Yubing Wen

Conventional versus ultrapure dialysate for lowering serum lipoprotein(a) levels in patients on long-term hemodialysis: A randomized trial

Purpose In patients on long-term hemodialysis, high lipoprotein(a) [Lp(a)] levels are difficult to lower with medications, although they remain a risk factor for cardiovascular disease. We investigated whether ultrapure dialysate (UPD) could lower Lp(a). Methods: We randomly assigned patients stabilized on long-term dialysis to either a low-flux synthetic polysulphone membrane (the UPD group; n=14) or to a conventional dialysate (the CD group; n=13). Blood samples were collected 1 week before dialysis and 1 week, 1 month, 6 months and 12 months after dialysis; Lp(a) was measured by the immunotur-bidimetry method. Hemoglobin, interleukin-6, hypersensitive C-reactive protein, β2 microglobulin and albumin were also measured. The erythropoietin dosage, Kt/V, and normalized protein catabolic rate were recorded monthly. Results At 12 months, mean (SD) serum levels of Lp(a) in the CD patients increased from 143.46 (125.11) to 283.89 (145.81) mg/L (p<0.01), whereas levels in the UPD group remained unchanged: 131.38 (201.45) to 120.90 (122.11) mg/L. Endotoxin levels in the 10 CD patients who completed the study ranged from 0.116 to 0.349 EU/mL and were undetectable in the 11 UPD patients who completed the study. The cultures were less than 200 CFU/mL in CD patients and negative all the time for all UPD patients. Changes in Lp(a) from baseline values were lower in the UPD group than in the CD group (p<0.05). However, changes in other variables did not differ between groups. Conclusions Ultrapure dialysate can prevent the rise of Lp(a), potentially decreasing the risk of cardiovascular disease in hemodialysis patients.

Glomerular Disease Associated with Takayasu Arteritis: 6 Cases Analysis and Review of the Literature

OBJECTIVE To evaluate the clinical features, renal histopathology and therapeutic response to glucocorticoid and immunosuppressive agents in patients with glomerular disease associated with Takayasu arteritis (TA). METHODS Patients with TA and renal biopsy-confirmed glomerular disease were investigated retrospectively. None of them had renal artery stenosis or occlusive changes. RESULTS Six patients with glomerulopathy, accounting for 3.75% of the 160 TA patients admitted to our hospital at the same period, were analyzed. All of them were females with a mean age of 35.5 +/- 10.0 years. Four cases presented with lower extremity edema. Laboratory tests showed that one was nephrotic syndrome, three were nephrotic range proteinuria, and two of them had mild renal dysfunction. The other two patients were asymptomatic microscopic hematuria and proteinuria. Renal pathology revealed mild immunoglobulin A nephropathy in two cases, mild mesangial proliferative glomerulonephritis (GN), membranoproliferative GN, minimal change disease, and fibrillary GN in one case respectively. Five cases received glucocorticoids and cyclophosphamide therapy. Proteinuria and microscopic hematuria disappeared in 2 to 4 weeks after the initiation of therapy in three cases. The patient with membranoproliferative GN also reached complete remission of proteinuria and recovered renal function 6 months after the treatment. CONCLUSIONS TA may induce glomerular disease as a part of its histological spectrum. Apart from ischemic glomerular disease, glomerular disease should be suspected when TA patients have microscopic hematuria or proteinuria, that may be therapeutically responsive to glucocorticoids and immunosuppressive agent in relative early phase.

Endoplasmic Reticulum Stress Predicts Clinical Response to Cyclosporine Treatment in Primary Membranous Nephropathy

