Summarize The Current Status Of Kidney Disease in China

From March 30 to April 2, 2023, the 2023 International Society of Nephrology (ISN) World Congress of Nephrology (WCN) and the 21st Congress of the Asia-Pacific Society of Nephrology (APCN) will be held in Bangkok, Thailand. At this conference, Prof. Zhang Hong and Prof. Zhang Luxia from Peking University First Hospital summarized the epidemiology, clinical manifestations, and current status of diagnosis and treatment of nephropathy in China1,2.

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Prof. Hong Zhang: Current status of IgA nephropathy in China

Professor Zhang Hong introduced the current situation of immunoglobulin A (IgA) nephropathy in China from three aspects: epidemiology, clinical symptoms, and treatment. Based on these differences, Professor Zhang Hong believes that IgA nephropathy may have certain heterogeneity, that is, its pathogenesis may be different in different populations. At the same time, Professor Zhang Hong said that compared with other populations, immunosuppressants are more suitable for Chinese IgA nephropathy patients.

01 Epidemiology of IgA nephropathy

IgA nephropathy is the most common primary glomerular disease in the world, and it is also the most common glomerular disease in China, but the incidence rate varies greatly among different countries and regions, and the incidence rate of IgA nephropathy in Asia is the highest (About 40%~50% of patients with primary glomerular disease).

Differences in incidence also result in differences in the prevalence of IgA nephropathy. In China, 54.3% of patients with primary glomerular disease had IgA nephropathy after confirmation by renal biopsy. Other Asian countries accounted for more than 28%, but the United States, Brazil, and other countries accounted for about 20%, while African Morocco accounted for only 12.0%. It can be seen that the incidence of IgA nephropathy in China is high, the prevalence rate is high, and the number of patients is large. It is a common kidney disease among Chinese nephrologists.

02 Clinical manifestations of IgA nephropathy

Compared with other countries, there are two important differences in the clinical manifestations of patients with IgA nephropathy in China, namely estimated glomerular filtration rate (eGFR) and pathological type.

In terms of eGFR, the eGFR of foreign patients with IgA nephropathy is generally lower than that of Chinese patients with IgA nephropathy. Between 1.73㎡ (several Chinese population studies).

Among the pathological types, the M1 and C1+C2 types accounted for a large proportion of Chinese IgA nephropathy patients. Among them, the M1 type accounted for more than 40%, and the C1+C2 accounted for between 37% and 59.5%. However, the M1 type accounted for only 28% of the foreign population, and the C1+C2 accounted for only 11%.

In addition, compared with Caucasians, Chinese patients with IgA nephropathy had a higher correlation of eGFR decline rate with proteinuria. If the level of proteinuria is the same, eGFR is more likely to decrease in Chinese patients with IgA nephropathy.

At the same time, studies have also confirmed that after adjusting for age, gender, and drug use, compared with other populations, the decline rate of eGFR in patients with IgA nephropathy in the Asia-Pacific region is higher, with an absolute difference of 1.62ml/min/1.73㎡ (95% CI, - 3.19~-0.50; P=0.04). That is, after adjusting for age, gender, and drug use, patients in the Asia-Pacific region were more likely to develop the end-stage renal disease (HR=1.56; 95% CI, 1.10-2.22; P=0.01) and eGFR compared with other populations Decrease ≥50% (HR = 1.81; 95% CI, 1.25-2.62; P = 0.002).

03 IgA nephropathy treatment plan

The biggest difference between patients with IgA nephropathy in China and patients with IgA nephropathy in other countries is the utilization rate of immunosuppressive therapy. Most (19%-54.7%) patients with IgA nephropathy in China and Japan received immunosuppressant therapy, while only a small number of patients in Canada (15.7%) and France (19.6%) received immunosuppressant therapy. Currently, immunosuppressants commonly used in patients with IgA nephropathy include glucocorticoids and mycophenolate mofetil (MMF). So, what are the effects of these two drugs on IgA nephropathy?

① Glucocorticoids

Regarding glucocorticoids, the Testing study and the STOP IgAN study gave different answers. The Testing study found that glucocorticoids can reduce the risk of renal composite endpoints (end-stage renal disease, death due to renal disease, or eGFR decline ≥ 40%) in patients (HR=0.37; 95% CI, 0.17-0.85; P=0.019), while the STOP IgAN study had no similar results.

