Chinese Herbal Medicine for Proteinuria and Chronic Kidney Disease: From “Renal Micro-Masses” to Modern Kidney Research
Chronic kidney disease (CKD) can present with proteinuria, hematuria, edema, and a progressive decline in kidney function. In Traditional Chinese Medicine (TCM), chronic kidney disorders are not viewed solely as a state of deficiency. Some TCM nephrology specialists propose that prolonged kidney injury may involve an accumulation of dampness, blood stasis, turbidity, and pathological products within the kidney collaterals.
This concept has been described as “renal micro-masses” (腎微癥瘕). Rather than relying only on kidney-tonifying or astringent herbs, this approach combines methods such as replenishing Qi, removing dampness, improving blood circulation, clearing pathological heat, resolving turbidity, and dispersing chronic pathological accumulation.
Interestingly, some aspects of this traditional hypothesis can now be explored through modern concepts such as podocyte injury, glomerular endothelial dysfunction, chronic inflammation, extracellular matrix deposition, glomerulosclerosis, and renal fibrosis.
What Is the TCM Concept of “Renal Micro-Masses”?
In classical Chinese medicine, the term “Zheng Jia” (癥瘕) describes pathological accumulations that may involve blood stasis, phlegm, dampness, and other persistent pathological products.
When this concept is applied to chronic kidney disease, prolonged injury to the kidney collaterals is hypothesized to result in an interaction between blood stasis, dampness, turbidity, and toxins. This pathological state may contribute to persistent proteinuria and progressive deterioration of kidney function.
It is important to emphasize that “renal micro-masses” are not equivalent to renal fibrosis or glomerulosclerosis. They belong to different medical frameworks. However, the TCM concept can be treated as a research hypothesis and investigated using measurable biological markers involving podocyte injury, microvascular dysfunction, inflammation, extracellular matrix deposition, and fibrosis.
1. Shen Yan Fang: A TCM Formula for Proteinuria and Hematuria
Formula Composition
Shen Yan Fang:
Astragalus membranaceus (Huang Qi) 20 g, Saposhnikovia divaricata (Fang Feng) 15 g, Rubia cordifolia (Qian Cao) 15 g, Atractylodes macrocephala (Bai Zhu) 15 g, Cirsium setosum (Xiao Ji) 15 g, Euonymus alatus (Gui Jian Yu) 15 g, Malva verticillata seed (Dong Kui Zi) 15 g, Hedyotis diffusa (Bai Hua She She Cao) 15 g, Hirudo (Shui Zhi) 6 g, Lobelia chinensis (Ban Bian Lian) 15 g, Dioscorea hypoglauca (Bi Xie) 15 g, Dipsacus asper (Xu Duan) 15 g, Dioscorea opposita (Shan Yao) 15 g, Jiao San Xian 15 g each, Amomum kravanh (Bai Dou Kou) 15 g, Amomum villosum (Sha Ren) 15 g, Polyporus umbellatus (Zhu Ling) 15 g, Cornus officinalis (Shan Zhu Yu) 15 g, and prepared Glycyrrhiza (Zhi Gan Cao) 8 g.
How Is the Formula Designed?
Astragalus, Saposhnikovia, and Atractylodes form the basic structure of the traditional formula Yu Ping Feng San. The combination is traditionally used to replenish Qi and strengthen the body’s defensive functions.
Cirsium and Rubia are used to cool the blood, disperse blood stasis, and control bleeding, making them particularly relevant when hematuria accompanies proteinuria.
A particularly interesting group consists of Hedyotis diffusa, Euonymus alatus, Malva seed, Hirudo, and Lobelia chinensis. In the original clinical theory, these herbs were used to clear pathological heat, promote blood circulation, disperse pathological accumulations, and reduce persistent proteinuria.
Dioscorea hypoglauca is used to resolve dampness and turbidity, while Dipsacus and Cornus officinalis support the kidney system. Dioscorea opposita, cardamom, Amomum villosum, and Jiao San Xian support digestive function and dampness metabolism. Polyporus is added when fluid retention is present.
