Introduction to RA and CKD: 

Rheumatoid arthritis (RA), a systemic autoimmune diseased condition characterized by pain, stiffness, and swelling, and is best known for its effects on the joints. Rheumatoid arthritis is a systemic disease, because it can affect the entire body, causing damage to the major organs including the kidney and even shortening one’s life span.

Kidney diseases (both chronic and acute kidney disease) can result, owing to the non functioning of the kidney, which normally functions to remove toxic waste products from the body and aids in the blood filtration process. In chronic kidney disease (CKD), the kidney is unable to filter out the toxins from blood and they end up accumulating in the blood instead. The glomerular filtration rate (GFR) drops down significantly which is indicative of kidney disease . 

Pathophysiology of RA and its association with CKD:

Rheumatoid arthritis and CKD are interrelated. Secondary renal amyloidosis, nephrotoxic effects of antirheumatic drugs, and nephropathies as extra-articular manifestations are all examples of kidney injury in RA. Amyloidosis (a condition characterized by abnormal buildup of amyloids in the kidney) reduces survival rate, increases morbidity, and is the leading cause of end-stage renal disease (ESRD) in RA and other patients suffering from nephropathy. Amyloid protein concentration in the blood is elevated in kidney failure and these proteins can separate and clump together, forming amyloid deposits in a variety of tissues and organs, including joints and tendons. This can cause symptoms such as pain and stiffness, pain, which is the case in RA.

Proteinuria is a common nephropathy symptom in RA. One of the most serious complications of rheumatoid arthritis is AA amyloidosis (RA). The disease causes rapid end stage renal failure, and dialysis is frequently ineffective in preventing death.

Familial renal amyloidosis (FRA) is a group of hereditary disorders characterized by the accumulation of misfolded proteins (amyloid) in the kidneys, resulting in proteinuria and/or hypertension, followed by progressive renal failure.

RA Medications and their association with CKD: – The majority of RA medications are not directly toxic to the kidneys. Some, however, can be harmful if administered to a patient having impaired kidney function.

NSAIDS: Asymptomatic rises in creatinine levels caused by NSAIDs (Non steroidal anti inflammatory drugs) are common in RA patients taking long-term NSAIDs. Regular doses of nonsteroidal anti-inflammatory drugs (NSAIDS) like ibuprofen and naproxen are usually not a problem for relatively healthy people. NSAIDs, however, reduce blood flow to the kidneys. This could be hazardous for those with impaired kidney function, which includes a large number of elderly patients.

Corticosteroids: Prednisone and other corticosteroids cause fluid retention, which can increase blood pressure and cause hypotension. This can aggravate kidney disease over time.

Methotrexate: This medication is excreted through the kidneys. If the kidneys aren’t working as well as they should, it can accumulate in the bloodstream, potentially resulting in CKD.

Cyclosporine: Cyclosporine, a potent immunosuppressant, may impair kidney function. According to the American College of Rheumatology, half of the patients on cyclosporine medication develop chronic kidney disease and discontinuation of this drug has been found to be associated with better patient outcomes and improved renal functioning. 

Patients with RA are more likely to develop glomerulonephritis, which is an inflammation of the kidney’s filtering units (called glomeruli) that can impair kidney function and lead to chronic kidney disease.

Cardiac problems also play a role. RA patients have higher blood pressure and other cardiovascular risk factors, which can also be risk factors for chronic kidney disease, Obesity, high blood pressure, and high cholesterol have all been linked to an increased risk of kidney disease in RA patients, according to a study published in the American Journal of Kidney Diseases.

Diagnosis of CKD:

Microbiological urine culturing: Serum parameters may not indicate damage to the glomerular filtration barrier, which only becomes evident on urinalysis. 

Dipstick method of analysis: Proteinuria and hematuria, as detected by urine dipstick analysis, are signs of glomerulonephritis (GN) – for example, in systemic lupus erythematosus (SLE) or anti-neutrophil cytoplasmic antibody (ANCA) vasculitis – and massive proteinuria is a sign of membranous lupus nephritis, amyloid-A amyloidosis. Most rheumatologists perform dipstick urinalysis during the initial evaluation and monitoring visits.

Serum creatinine and GFR: In all patients, routine testing should include serum creatinine with estimated GFR, electrolytes, urine dipstick analysis, and blood pressure. In CKD patients, the urinary protein/creatinine ratio or urinary albumin/creatinine ratio, blood urea nitrogen, uric acid, cystatin C, serum bicarbonate, hemoglobin, serum calcium, phosphorus, and intact parathyroid hormone (iPTH) levels must be monitored. 

Kidney biopsy: A nephrologist should be consulted to determine whether a kidney biopsy is necessary. A kidney biopsy can detect kidney tissue damage, post microscopy imaging, that reveals scarring, inflammation or any abnormal deposition of protein.

Source: Bar graph representation of different serum biochemical parameters in RA patients ( CKD vs non CKD patients. Available at https://ard.bmj.com/content/78/Suppl_2/2112.3.

The above graph reveals that the amount of albumin, cholesterol, triglycerides, C reactive protein along with the erythrocyte sedimentation rate is higher in RA patients with CKD than those without CKD. 

Drugs of choice for RA patients having CKD :

• Tylenol (generic acetaminophen) is often the best choice for people with high blood pressure, heart failure, or kidney problems.
• HCQ: All lupus nephritis patients are recommended to take hydroxychloroquine (HCQ) to reduce the risk of kidney flares, end-stage kidney disease (ESKD), and death.
• Diclofenac: When used at the lowest effective dose for the shortest dose duration, diclofenac may be well tolerated in patients with renal impairment. Diclofenac should be considered in mild to moderate cases of CKD.

Future prospects of anti-TNF treatments: TNF (tumor necrosis factor alpha) is a pleiotropic cytokine produced primarily by activated macrophages that is widely implicated in immune regulation. TNF is now better understood for its role in inflammatory and autoimmune diseases like sepsis, rheumatoid arthritis, inflammatory bowel disease, psoriasis, and multiple sclerosis. TNF has been implicated in the inflammatory cascade leading to renal injury, which is common in inflammatory and autoimmune diseases. TNF and its receptors in renal inflammatory diseases, as well as the future potential of anti-TNF treatments Infliximab, an anti-TNF antibody, may also be beneficial in lupus nephritis, and the results of an ongoing controlled clinical trial are expected soon. 

Conclusion: According to the researchers, doctors should check rheumatoid arthritis patients for signs of kidney problems on a regular basis. Patients must control their blood pressure, consume a low-salt diet, and reduce or discontinue the use of medications that can harm their kidneys, such as nonsteroidal anti-inflammatory drugs (NSAIDS). This is particularly pertinent to the RA patients and alternative therapeutic options can be undertaken to achieve better outcomes. In CKD patients, with RA, glucocorticoids, acetaminophen, metamizol/dipyrone, or opioids can be used instead of NSAIDs.

Healthy rheumatoid arthritis kidney donors have favorable outcomes, with no increased risk of decline in renal function, end-stage renal disease, or death.