Prognostic nutritional index as an indicator for the development of bone fragility fracture in patients with rheumatoid arthritis.

OBJECTIVES: The validity of prognostic nutritional index (PNI) as an index of incident bone fragility fracture (inc-BFF) in rheumatoid arthritis (RA) patients was investigated. METHODS: RA patients whom continuously followed up for >3 years were picked up. Patients were classified in accordance with inc-BFF positivity (BFF+ and BFF-). Their clinical background including PNI was statistically examined for inc-BFF. The background factors were compared between the two groups. Patients were narrowed into subgroups according to the factor that showed a significant difference between the two groups, and they were statistically examined according to the PNI for the inc-BFF. The two groups were narrowed with propensity score matching and compared to the PNI. RESULTS: A total of 278 patients with 44 BFF+ and 234 BFF- were recruited. In the background factors, the presence of prevalent BFF and the simplified disease activity index remission rate had a significantly higher risk ratio. In a subgroup who comorbid lifestyle-related diseases, PNI had a significantly higher risk ratio for the inc-BFF. After the propensity score matching, the PNI showed no significant difference between the two groups. CONCLUSIONS: PNI is available when patients with RA comorbid lifestyle-related diseases. PNI is not an independent key for the inc-BFF in RA patients.

The impact of time length to Boolean remission for tight disease activity control after acquisition in rheumatoid arthritis patients.

Clinical importance of time length from initiation under treat-to-target (T2T) strategy to acquisition of clinical remission (TL) in treating patients with rheumatoid arthritis (RA) on disease activity control, daily activities, and quality of life maintenance was investigated. In patients who achieved Boolean remission once or more, relationship between TL and patients' background data at initiation, and relationship between TL and mean simplified disease activity score (SDAI), Health Assessment Questionnaire Disability Index (HAQ-DI) score, pain score with visual analog scale (PS-VAS), Sharp/van der Heijde Score (SHS) and quality of life score (QOLS) at the first remission and thereafter were evaluated statistically. Patients were divided into two groups whether TL was within 6 months or longer (G ≤ 6 and G > 6). Change of the parameters and Boolean remission rate (BRR) after the first remission between the two groups were compared statistically. In 465 patients, TL correlated significantly with the SDAI score, the HAQ score, PS-VAS, SHS, and the QOLS after the remission. The SDAI score and the BRR after the remission were significantly better in the G ≤ 6 than in the G > 6. TL is an important key to guarantee good and stable clinical course in treating under T2T.

Clinical significance of serum cystatin C-to-creatinine ratio as a surrogate marker for incident osteoporotic fracture predictions.

Background: Detection of appropriate indicators is valuable for preventing incidental osteoporotic fractures. We statistically evaluated the significance of serum cystatin C-to-creatinine ratio (CysC/Cr) as a surrogate marker for incident major osteoporotic fractures (MOF) prediction. Methods: Eligible patients with simultaneous measurement of CysC/Cr and bone mineral density in the lumbar spine and proximal femur were selected, and their fracture histories until 5 years after baseline were observed in the retrospective area cohort data. Patients who were followed up until termination or the first osteoporotic fracture were included, and loss of follow-up or death was excluded. Candidate risk factors for osteoporotic fractures were tested for risk ratios using a cox regression analysis. Receiver operating characteristic tests were performed on factors with significantly higher risk ratios and evaluated with Kaplan-Meier survival analysis to determine the hazard ratios of the factors. Results: A total of 175 patients of whom 28 had incident MOF, 38 men, and 137 women, were enrolled. The mean age was 70.2 years. A significantly higher risk ratio was shown in the presence of prevalent MOF, hyper fall-ability, lifestyle-related diseases, chronic kidney diseases ≥ Grade3a, and higher CysC/Cr. All parameters had cutoff indices and showed significantly higher hazard ratios. Conclusions: These results suggested that CysC/Cr may be a predictive marker of incident osteoporotic fractures. It might work as a screening tool for MOF risk.

Associations between clinical metrics of joint deformity, disease duration, disease activity, functional capacity, quality of life, pain, and fatigue in patients with rheumatoid arthritis.

