1. Characteristics of CKD in the elderly
Chronic kidney disease (CKD) in the elderly is characterized by: ① atypical clinical manifestations, easy to miss or misdiagnose. ②Elderly patients are prone to combined underlying diseases, poor prognosis and high mortality. In addition, some etiologies are less common in younger patients, such as prerenal azotemia caused by blood volume deficiency, postrenal azotemia caused by prostate disease, renal injury caused by vascular degenerative changes, drug-induced renal failure, etc. The causes of CKD in the elderly are, in order of prevalence: proliferative-sclerotic lesions (36.5%), renal vascular lesions (25.3%), proliferative active lesions (12.6%), amyloidosis (6.9%), and hereditary nephropathy (6%). Our 06 survey on renal pathology in the elderly (>60 years old) showed that secondary causes accounted for 61.9%, in order of proportion: systemic vasculitis (38.1%), multiple myeloma (23.1%), lupus nephritis (23.1%), diabetic nephropathy (7.1%), amyloidosis (7.1%); and the three highest proportions of primary glomerular diseases were membranous nephropathy (25%), IgA nephropathy (14%) and microscopic lesions (12.5%) [1]. The results of the Andrew cohort study in 2004 showed that the GFR of adults aged 20 years was 111 mL/min; the CFR decreased by 4.9 mL/min for every 10 years of age thereafter, and by 10 mL/min for every 10 years after the age of 50 years, and by analogy, the GFR of a normal population should be about 66 mL/min at the age of 80 years. The decrease in renal reserve function is likely to cause drug-related kidney damage and other acute exacerbations. Wei Lianbo, Department of Nephrology, Zhujiang Hospital, Southern Medical University
2. Risk factors for acute exacerbation of CKD in the elderly
Due to the degenerative changes of the kidneys and the combination of multiple diseases in the elderly, the renal function of elderly patients with CKD can decline sharply under the effect of certain triggers. The Dutch PREVEND study found that gender, hypertension, diabetes mellitus and smoking were independent risk factors for CKD. Manuel et al. found that the blood creatinine and uric acid levels were higher and the erythrocyte specific volume level was lower in elderly people with acute exacerbation of CKD [2]. Comprehensive domestic multi-point report, the risk factors for acute exacerbation of CKD in the elderly in China are, in order: infection, nephrotoxic drugs, hypovolemia and anemia; and in middle-aged and young people, malignant hypertension and progression of primary disease. Most risk factors for acute exacerbation of CKD in the elderly can be prevented and intervened, and if corrected in time, the arrival of end-stage renal disease (ESRD) can be delayed [3-4].
2,1 Infection:
Infection is the leading cause of acute exacerbation in the elderly CKD population in China. Elderly CKD patients are prone to complicate systemic infections and further aggravate renal impairment due to decreased immune function. patients with CKD are highly susceptible to concurrent infections, especially pulmonary and urinary tract infections, and the mortality rate will increase dramatically when infections occur. Domestic reports have found that the age of patients with CKD complicated by pulmonary infection is 60-75 years old, and the recovery and improvement rate can be as high as 73.8% if the treatment is timely and effective [5]. Therefore, fever, pyuria and primary diseases with easy complication of infection in elderly CKD patients should be paid attention to, and should be treated actively once detected.
2. 2 Nephrotoxic drugs
Drug-related renal damage is one of the most important causes of acute exacerbation in elderly patients with CKD, and there is a significant trend of increase in recent years. On the one hand, patients with chronic renal impairment have increased susceptibility to drug side effects, and on the other hand, due to renal impairment, drugs tend to accumulate in the body. It is reported that the drugs associated with acute exacerbation in Chinese elderly patients with CKD are: contrast agents, ACEI/ARB, Chinese herbs, aminoglycosides, NSAIDs, and other antibiotics in order of prevalence.
The Rich study found that the risk of AKI after imaging was 19 times higher in young and middle-aged CKD patients in the age group >55 years. Domestic and international studies have reported that advanced age, diabetes mellitus, and hyperosmolar ionic contrast agents are all risk factors for contrast renal injury and should be avoided together [6].
2,3 Hypovolemia and hypertension
Relevant domestic studies have shown that, in contrast to young and middle-aged people, the proportion of acute exacerbations of CKD caused by hypovolemia is much higher than that of hypertensive factors in the elderly population. Increased thirst threshold and decreased responsiveness of antidiuretic hormone and aldosterone in elderly CKD patients lead to impaired regulation of water balance. Some other common diseases in the elderly such as infection, fever, sweating, impaired consciousness, diabetes mellitus, and diuretic use for gastrointestinal diseases are common triggers for dehydration. Cardiac and renal insufficiency, severe liver disease with ascites and diuresis, and the use of ACEI/ARB drugs in renal arteriosclerotic stenosis are all known to cause acute kidney damage (AKI) due to insufficient renal blood perfusion. In elderly patients with CKD, glomerular filtration rate decreases due to insufficient blood volume, which further impairs renal function and leads to acute exacerbation of CKD [7].
