Quercetin and Kidney Health: What a 2022 Study Really Says

The study “ Protective effect of quercetin on kidney diseases: From chemistry to herbal medicines ” by Yi-Qin Chen et al. (2022) is a scientific review of existing experimental research on quercetin and kidney health. The authors summarize data from cell experiments, animal models, and a small early human study to explore how quercetin may help modulate nephrotoxicity, acute kidney injury (AKI), chronic kidney disease (CKD), diabetic nephropathy (DN), and kidney aging in research settings. This blog presents a paraphrase or direct quote of that scientific paper, without adding new scientific claims beyond what the authors reported.

The authors state that “quercetin may protect kidneys by alleviating renal toxicity, apoptosis, fibrosis, and inflammation in a variety of kidney diseases,” and suggest that it could be a promising candidate drug for renal disorders in future research.

For over 2,000 years, Phyllanthus amarus has been used in traditional medicine systems like Ayurveda, Unani, and folk medicine across South America and Africa. Known by many names—such as “Bhuiamla” in India and “Chanca Piedra” in Spanish-speaking countries—this small, leafy plant has been used to treat liver problems, kidney stones, diabetes, and more.

The study explains that while P. amarus is popular in herbal traditions, its identity is often confused with similar species like Phyllanthus niruri. This confusion makes research harder and has led scientists to focus more on accurate classification, phytochemical content, and understanding the true healing power of this herb.

Kidney diseases are described as “life-threatening diseases with high mortality rates.” Kidney injury can be triggered by nephrotoxins, oxidative stress, or inflammation and can progress to renal fibrosis, chronic kidney disease (CKD), and end-stage renal disease (ESRD). The authors note that effective drugs and therapeutic strategies for renal injury are still limited, so new options are badly needed.

Natural products, especially compounds from herbal medicines, have long been used in managing kidney problems. Quercetin is one of the most abundant flavonoids in plants and is present in many foods and herbs. Because of its antioxidative, anti-hypertensive, and anti-diabetic properties in research models, quercetin has been studied in the context of cancer, cardiovascular disease, and metabolic disease. The authors point out that despite many individual studies, a recent overview of quercetin’s actions in kidney diseases was missing, which is why this review was written.

Quercetin is also widely found in traditional Chinese medicines. The paper reports that nearly 200 herbal medicines contain measurable quercetin. Some herbs used for “heat clearing” and urinary problems contain especially high amounts, such as Houttuynia cordata (about 315.8 mg/g), Pyrrosia lingua (234.6 mg/g), and Centella asiatica (77.6 mg/g). The authors link traditional functions like reducing “damp heat,” promoting urination, and nourishing the kidney to quercetin’s antioxidant and vasodilating effects.

This scientific paper is a narrative review, not a new clinical trial. The authors gathered and synthesized findings from many previous in vivo (animal) and in vitro (cell) studies, plus one early open-label human study. They focus on:

• Quercetin’s chemistry, pharmacokinetics, and bioavailability
• The amount of quercetin in different herbal medicines
• Experimental models of nephrotoxicity, AKI, chronic kidney injury and fibrosis, diabetic nephropathy (DN), kidney aging, hypertension, renal cell carcinoma (RCC), autosomal dominant polycystic kidney disease (ADPKD), and kidney stones

They highlight the molecular pathways that quercetin appears to affect, such as nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), transforming growth factor beta (TGF-β), nuclear factor κ-B (NF-κB), and AMP-activated protein kinase (AMPK). All descriptions of mechanisms and effects here are paraphrased directly from the scientific paper.

Quercetin (also called 3,5,7,3′,4′-pentahydroxyflavone) exists in nature mainly as glycosides, which are more water-soluble than the aglycone form. However, the authors stress that quercetin itself has very low water solubility and note that quercetin aglycone has a poor oral bioavailability of about 2 percent. After intake, quercetin glycosides are broken down by enzymes such as lactase, phloridzin hydrolase, and β-glucosidases to release quercetin aglycone.

