Naoki Sugano

Plasma cell-rich rejection accompanied by acute antibody-mediated rejection in a patient with ABO-incompatible kidney transplantation

We report a case of plasma cell‐rich rejection accompanied by acute antibody‐mediated rejection in a patient with ABO‐incompatible kidney transplantation. A 33‐year‐old man was admitted for an episode biopsy; he had a serum creatinine (S‐Cr) level of 5.7 mg/dL 1 year following primary kidney transplantation. Histological features included two distinct entities: (1) a focal, aggressive tubulointerstitial inflammatory cell (predominantly plasma cells) infiltration with moderate tubulitis; and (2) inflammatory cell infiltration (including neutrophils) in peritubular capillaries. Substantial laboratory examination showed that the patient had donor‐specific antibodies for DQ4 and DQ6. Considering both the histological and laboratory findings, we diagnosed him with plasma cell‐rich rejection accompanied by acute antibody‐mediated rejection. We started 3 days of consecutive steroid pulse therapy three times every 2 weeks for the former and plasma exchange with intravenous immunoglobulin (IVIG) for the latter histological feature. One month after treatment, a second allograft biopsy showed excellent responses to treatment for plasma cell‐rich rejection, but moderate, acute antibody‐mediated rejection remained. Therefore, we added plasma exchange with IVIG again. After treatment, allograft function was stable, with an S‐Cr level of 2.8 mg/dL. This case report demonstrates the difficulty of the diagnosis of, and treatment for, plasma cell‐rich rejection accompanied by acute antibody‐mediated rejection in a patient with ABO‐incompatible kidney transplantation. We also include a review of the related literature.

Augmented antihypertensive effect of a fixed combination formula of candesartan and hydrochlorothiazide combined with furosemide in a patient on peritoneal dialysis

A 38-year-old female patient on peritoneal dialysis (PD) due to type 1 diabetic nephropathy with a well-preserved residual renal function did not respond well to the conventional antihypertensive therapy consisting of candesartan, furosemide, and bunazosin. Switching candesartan for a fixed combination formula of candesartan plus hydrochlorothiazide (HCTZ) while the rest of the other two agents remained unchanged led to the remarkable reduction in both systolic and diastolic blood pressure (BP) without significant changes in the cardiothoracic ratio (CTR), body weight (BW), and residual renal function. This case suggests that when used in combination, diuretics acting on different functional segment of the nephron hold greater potential for enhanced antihypertensive effect, especially in patients on PD whose residual renal function is well preserved. A small dose of HCTZ with an angiotensin II receptor blocker (ARB) may partially explain the therapeutic benefit of this combination therapy in terms of a reliable hypotensive effect, a better adherence, and fewer side effects.

Forced expression of vascular endothelial growth factor-A in podocytes decreases mesangial cell numbers and attenuates endothelial cell differentiation in the mouse glomerulus

BackgroundGlomerular podocyte-derived vascular endothelial growth factor (VEGF) is indispensable for the migration and proliferation of glomerular endothelial cells. In contrast, podocyte-specific Vegf overexpression leads to the collapse of glomerular tufts; however, the mechanisms underlying this outcome have not yet been reported.MethodsTo further clarify the effects of elevated levels of Vegf expression on glomerular cells, we established a dual transgenic mouse line in which Vegf was exclusively and inducibly expressed in podocytes under the control of the “Tet-on system” (Podocin-rtTA/TetO-Vegf164 mice).ResultsMacroscopic and microscopic examination of Podocin-rtTA/TetO-Vegf164 animals following Vegf induction identified the presence of prominent red bloody spots. In addition, the endothelial cell number was increased along with enlargement of the subendothelial spaces. We also observed impaired endothelial fenestrations and aberrant plasmalemmal vesicle-associated protein-1 (PV-1) expression. In contrast, the mesangial cell number markedly decreased, resulting in a glomerular tuft intussusceptive splitting defect. Furthermore, whereas platelet-derived growth factor-B (PDGF-B) expression in the glomerular cells of Podocin-rtTA/TetO-Vegf164 mice was not decreased, phospho-PDGF receptor immunoreactivity in the mesangial cells was significantly decreased when compared to wild-type animals.ConclusionTaken together, the results of this study indicated that the upregulation of podocyte VEGF decreased the number of mesangial cells, likely owing to inhibition of PDGF-B-mediated signaling.