Professor Zhang Hong pointed out that the biggest difference between the Testing study and the STOP IgAN study is the difference in the participating populations. The IgA nephropathy patients participating in the Testing study were from China, Australia, India, Canada, and Malaysia, among which 75.3% of the patients were from China, while the patients in the STOP IgAN study were all from Germany.

In addition, the inclusion and exclusion criteria of the two studies were somewhat different. The population included in the Testing study was proteinuria > 1g; at the same time, different intervention methods were adopted according to the baseline eGFR. For example, patients with an eGFR of 20-120ml/min/1.73㎡ received full-dose glucocorticoid therapy, while patients with an eGFR of 30-120ml /min/1.73㎡ patients received reduced doses of glucocorticoids. In the STOP-IgAN study, the proteinuria level of the patients was >0.75g, and the eGFR was >30ml/min/1.73㎡, but there was no difference in the dosage of glucocorticoids. At the same time, there were some differences in the pathological types of the participants in the two studies. The above comparisons suggest that glucocorticoids may be more effective for patients with IgA nephropathy in China or the Asia-Pacific region.

②MMF

A meta-analysis (n=347) including 8 studies showed that compared with placebo or glucocorticoid alone, MMF monotherapy had better efficacy but more adverse events. Compared with another immunosuppressant + glucocorticoid therapy, MMF has a better curative effect, can reduce the risk of creatinine doubling and progression to end-stage renal disease, and has a lower incidence of adverse events. However, most of the evidence that MMF is beneficial for IgA nephropathy comes from Asian populations.

04 Heterogeneity of IgA nephropathy

All of the above evidence suggests that patients with IgA nephropathy in the Asia-Pacific region and Europe differ considerably in terms of epidemiology, clinical presentation, and treatment options. Basic research has found that compared with Caucasian patients, Chinese IgA nephropathy patients have lower serum galactose-deficient IgA1 (Gd-IgA1) levels (P<0.0001), and Asian IgA nephropathy patients have unique gene mutation sites, C1GALT1 also exists in different variants.

In terms of compliment, the Asian population is also quite different from the Caucasian population. From the perspective of the alternative pathway (AP), the protective genes of the Chinese population were significantly lower than those of the Caucasian population. In the lectin pathway (LP), Asians have a higher risk of C4d deposition than Caucasians.

Existing studies have shown that differences in complement activation in patients with IgA nephropathy can be reflected in glomerular vascular lesions and Gd-IgA1 immune complex deposition, which may lead to differences in clinical manifestations and therapeutic effects. Because the pathogenesis of IgA nephropathy is currently unknown, it is unclear whether differences in biomarkers (Gd-IgA1 levels), genes, and complement systems are the entire source of heterogeneity in patients with IgA nephropathy.

In general, the Chinese population is more prone to IgA nephropathy. Chinese patients with IgA nephropathy respond better to immunosuppressive therapy than other populations. In the future, we should pay more attention to the pathological mechanism of IgA nephropathy and carry out individualized medical services.

Professor Luxia Zhang: Big Data and Kidney Disease

At present, China has entered the digital age, and many industries generate a lot of data, and the medical industry is no exception. Big data can collect information from different sources, then analyze the information to reveal trends, and insights that cannot be found by other methods, and thus create solutions.

Professor Zhang Luxia revealed the integration of China's big data industry and medical care in many ways from big to small, from surface to a point. These new achievements will comprehensively promote the progress of kidney disease research and management.

01 Big Data and Medicine

At present, the integration of big data, AI, and other information technologies with medical care is getting closer and closer. It is worth noting that the "big insights" provided by big data can solve some of the pain points of an existing medicine because big data has four important characteristics: volume, variety, rapidity ( Velocity), and authenticity (Veracity). The above four characteristics lead to differences between big data analysis and traditional data analysis and research. In this context, data science came into being. Data science is a science that uses AI, big data, and powerful computing power (hardware) to integrate and process data to form corresponding information and knowledge, and finally to form practical and feasible practical opinions.

To better serve medicine, data science has produced a branch of health data science (HDS). Currently, HDS is facing three important challenges, namely hypothesis-driven vs data-driven, real-world vs research scenarios, and interdisciplinary challenges.

① Hypothesis-driven vs data-driven

Hypothesis-driven is a scientific reasoning method that asks questions, formulates test plans, collects data, and conducts analysis and demonstration through conjectures and assumptions. It is also a common design method for current clinical research.