In the gut and liver, quercetin undergoes glucuronidation, methylation, and sulfation, forming metabolites like quercetin 3-O-glucuronide and quercetin 3′-O-sulfate. About 80 percent of aglycone and metabolites bind to plasma albumin, while 20 percent circulates freely and can enter tissues. In the kidney, metabolites are filtered, partially reabsorbed by tubular epithelial cells (TECs), and then excreted in urine. The paper notes that “up to 20%–60% of the quercetin intake may be secreted into the urine,” mainly as conjugated forms.

Because of low solubility, rapid elimination, and low bioavailability, practical use is difficult. The authors describe work where quercetin was encapsulated in Pluronic F127 micelles, which increased water solubility and improved kidney protection in animal models.

The review summarizes many studies where quercetin was associated with reduced markers of nephrotoxicity caused by antineoplastic drugs such as cisplatin, methotrexate, doxorubicin, and cyclophosphamide, as well as antibiotics like gentamicin, antiretroviral combinations, and chemicals such as cadmium, organophosphate pesticides, acrylamide, and diesel exhaust particles in experimental models.

In cisplatin-treated rats, quercetin was reported to reduce tubular injury, downregulate pro-inflammatory mediators, help maintain renal blood flow, and show antioxidant and anti-apoptotic effects. Importantly, the authors report that quercetin did not interfere with the anti-tumor activity of cisplatin and may even enhance that activity in the research conditions studied. Mechanistically, quercetin often acts by scavenging reactive oxygen species (ROS), lowering malondialdehyde (MDA), and activating the Nrf2/HO-1 pathway to boost antioxidant defenses like glutathione (GSH), glutathione peroxidase (GPx), and superoxide dismutase (SOD).

The authors also note that dose matters. In one doxorubicin-induced injury model, a high dose of 100 mg per kilogram per day did not significantly improve renal function, which suggests a complex dose-response.

In acute kidney injury (AKI) models, quercetin prevented loss of glomeruli after renal ischemia and reduced markers of oxidative stress in ischemia/reperfusion injury. It also inhibited what the authors describe as “iron apoptosis,” an iron-dependent form of regulated necrosis in proximal tubular epithelial cells, which was associated with less AKI in these studies.

Quercetin modulated immune responses in AKI models by influencing macrophages. It reduced inflammatory signaling through pathways such as Mincle/Syk/NF-κB and toll-like receptor 4 (TLR4)/NF-κB, and by upregulating silent information regulator 1 (Sirt1). In lipopolysaccharide (LPS)-induced sepsis models, quercetin decreased inflammatory signaling and improved kidney function. The authors also mention that because kidneys are targets of SARS-CoV-2 and many COVID-19 patients develop AKI, quercetin’s ability to inhibit inflammatory and apoptosis-related pathways and potentially target the viral 3CL protease may be relevant, although this remains experimental.

In chronic kidney injury and fibrosis, quercetin reduced inflammatory cytokines, decreased macrophage accumulation, and inhibited extracellular matrix (ECM) buildup. It upregulated miR-124 to dampen NF-κB signaling in tubular epithelial cells and downregulated TGF-β-driven epithelial-to-mesenchymal transition (EMT) through Sonic Hedgehog, PTEN/TIMP3, and PI3K/Akt pathways, all of which point to an anti-fibrotic role in research models.

In diabetic nephropathy (DN), both high blood sugar and abnormal lipids damage kidney structure and function. The paper describes quercetin as an “anti-hyperglycemic agent” in research settings, noting that in experimental models it was reported to lower blood glucose by increasing insulin release, reducing hepatic glucose production, and improving glucose uptake through effects on the insulin receptor and glucose transporter type 4 (GLUT4).

In diabetic animal models, doses around 10 to 100 mg per kilogram per day were associated with lower blood glucose, triglycerides, and cholesterol, reduced albuminuria, and improved markers of renal function.

Oxidative stress is a key feature in DN. Excess ROS drives podocyte damage and ECM production. In DN models, quercetin and its derivative dihydroquercetin acted as free radical scavengers, decreased ROS-related proteins, and reduced activation of the NLRP3 inflammasome. Quercetin and quercetin-nanoparticle complexes also decreased expression of intercellular adhesion molecule-1 (ICAM-1), improved kidney structure, and lowered oxidative markers.

