Is Diabetic Nephropathy The Sooner You Start Dialysis, The Better?

What is the final outcome of diabetic nephropathy?

If diabetic nephropathy is not effectively controlled, kidney function is gradually damaged, and it will develop into uremia. Chronic kidney disease is clinically staged according to the estimated glomerular filtration rate (eGFR). According to statistics, diabetic nephropathy has become the No. 1 cause of uremia in developed countries such as the United States, Europe, and Japan. Glomerulonephritis is currently the leading cause of uremia in China, followed by diabetic nephropathy. It is expected that in a few years, diabetic nephropathy will become the leading cause of uremia in China.

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Diabetic nephropathy has reached the stage of uremia, and the renal function cannot meet the normal physiological functions of the human body. Renal replacement therapy is required, including hemodialysis, peritoneal dialysis, and kidney transplantation. The effect of kidney transplantation is the best, but due to various factors, it is difficult to become the first choice for ordinary uremia patients, and most ordinary uremia patients choose dialysis treatment.

Is Diabetic Nephropathy the sooner you start dialysis, the better?

Is it necessary to replace the treatment in the period of uremia? If dialysis, is it better to have dialysis earlier or later? In the past, it was believed that as long as the uremic stage was reached, replacement therapy should be started. It was even once believed that dialysis should be advanced for diabetic nephropathy, but now it is found that the above point of view is inappropriate.

In 2010, Australia and New Zealand collaborated on a large clinical study (IDEAL study), which included 828 patients with uremia with an eGFR of 10-15ml/min, of which 355 patients had diabetes. All patients were randomly divided into the early dialysis group (eGFR 10-14ml/min) and the late dialysis group (eGFR 5-7ml/min), and the mean (median) follow-up was 3.6 years. It was found that there was no significant survival rate between the two groups. There were no (statistically) significant differences in cardiovascular events, infections, or dialysis complications.

However, the early dialysis group had higher treatment costs and lower satisfaction.

High cost, low satisfaction, and no benefit, why early dialysis?

The IDEAL study was designed to allow clinicians to decide when to initiate dialysis based on a patient's uremic symptoms, volume overload, and GFR. The results showed that 75.9% of patients in the later dialysis group started dialysis when their eGFR was greater than 7 ml/min. The latest guidelines suggest that dialysis preparation can be started when eGFR is <15ml/min

Based on the IDEAL study, most European and American guidelines recommend starting dialysis with an eGFR of 6-8 ml/min. The Kidney Disease Improvement Organization (KDIGO) guidelines published in 2013 suggested that an eGFR of 5-10ml/min is an appropriate time to start dialysis, while the Japanese guidelines recommend that for asymptomatic patients with uremia, an eGFR of 2-8ml/min is recommended. Start dialysis.

Of course, whether to start dialysis, in addition to considering eGFR, other systemic symptoms should also be considered. Not long ago, China issued the "Chinese Guidelines for Renal Replacement Therapy in End-Stage Diabetic Nephropathy", which regulates the timing and method of dialysis for diabetic nephropathy with uremia. The primary source of evidence for the new guidelines is also based on the IDEAL study [1].

The alternative treatments mentioned in the guideline include hemodialysis, peritoneal dialysis, and kidney transplantation. Since kidney transplantation involves many specialties, I will not discuss it here. The following mainly discusses hemodialysis and peritoneal dialysis.

The IDEAL study conducted a subgroup analysis of patients with diabetes, and the results showed that there was no significant difference in mortality between early dialysis and later dialysis patients compared with patients without diabetes. Currently, there is no evidence of an additional benefit from earlier initiation of dialysis in patients with end-stage diabetic nephropathy.

Patients who started dialysis later may have a lower mortality rate, but the quality of the evidence was not very high, according to a study in Taiwan. Considering that patients with diabetic nephropathy are more complicated with cardiovascular and cerebrovascular disease, lower extremity vascular disease, anemia, and other factors, appropriate early dialysis can be considered.

However, the "Chinese Guidelines for Renal Replacement Therapy for End-stage Diabetic Nephropathy" does not give the exact value of eGFR at the start of dialysis, but only suggests that when eGFR is less than 15ml/min, pre-dialysis preparations can be made. Dialysis treatment should be started, as indicated below:

①Unrelieved fatigue, nausea, vomiting, itching, etc.;

② hyperkalemia that is difficult to correct;

③ uncontrollable metabolic acidosis;

④ Uncontrollable water and sodium retention, refractory hypertension, severe edema, special attention should be paid to patients with congestive heart failure or acute pulmonary edema;

⑤ Uremic pericarditis;

⑥ Uremic encephalopathy and progressive neuropathy;

⑦ Other symptoms, signs, and auxiliary examination results that require dialysis shall be determined by the physician according to the specific clinical situation.

In other words, if there are no above-mentioned complications, according to the KDIGO guidelines, the timing of dialysis for end-stage diabetic nephropathy can also be later, such as eGFR 6~8ml/min. Other new drugs, such as potassium-lowering drug sodium zirconium cyclosilicate, sacubitril, and valsartan to correct heart failure, are also available for uremia patients who are difficult to correct hyperkalemia and refractory heart failure. Entering dialysis offers a solution.

Because hemodialysis will accelerate the decline of residual renal function, and this decline is irreversible, the choice of the timing of hemodialysis should be more careful.

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