Hypertension in elderly CKD patients is characterized by the prevalence of simple systolic hypertension (ISH), and the status quo is a high rate of awareness and treatment and a low rate of control. In the US CRIC study, the awareness rate of hypertension in CKD patients was 98.9% and the treatment rate was 98.3%, but the blood pressure control rate was less than 50%. In contrast, a survey on the treatment and control of hypertension in CKD patients in 20 hospitals in China from 2004 to 2005 found that the awareness rate of hypertension was 90.6%, the treatment rate was 86.8%, and the blood pressure control rate was 7.8%, suggesting that there is still a gap between the treatment and control rate of hypertension in elderly CKD patients in China compared with developed countries such as the United States [8].
2,4 Obstructive nephropathy
The incidence of AKI due to obstructive nephropathy in elderly CKD patients is about 2.5 times higher than that in young and middle-aged CKD patients. The common causes of obstructive nephropathy can be divided into 3 categories: intraluminal, intramural and extramural. The common causes of intraluminal obstruction are renal stones, blood clots or necrotic detached tissue from the renal papillae, which tend to occur in the urological stenosis. Obstruction caused by intramural lesions is divided into functional and organic, the former being more common in neurogenic bladder and the latter seen in inflammatory ureteral strictures or migratory epithelial malignancies. Obstruction caused by extra-mural lesions is mainly seen in men with prostatic hypertrophy and retroperitoneal fibrosis. Because of the atypical symptoms in the elderly, the first symptom is usually oliguria or anuria, and the first symptom is colic and or hematuria, which is less common. Urinary stones are the first cause of obstructive nephropathy in the young and middle-aged population, and they are also common in the elderly [9].
2.5 Anemia and malnutrition
Anemia is one of the common and serious complications of late CKD and one of the important factors in the exacerbation of CKD in the elderly. Chronic anemia leads to tissue hypoxia, congestive heart failure, and depressed immune function in CKD patients, resulting in decreased quality of life and survival. Inadequate intake and increased catabolism are important causes of malnutrition in elderly CKD patients, with an incidence of more than 50%. Severe malnutrition can lead to cachexia, induce acute exacerbation of CKD and cardiovascular events, and is an independent risk factor in the progression of CKD. Malnutrition can lead to hypoproteinemia, which in turn leads to edema and organ dysfunction, decreased ability of the blood to carry drugs, decreased non-specific immunity, and aggravated infection. Studies have shown that 90% of patients with severe malnutrition have a history of recurrent co-infections, and the 5-year survival rate of combined hypoproteinemia is less than 50%. Therefore, nutritional and metabolic support is needed to improve the immunity of elderly patients and reduce the incidence of infections and mortality [10].
3. Prevention and treatment of acute exacerbation of CKD in the elderly
Once exacerbations occur clinically in elderly CKD patients, it is difficult to improve or maintain normal renal function. The measures for acute exacerbation of chronic CKD in various guidelines are based on prevention and control of risk factors as the main means. The preventive management approach is consistent with that of adults in most aspects, but still differs in some target management details due to some special conditions of the elderly, as summarized below.
3.1 Antibiotic use
When elderly CKD patients develop infectious complications, antibiotics should be selected reasonably according to the infectious etiology and drug resistance. The specific principles are: 1. Select antibiotics according to the severity of the infection, the type of pathogenic bacteria and drug sensitivity results; 2. Adjust antibiotics according to GFR, which can be used to calculate the drug dose adjustment factor (Q) data (Q=1-[percentage of drug excreted by kidney (1-1/ Scr]) and adjust the dose of each administration without changing the dosing interval; 3. Try not to use antibiotics that are metabolized by kidney, such as Erythromycin, lincomycin, chloramphenicol, cefoperazone, ceftriaxone sodium, etc. are mainly metabolized and excreted by the hepatobiliary system, and in elderly patients with CKD, the blood concentration does not increase significantly, and the drug itself is less toxic, so the original dose can be maintained or slightly reduced; 4. Do not use nephrotoxic antibiotics, such as aminoglycosides, etc. [11].
3.2 Blood volume maintenance
Domestic studies have found that the triggers of hypovolemia in the Chinese elderly CKD population are mainly complications leading to insufficient perfusion of renal units, bleeding and postoperative fluid loss, and interventions are still based on preventive control. If AKI occurs due to inadequate perfusion of the renal unit caused by infection, cardiovascular pathology, or improper therapeutic measures, the key to treatment at this time is timely control of various comorbidities, correction of hypovolemia and strengthening of anti-infective therapy to restore renal perfusion. In case of septic shock, low-dose norepinephrine should be applied to elevate blood pressure to ensure that the mean arterial pressure is above 80 mmHg to restore adequate blood supply to the kidney; maintain central venous pressure at 8-250 pxH2O, either too high or too low central venous pressure will affect transrenal filtration pressure and lead to a decrease in GFR; in patients after major cardiac surgery, if the patient’s cardiac function is extremely poor, short-term postoperative applications such as aortic balloon counterpulsation are recommended. methods such as aortic balloon counterpulsation to maintain cardiac output function and to strictly control volume balance [12].
