, especially in the more advanced stages, is an important risk factor for the development of cardiac pathology, in particular for the development of left ventricular hypertrophy, very prevalent in patients with CRF and conditioning their prognosis severely. This association between left ventricular hypertrophy and anemia may explain the worsening of the prognosis of renal patients with both of these complications. The important aspect is that this anemia can be corrected, initially with iron supplements by mouth and in the most serious cases or of poor tolerance or poor efficacy of oral therapy, intravenously. Subsequently, if the anemia is not sufficiently corrected, it will be necessary to resort to drugs stimulating erythropoiesis (erythropoietin) in order to have a more complete correction of the anemia, but without reaching the normalization of hemoglobin levels, to avoid possible cardiovascular risks . The partial correction of anemia not only improves the quality of life and the psycho-physical performance of patients with CRF but also improves their cardiovascular situation, also avoiding the risk of transfusion, with all its problems. The European and Italian guidelines recommend a hemoglobin target of 10-12 g / dl, aiming for the highest levels in younger patients without cardiovascular complications.
Correction of alterations in phospho-calcium metabolism
The retention of phosphorus with the reduction of renal function is a relatively early occurrence, and also occurs when, for a long time, the phosphorus remains normal. More and more are the clues that consider the elevation of phosphorus not only as a factor responsible for the secondary hyperparathyroidism of the patient with CRF, with all its bone and cardiovascular complications, but also as a factor in the progression of CRI itself. Hence the increasing importance given to the control of phosphorus already in the early stages of CRI, both with dietary measures and possibly with phosphate binders. The role of phosphate in the increase in cardiovascular calcifications and in phospho-calcium precipitations in noble and in soft tissue is widely demonstrated in dialysis patients, hence the keen attention to control the phosphorus in these patients with an appropriate diet, effective dialysis and the use of phosphate binders, possibly calcium-free, to further reduce the risk cardio-vascular calcifications which, in addition to causing cardiovascular disease, also compromise the success of a kidney transplant, due to the surgical difficulty of operating on calcific vessels to be sutured with the donor kidney vessels.
Control of dyslipidemia
Recent studies have highlighted the importance of controlling dyslipidemia to prevent the cardiovascular risk of patients with CRI, but it is not yet clear whether this can also slow down the progression of CRI. However, considering the serious cardiovascular risk of CRI patients. patients with CRF, which involves more patients who die particularly from cardiovascular complications, than those who come to the need for dialysis or transplantation, it is evident that particular attention must be paid to controlling dyslipidemia with an appropriate diet and drugs, especially statins
Today, the CRI represents a pathology not only important for the patient and his family, but since it affects just under the 10% of the Italian general population, it also represents a very important social, organizational and economic problem. This is especially true when considering the costs of end-stage renal failure requiring replacement dialysis and renal transplantation. Prevention of progression of CRI automatically leads to prevention of the cardiovascular risk associated with CRI.
The therapeutic approach must be particularly articulated, starting with a control of body weight to avoid overweight, not only with a control of caloric intake, but above all with adequate progressive physical activity. In fact, the relationship between excess is increasingly evident. ponderal disease and nephropathy, which until recently was thought to be a primary focal glomerulosclerosis.
Another therapeutic cornerstone must be the absolute abolition of smoking, increasingly recognized not only as a cause of tumors and not only lungs, but also in other locations, in particular the bladder; but smoking is above all considered a very important cardiovascular risk factor and the progression of renal disease, especially in diabetics.
A dietary education, which avoids the excessive intake of proteins, phosphorus and sodium is important from the earliest stages of the CRI, together with a correct caloric intake. Sodium restriction is important for the control of any hypertension, to reduce the possible presence of proteinuria and, in the most advanced stages of CRI, to avoid the risk of salt and water overload up to pulmonary edema.
Additional dietary restrictions may be necessary in the more advanced stages of chronic renal failure, particularly paying close attention to potassium levels, as high blood potassium levels can cause severe changes in heart rhythm up to stopping, but keep this in mind that the prevention of the risk of malnutrition must always be a top priority.
The correction of metabolic acidosis with a predominantly vegetarian diet and possibly with sodium bicarbonate supplements is also essential to reduce nausea, which often interferes with an adequate dietary intake and consequently causes malnutrition, also favored by the protein catabolism induced by metabolic acidosis.
The treatment of arterial hypertension and the reduction of proteinuria are the therapeutic cornerstones for slowing the progression of CRI. In this regard, ACE inhibitor and sartanic drugs are considered first choice in the presence of proteinuria.
The control of dyslipidemia with physical activity, diet and possibly drugs is most appropriate, given the high cardiovascular risk of these patients.
The partial correction of the anemia of CRF patients improves the quality of their life and their psycho-physical performance and improves the cardiovascular situation, also avoiding the risk of transfusion.
The therapy of the CRI must be the least invasive possible, intervening only in correcting any dietary errors, without possibly upsetting the patient's dietary habits, in order not to heavily interfere in his daily, family and social life and therefore in his quality of life.
Author: Prof Francesco Locatelli, Scientific Director of the Department of Nephrology, Dialysis and Renal Transplant at the A. Manzoni Hospital in Lecco
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