OBJECTIVES: Aim of this study is to clarify associations between metrics of patient's clinical status statistically using retrospective cohort data. METHODS: Patients with RA who were followed up more than 3 years were recruited. Their EuroQol-5th dimension (EQ5D) as an index of quality of life (QOL), Health Assessment Questionnaire Disability Index (HAQ) as an index of functional capacity (FC), simplified disease activity index (SDAI), pain score using visual analog scale (PS-VAS), and fatigue score using visual analog scale (FS-VAS) were monitored every three months. Sharp/van der Heijde score (SHS) was calculated annually. Associations between average values of these factors at beginning of follow-up (baseline) and change from baseline to final year in follow-up (change), and patient's sex, age, and disease duration (DD) were evaluated statistically. RESULTS: A total of 447 patients were analyzed. EQ5D score correlated significantly with HAQ score both at baseline and change of that, and FS-VAS. HAQ score correlated significantly with EQ5D and HAQ score at baseline. SDAI score correlated significantly with SHS and FS-VAS at baseline. SHS correlated significantly with the SHS at baseline. PS-VAS correlated significantly with the PS-VAS, EQ5D at baseline, change of theEQ5D and HAQ scores. FS-VAS correlated significantly with change of the EQ5D score and FS-VAS at baseline. CONCLUSIONS: These results suggested that these clinical metrics are influenced by each variable at baseline. QOL and fatigue are correlated each other, as well as QOL and FC, whereas disease activity correlated with joint deformity level and fatigue. Key Points • It is questionable whether improvement of disease activity leads to improvements in functional capacity and QOL in treating rheumatoid arthritis. • We evaluated the association among metrics of clinical outcomes, such as EQ5D, HAQ, SDAI, SHS, pain score, and fatigue score using retrospective cohort data. • Results suggested that metrics are influenced by each items at baseline, and QOL and fatigue are correlated each other, as well as QOL and functional capacity.

Pain score as a predictor of subsequent fragility fracture in postmenopausal patients with rheumatoid arthritis: A retrospective case-control study.

Objectives: Bone fragility fracture (BFF) is a serious incident in treating rheumatoid arthritis (RA). We hypothesized that pain degree during treatment RA correlated with incident BFF and validated how pain affects incident BFF (inc-BFF). Methods: Postmenopausal RA patients treated for at least 3 years were recruited. The primary endpoint was the development of inc-BFF. Follow-up began with the first bone mineral density measurement (baseline) and continued until the development of the first BFF or termination of the study. Clinical indicators at baseline, including pain score using a visual analog scale (PS-VAS), were analyzed statistically using Cox regression analysis, receiver operation characteristics (ROC), Kaplan-Meier survival curve analysis (K-M), and chi-square test. Results: A total of 239 patients were recruited. Using a multivariate Cox regression analysis, the baseline's PS-VAS and prevalent BFF (pr-BFF) demonstrated significantly higher risk ratios. For ROC, pr-BFF and PS-VAS had significant cutoff index (COI) (positive, 21.0) and an area under-curve of 0.692 (P < 0.001) and 0.616 (P < 0.01), respectively. PS-VAS > COI had a 2.24-fold higher hazard ratio than PS-VAS ≤ COI using K-M. When these 2 conditions were combined, patients with pr-BFF-positive and PS-VAS-positive had a sensitivity of 42.3% and a specificity of 88.8% for the inc-BFF. PS-VAS > COI had no statistical significance in the subgroup without pr-BFF, whereas the existence of pr-BFF had a significantly higher risk ratio in the PS-VAS ≤ COI. Conclusions: The PS-VAS during RA treatment is a good indicator for predicting the inc-BFF in postmenopausal RA patients with pr-BFF.

Clinical Advantage of Attaining Index-Based Remission Prior to Composite Remission in Treating Rheumatoid Arthritis.