3.3 Contrast agent renal injury prevention
Before contrast injection in elderly patients with CKD, it is best to correct all risk factors as much as possible before contrast, and to use the contrast agent reasonably according to the patient’s specific situation, such as selecting a hypotonic contrast agent. And prophylactic hydration therapy should be performed within 12h before and after contrast. There is no evidence-based medical evidence reporting specific drugs, but some small samples have reported that some drugs such as N-acetylcysteine, fenoldopam, and atrial peptides may be able to reduce the risk of contrast renal damage. In addition, prophylactic blood purification therapy is currently more controversial, with some studies suggesting that it is effective and some suggesting that it is not only ineffective but harmful. Some national experience reports recommend not to perform dialysis in patients with Scr <4 mg/dL. When Scr is higher than this value, or when it is accompanied by significant electrolyte disturbances, acidosis, heart failure, or water intoxication, prophylactic dialysis or other hemodialysis treatment is given to prevent contrast renal damage [6].
3,4 Treatment of obstructive nephropathy
Because elderly patients with CKD with obstructive nephropathy are prone to AKI, it is necessary to remove the obstruction as soon as possible. It is generally believed that if the obstruction is removed within 1 week, the kidney can fully recover its original function, but if the obstruction is complete for more than 1 week, it is difficult to fully recover the kidney function after removing the obstruction. For complete obstruction of 2 weeks, the glomerular filtration rate can only be restored to 70% within 3~4 months after lifting the obstruction, and for complete obstruction of more than 4 weeks, the glomerular filtration rate can only be restored to 30% after lifting the obstruction. In complete obstruction of more than 6 weeks, even if the obstruction is removed, it is extremely difficult to restore renal function. After 8 weeks, renal function can hardly be restored. The usual treatment is drainage by indwelling ureteral cannula or surgical treatment to relieve the compression. If there is severe acidosis and electrolyte imbalance, dialysis treatment should be given and surgical treatment should be transferred after the condition is in remission [13].
3.5 Blood pressure management
There is still controversy about the target value of blood pressure lowering in the elderly. The Chinese guidelines for the prevention and treatment of hypertension recommend lowering systolic blood pressure to <150 mmhg in the elderly, with further reductions if tolerated. 2007 European Society of Hypertension (ESH) recommends lowering blood pressure to <130/80 mmHg in elderly patients with CKD. 2011 US consensus on geriatric hypertension recommends a target blood pressure of <140/90 mmHg for those under 70 years of age; 70-79 years of age to control mean systolic blood pressure at 135 mmHg; special emphasis is placed on avoiding systolic blood pressure <135 mmhg and diastolic blood pressure <65 mmhg in patients over 80 years of age. The selection of antihypertensive drugs for elderly patients needs to emphasize individualized treatment. Several hypertension guidelines state that combination therapy is usually required to achieve blood pressure targets in CKD patients, and CCB + renin angiotensin aldosterone system (RAAS) inhibitors are their preferred recommended drug combinations. However, the expert consensus on protein nutritional therapy in CKD suggests that ACEI/ARB analogs in the elderly still need to be applied starting with small amounts to avoid excessive blood pressure lowering . Also, non-pharmacological interventions (e.g., lifestyle improvement, salt restriction, and weight reduction) are important [14-15].
3,6 Protein nutrition management
Elderly people show mostly physiological decline in the function of internal organs, which may cause malnutrition if protein intake is further restricted. Also, with increasing age and further aggravation of malnutrition, their risk of developing infections gradually accumulates. In a prospective study in China, it was suggested that malnutrition may occur or be further aggravated in elderly people who are given a low-protein diet alone. In contrast, serum albumin and prealbumin levels improved significantly in patients taking kaito preparations compared to those not taking them. brunori et al. found that a low-protein diet supplemented with kaito delayed entry into dialysis in 56 elderly non-diabetic CKD patients. The prospective multicenter DODE study showed that elderly patients treated with a very low protein diet plus alpha-keto acid had good nutritional status over an 18-month period compared with renal replacement therapy [16].
3,7 Renal replacement therapy
The KDIGO-AKI clinical guidelines recommend that RRT should be started urgently in acute exacerbations of CKD, including in the elderly, when life-threatening changes in volume, electrolyte and acid-base balance occur. The decision to initiate RRT should be based on the full clinical picture and not only on the creatinine level. However, premature RRT can induce the risk of venous thrombosis, infection, and bleeding, especially in elderly patients with CKD [2].