Everything knows: a large inventory of treatment measures to control the progression of chronic kidney disease and delay the decline of renal function
Tianjin University TEDA Hospital Li Qing
In general, chronic kidney disease is irreversible, and the doctor's active treatment aims to stop or delay the progression of kidney disease. At present, drugs or measures that are recognized as having the effect of "protecting the kidneys" only delay the kidney damage, rather than curing or reversing them.
So what are the specific drugs or measures to control the progression of chronic kidney disease and delay the decline of renal function?
First of all, what I am taking stock of today is the treatment of chronic kidney disease.
Various acute kidney injuries, such as renal hypoperfusion caused by renal ischemia, acute tubular interstitial injury caused by certain drugs, acute obstructive nephropathy caused by urinary tract obstruction, etc., when the acute factors are eliminated, renal function will partially or even completely return to normal.
These acute kidney injuries are not what I'm going to talk about today.
1. Treatment for the cause
Controlling the cause and treating the primary disease can fundamentally control the progression of chronic kidney disease.
Chronic kidney disease is not a disease, but a general term for kidney damage caused by various causes. Before treatment of kidney disease, it is important to determine the cause.
At present, the three major causes of chronic kidney disease in China are diabetes, primary glomerulonephritis and hypertension, while the three major causes in Europe, the United States and Japan are diabetes, hypertension and primary glomerulonephritis.
The root cause of diabetic nephropathy is hyperglycemia, so to strictly control blood sugar, the hypoglycemic drugs SGLT2 inhibitors with renal protective effects (Liegent hypoglycemic drugs) and GLP-1 receptor agonists (peptide hypoglycemic drugs) are preferred, which are introduced later. On the basis of the two, other types of hypoglycemic drugs can be combined.
Primary glomerulonephritis, as well as systemic lupus erythematosus, systemic small-vesselritis nephritis, purpura nephritis, etc., are all autoimmune injuries involved in the pathogenesis process, so for those who meet the conditions, immunotherapy is generally suppressed, including the use of glucocorticoids, or the use of a combination of immunosuppressants.
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The root cause of hypertensive nephropathy is hypertension, so it is necessary to reduce blood pressure, preferably ARB (sartan antihypertensive drugs) or ACEI (praline antihypertensive drugs) with renal protective effects and the newly marketed ARNI (sakuba triacchartan), which will be introduced later. On this basis, other types of antihypertensive drugs can be combined.
Gouty nephropathy should lower uric acid, obesity-related nephropathy should lose weight, and drug-inducing nephropathy should be discontinued.
ARB (sartan antihypertensive drugs) or ACEI (praline antihypertensive drugs) and ARNI (sakuba tri valsartan)
Both ARB and ACEI are antagonists of the renin-angiotensin-aldosterone system, both work against angiotensin II, arb blocks its receptors, and ACE inhibitors reduce its production.
Both are antihypertensive drugs, but 20 years ago, it has been clinically found that the two have anti-urine protein and renal protective effects at the same time as lowering blood pressure.
For example, the 2001 RENAAL study and the IDNT study have demonstrated that losartan and irbesartan can benefit from renal hard endpoints, delay renal decline, and reduce the incidence of death from uremia and kidney disease, respectively.
ARNI (sacobatri valsartan) is a cocrystalline drug of cerebral liningase inhibitors and ARB, and large clinical studies have confirmed that the protective effect of sakubatri valsartan on the kidneys is superior to that of the classic kidney protection drug enalapril, see figure.
ACE Inhibitor, ARB and ARNI are the core treatment drugs for various chronic kidney diseases at present, no matter what the cause of chronic kidney disease, as long as there are no contraindications, they should be used as much as possible, and should be used throughout the treatment of chronic kidney disease.
ACE Inhibitor is not recommended in combination with two classes of drugs.
To control blood pressure, the three can use the usual dose, and in order to reduce proteinuria, often 2 to 4 times the dose is required.
Hypertension and proteinuria are major risk factors for the progression of chronic kidney disease, while controlling blood pressure and urine protein standards can delay nephropathy progression. In chronic kidney disease, blood pressure should be controlled below 130/80 mmHg. However, blood pressure intolerance, such as systolic blood pressure below 110 mmHg or significant orthostatic hypotension, may be considered to reduce the dose or discontinue the drug.
For chronic kidney disease, urine protein quantification is best controlled below 0.3g/day.
III. SGLT2 inhibitors (liecinoid hypoglycemic drugs)
SGLT2 inhibitors (liecinoid hypoglycemic drugs) are a class of newly marketed hypoglycemic drugs. Cardiovascular safety studies that must be completed before marketing (such as the CANVAS study of kagliflozin, the DECLARE study of dapagliflozin and the EMPA-RGE study of empagliflozin) have been found that SGLT2 inhibitors have hypontic protein and renal protection in addition to hypoglycemic.
Caspagliflozin therefore restarted a CREDENCE study, with diabetes mellitus and chronic kidney disease as the main observations, with hard renal endpoints such as serum creatinine multiplication, progression to end-stage renal disease, and renal or cardiovascular death as the main observation indicators. The results showed that caspagliflozin significantly reduced the risk of occurrence of renal composite hard endpoints by up to 30%, as shown in the figure.