The overall strategy can therefore be summarized as: replenish Qi, remove dampness, improve circulation, resolve pathological accumulation, and support the kidney.
2. Shen Shuai Fang: A Formula for Chronic Renal Insufficiency
Formula Composition
Shen Shuai Fang:
Astragalus (Huang Qi) 20 g, Angelica sinensis (Dang Gui) 15 g, Saposhnikovia (Fang Feng) 15 g, rhubarb (Da Huang) 15 g, Atractylodes macrocephala (Bai Zhu) 15 g, Areca seed (Bing Lang) 15 g, Cirsium (Xiao Ji) 15 g, immature bitter orange (Zhi Shi) 15 g, prepared Pinellia (Zhi Ban Xia) 15 g, Acorus (Shi Chang Pu) 15 g, cardamom (Bai Dou Kou) 15 g, citrus peel (Chen Pi) 15 g, Magnolia bark (Hou Po) 15 g, Chinese yam (Shan Yao) 15 g, Poria (Fu Ling) 15 g, Dipsacus (Xu Duan) 15 g, Amomum villosum (Sha Ren) 15 g, Jiao San Xian 15 g each, and prepared licorice (Zhi Gan Cao) 15 g.
The Concept of Removing “Turbidity” in Chronic Kidney Disease
This formula differs substantially from Shen Yan Fang. Its focus shifts from proteinuria and hematuria toward declining renal function, gastrointestinal symptoms, fluid retention, and the accumulation of what TCM describes as “turbidity.”
Six therapeutic strategies were proposed: aromatic transformation of turbidity, separation of clear and turbid substances, removal of dampness and turbidity, purging the intestines to eliminate turbidity, improving blood circulation to remove pathological accumulation, and clearing accumulated pathological toxins.
Rhubarb, Areca seed, immature bitter orange, and Magnolia bark are used to promote intestinal elimination. Acorus, cardamom, Amomum, Magnolia, and citrus peel are used for symptoms such as abdominal fullness, nausea, poor appetite, fatigue, and a greasy sensation in the mouth.
Why Is Rhubarb Interesting in CKD Research?
Rhubarb is one of the most extensively studied herbs in this formula. A meta-analysis involving 34 studies and 2,786 participants reported signals of improvement in serum creatinine, blood urea nitrogen, and uric acid among patients receiving rhubarb-containing interventions.[1]
However, many of the included trials had methodological limitations, and rhubarb was frequently administered as part of a multi-herb treatment. These results therefore do not prove that 15 g of rhubarb alone can restore kidney function, slow CKD progression, or prevent dialysis.
3. Tang Shen Fang: A Formula for Diabetic Kidney Disease
Formula Composition
Tang Shen Fang:
Astragalus (Huang Qi) 20 g, Anemarrhena asphodeloides (Zhi Mu) 15 g, Saposhnikovia (Fang Feng) 15 g, mulberry leaf (Sang Ye) 15 g, Atractylodes macrocephala (Bai Zhu) 15 g, Epimedium (Yin Yang Huo) 15 g, Euonymus alatus (Gui Jian Yu) 15 g, Malva seed (Dong Kui Zi) 15 g, Hirudo (Shui Zhi) 15 g, Dioscorea hypoglauca (Bi Xie) 15 g, Cornus officinalis (Shan Zhu Yu) 15 g, Euryale ferox (Qian Shi) 15 g, Chinese yam (Shan Yao) 15 g, winter melon peel (Dong Gua Pi) 15 g, cardamom (Bai Dou Kou) 15 g, litchi seed (Li Zhi He) 15 g, Hedyotis diffusa (Bai Hua She She Cao) 15 g, Lobelia chinensis (Ban Bian Lian) 15 g, Jiao San Xian 15 g each, and Amomum villosum (Sha Ren) 15 g.
Why Is This Formula Particularly Interesting for Diabetic Kidney Disease?
The therapeutic principle of Tang Shen Fang is described as replenishing Qi, nourishing Yin, clearing pathological products, and resolving chronic renal accumulation.
Astragalus, Saposhnikovia, and Atractylodes replenish Qi. Anemarrhena and mulberry leaf address internal heat and dryness. Epimedium and Cornus officinalis are used to support the kidney system within the TCM framework.
