Hyeon Joo Jeong

Live donor renal allograft in end-stage renal failure patients from immunoglobulin A nephropathy.

Background. The purpose of this study was to attempt to resolve two important issues, i.e. to determine (1) whether the course of recurrent immunoglobulin A nephropathy (IgAN) is benign, and (2) whether it is advisable to use a related donor. Methods. We evaluated the long-term outcome, in terms of recurrence and graft survival, after live related or unrelated donor renal transplantation, and assessed the validity of the use of related donors in 90 grafts in 89 IgAN patients. Results. Ten-year graft survival for IgAN patients was 66%, compared with 84% for 107 reference recipients who had other kinds of glomerulonephritis (GN), and with 69% in 90 other recipients who had non-GN renal failure (P =0.27). In 43 grafts, 54 event graft biopsies were performed, documenting the presence of mesangial IgA deposits in 19 of those grafts. In eight grafts, lesions were accompanied by chronic rejection (CR). Ten-year cumulative recurrence was 44%. Ten grafts were lost: by CR (n=3) or acute rejection (n=1) in 24 recurrence-free recipients, by CR (n=2) or recurrence (n=2) in 19 recurrent patients, and by patient death (n=2) in 46 patients devoid of graft biopsy. We found no difference in 10-year graft survival between the recurrent and recurrence-free patients (63% vs. 74%, P =0.98), or the proportion of related donors (68% vs. 83%, P =0.25). The presence or matching of HLA B12, B35, or DR4 did not affect the recurrence. Conclusions. Recurrence increased to 44% with longer follow-up, but this did not limit the graft outcome. Recurrence was not affected by the kind of live donor. We conclude that live related or unrelated kidneys should be offered to IgAN patients.

Decreased circulating C3 levels and mesangial C3 deposition predict renal outcome in patients with IgA nephropathy.

Background and Aims Mesangial C3 deposition is frequently observed in patients with IgA nephropathy (IgAN). However, the role of complement in the pathogenesis or progression of IgAN is uncertain. In this observational cohort study, we aimed to identify the clinical implications of circulating C3 levels and mesangial C3 deposition and to investigate their utility as predictors of renal outcomes in patients with IgAN. Methods A total of 343 patients with biopsy-proven IgAN were enrolled between January 2000 and December 2008. Decreased serum C3 level (hypoC3) was defined as C3 <90 mg/dl. The study endpoint was end-stage renal disease (ESRD) and a doubling of the baseline serum creatinine (D-SCr). Results Of the patients, there were 66 patients (19.2%) with hypoC3. During a mean follow-up of 53.7 months, ESRD occurred in 5 patients (7.6%) with hypoC3 compared with 9 patients (3.2%) with normal C3 levels (P = 0.11). However, 12 patients (18.2%) with hypoC3 reached D-SCr compared with 17 patients (6.1%) with normal C3 levels [Hazard ratio (HR), 3.59; 95% confidence interval (CI), 1.33–10.36; P = 0.018]. In a multivariable model in which serum C3 levels were treated as a continuous variable, hypoC3 significantly predicted renal outcome of D-SCr (per 1 mg/dl increase of C3; HR, 0.95; 95% CI, 0.92–0.99; P = 0.011). The risk of reaching renal outcome was significantly higher in patients with mesangial C3 deposition 2+ to 3+ than in patients without deposition (HR 9.37; 95% CI, 1.10–80.26; P = 0.04). Conclusions This study showed that hypoC3 and mesangial C3 deposition were independent risk factors for progression, suggesting that complement activation may play a pathogenic role in patients with IgAN.

Clinical Features and Outcomes of IgA Nephropathy with Nephrotic Syndrome

BACKGROUND AND OBJECTIVES Nephrotic syndrome (NS) is a rare manifestation of IgA nephropathy (IgAN). Clinical characteristics and long-term outcomes of this condition have not yet been explored. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS A multicenter observational study was conducted between January 2000 and September 2010 in 1076 patients with biopsy-proven IgAN from four medical centers in Korea. The primary outcome was a doubling of the baseline serum creatinine concentration. RESULTS Of the 1076 patients, 100 (10.2%) presented with NS; complete remission (CR), partial remission (PR), and no response (NR) occurred in 48 (48%), 32 (32%), and 20 (20%) patients, respectively. During the median follow-up of 45.2 months, 24 patients (24%) in the NS group reached the primary endpoint compared with 63 (7.1%) in the non-NS group (P<0.001). The risk of reaching the primary endpoint was significantly higher in the PR (P=0.04) and NR groups (P<0.001) than in the CR group. Among patients with NS, 24 (24%) underwent spontaneous remission (SR). SR occurred more frequently in female patients and in patients with serum creatinine levels ≤1.2 mg/dl and a >50% decrease in proteinuria within 3 months after NS onset. None of the patients with SR reached the primary endpoint and they had fewer relapses during follow-up. CONCLUSIONS This study demonstrated that the prognosis of NS in IgAN was not favorable unless PR or CR was achieved. In addition, SR was more common than expected, particularly in patients with preserved kidney function and spontaneous decrease in proteinuria shortly after NS onset.

