Kidney Coach

Lupus Nephritis and kidney disease

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lupus word written on wooden blocks and stethoscope on light gray background

Lupus is an autoimmune disease that can affect the kidneys, cause inflammation, protein and blood in urine, high blood pressure and kidney failure. There are two types of lupus; systemic lupus erythematosus (SLE) and ‘discoid’ lupus erythematosus.   Discoid lupus erythematosus affects the skin only, whereas SLE can harm the kidneys, skin, joints, and brain and can be fatal. When lupus impacts the kidneys, it is called lupus nephritis (LN). LN is a form of glomerulonephritis; it is a severe organ manifestation of SLE. As with all autoimmune diseases, in LN the immune system mistakenly attacks the kidneys causing inflammation and damage. Patients with SLE who develop LN do so within 5 years of their diagnosis.

Within 10 years of an SLE diagnosis, 5-20% of patients with LN will develop end-stage kidney disease; adding to this, multiple issues associated with immunosuppressant treatment, such as infections, osteoporosis, cardiovascular and reproductive issues remain a big concern.

The treatment of LN usually involves immunosuppressive therapy, typically; mycophenolate mofetil or cyclophosphamide and glucocorticoids. However, research has shown these treatments are not uniformly effective, making it more important to improve treatment options.

Lupus nephritis | Nature Reviews Disease Primers

Signs and symptoms

  • Blood in urine
  • Foamy urine- due to excess protein in the urine
  • High blood pressure
  • Swelling of the hands, ankles or feet
  • High levels of creatinine in the blood
  • Muscle pain
  • Fever with no known cause

Cause of lupus nephritis

1. Genetic predisposition

People with a family history of lupus or other autoimmune diseases are more likely to develop the condition.

2. Gender and hormonal factors

Lupus and lupus nephritis are more common in women, especially during the reproductive years. Hormonal factors, such as estrogen, may trigger or exacerbate the body’s immune response. One study concluded that plasma estradiol (E2) increment is associated with lupus activity in male and female patients. A decrease in plasma testosterone in female patients only is also related to lupus activity.

Blood levels of sex hormone in lupus nephritis and their relationship to lupus activity – PubMed (nih.gov)

3. Environmental factors

Various environmental triggers, including infections, certain medications or exposure to chemicals and ultraviolet light, have been associated with the development of LN. The role of Epstein-Barr virus (EBV) infection has also been investigated. Researchers in a recent study collected 58 renal tissue samples from patients with LN and then compared them with samples from patients with non-glomerular haematuria and patients with minimal change nephropathy. They found an expression of EBV-latent membrane protein 1 (LMP1) in renal tissues and detected the expression of EBV-encoded RNA 1 (EBER-1). They concluded their results showed that positive rates of renal viral proteins EBER-1 and LMP-1 were higher in lupus patients compared to the control group.

The Role of Autophagy in Lupus Nephritis – PMC (nih.gov)

4. Immune system dysfunction

LN is an autoimmune disease; for people who have LN, the immune system has failed to distinguish between self and non-self. This, in turn, leads to the production of autoantibodies and immune complex deposition within the kidneys.

5. Inflammation and immune complex deposition

In LN, antibodies and antigens accumulate in the kidneys, triggering an immune response that causes damage to the kidneys causing damage to kidney tissue and impairing normal function. Neutrophils are implicated in the pathogenesis of LN. When neutrophils die, the can release neutrophil extracellular traps (NETs). NETS are composed of chromatin fibrils, histones, and neutrophil antibacterial and immunostimulatory proteins.

Update on Lupus Nephritis: Clinical Journal of the American Society of Nephrology (lww.com)

Lupus and kidney disease (lupus nephritis) – Symptoms, treatment, & stages | National Kidney Foundation

Stages

Your healthcare provider will determine the level of kidney damage using a lupus nephritis classification system developed by the World Health Organisation (WHO), then modified by the International Society of Nephrology and the Renal Pathology Society.

The six classes are:

  • Class 1: Minimal mesangial lupus nephritis.
  • Class 2: Mesangial proliferative lupus nephritis.
  • Class 3: Focal lupus nephritis (active and chronic, proliferative and sclerosing).
  • Class 4: Diffuse lupus nephritis (active and chronic, proliferative and sclerosing, segmental and global).
  • Class 5: Membranous lupus nephritis.
  • Class 6: Advanced sclerosis lupus nephritis.

Lupus Nephritis: Symptoms, Stages, and More (healthline.com)

Complications

If treatment does not work well to control this condition, you may experience some complications.

Diffuse proliferative nephritis is the most severe form of LN. This condition can cause permanent scarring on the kidneys, and kidney function will often decline as more scarring occurs. Early diagnosis and treatment are essential.

Between 10-30% of patients with LN will develop kidney failure. There is a high risk of cancer associated with LN, primarily B-cell lymphoma.