The combination of Euonymus alatus, Hirudo, Hedyotis diffusa, Malva seed, and Lobelia is particularly noteworthy because it targets the proposed “renal micro-mass” component associated with persistent proteinuria.
Euonymus alatus: An Emerging Herb for Diabetic Kidney Disease Research
Euonymus alatus, known as Gui Jian Yu in Chinese medicine, has recently attracted attention in experimental diabetic kidney disease research.
Recent animal and cellular studies suggest that Euonymus alatus may influence signaling pathways involving AGEs-RAGE, NF-κB, EGFR/AKT, Nrf2/ARE, and TGF-β/Smads.[2]
One particularly interesting area involves podocyte protection. Advanced glycation end products (AGEs), which accumulate in diabetes, can activate RAGE and downstream inflammatory pathways. Experimental studies suggest that Euonymus alatus may reduce RAGE-related signaling and inflammatory mediators such as NF-κB, TNF-α, IL-6, and VEGFA.
This raises the possibility that the herb may influence inflammation, oxidative stress, podocyte injury, and renal fibrosis. Nevertheless, these findings remain primarily preclinical, and high-quality randomized clinical trials in humans are still needed.
Hirudo and Hirudin: Potential Effects on Kidney Fibrosis
Hirudin is one of the major biologically active compounds associated with medicinal leech. Experimental kidney research suggests potential effects on TGF-β-related fibrosis, inflammation, pyroptosis, abnormal VEGF signaling, and podocyte injury.[3]
Recent experimental work has also investigated the mTOR/HIF-1α pathway as a possible mechanism through which hirudin may reduce renal fibrosis.
However, medicinal leech is not equivalent to purified hirudin. This distinction is important when interpreting experimental studies. Hirudo also has clinically important anticoagulant effects, and particular caution is required in patients receiving antiplatelet or anticoagulant medications because of the potential for increased bleeding risk.
Epimedium and Icariin
Icariin is a major bioactive compound studied from Epimedium species. A 2025 systematic review and meta-analysis of nine preclinical studies involving 308 animals reported that icariin treatment was associated with improvements in serum creatinine, blood urea nitrogen, 24-hour urinary protein, oxidative stress markers, and inflammatory markers in experimental diabetic nephropathy.[4]
These findings are promising but remain animal evidence. They should not be interpreted as proof that Epimedium at a particular human herbal dose can treat diabetic kidney disease.
Anemarrhena and Podocyte Autophagy
Sarsasapogenin, a compound isolated from Anemarrhena asphodeloides, has also been studied in experimental diabetic nephropathy. Animal studies have reported reductions in albuminuria and extracellular matrix accumulation, while mechanistic research suggests that regulation of GSK3β-related podocyte autophagy may contribute to its kidney-protective effects.[5]
Evidence for an isolated compound should not automatically be interpreted as evidence that the whole herb produces the same clinical effect.
4. Zi Dian Shen Yan Fang: A Formula for IgA Vasculitis Nephritis
Formula Composition
Zi Dian Shen Yan Fang:
Astragalus (Huang Qi) 20 g, Saposhnikovia (Fang Feng) 15 g, Atractylodes macrocephala (Bai Zhu) 15 g, Smilax glabra (Tu Fu Ling) 15 g, Stellaria root (Yin Chai Hu) 15 g, Lithospermum (Zi Cao) 15 g, Cirsium (Xiao Ji) 15 g, Rubia cordifolia (Qian Cao) 15 g, Schisandra (Wu Wei Zi) 15 g, Agrimonia (Xian He Cao) 15 g, Hedyotis diffusa (Bai Hua She She Cao) 15 g, Euonymus alatus (Gui Jian Yu) 15 g, Malva seed (Dong Kui Zi) 15 g, Hirudo (Shui Zhi) 6 g, Lobelia chinensis (Ban Bian Lian) 15 g, charred lotus rhizome node (Ou Jie Tan) 15 g, Jiao San Xian 15 g each, Amomum villosum (Sha Ren) 15 g, Imperata cylindrica rhizome (Bai Mao Gen) 15 g, and licorice (Gan Cao) 8 g.