Kapogliflozin can also significantly reduce proteinuria in patients with diabetes mellitus and chronic kidney disease, see figure, and greatly delay the decline rate of renal function in patients with diabetes mellitus and chronic kidney disease, see figure.
Dapa-CKD study was conducted in a large-scale clinical study of various chronic kidney diseases (including diabetic nephropathy and non-diabetic nephropathy), and it was found that dapagliflozin can significantly reduce the risk of developing the renal complex hard endpoints of chronic kidney disease (end-stage renal disease, serum creatinine multiplication, renal or cardiovascular death) by up to 39%, as shown in the figure.
At present, SGLT2 inhibitors have been approved for non-diabetic nephropathy with proteinuria due to their hypotropic protein and renal protective effects, in addition to being recommended as the preferred drug for diabetes mellitus with chronic kidney disease, such as IgA nephropathy, membranous nephropathy and other indications.
It is currently believed that sartan-type antihypertensive drugs and liergine hypoglycemic drugs are the best combination of treatment for various chronic kidney diseases, including diabetic nephropathy and non-diabetic nephropathy dominated by proteinuria.
Fourth, the third generation of aldosterone antagonists
In October 2020, the results of the FIDELIO-DKD study were announced, showing that the aldosterone antagonist Finerenone (tentatively translated as "nonelidone") can significantly reduce the renal compound endpoint event in patients with chronic kidney disease combined with type 2 diabetes by 18%, delay the progression of slow nephropathy, and have a protective effect on both cardiovascular and renal diseases, as shown in the figure. This offers a new hope for the treatment of chronic kidney disease.
Finerenone is a third-generation aldosterone receptor antagonist, compared with the first generation of spironolactone and the second generation of eplerenone, has a higher selectivity and stronger affinity for aldosterone receptors, better therapeutic effect, less side effects, and better protective effects on the heart, kidneys, especially for patients with impaired renal function.
Whether the fidelio-DKD study also predicts that the first generation of spironolactone and the second generation of eplerenone also have cardiac and renal protective effects on people with chronic kidney disease and diabetes mellitus is still unknown.
5. GLP-1 receptor agonists
This is also a class of hypoglycemic drugs, and it has been confirmed that the GLP-1 receptor agonists with cardiac and renal benefits are liraglutide, dula glycopeptide and semegluotide (formerly translated as somaglutide), of which liraglutide is a daily preparation, injected subcutaneously once a day; dulaglutide and smeglutide are weekly preparations, and are injected subcutaneously once a week.
The LEADER study of liraglutide found that liraglutide significantly reduced the risk of complex renal events by 22%, as shown in the figure; the REWIND study of dulaglutide showed that dulaglutide can reduce the risk of complex kidney events by 15%, see figure; semegglutide can significantly reduce the risk of complex renal events by up to 36%, see figure.
However, careful observation found that the efficacy of the three for renal events mainly came from the effect of urinary protein, and there was no significant improvement in the above-mentioned renal complex hard endpoints (end-stage renal disease, serum creatinine multiplication, renal or cardiovascular death).
Sixth, control diet + open the same (compound α ketoacid)
Too much sodium intake, the higher the blood pressure, and the heavier the burden on the kidneys. Therefore, chronic kidney disease, regardless of kidney function, first of all, to control the intake of salt, it is recommended to be less than 5g of salt (or 2.5g of sodium) per day or less.
Glomerular filtration rate of more than 60 ml / min, in addition to controlling the intake of sodium, there are no special requirements on the diet. Of course, if it is diabetic nephropathy, it is also necessary to control the diet according to the dietary requirements of diabetes.
Glomerular filtration rate of less than 60ml / min, that is, patients with chronic kidney disease stage 3 and later, the diet should be strictly controlled, the overall diet requirements are low salt, low fat, high quality and low protein diet.
The recommended protein intake should be controlled below 0.6 to 0.8 g/day/kg body weight.
There seems to be a contradiction in the control of protein in patients with chronic renal failure. One is that the human metabolism needs protein, the other is to control the intake of protein, in order to meet the requirements of these two aspects, you can supplement essential amino acid drugs such as kaitong (α-ketoacid) under the premise of a very low protein diet.
Studies have found that kaitong plus a low-protein diet can effectively delay the progression of slow kidney disease. A 2016 study showed that for patients with CKD (chronic kidney disease) stage 4 to 5, that is, glomerular filtration rate of 30 ml/min or less, the glomerular filtration rate decreased by an average of 3.2 ml/min per year compared with the low-protein diet group; a 2009 study showed that for patients with CKD (chronic kidney disease) stage 3 to 4, that is, glomerular filtration rate of 60 ml/min, compared with the low-protein diet group, After 6 months of prescribed therapy, the decrease in glomerular filtration rate in patients was slowed by 64%. Undoubtedly, Kaitong plus low-protein diet plays an important role in improving kidney function and delaying disease progression.
Seventh, do not use drugs indiscriminately
This is something that is difficult to express.
There are a large number of drugs on the market with "kidney protection, kidney benefit, kidney protection, strong kidney", and their protective effect on kidney function has hardly been confirmed by large-scale clinical studies designed by science. Some of these drugs may be harmless, but some may have the opposite effect.
For the kidneys, not harming is the best protection, and not taking drugs indiscriminately may be the best treatment.