BACKGROUND AND OBJECTIVES: The clinical advantage of targeting index-based remission prior to Boolean remission was evaluated retrospectively. MATERIALS AND METHODS: A total of 578 patients with rheumatoid arthritis (RA), who were treated for more than three years, were recruited. Patients who were treated to targeted index-based remission and composite measure remission criteria such as Boolean remission from the first consultation were divided according to the turn of attaining Boolean remission and index-based remission: G-IBR, a group that matched index-based remission at the same time Boolean remission is attained or earlier; G-BR_IF, a group that attained Boolean remission followed by index-based remission or failed; G-IR_BF, a group that could not attain Boolean remission despite attaining index-based remission; G-BothF, a group that failed to attain either Boolean remission or index-based remission. Background factors were statistically compared among groups. The Boolean remission rate in patients who attained index-based remission (BRR) and the rate of failure to attain index-based remission in patients who failed to attain Boolean remission (BFR) were statistically evaluated. RESULTS: Groups comprising 225, 231, and 482 in G-IBR; 160, 154, and 8 in G-BR_IF; 18, 18, and 75 in G-IR_BF; and 175, 175, and 13 in G-BothF when indexing the clinical disease activity index (CDAI), simplified disease activity index (SDAI), and 28-joints disease activity score with C-reactive protein (DAS28-CRP), respectively. Disease activity indices' scores after Boolean remission were demonstrated to be significantly higher in the G-BR_IF group than in the G-IBR group. BRR was 92.6%, 92.8%, and 86.5%, while BFR was 71.3%, 71.3%, and 13.8% when indexing CDAI, SDAI, and DAS28-CRP, respectively. CONCLUSIONS: Targeting CDAI and SDAI remission prior to Boolean remission contributes to a stable clinical course.

Clinical characteristics and variants that predict prognosis of difficult-to-treat rheumatoid arthritis.

Factors influencing prognosis after administration of the last biologic or targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD) to patients with difficult-to-treat rheumatoid arthritis (D2T_RA) were evaluated in a clinical setting. RA patients who met the EULAR definition of D2T_RA were recruited. These patients were grouped according to success/failure. Success was defined as sustained within light disease activity or discontinued after clinical remission, and all of the following were met, including glucocorticoid (GCS) < 7.5 mg/day, no rapid radiographic progression, and improved quality of life from the beginning of the b/tsDMARD (baseline). Failure was defined as any other condition from success. The primary endpoint of the study was success or failure at 12 months after baseline. Factors influencing success/failure were statistically evaluated. A total of 71 D2T_RA patients were selected, 22 were in the success group and 49 in the failure group. For patients taking GCS and methotrexate (MTX) ≤ 8.6 mg/week, only one was included in the success group and the other 24 were included in the failure group (p < 0.001). Of the 18 patients without GCS and with MTX ≥ 8.7 mg, 12 patients whose 28-joint disease activity score ≤ 1.90 at 3 months or ≤ 2.54 at 6 months were in the success group (p < 0.01). D2T_RA patients with GCS or MTX ≤ 8.6 mg at baseline are considered to be at high risk of repeat D2T_RA. Patients with no GCS and MTX ≥ 8.7 mg are more likely to withdraw from D2T_RA if their disease activity is tightly controlled.

Validity and risk of adopting PGA ≤ 2 as a remission criteria of Boolean in clinical practice in patient with rheumatoid arthritis.

Validity and risk of setting patient's global assessment (PGA) ≤ 2 as a Boolean remission criteria substituting PGA ≤ 1 in treating rheumatoid arthritis (RA) was investigated. Patients were recruited from an area cohort, of whom attained Boolean remission (Boolean-1) or near remission with PGA ≤ 2 and the rest components were ≤ 1 (Boolean-2). Simplified disease activity index (SDAI) score was compared according to the criteria variations. A total of 517 patients were studied. Mean SDAI score of patients with Boolean-1 was significantly lower than that of patients with Boolean-2 at acquisition. The trend was evident in the patients who attained Boolean-1 remission. Mean SDAI score at acquisition, 6 months after, and 1 year after of patients who attained Boolean-2 first and then Boolean-1, was significantly inferior to that of patients who attained the remissions at the same time. The mean SDAI score at month 6 in the Boolean-2 was not SDAI remission at all. We concluded that setting PGA ≤ 2 as a remission criteria may not have statistical difference in disease activity from PGA ≤ 1, however, there was an determinant risk to misread that includes patient who losses clinical remission after acquisition.

Usefulness of cortical thickness ratio of the third metacarpal bone for prediction of major osteoporotic fractures.