Gender interaction of uric acid in the development of hypertension

ABSTRACT Aim: The present study explored the gender interaction on the risk of uric acid in the new development of hypertension. Study Design: A longitudinal retrospective cohort. Subjects & Methods: A total of 5,807 individuals with an average age of 38 ± 7 years old were recruited. Individuals whose blood pressure rose more than 140/90mmHg or those who newly commenced antihypertensive treatment were defined as a new onset of hypertension. Cox regression analysis was employed for the analysis. Results: During the 10-years follow-up, 42.8% of men and 22.2% of women had developed hypertension. Factors to predict the hypertension development were male gender, older age, higher BMI, higher uric acid, and higher mean blood pressure. An association between higher uric acid levels and higher incidence of hypertension remained statistically significant in women in a multivariate model adjusted for various clinical variables (Hazard ration (HR), 1.180; 95%CI, 1.018 to 1.369), whereas such association was not found in men (HR, 1.034; 95%CI, 0.994 to 1.075). The interaction between the two genders reached statistical significance (p for interaction = 0.007). Conclusion: Higher uric acid is associated with the incident hypertension in the both genders. Women are more susceptible to the development of hypertension than men.

Monitoring of body water composition by the simultaneous use of bioelectrical impedance analysis and Crit-Line® during hemodialysis

BackgroundBioelectrical impedance analysis (BIA) is a non-invasive method to estimate total body water (TBW) and extracellular water (ECW) volume. Crit-Line® (CL), on the other hand, assesses intravascular water (IVW) volume. We evaluate continuous changes in body water composition during hemodialysis (HD) with concurrent use of BIA and CL.MethodsBIA at the start and the end of the HD session was measured using a BIA device. To investigate the shifting pattern of body water composition, patients were subjected to simultaneous monitoring of BIA with CL.ResultsBoth TBW resistance (Rt) and ECW resistance (Re) increased in response to changes in the ultrafiltration (UF) ratio. There was a positive correlation between ΔRe/Rt and the UF ratio, and the ratio of Re/Rt at the end of HD was significantly higher than that at the start of HD. Simultaneous monitoring of BIA with CL showed a parallel shift of the change in the Re (ΔRe) and the change in hematocrit (ΔHt). In one patient with increasing inflammatory response, change in ΔHt was dissociated from change in ΔRe. One hyponatremic patient showed a different pattern of changing ΔRe between the first half and the latter half of the HD session.ConclusionOur study suggests that the concurrent use of BIA and CL may be a useful technique to simulate water shift patterns across the different compartments in HD.

1034 CIRCULATING RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM (RAAS) IN PATIENTS ON HEMODIALYSIS (HD) -MODULATING EFFECT OF RAAS INHIBITORS DURING HD-

Background: Fluid removal by HD is accompanied by the modulation of circulating RASS. The present study explored changes in the RAAS hormones during HD session, analyzing factors to affect such changes. Methods: Plasma renin activity (PRA) and plasma aldosterone concentration (PAC) were measured before and after HD in 109 patients (59 diabetics and 50 non-diabetics). We then examined any association of these RAAS hormones with fluid removal, BP, the use of RAAS inhibitors, and the presence of diabetes. Results: The ratio of water removal by HD correlates with both changes in the ratio of PRA (&Dgr;PRA) and the changes in the ratio of PAC (&Dgr;PAC) only in patients taking RAAS inhibitors. In non-diabetics, the ratio of water removal is correlated with &Dgr;PRA and the changes in the ratio of BP (&Dgr;BP) is correlate with &Dgr;PAC. However, in diabetes patients there were no such changes. The ratio of water removal has no correlation with &Dgr;BP regardless of diabetes and the use of RASS inhibitors. Conclusion: Change in BP during HD is not associated with water removal, but is correlated with the changes in RAAS hormones. Moreover, the response of RAAS hormone to fluid removal is improved in the presence of RAAS inhibitors, suggesting that RAAS blocking modulates BP controlling mechanism in HD patients. This abnormal BP regulation may have been accelerated in the presence of diabetes.