Cooling the Blood While Removing Blood Stasis
IgA vasculitis nephritis may involve purpura, hematuria, and proteinuria. The therapeutic structure of this formula therefore differs from formulas designed primarily for diabetic kidney disease or chronic renal insufficiency.
Stellaria root and Lithospermum are used to cool pathological heat, while Agrimonia, Rubia, Cirsium, charred lotus node, and Imperata are used to control bleeding. At the same time, Euonymus alatus and Hirudo are included to address blood stasis and persistent kidney collateral injury.
The therapeutic concept is therefore not simply “bleeding means stopping the bleeding.” Instead, it combines cooling the blood, controlling bleeding, improving circulation, and addressing kidney collateral injury.
Imperata cylindrica and Renal Fibrosis
Imperata cylindrica is traditionally used for bleeding and urinary disorders. Modern experimental research has identified cylindrin as one potentially relevant compound.
A 2023 study reported that cylindrin may inhibit M2 macrophage polarization through the LXR-α/PI3K/AKT pathway, resulting in reduced experimental renal fibrosis.[6] Other preclinical research has explored Imperata in models related to IgA nephropathy, hyperuricemic nephropathy, and renal fibrosis.
How Are These Kidney Formulas Modified According to Symptoms?
| Clinical Pattern | Commonly Added Herbs | Therapeutic Goal |
|---|---|---|
| Edema and fluid retention | Fang Ji, winter melon peel, Areca peel, Poria, Polyporus, Coix seed, Imperata | Promote fluid elimination |
| Edema with blood stasis | Spatholobus, earthworm, Leonurus | Improve circulation and fluid metabolism |
| Damp-heat pattern | Gardenia, Scutellaria, Rehmannia, rice-paper plant pith | Clear heat and dampness |
| Proteinuria worsened after upper respiratory infection | Arctium, Lonicera, Forsythia, Scrophularia, Ophiopogon | Address inflammatory throat symptoms |
| Low back soreness and kidney deficiency pattern | Cibotium, Taxillus, Morinda, Achyranthes, Acanthopanax | Support the liver and kidney system |
| Qi and Yin deficiency | Rehmannia, Scrophularia, Ophiopogon, Schisandra, Codonopsis | Replenish Qi and nourish Yin |
| Persistent proteinuria with spleen-kidney deficiency | Euryale, Rosa laevigata, Poria, mantis egg case, Alpinia oxyphylla | Strengthen and consolidate |
| Abdominal fullness and constipation | Areca, immature bitter orange, Magnolia, Eupatorium, Aucklandia | Promote gastrointestinal movement and resolve turbidity |
| Marked blood stasis | Ligusticum, Curcuma, peach kernel, Angelica | Improve circulation |
| Purpura with itching | Smilax glabra, Dictamnus | Reduce dampness and itching |
| Purpura with joint pain | Angelica pubescens, mulberry twig, Curcuma longa, Chaenomeles | Improve circulation through the joints |
| Hematuria with urinary heat symptoms | Pyrrosia, Cirsium, Plantago seed, Dianthus, Polygonum aviculare | Promote urination and address bleeding |
Which Herbs Have the Strongest Modern Kidney Research?
Astragalus: One of the Most Clinically Studied Herbs
Among the herbs appearing in these formulas, Astragalus has one of the larger bodies of human clinical research.
A Cochrane review involving 22 studies and 1,323 participants with chronic kidney disease found signals suggesting reductions in urinary protein and serum creatinine with Astragalus-containing treatment.[7]
However, study quality was generally limited, heterogeneity was substantial, and evidence regarding clinically important outcomes such as progression to kidney failure or dialysis remained insufficient.
The appropriate interpretation is therefore: Astragalus has clinical signals for reducing proteinuria, but it has not been conclusively proven to prevent end-stage kidney disease.
Which Herbs May Be Most Interesting for Future Research?
Based on the combination of human evidence, experimental evidence, and biologically plausible kidney mechanisms, several herbs deserve particular attention.