DOES DELAYED OPERATION FOR PEDIATRIC URETEROPELVIC JUNCTION OBSTRUCTION CAUSE HISTOPATHOLOGICAL CHANGES

PURPOSE We studied histopathological changes in kidneys with demonstrable ureteropelvic junction obstruction in relation to patient age, differential renal function and urinary tract infection. MATERIALS AND METHODS Renal biopsy was performed in 42 children (44 kidneys) with a mean age of 3 years 6 months who underwent open pyeloplasty due to ureteropelvic junction obstruction. Each specimen was examined for reversible inflammatory cell infiltration and irreversible change, including interstitial fibrosis, arteriolar thickening and glomerular sclerosis. Each pathological finding was scored 0 to 3 in increasing grades of severity, and correlated with patient age, differential renal function and history of urinary tract infection. RESULTS Of the 44 kidneys 20 (45%) had irreversible change. Correlation study revealed no association between patient age and histological findings, and there was no statistically significant difference in any histopathological category regardless of age. Differential renal function correlated with inflammatory cell infiltration and interstitial fibrosis. There were significantly worse histopathology scores in all categories when differential renal function was less than 30 versus 40% or greater. Interstitial fibrosis was significantly worse in the 30 to 40% group than in the greater than 40% group. The histopathological score of interstitial fibrosis was significantly higher in patients with than without urinary tract infection. CONCLUSIONS Early correction in infants with ureteropelvic junction obstruction may not be necessary when initial differential renal function is greater than 40%. However, any decrease in differential renal function or recurrent urinary tract infections despite antibiotic prophylaxis warrant surgical correction of obstruction.

Primary malignant fibrous histiocytoma of the liver: imaging features of five surgically confirmed cases

AbstractBackground: The purpose of the present study was to describe the various imaging features of primary malignant fibrous histiocytoma (MFH) of the liver, a rare tumor of mesenchymal origin. Methods: Sonography (n= 5), computed tomography (CT; n= 5), magnetic resonance (MR) imaging (n= 2), and hepatic arteriography (n= 3) in five patients who underwent partial hepatectomy for tumor resection were retrospectively reviewed and correlated with pathologic findings. Results: All tumors were clearly demarcated from surrounding hepatic parenchyma in sectional imaging with (n= 2) or without (n= 3) a fibrous capsule, which was pathologically verified. Internal architecture of abundant fibrosis, myxoid degeneration, and/or hemorrhagic necrosis reflected the sonographic, CT and MR imaging findings. Marginal tumor staining without definite tumor vasculature was the main feature of hepatic arteriography. There was no intratumoral calcification. All three tumors involving the right lobe of the liver invaded the right hemidiaphragm. Conclusion: Although there were no unique findings of primary hepatic MFH, a combined interpretation of various imaging modalities may elucidate the malignant nature of the tumor.

PRIMARY LEIOMYOSARCOMA OF THE GREATER OMENTUM : CT FINDINGS

Three cases of primary leiomyosarcoma arising from the greater omentum are described. On CT the tumors were multilobulated, flat, and pancake-like, with enhancing solid and multicystic densities. The masses in all cases were located in the most anterior part of peritoneal cavity. These CT findings are useful in the preoperative diagnosis of omental leiomyosarcoma.

Decreased Interstitial Cells of Cajal-like Cells, Possible Cause of Congenital Refluxing Megaureters: Histopathologic Differences in Refluxing and Obstructive Megaureters

OBJECTIVES To evaluate the location of interstitial cells of Cajal-like cells and the ureteral aspect using histopathologic studies of obstructive and refluxing megaureters to reveal the different pathogenesis of megaureters in the human urinary tract. The underlying pathophysiology of obstructive megaureter and refluxing megaureter is poorly understood. METHODS The data from 14 patients with obstructive megaureter (7 boys and 7 girls), with a mean age of 12 months (range 2-84), and 9 patients with refluxing megaureter (7 boys and 2 girls), with a mean age of 11 months (range 4-24), were compared. We investigated the difference in the histopathologic aspects using Massons trichrome, terminal uridine deoxynucleotidyl transferase dUTP nick end labeling (for apoptosis), and human c-kit antibody (CD117 for interstitial cells of Cajal-like cells) between the obstructive and refluxing megaureters. RESULTS The proportion of smooth muscle was significantly lower in segments of refluxing megaureter (32.04% +/- 4.96%) than in the segments of obstructive megaureter (52.48% +/- 3.46%; P < .01). The number of apoptotic cells was significantly increased in the obstructive megaureter (mean 1661 +/- 135.1 cells) compared with the refluxing megaureter (mean 375.2 +/- 65.14 cells; P < .0001). The number of c-kit positive cells was significantly lower in the refluxing megaureter (mean 83.60 +/- 48.84 cells) than in the obstructive megaureter (mean 463.6 +/- 100.4 cells; P < .05). CONCLUSIONS The differences in the histopathologic aspects can provide information on the possible pathophysiology of obstructive and refluxing megaureters. Ureteral peristalsis can be affected by the increased myocyte apoptosis in the obstructive megaureter and by the decreased number of interstitial cells of Cajal-like cells and smooth muscle content in refluxing megaureters. Additional research is warranted to elucidate the exact pathophysiology.

