PARIS, France—Data from the MATRIX (MeThotreXate And Renal Insufficiency) prospective observational study show that renal damage in rheumatoid arthritis (RA) patients is much more common than had been expected, is routinely missed if patients are checked only with serum creatinine (SCr) testing, and is not taken into account in half of the patients who should have dosage adjustments to prevent drug toxicity. Svetlana Karie, MD, et al report the MATRIX data early online in Rheumatology.¹

"The necessity of a dose adjustment or drug avoidance is underestimated in clinical practice; half of the patients in our study did not have appropriate MTX [methotrexate] dosage," Dr. Karie wrote.


SCr misses nearly half of kidney disease cases

The researchers prospectively assessed renal function in 129 community-dwelling patients (109 women, 20 men) who had RA. They measured SCr, proteinuria, and abnormal urinary sediments from single urine dipsticks. They estimated kidney damage from the glomerular filtration rate (GFR) calculated from SCr levels using both the Cockcroft-Gault (CG) formula and the abbreviated Modification of Diet in Renal Disease Study (aMDRD) formula, and classified damage according the National Kidney Foundation classification [Table 1].

"We found that [kidney disease] was highly prevalent in our population of RA patients and that its frequency is clearly underestimated in clinical practice if physicians base their diagnosis on SCr measurements and if urine dipstick is not systematically used in practice. Of the patients, 46.3% to 57% had either a GFR reduction or a renal abnormality on urine dipstick, whereas SCr was normal in 81.4% of patients," Dr. Karie noted.

The problem appears to be that SCr was often not interpreted in the context of the patient's gender, age, and weight. "These parameters represent the muscle mass of the patient and, therefore, the creatinine production rate. It is…crucial…that [renal function] is evaluated with the appropriate tools in all patients, including RA patients, by estimating GFR calculated using the CG or aMDRD formula," Dr. Karie continued.

National Kidney Foundation Classification of Kidney Damage and Function

Stage	Criteria
1: Normal kidney function with markers of kidney damage	GFR >e;90 mL/min
2: Mild reduction of GFR with markers of kidney damage	GFR 60-89 mL/min
3: Moderate reduction of GFR	GFR 30-59 mL/min
4: Severe reduction of GFR	GFR 15-29 mL/min
5: Kidney failure	GFR <15 mL/min

Translating research into practice: implications for RA medications

Many RA drugs either should not be used in patients who have kidney damage or should have dosage modifications. According to Dr. Karie, this is not being done. "In the MATRIX study, of the 352 prescriptions, 41% were potentially nephrotoxic, and 54% needed a dosage adjustment in case of renal insufficiency," she commented. Nearly half of the patients in this group who had GFR <60 mL/min/1.73 m2 and who were taking MTX did not have their MTX dosage adjusted appropriately to compensate for their stage of kidney disease.

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