Pre-pregnancy kidney function and subsequent adverse pregnancy outcomes.

BACKGROUND: Renal insufficiency is associated with pregnancy complications including fetal growth restriction, preterm birth (PTB), and pre-eclampsia. OBJECTIVE: To determine the effect of preconception kidney function within the normal range on pregnancy outcome. METHOD: 1043 (50% black, 50% white) women who participated in the CARDIA study who had kidney function and biochemical analyses measured before at least one pregnancy delivered during the 20 years post-baseline period were included in analysis. Kidney function estimated as glomerular filtration rate (eGFR) via modified CKD-EPI equations, serum creatinine, and urinary albumin/creatinine ratio were evaluated as predictors of infant birthweight, gestational age, birthweight-for-gestational-age, and hypertensive disorders of pregnancy via self-report, using multiple regression with adjustment for confounders (age, race, smoking, BMI, center, parity, systolic blood pressure at baseline). Serum uric acid was also examined at both baseline and year 10. RESULTS: Unadjusted pre-pregnancy eGFR (baseline) was associated with lower average birthweight-for-gestational-age, but this disappeared after adjustment for confounders. A decline in GFR from baseline to year 10 was associated with lower birthweight (adjusted estimate -195 g, p = 0.03 overall), especially among whites. After adjustment for confounders, no association was found with gestational age or hypertensive disorders. CONCLUSIONS: No strong evidence for an association between preconception kidney function in the normal range and birthweight or gestational age was found. Possible racial differences in these relationships warrant further examination.

Comparing the functional impact of knee replacements in two cohorts.

BACKGROUND: To examine if different rates of total knee replacement (TKR) in two similar cohorts with symptomatic knee osteoarthritis (OA) were associated with different functional impact of disease. METHODS: Subjects from the Multicenter Osteoarthritis Study (MOST) and the Osteoarthritis Initiative (OAI), persons with or at high risk of OA, had knee radiographs, completed Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) surveys and had TKRs confirmed at each visit. At each visit, subjects were defined as having symptomatic OA (SxOA) if ≥ one knee had pain and radiographic OA or if they had a TKR. WOMAC function scores at each visit were compared by analysis of covariance adjusting for age, sex, body mass index, race, site, depression, comorbidity, painful leg joints and knees affected. Post-TKR function scores were imputed to estimate scores that would have been present without TKR. RESULTS: Subjects with SxOA (n>750 in MOST and in OAI) had a mean age 66 to 67 years; most were women and were White. Subjects were followed 4-5 years. Among those with SxOA, more TKRs were done in MOST (35%) than OAI (19%). Adjusted mean WOMAC function (0-68, 68 = worst) improved from 26.9 to 21.9 in MOST and from 24.5 to 22.0 in OAI (difference between MOST and OAI in change in WOMAC function, p = .01). Estimates of function without TKRs showed function would not have changed in MOST (23.2 at baseline to 22.4). CONCLUSIONS: Functional status of subjects with knee OA in MOST improved more than in OAI, probably because of higher rates of TKRs. The decline suggests that TKR diminishes the functional impact of OA in the community.

Valgus malalignment is a risk factor for lateral knee osteoarthritis incidence and progression: findings from the Multicenter Osteoarthritis Study and the Osteoarthritis Initiative.

OBJECTIVE: To study the effect of valgus malalignment on knee osteoarthritis (OA) incidence and progression. METHODS: We measured the mechanical axis from long limb radiographs from the Multicenter Osteoarthritis Study (MOST) and the Osteoarthritis Initiative (OAI) to define limbs with valgus malalignment (mechanical axis of ≥1.1° valgus) and examined the effect of valgus alignment versus neutral alignment (neither varus nor valgus) on OA structural outcomes. Posteroanterior radiographs and knee magnetic resonance (MR) images were obtained at the time of the long limb radiograph and at followup examinations. Lateral progression was defined as an increase in joint space narrowing (on a semiquantitative scale) in knees with OA, and incidence was defined as new lateral narrowing in knees without radiographic OA. We defined lateral cartilage damage and progressive meniscal damage as increases in cartilage or meniscus scores at followup on the Whole-Organ Magnetic Resonance Imaging Score scale (for the MOST) or the Boston Leeds Osteoarthritis Knee Score scale (for the OAI). We used logistic regression with adjustment for age, sex, body mass index, and Kellgren/Lawrence grade, as well as generalized estimating equations, to evaluate the effect of valgus alignment versus neutral alignment on disease outcomes. We calculated odds ratios (ORs) and 95% confidence intervals (95% CIs). RESULTS: We studied 5,053 knees (881 valgus) of subjects in the MOST cohort and 5,953 knees (1,358 valgus) of subjects in the OAI cohort. In both studies, all strata of valgus malalignment, including 1.1° to 3° valgus, were associated with an increased risk of lateral disease progression. In knees without radiographic OA, valgus alignment >3° was associated with incidence (e.g., in the MOST, adjusted OR 2.5 [95% CI 1.0-5.9]). Valgus alignment >3° was also associated with cartilage damage on MR imaging in knees without OA (e.g., in the OAI, adjusted OR 5.9 [95% CI 1.1-30.3]).We found a strong relationship of valgus malalignment with progressive lateral meniscal damage. CONCLUSION: Valgus malalignment increases the risk of knee OA radiographic progression and incidence as well as the risk of lateral cartilage damage. It may cause these effects, in part, by increasing the risk of meniscal damage.