Successful use of cyclosporin A in severe Schönlein–Henoch nephritis resistant to both methylprednisolone pulse and azathioprine

Schönlein–Henoch nephritis (SHN) usually presents with micro-haematuria or mild proteinuria but can be associated with heavy proteinuria and nephrotic or acute nephritic syndrome. Although the treatment of SHN is still under debate, it has been suggested that cyclosporin A (CsA) may be beneficial in children with severe SHN, as reported by Ronkainen et al. (Pediatr Nephrol 18:1138–1142, 2003) and Someya et al. (Pediatr Int 46:111–113, 2004). However, histological effects of CsA on severe SHN had not been evaluated in their evaluations. We report the successful use of CsA in a male patient with severe SHN with nephrotic-range proteinuria, who failed to respond to methylprednisolone pulse and azathioprine therapy.

Clinical implication of crescentic lesions in immunoglobulin A nephropathy

BACKGROUND To date, there has been much controversy about the role of crescentic lesion as a significant prognostic factor in immunoglobulin A nephropathy (IgAN). This study evaluated whether crescentic lesions predict adverse renal outcomes in IgAN patients. METHODS A total of 430 patients with biopsy-proven IgAN between January 2000 and December 2009 were included. Histological variables of the Oxford classification (Oxford-MEST) and the presence of crescents were assessed. The primary endpoint was a 50% decline in estimated glomerular filtration rate. RESULTS Of the 430 patients, 81 (18.8%) had a crescentic lesion. During a mean follow-up of 61 months, the primary outcome occurred in 19 (23.5%) patients with crescents compared with 40 (11.5%) patients without crescents (P=0.01). A Kaplan-Meier plot showed that the 10-year renal survival rate was significantly lower in patients with crescents than patients without crescents (P=0.01). However, in a multivariable Cox analysis which included clinical factors and the Oxford-MEST, crescents were not significantly associated with an increased risk of developing the primary outcome [hazard ratio: 0.71, 95% confidence interval (CI) 0.36-1.41, P=0.33]. Furthermore, adding crescents to the Oxford-MEST did not improve the discriminative ability for the prediction of renal outcomes [c-statistic: 0.86 (0.81-0.91) vs. 0.86 (0.80-0.91), P=0.21]. CONCLUSION Crescentic lesion was not an independent prognostic factor, suggesting that crescents have limited value in predicting renal outcomes of IgAN.

Comparison of the Haas and the Oxford classifications for prediction of renal outcome in patients with IgA nephropathy

Pathologic features can provide valuable information for determining prognosis in IgA nephropathy (IgAN). However, it is uncertain whether the Oxford classification, a new classification of IgAN, can predict renal outcome better than previous ones. We conducted a retrospective cohort study in 500 patients with biopsy-proven IgAN between January 2002 and December 2010 to compare the ability of the Haas and the Oxford classifications to predict renal outcome. Primary outcome was a doubling of the baseline serum creatinine concentration (D-SCr). During a mean follow-up of 68 months, 52 (10.4%) and 35 (7.0%) developed D-SCr and end-stage renal disease, respectively. There were graded increases in the development of D-SCr in the higher Haas classes. In addition, the primary endpoint of D-SCr occurred more in patients with the Oxford M and T lesions than those without such lesions. In multivariate Cox regression analyses, the Haas class V (HR, 12.19; P=.002) and the Oxford T1 (hazard ratio [HR], 6.68; P<.001) and T2 (HR, 12.16; P<.001) lesions were independently associated with an increased risk of reaching D-SCr. Harrells C index of each multivariate model with the Haas and the Oxford classification was 0.867 (P=.015) and 0.881 (P=.004), respectively. This was significantly higher than that of model with clinical factors only (C=0.819). However, there was no difference in C-statistics between the 2 models with the Haas and the Oxford classifications (P=.348). This study suggests that the Haas and the Oxford classifications are comparable in predicting progression of IgAN.