Lupus and Kidney Disease (Lupus Nephritis) – NIDDK (nih.gov)

The Role of the Microbiota

In recent years there have been investigations into the role of the microbiota in the pathogenesis of LN and SLE. Our gut microbiota plays a major role in antibody production, homeostasis of different populations of helper T cell and Th17: Treg balance, and regulation of the levels of different Th17 cell subpopulations. Research shows dysbiosis or disturbance in the gut microbiota, leads to the development of autoimmunity. At this point in time, the exact cause of LN is poorly understood. Investigating whether dysbiosis is a trigger can shed more light on this condition. There are approximately 1000 species of bacteria representing the microbiota. These microbial communities support the host by extracting nutrients and energy from the diet, protecting from entero-pathogen invasion and regulating adaptive and innate immunity.

Inflammation within the gut allows pathogenic bacteria to enter the bloodstream to form immune complexes, which, in turn, will impact the kidneys. Dysbiosis causes intestinal barrier function impairment, leading to an increase in intestinal permeability, allowing certain viruses, pathogens and pathogenic antigens into internal organs.

Recently published research showed poor barrier function was observed in the bloodstream of lupus-prone mice in the endotoxin lipopolysaccharides (LPS). The increase in LPS caused further damage to the gut in these mice. The exposure of LPS in the lupus gut was also found to disrupt the tight junction proteins within the gut. The exposure of LPS in nephritic mice was found to increase the production of DNA autoantibodies.

That is another reason why a healthy microbiome is always so important!

Image via Involvement of Gut Microbiota in SLE and Lupus Nephritis – PMC (nih.gov)

The role of microbiota in the pathogenesis of lupus: Dose it impact lupus nephritis? – PubMed (nih.gov)

Vitamin D

The synthesis of vitamin D active form, the 1α, 25-dihydroxy vitamin D3, (calcitriol), mainly occurs within the kidneys by 1α-hydroxylase (CYP27B1). However, this action declines as nephron mass declines. Vitamin D has been implicated in conditions such as hypertension, kidney disease and diabetes due to its ability to negatively regulate the renin-angiotensin system (RAS). Research has shown that the activity of vitamin D metabolites in animals is associated with reduced blood pressure, proteinuria, renal injury and improved β-cell function.

Vitamin D supplementation has been shown to significantly slow kidney disease progression. It also has potent antiproliferative and immunomodulating functions, helping to inhibit kidney inflammation. Patients with LN have lower vitamin D levels than subjects with inactive SLE or active SLE without LN. In vitro experiments have shown the nephroprotective role versus LN antibodies as serum 25(OH)2D3 has been linked to the downregulation in the autophagy of podocytes.

Expression of vitamin D receptor in renal tissue of lupus nephritis and its association with renal injury activity – PubMed (nih.gov)

The relationship between vitamin D and the renin-angiotensin system in the pathophysiology of hypertension, kidney disease, and diabetes – PubMed (nih.gov)

N-acetylcysteine (NAC) and lupus nephritis

A 2010 case report and literature review showed that co-administration of NAC with conventional therapy may produce a satisfactory therapeutic outcome. NAC produces strong antioxidant activity. The case report involved a 46-year-old LN patient who received 1,800mg of NAC orally. After the use of NAC, the patient showed higher glutathione levels and a normal level of malondialdehyde, a lipid peroxidation product. In addition, urinary protein levels, complete blood counts and a physical examination of affected organs showed improvement.

The effect of high dose of N‐acetylcysteine in lupus nephritis: a case report and literature review – Tewthanom – 2010 – Journal of Clinical Pharmacy and Therapeutics – Wiley Online Library

Quercetin and Lupus Nephritis

A recent in vitro study showed quercetin ameliorated the accumulation of fibrosis and inflammation related proteins and improved renal cell pyroptosis via the IL33/ST2 pathway. This suggests quercetin can improve LN related renal fibrosis and inflammation. The study findings showed quercetin could decrease plasma levels of BUN and creatinine and decrease deterioration in kidney tissue sections. Researchers proposed quercetin as a potential therapeutic option in the management of LN.

Quercetin Ameliorates Renal Injury and Pyroptosis in Lupus Nephritis through Inhibiting IL-33/ST2 Pathway In Vitro and In Vivo – PubMed (nih.gov)

Epigallocatechin-3-Gallate (EGCG)

EGCG is a bioactive polyphenol found in green tea, and it has anti-inflammatory and antioxidant activity. Research has shown ECGC reduced ROS (reactive oxygen species) levels in the serum and urine of lupus-prone NZB/W F1 mice. This research highlights the beneficial effects of EGCG in different types of kidney disease including kidney stones, cisplatin-induced nephrotoxicity, acute kidney injury, CKD, diabetic nephropathy, renal cell carcinoma and renal fibrosis.

Image via Protective Effects of Epigallocatechin-3-Gallate from Green Tea in Various Kidney Diseases – PMC (nih.gov)

So, there you go!

We hope you find this helpful information!

Remember, if you start any new natural herbal or nutritional remedy, check that it is safe to take with your health care provider. If you liked this article, please feel free to share it.

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