First research tier: Astragalus, Euonymus alatus, Hirudo/hirudin, and rhubarb.
Second research tier: Epimedium/icariin, Cornus officinalis, Anemarrhena/sarsasapogenin, and Imperata cylindrica.
Exploratory research tier: Hedyotis diffusa, Lobelia chinensis, Malva seed, Dioscorea hypoglauca, Rubia cordifolia, and Cirsium.
Euonymus alatus may be particularly interesting because recent studies increasingly connect it with podocyte injury, AGEs-RAGE signaling, NF-κB-mediated inflammation, oxidative stress, and TGF-β/Smad-related renal fibrosis.
Important Safety Considerations in Patients With CKD
Licorice
Glycyrrhizin-containing licorice can cause pseudoaldosteronism, potentially resulting in hypertension, sodium and fluid retention, and hypokalemia. These effects are particularly relevant in CKD patients who already have hypertension or edema.
Medicinal Leech and Anticoagulant Therapy
Medicinal leech and hirudin-related compounds may affect coagulation. Patients receiving aspirin, clopidogrel, warfarin, or direct oral anticoagulants require particular caution because combined use may increase bleeding risk.
Fang Ji and Aristolochic Acid
Correct botanical identification is critical. Stephania tetrandra (Han Fang Ji) should not be confused with Aristolochia fangchi (Guang Fang Ji). Aristolochic acid exposure is associated with severe progressive tubulointerstitial kidney disease and urothelial malignancy.
FAQ: Can Chinese Herbal Medicine Reduce Proteinuria?
Some Chinese herbal medicines and multi-herb formulas have shown reductions in proteinuria in clinical studies. Astragalus-containing treatments, for example, have been evaluated in systematic reviews.
However, reducing proteinuria is not automatically equivalent to preventing kidney failure. High-quality long-term studies evaluating eGFR decline, kidney failure, dialysis, cardiovascular outcomes, and mortality remain necessary.
FAQ: Does a Lower Creatinine Level Mean the Kidneys Have Recovered?
Not necessarily. Serum creatinine is influenced by glomerular filtration, muscle mass, dietary intake, medications, intestinal elimination, and fluid status.
When evaluating CKD progression, clinicians should consider multiple measurements, including eGFR, UACR or UPCR, blood pressure, serum potassium, and the long-term rate of kidney function decline.
FAQ: Is “Renal Micro-Mass” the Same as Kidney Fibrosis?
No. Renal micro-mass is a theoretical concept derived from Traditional Chinese Medicine, whereas renal fibrosis, glomerulosclerosis, and podocyte injury have specific pathological definitions in modern medicine.
However, this traditional theory can generate research hypotheses. Researchers could investigate whether herbs traditionally described as “resolving renal micro-masses” influence measurable processes such as podocyte injury, microvascular dysfunction, chronic inflammation, extracellular matrix deposition, TGF-β/Smad signaling, or renal fibrosis.
References
[1] Huang Y, et al. Clinical effect of rhubarb on the treatment of chronic renal failure: a meta-analysis. Front Pharmacol. 2023.
[2] Experimental studies of Euonymus alatus in diabetic kidney disease and AGEs-RAGE-mediated podocyte injury. 2024–2025.
[3] Research progress on medicinal leech and its active ingredients in diabetic nephropathy. 2024.
[4] Preclinical evidence of the effect of icariin on diabetic nephropathy: a systematic review and meta-analysis. Diabetol Metab Syndr. 2025.
[5] Sarsasapogenin restores podocyte autophagy in diabetic nephropathy by targeting the GSK3β signaling pathway. Biochem Pharmacol. 2021.
[6] Cylindrin from Imperata cylindrica inhibits M2 macrophage formation and attenuates renal fibrosis through the LXR-α/PI3K/AKT pathway. Eur J Pharmacol. 2023.
[7] Zhang HW, et al. Astragalus for treating chronic kidney disease. Cochrane Database Syst Rev. 2014.
[8] Research progress on Cornus officinalis and its active compounds in diabetic nephropathy. Front Pharmacol. 2023.
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