Reduced Kidney Function in Rheumatoid Arthritis
Reduced Kidney Function in Rheumatoid Arthritis
Background: Rheumatoid arthritis (RA) is associated with a variety of kidney disorders. However, it is unclear whether the development of reduced kidney function is higher in patients with RA compared to the general population.
Study Design: Retrospective review.
Setting & Participants: Incident adult-onset RA cases (813) and a comparison cohort of non-RA individuals (813) in Olmsted County, MN, in 1980–2007.
Predictor: Baseline demographic and clinical variables.
Outcomes: Reduced kidney function: (1) estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m and (2) eGFR < 45 mL/min/1.73 m on 2 consecutive occasions at least 90 days apart; cardiovascular disease (CVD); and death.
Measurements: The cumulative incidence of reduced kidney function was estimated adjusting for the competing risk of death.
Results: Of 813 patients with RA and 813 non-RA individuals, mean age was 56 ± 16 (SD) years, 68% were women, and 9% had reduced kidney function at baseline. The 20-year cumulative incidence of reduced kidney function was higher in patients with RA compared with non-RA participants for eGFR < 60 mL/min/1.73 m (25% vs 20%; P = 0.03), but not eGFR < 45 mL/min/1.73 m (9% vs 10%; P = 0.8). The presence of CVD at baseline (HR, 1.77; 95% CI, 1.14–2.73; P = 0.01) and elevated erythrocyte sedimentation rate in patients with RA (HR per 10-mm/h increase, 1.08; 95% CI, 1.00–1.16; P = 0.04) was associated with increased risk of eGFR < 60 mL/min/1.73 m. eGFR < 60 mL/min/1.73 m was not associated with increased risk of CVD development in patients with RA (HR, 0.99; 95% CI, 0.63–1.57; P = 0.9), however, a greater reduction in GFR (eGFR < 45 mL/min/1.73 m) was associated with increased risk of CVD (HR, 1.93; CI, 1.04–3.58; P = 0.04).
Limitations: Reduced kidney function was defined by estimating equations for kidney function. We are limited to deriving associations from our findings.
Conclusions: Patients with RA were more likely to develop reduced kidney function over time. CVD and associated factors appear to play a role. The presence of RA in individuals with reduced kidney function may lead to an increase in morbidity from CVD development, for which awareness may provide a means for optimizing care.
Chronic kidney disease (CKD) affects more than 26 million adults in the United States. Although diabetes mellitus and hypertension are the 2 primary causes of kidney failure, other conditions, including autoimmune processes, contribute to the burden of kidney disease. The reported kidney disease prevalence in patients with rheumatoid arthritis (RA) ranges from 5%-50% based on studies of different designs, and the true prevalence of kidney disease remains unclear.
RA has been associated with a variety of kidney disorders due principally to chronic inflammation and drug exposure or toxicity. The most commonly observed kidney diseases in patients with RA who have undergone kidney biopsy include mesangial proliferative glomerulonephritis, membranous nephropathy, immunoglobulin A nephropathy, minimal change disease, pauci-immune glomerulonephritis, analgesic nephropathy, interstitial nephritis, and AA amyloidosis.
As treatment patterns for RA have changed over the years, the incidence of kidney disease may be altered. Agents such as gold salts and d-penicillamine more commonly used in the past were linked directly to proteinuria and kidney disease. Cyclosporine therapy is associated with a dose-related nephrotoxicity in patients with RA. More recently, biologic agents including tumor necrosis factor α inhibitors have emerged as effective treatment. A variety of case reports suggesting a link to etanercept and glomerulonephritides indicate that kidney disease continues to be a disease- and treatment-related feature of RA. Finally, long-term maintenance anti-inflammatory therapy with nonsteroidal anti-inflammatory drugs (NSAIDs) or cyclooxygenase 2 inhibitors is a well-recognized cause of kidney injury.
Patients with kidney disease face increased morbidity and mortality, most of which is attributed to an increased burden of cardiovascular (CV) disease (CVD). Historically, patients with RA-associated renal amyloidosis had higher mortality rates relative to the general population. The occurrence of hematuria, proteinuria, or CKD has been reported to be associated with a 3- to 4-fold increased risk of death. Patients with RA have an excess burden of CVD for which CV risk has been underestimated previously by standard risk scores. Subclinical decreased kidney function has been identified as an independent risk factor for CV events in patients with RA.
The objective of this study was to determine the rate of and associated factors related to the development of reduced kidney function in patients with RA.