Autophagy, a cell “recycling” process, is disrupted by chronic high glucose in kidney cells. The authors report that quercetin and quercetin-rich guava can protect against type 2 diabetes-induced renal and pancreatic dysfunction by modulating apoptosis, autophagy, and pyroptosis in animal models. In various studies, quercetin appears to regulate AMPK-dependent autophagy, inhibit mammalian target of rapamycin complex 1 (mTORC1)/p70S6K signaling, and activate Hippo pathways, which may help restore cellular homeostasis in DN models.

Cellular senescence, where cells stop dividing but remain metabolically active and secrete inflammatory factors, contributes to kidney aging and fibrosis. In this scientific paper, the term “senolytics” refers to drug combinations that aim to selectively clear senescent cells in experimental research. The paper highlights the combination of quercetin and dasatinib as a senolytic strategy in kidney disease models.

Senescent tubular epithelial cells (TECs) drive fibrosis by activating fibroblasts. In animal models, dasatinib plus quercetin induced apoptosis of senescent TECs, improved renal fibrosis, and restored kidney function markers in conditions such as renal ischemia and renal artery stenosis. Markers of senescence such as p16, p19, p21, and p53 were reduced.

The authors also describe an open-label Phase 1 pilot study (NCT02848131) in patients with diabetic kidney disease, where dasatinib plus quercetin eliminated senescent cells and significantly reduced senescent cell burden in adipose and skin tissue within 11 days. They link this to decreases in p16- and p21-positive cells and in senescence-associated secretory phenotype factors such as interleukin-6 (IL-6), interleukin-1α (IL-1α), and matrix metalloproteinase-9 (MMP-9).

The scientific paper also describes several other kidney-related effects seen in experimental models:

• Hypertension: In hypertensive rat models, dietary quercetin was reported to lower blood pressure, improve endothelial function, and reduce α1-adrenoceptor-mediated contractions, which the authors describe as consistent with a potential cardioprotective and anti-hypertensive effect in research settings.
• Renal cell carcinoma (RCC): Quercetin showed anti-tumor effects in renal cancer cell models. When combined with antisense oligo gene therapy, it exerted stronger suppression of RCC cell migration and invasion than either treatment alone.
• Autosomal dominant polycystic kidney disease (ADPKD): In experimental models, quercetin “dramatically inhibited the formation and growth of the cyst,” which suggests a possible effect on cyst progression that requires further study.
• Kidney stones: In urinary tract models, quercetin reduced the reabsorption of sodium, calcium, and water, and this change was associated with less kidney stone formation.

All of these findings are preclinical and come from the cited experimental studies summarized in the scientific paper.

Overall, the authors present quercetin as a multi-target natural compound that may support kidney health in experimental models through antioxidant, anti-inflammatory, anti-fibrotic, metabolic, autophagy-modulating, and senolytic actions.

They emphasize that quercetin “could be one of the promising drugs in the treatment of renal disorders,” while also outlining major limitations and the need for more research. Most of the evidence reviewed comes from animal and cell studies, with only one small early human trial in diabetic kidney disease using dasatinib plus quercetin as a senolytic combination. The paper repeatedly notes quercetin’s “low water solubility, oral absorption rate, rapid elimination, and low bioavailability,” which “greatly hindered the application of quercetin in pre-employment drug testing and clinical practice.” To move toward real-world use, the authors argue that new delivery systems, such as nanoparticles, liposomes, micelles, or other novel materials, are urgently needed to improve solubility, stability, and effective dosing.

This blog paraphrases and quotes the scientific paper and does not give advice about how individuals should use quercetin.

This 2022 scientific paper paints a hopeful but careful picture of quercetin for kidney health. Across many experimental models, quercetin was associated with less nephrotoxicity, fewer signs of acute kidney injury (AKI) and chronic fibrosis, improved markers of diabetic nephropathy (DN), clearance of senescent cells when combined with dasatinib, and favorable changes in models of hypertension, renal cell carcinoma (RCC), autosomal dominant polycystic kidney disease (ADPKD), and kidney stones.

At the same time, the authors stress that poor solubility, extremely low oral bioavailability, and limited clinical data are major barriers. They write that “further research on nanoparticles, liposomes, micelles, or novel materials is in urgent need” to bring quercetin closer to real therapeutic use in kidney disease. This blog is a summary and paraphrase of that scientific paper, written to convey the findings in simpler language without adding claims beyond what the authors reported.