OBJECTIVE: Patients with rheumatoid arthritis (RA) are at high risk for osteoporotic fractures. We developed an index called the third metacarpal cortical thickness ratio (CTR), which reflects bone mineral density (BMD) in RA patients. A longitudinal study was conducted to verify the usefulness of CTR during the follow-up period. METHODS: Patients with RA who underwent dual energy X-ray absorptiometry (DXA) and hand X-ray simultaneously were monitored for disease activity and activities of daily living at 3-month intervals, and BMD and CTR were measured at 1-year intervals. Mean CTR during follow-up was tested for correlation with mean BMD at both the lumbar spine (LS) and femoral neck (FN) during follow-up. Correlations were examined, including other variants potentially correlated with BMD. The risk ratio of accidental major osteoporotic fractures (MOF) in the variance including CTR and BMD was evaluated. RESULTS: A total of 300 patients, 40 men and 260 women, were enrolled. Mean follow-up length was 49.6 months. CTR was significantly associated with BMD in FN using a multivariate model of linear regression analysis (p < 0.0001), whereas CTR was significantly associated with BMD in LS using only a univariate model (p < 0.01). The only variant with a significantly higher risk ratio for incident MOF was the presence of prevalent MOF. CTR and BMD did not show a significantly higher risk ratio using Cox regression analysis. CONCLUSION: CTR correlated significantly with BMD even during follow-up, especially in FN. However, CTR and BMD were not risk factors for major MOF.

Musculoskeletal ambulation disability symptom complex as a risk factor of incident bone fragility fracture.

OBJECTIVES: Influence of presenting musculoskeletal ambulation disability symptom complex (MADS) on occurrence of bone fragility fracture (BFF) is investigated with retrospective cohort study. METHODS: A total of 931 subjects joined in the study. Subjects were selected as bone fragility risk positive in the fracture assessment tool questionnaire. Their assumed risk factors were harvested from the medical records and X-ray pictures. They were followed up at least 8 years consecutively, and occurrence of incident BFF was set as primary endpoint. Each assumed risk factor including MADS was evaluated using Cox regression analysis. Subjects were divided into 2 groups according to presence of MADS (G-MADS and G-noMADS). Adjusted hazard ratios between the 2 groups was evaluated using Cox regression analysis. The statistical procedures were performed before and after propensity score matching (PSM) procedures in order to make parallel with assumed risk factors. RESULTS: Statistically significant risk factors within 5% were prevalent vertebral body fracture, disuse, MADS, cognitive disorder, hypertension, contracture, Parkinsonism, being female sex, hyperlipidemia, insomnia, T-score in the femoral neck ≤ -2.3, chronic kidney disease ≥ stage 2, chronic obstructive pulmonary diseases, glucocorticoid steroid administrated, and osteoarthritis in order of the adjusted hazard ratios (from highest to lowest). Adjusted hazard ratios between G-MADS and G-noMADS were 2.70 and 1.83 for before and after PSM, respectively. CONCLUSIONS: MADS demonstrated as a significant risk factor of BFF occurrence. In treating osteoporosis, fall risk should be aware of as well as bone fragility risk.

Rheumatoid arthritis in tight disease control is no longer risk of bone mineral density loss.

OBJECTIVES: Rheumatoid arthritis (RA) is an independent risk factor of osteoporosis. However, if disease activity is successfully controlled using the treat-to-target (T2T) strategy, the risk of bone mineral density (BMD) loss can be diminished. We evaluated if RA is a risk factor even when the T2T is applied in clinical cases. METHODS: From September 2017 to August 2019, 741 patients were examined using dual-energy X-ray absorptiometry; of these, 279 were diagnosed with RA who attained clinical remission within 6 months (RA-rem) and 53 could not attain clinical remission (RA-nonrem), while 409 were not diagnosed with RA (non-RA). The following characteristics between RA-rem and non-RA were matched using the propensity score matching (PSM) technique: age, sex, past bone fragility fracture experience, osteoporosis drug intervention ratio, glucocorticoid administration ratio, mean dose, Barthel Index score, body mass index, serum-creatinine-to-cystatin C ratio, and the number of comorbidities. The BMDs and changes of the lumbar spine, femoral neck, total hip, and greater trochanter were statistically compared between the RA-rem and the non-RA after PSM, and between RA-nonrem and RA-rem after PSM using the Mann-Whitney U test. RESULTS: In total, 107 patients of RA-rem and 108 of non-RA were recruited. BMDs and changes of every part demonstrated no significant differences between the 2 groups. BMDs in every part of RA-rem after PSM were significantly greater than those in every part of RA-nonrem, while no significant difference in change during follow-up. CONCLUSIONS: If disease activity is controlled in clinical remission, RA will not contribute to BMD reduction.