Abstract and Introduction
Abstract
Background: Rheumatoid arthritis (RA) is associated with a variety of kidney disorders. However, it is unclear whether the development of reduced kidney function is higher in patients with RA compared to the general population.
Study Design: Retrospective review.
Setting & Participants: Incident adult-onset RA cases (813) and a comparison cohort of non-RA individuals (813) in Olmsted County, MN, in 1980–2007.
Predictor: Baseline demographic and clinical variables.
Outcomes: Reduced kidney function: (1) estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m and (2) eGFR < 45 mL/min/1.73 m on 2 consecutive occasions at least 90 days apart; cardiovascular disease (CVD); and death.
Measurements: The cumulative incidence of reduced kidney function was estimated adjusting for the competing risk of death.
Results: Of 813 patients with RA and 813 non-RA individuals, mean age was 56 ± 16 (SD) years, 68% were women, and 9% had reduced kidney function at baseline. The 20-year cumulative incidence of reduced kidney function was higher in patients with RA compared with non-RA participants for eGFR < 60 mL/min/1.73 m (25% vs 20%; P = 0.03), but not eGFR < 45 mL/min/1.73 m (9% vs 10%; P = 0.8). The presence of CVD at baseline (HR, 1.77; 95% CI, 1.14–2.73; P = 0.01) and elevated erythrocyte sedimentation rate in patients with RA (HR per 10-mm/h increase, 1.08; 95% CI, 1.00–1.16; P = 0.04) was associated with increased risk of eGFR < 60 mL/min/1.73 m. eGFR < 60 mL/min/1.73 m was not associated with increased risk of CVD development in patients with RA (HR, 0.99; 95% CI, 0.63–1.57; P = 0.9), however, a greater reduction in GFR (eGFR < 45 mL/min/1.73 m) was associated with increased risk of CVD (HR, 1.93; CI, 1.04–3.58; P = 0.04).
Limitations: Reduced kidney function was defined by estimating equations for kidney function. We are limited to deriving associations from our findings.
Conclusions: Patients with RA were more likely to develop reduced kidney function over time. CVD and associated factors appear to play a role. The presence of RA in individuals with reduced kidney function may lead to an increase in morbidity from CVD development, for which awareness may provide a means for optimizing care.
Introduction
Chronic kidney disease (CKD) affects more than 26 million adults in the United States. Although diabetes mellitus and hypertension are the 2 primary causes of kidney failure, other conditions, including autoimmune processes, contribute to the burden of kidney disease. The reported kidney disease prevalence in patients with rheumatoid arthritis (RA) ranges from 5%-50% based on studies of different designs, and the true prevalence of kidney disease remains unclear.
RA has been associated with a variety of kidney disorders due principally to chronic inflammation and drug exposure or toxicity. The most commonly observed kidney diseases in patients with RA who have undergone kidney biopsy include mesangial proliferative glomerulonephritis, membranous nephropathy, immunoglobulin A nephropathy, minimal change disease, pauci-immune glomerulonephritis, analgesic nephropathy, interstitial nephritis, and AA amyloidosis.
As treatment patterns for RA have changed over the years, the incidence of kidney disease may be altered. Agents such as gold salts and d-penicillamine more commonly used in the past were linked directly to proteinuria and kidney disease. Cyclosporine therapy is associated with a dose-related nephrotoxicity in patients with RA. More recently, biologic agents including tumor necrosis factor α inhibitors have emerged as effective treatment. A variety of case reports suggesting a link to etanercept and glomerulonephritides indicate that kidney disease continues to be a disease- and treatment-related feature of RA. Finally, long-term maintenance anti-inflammatory therapy with nonsteroidal anti-inflammatory drugs (NSAIDs) or cyclooxygenase 2 inhibitors is a well-recognized cause of kidney injury.
Patients with kidney disease face increased morbidity and mortality, most of which is attributed to an increased burden of cardiovascular (CV) disease (CVD). Historically, patients with RA-associated renal amyloidosis had higher mortality rates relative to the general population. The occurrence of hematuria, proteinuria, or CKD has been reported to be associated with a 3- to 4-fold increased risk of death. Patients with RA have an excess burden of CVD for which CV risk has been underestimated previously by standard risk scores. Subclinical decreased kidney function has been identified as an independent risk factor for CV events in patients with RA.
The objective of this study was to determine the rate of and associated factors related to the development of reduced kidney function in patients with RA.