Data-driven is another reasoning method, and its core is divided into three steps:

1) Collect massive data; 2) Data modeling and data analysis; 3) Data feedback.

Data modeling and analysis will provide guidance and decision-making suggestions in an automated, intelligent, and scientific manner.

In short, HDS will no longer produce the two processes of proposing conjectures and designing experiments, but will directly start from existing data, combine AI and computing power, and directly provide decision-making suggestions for users (doctors) (

②Real world vs research scenarios

At present, clinical research cannot fully simulate the real world, and there is a certain lag in making conjectures, which is the deficiency of previous research methods. However, the four characteristics of big data can record medical information in the real world in a real, rapid, multi-faceted, and comprehensive manner, enabling HDS to quickly give relevant recommendations that are comprehensive and in line with clinical practice.

③ Interdisciplinary challenges

Currently, the biggest challenge for HDS is how to effectively integrate clinicians, electronics technicians, and policymakers. Since HDS is an emerging subject, other industries know little about it, and some proper terms and concepts need to be popularized. So that's a challenge right now.

02 HDS and kidney health

① Extensive data sources

Data sources for HDS are diverse and new sources are constantly being developed. Currently, the sources of HDS data most relevant to nephrologists and researchers are:

Epidemiological studies (such as the NHANES study);

Large cohort studies (eg, DOPPS study, iNet-CKD);

Patient registry data (e.g. USRD, UK Renal Registry); clinical studies.

In addition, electronic health records and medical insurance data are also important sources of HDS. They were not originally developed for research purposes, and as such, the data are large and varied. When they are associated with other data, they can better serve clinical decision-making, which is one of the directions for future research. However, due to the poor quality of electronic health records and medical insurance data, the requirements for data analysis and management are relatively high. Some studies in recent years have found that data related to molecular biology, mobile phones, and social media can also be effective sources of HDS.

②Existing achievements of HDS

In China, HDS is developing rapidly, and the Kidney Disease Data Network (CK-NET; Link: www.chinakidney.net) is one of the most outstanding achievements. The mission of CK-NET is to integrate various data on kidney diseases in China and use cutting-edge technology to provide data-driven evidence for policy decisions, strengthen academic research, and promote effective disease management in the field of kidneys.

CK-Net regularly releases scientific reports on kidney diseases in China, including three chapters, chronic kidney disease (CKD), end-stage kidney disease (ESKD), and special patients, covering most of the kidney disease patients and accurately showing The status quo of kidney disease is helpful for drug development, policy formulation and establishment of related prevention and control programs.

In addition, HDS plays an important role in the prediction of renal disease progression and the study of renal pathology. Machine learning and other methods can be used to predict the progression of kidney disease in patients and to automatically detect kidney biopsy samples and draw biopsy conclusions.

In terms of research, HDS can conduct real-world research. Compared with traditional research, real-world research can include more people, the data is more real-time, and it is closer to clinical practice. In addition, HDS can make risk stratification, new mechanistic insight, and targeted therapy of subpopulations easier.

HDS is already changing the way of diagnosis and treatment. Take Minuteful Kidney as an example. This is a mobile app + self-test test strip product that allows patients to check the level of proteinuria at home. This will change the screening, diagnosis,, and follow-up of CKD patients and contribute to the ultimate prognosis of patients. It is reported that the product has been launched in the United States.

Can Cistanche treat kidney disease?

Cistanche has been traditionally used in Chinese medicine to treat kidney disorders such as renal failure, kidney deficiency, and urinary incontinence. Recent studies have also shown that cistanche may have potential benefits for kidney health. Cistanche is believed to have immunomodulatory, anti-inflammatory, and antioxidant properties that may help protect the kidneys from damage caused by oxidative stress and inflammation. It may also improve kidney function by promoting blood flow to the kidneys and increasing urine output. However, more studies are needed to fully understand the effects of cistanche on kidney disease and its safety and efficacy. It is important to consult with a healthcare professional before taking any herbal supplements, especially if you have a kidney condition.

References:

1. Hong Zhang, IgA Nephrology epidemiology, clinical pathological features, and treatment in China Mar 30, 2022. WCN Virtual Congress.

2. Luxia Zhang. Improving Kidney Health Through Big Data and Data science. Mar 30, 2022. WCN Virtual Congress.