Efficacy and Safety of Targeted Strategy for Treating Rheumatoid Arthritis Patients Aged 75 Years or Older.

The efficacy and safety of targeted treatment for elderly patients with rheumatoid arthritis (RA) was considered. Patients with RA who met the ACR/EULAR 2010 classification criteria and were treated consecutively for > 3 years, were recruited and classified into three age groups with 10-year increments from 65 years. Treatment protocol that aims to achieve clinical remission within 6 months was commonly adopted. The salient features are the rapid increase in dosages of conventional synthetic anti-rheumatic drugs (csDMARDs) and the administration of need-based concomitant biologic/targeted synthetic drugs and/or glucocorticoid steroid, and immediate tapering of glucocorticoid steroid and csDMARDs is required on attaining clinical remission. Disease activity score and other clinical indices specific for RA treatment, and the prevalence of adverse events were compared between the groups. The numbers of patients in the groups of the < 65 years, 65-74 years, and ≥ 75 years were 269, 155, and 152. No significant difference was observed between any pairs of groups with respect to disease activity; stable course after achievement of minimum disease activity was observed in all groups. However, the prevalence of adverse events, especially serious infection, in the oldest group was higher than that in the younger groups, which was likely attributable to the higher frequency of administration of glucocorticoid steroid after minimum disease activity obtained and higher prevalence of cardiovascular comorbidities. Targeted treatment is feasible even for patients aged ≥ 75. However, glucocorticoid steroid administration is considered as a risk of adverse events and should be tapered immediately.

Screening osteoporotic femoral neck without measuring bone mineral density with the use of tartrate resistant acid phosphatase-5b and serum-creatinine-to-cystatin C ratio in Japanese postmenopausal women.

BACKGROUND: Screening osteoporosis in Japanese postmenopausal women is an important subject for preventing bone fragility fracture (BFF). Measuring bone mineral density (BMD) is included in the criteria for osteoporosis diagnosis. However, it has not gained popularity. METHODS: BMD of lumbar spine (LS) and femoral neck (FN) were measured, the serum creatinine-to-cystatin C ratio (Cr/CysC), tartrate-resistant acid phosphatase-5b (TRACP-5b), body mass index (BMI) were also simultaneously measured. These subjects had no potential secondary osteoporosis factors or concomitant drug administration for osteoporosis (pSubjects; primary subjects). Best subsets regression analysis (BeStR) was evaluated for determining the statistically significant factors, and multivariate regression analysis (MLR) was used to assess the correlation of these factors with BMD at each part. Relationship between osteoporotic criteria whether T score≤-2.5 and each factor was also evaluated at each part with binary logistic regression analysis (BLR). Cut-off index (COI) at each part was determined, and sensitivity and specificity were evaluated in pSubjects and in subjects with whom potential secondary osteoporosis factors were included (sSubjects). RESULTS: BMI and Cr/CysC had a significant influence on BMD at the LS with BeStR, whereas only BMI demonstrated significant correlation with BMD both with MLR and BLR, with 22.7 of COI and sensitivity and specificity of 48.7% and 94.7%, respectively, in pSubjects with 60 and 49.1% and 87.5%, respectively, in sSubjects with 83. At the FN, Cr/CysC, BMI, and TRACP-5b significantly influenced BMD, whereas all these factors demonstrated significant correlation with BMD. Cr/CysC and TRACP-5b demonstrated significant correlation with T score≤-2.5 in BLR. With COI that was made in combination with these factors and subjects' age, sensitivity and specificity were 67.7% and 82.4%, respectively, in pSubjects and 55.8% and 82.8%, respectively, in sSubjects. CONCLUSIONS: These results suggested that BMI, TRACP-5b, and Cr/CysC may be realistic surrogate markers for screening osteoporosis in Japanese postmenopausal women.

Validity of adopting a Health Assessment Questionnaire Disability Index less than 0.5 as a target in elderly rheumatoid arthritis patients.