A new approach yields high rates of radiographic progression in knee osteoarthritis.

OBJECTIVE: Progression of knee osteoarthritis (OA) has typically been assessed in the medial tibiofemoral (TF) compartment on the anteroposterior (AP) or posteroanterior (PA) view. We propose a new approach using multiple views and compartments that is likely to be more sensitive to change and reveals progression throughout the knee. METHODS: We tested our approach in the Multicenter Osteoarthritis Study, a study of persons with OA or at high risk of disease. At baseline and 30 months, subjects provided PA (fixed flexion without fluoro) and lateral weight-bearing knee radiographs. Paired radiographs were read by 2 readers who scored joint space (JS) using a 0-3 atlas-based scale. When JS narrowed but narrowing did not reach a full grade on the scale, readers used half-grades. Change was scored in medial and lateral TF compartments on both PA and lateral views and in the patellofemoral (PF) joint on lateral view. A knee showed progression when there was at least a half-grade worsening in JS width in any compartment at followup. Disagreements were adjudicated by a panel of 3 readers. To validate progression, we tested definitions for TF progression to see if malalignment on long-limb radiographs at baseline (>or=3 degrees malaligned in any direction with nonmalaligned knees being reference) increased risk of progression. A valid definition of progression would show that malalignment strongly predicted progression. RESULTS: We studied 842 knees with either Kellgren-Lawrence grade>or=2 or PF OA at baseline in 606 subjects (age range 50-79 yrs, mean 63.9 yrs; 66.6% women). Mean body mass index was 31.9, and 32.8% of knees had frequent knee pain at baseline. Of these, 500 knees (59.4%) showed progression. Of the 500, 75 (15%) had progression only in the PF joint, while the remainder had progression in the TF joint. Malalignment increased the risk of overall progression in TF joint and increased the risk of half-grade progression, suggesting that half-grade progression had validity. CONCLUSION: PA and lateral views obtained in persons at high risk of OA progression can produce a cumulative incidence of progression above 50% at 30 months. Keys to increasing the yield include imaging PF and lateral compartments, using semiquantitative scales designed to detect change, and examining more than one radiographic view.

Correlation of the development of knee pain with enlarging bone marrow lesions on magnetic resonance imaging.

OBJECTIVE: Results of cross-sectional studies have suggested that bone marrow lesions (BMLs) visualized on magnetic resonance imaging (MRI) are related to knee pain, but no longitudinal studies have been done. This study was undertaken to determine whether enlarging BMLs are associated with new knee pain. METHODS: Subjects ages 50-79 years with knee osteoarthritis (OA) or at high risk of knee OA were asked twice at baseline about the presence of knee pain, aching, or stiffness (classified as frequent knee pain) on most days; absence of knee pain was the baseline eligibility criterion. At 15 months' followup, subjects were again queried twice about frequent knee pain. A case knee was defined as absence of knee pain at baseline but presence of knee pain both times at followup. Controls were selected randomly from among knees with absence of pain at baseline. All MR images were scored for volume of BMLs in the medial, lateral, and patellofemoral compartments. We focused on the maximal change in BML score among the knee compartments from baseline to 15 months. Multiple logistic regression, with adjustments for demographic and clinical variables, was used to assess whether an increased BML score is predictive of the development of knee pain. RESULTS: Among case knees, 54 of 110 (49.1%) showed an increase in BML score within a compartment, whereas only 59 of 220 control knees (26.8%) showed an increase (P < 0.001 by chi-square test). A BML score increase of at least 2 units was much more common in case knees than in control knees (27.5% versus 8.6%; adjusted odds ratio 3.2, 95% confidence interval 1.5-6.8). Among case knees with increased BMLs, most already had BMLs at baseline, with enlarging BMLs at followup, but among the subset of knees with no BMLs at baseline, new BMLs were more common in case knees (11 [32.4%] of 34) than in control knees (9 [10.8%] of 83). CONCLUSION: Development of knee pain is associated with an increase in BMLs as revealed on MRI.