OBJECTIVES: The effect of age on the Health Assessment Questionnaire Disability Index (HAQ-DI) scores of rheumatoid arthritis (RA) patients and the validity of adopting HAQ-DI < 0.5 as the target for functional remission and comprehensive disease control (CDC) under a treat-to-target (T2T) treatment strategy were investigated. METHOD: A total of 441 RA patients with > 3-year treatment under T2T were evaluated. The relationships between the HAQ-DI score at follow-up (HAQ) and 28-joint Disease Activity Score with C-reactive protein, Sharp/van der Heijde Score, age at follow-up, and HAQ-DI at baseline were statistically evaluated with best subset regression analysis in groups separated according to age and the EULAR response. CDC status was evaluated with a chi-square test. RESULTS: The HAQ score significantly correlated with all indices in the group ≥ 65 years old (G-O) and in the group with good or moderate EULAR responses (p < 0.01). No significant correlation was observed in the group < 65 years old (G-Y) or in the group with no EULAR response. The CDC ratio was not significantly different between the age groups, whereas the HAQ failure ratio was significantly greater in G-O than in G-Y (p < 0.01). No significant difference was found between the EULAR response groups. CONCLUSIONS: The HAQ score is influenced by age in patients > 65 years. T2T is appropriate for attaining good disease activity control but does not always lead to functional remission in these patients. The HAQ score < 0.5 is not an appropriate target for functional remission according to the CDC criteria for elderly patients.Key Points• ADL in elderly RA patient aged ≥ 65 years declines corresponding to his/her aging.• Functional remission for elderly RA patients is not the same as that for young RA patients.• The HAQ score < 0.5 in elderly RA patient is not an appropriate target for CDC.

Influence of pain score measured by a visual analog scale (PS-VAS) on the Health Assessment Questionnaire Disability Index and 28-joint Disease Activity Index with C-reactive protein in rheumatoid arthritis patients.

BACKGROUND: Pain is a serious burden for rheumatoid arthritis (RA) patients. However, the effect on Health Assessment Questionnaire Disability Index (HAQ-DI) and 28-joint Disease Activity Score (DAS28) has not been presented. The aim of this study is to evaluate them in a case series. METHODS: Three hundred and eighty-two RA patients who were treated for more than 5 years were studied. The parameters assessed included average value of the DAS28 with C-reactive protein (DAS28-CRP), the HAQ-DI score, the Sharp/van der Heijde Score (SvdHS), age, and the pain score measured by a visual analog scale (PS-VAS). Relationships among these factors and the relationships between the HAQ-DI score and the other factors, and the relationships between the change in HAQ-DI scores and the changes in other factors were evaluated statistically with multivariate linear regression analysis. The effect of PS-VAS on HAQ-DI was compared with that of DAS28-CRP on the overlapping data of each parameter. RESULTS: HAQ-DI demonstrated significant positive correlations with all parameters. However, PS-VAS demonstrated a stronger effect than DAS28-CRP, also demonstrated without overlapping data. After minimizing the effects of DAS28-CRP, age and SvdHS, there was a significant correlation between HAQ-DI and PS-VAS in all analyses. The change in HAQ-DI demonstrated a significant correlation with the change in PS-VAS. CONCLUSIONS: These results suggested that HAQ-DI is deeply influenced by PS-VAS. The effect of DAS28-CRP overlapped with the effect of PS-VAS in a major way. Pain control for RA patients is the most important factor contributing to activities of daily living, as well as disease activity control.

[Successful treatment of combination therapy using an angiotensin-converting enzyme inhibitor and an angiotensin II receptor blocker in a patient with IgA nephropathy].

A 24-year-old Japanese woman with IgA nephropathy was admitted to our hospital due to the development of proteinuria and pretibial edema while on glucocorticoids and an angiotensin-converting-enzyme(ACE) inhibitor. She had been on both medications for more than 2 years. Urinary protein excretion was 2.53 g/day and renal function laboratory data were within the normal range. Plasma aldosterone concentration was high at 248 pg/ml, with normal plasma renin activity. The renal biopsy specimens showed prominent glomerular hypertrophy. Four weeks after the addition of valsartan, an angiotensin II receptor blocker(ARB), urinary protein excretion was remarkably reduced to 0.6 g/day without adversely affecting blood pressure. During the treatment period, proteinuria was maintained at less than 0.6 g/day and renal function remained normal. We propose that glomerular hypertension caused by insufficient suppression of the renin-angiotensin system was an essential factor underlying the increased urinary protein excretion in this patient. Combination therapy of an ARB and an ACE inhibitor appears to have a beneficial effect in patients with IgA nephropathy patients with persistent glomerular hypertension.