Background: Little is known about the endoplasmic reticulum stress (ERS) marker glucose regulated protein 78 (GRP78) and calcineurin in the kidney in primary membranous nephropathy (PMN) and if they could predict post-cyclosporine treatment outcome. Methods: This is a retrospective study using a dataset of biopsy-confirmed PMN from Peking Union Medical College Hospital from 1996 to 2014. Seventy-six adult patients treated with cyclosporine as primary immunosuppression for at least 6 months were studied. Immunohistochemistry was used to detect GRP78 and calcineurin in the kidney. Serum calcineurin was assayed by ELISA. Patients were grouped into no-remission (NR, n = 17), partial remission (PR, n = 39), or complete remission (CR, n = 20) at the end of 6 months of treatment. Results: There was no difference of initial dose of cyclosporine among NR, PR, and CR groups. Kidney calcineurin expression in PMN was significantly increased compared to that in controls (p < 0.0083). The glomerular GRP78 in NR PMN was higher than that in control, CR and PR patients (p < 0.0083). Kidney calcineurin expression and GRP78 expression was positively correlated. However, there were no differences in either serum calcineurin levels or kidney calcineurin expressions among NR, PR or CR groups. There was a negative correlation between serum calcineurin activity and whole kidney calcineurin expression (p = 0.034) or glomerular calcineurin expression (p = 0.007). Neither kidney calcineurin nor GRP78 expression was correlated with proteinuria. Conclusions: ERS marker GRP78 in the glomeruli but not serum or kidney calcineurin expression could be a useful marker in PMN to negatively predict the response to cyclosporine treatment at the sixth month.

Postpartum Atypical Hemolytic Uremic Syndrome: an Unusual and Severe Complication Associated with IgA Nephropathy

IGA nephropathy (IgAN) is one of the most common types of primary glomerulonephritis, which occurs more frequently in patients of reproductive age. Atypical hemolytic uremic syndrome (aHUS) without diarrhea is rare and has a poor prognosis. In the absence of appropriate therapy, pregnancy-related aHUS is associated with high morbidity and mortality. This report described a successfully treated case of postpartum aHUS associated with IgAN. Repeated renal biopsy was per- formed to demonstrate serial renal pathologic changes after successful treatment.

Diffusional kurtosis imaging in assessing renal function and pathology of IgA nephropathy: a preliminary clinical study

AIM To evaluate renal fibrosis in immunoglobulin A nephropathy (IgAN) using diffusion kurtosis imaging (DKI). MATERIALS AND METHODS Twenty patients with biopsy-proven IgAN were enrolled. DKI was performed on a clinical 3 T magnetic resonance imaging (MRI) system, and region-of-interest measurements were conducted to determine mean kurtosis (K), mean diffusivity (D), and apparent diffusion coefficient (ADC) of the kidney cortex. Renal biopsy specimens were scored based on the severity of renal fibrosis. The associations between the DKI data and clinicopathological parameters were investigated. RESULTS Both the K and ADC were not only well correlated with the estimated glomerular filtration rate, but also significantly associated with the pathological scores of fibrosis, including the glomerular sclerosis index (K: r=0.759, p<0.001; ADC: r=-0.636, p=0.003) and the percentage of tubular atrophy and interstitial fibrosis (K: r=0.767, p<0.001; ADC: r=-0.702, p=0.001). Further receiver operating characteristic analysis showed that K demonstrated better diagnostic performance in discriminating severe glomerulosclerosis (area under curve [AUC] 0.970, sensitivity 81.8%, specificity 100%), and ADC displayed better capabilities in identifying severe tubular atrophy/interstitial fibrosis (AUC 0.976, sensitivity 100%, specificity 92.9%). CONCLUSION This DKI method can be used to detect renal fibrosis in IgAN in a non-invasive manner and may provide additional information for characterisation and surveillance.

The renal manifestations of type 4 familial partial lipodystrophy: a case report and review of literature

BackgroundLipodystrophy syndromes are rare disorders of variable body fat loss associated with potentially serious metabolic complications. Familial partial lipodystrophy (FPLD) is mostly inherited as an autosomal dominant disorder. Renal involvement has only been reported in a limited number of cases of FPLD. Herein, we present a rare case of proteinuria associated with type 4 FPLD, which is characterized by a heterozygous mutation in PLIN1 and has not been reported with renal involvement until now.Case presentationA 15-year-old girl presented with insulin resistance, hypertriglyceridaemia, hepatic steatosis and proteinuria. Her glucose and glycated haemoglobin levels were within normal laboratory reference ranges. A novel heterozygous frameshift mutation in PLIN1 was identified in the patient and her mother. The kidney biopsy showed glomerular enlargement and focal segmental glomerulosclerosis under light microscopy; the electron microscopy results fit with segmental thickening of the glomerular basement membrane. Treatment with an angiotensin-converting enzyme inhibitor (ACEI) decreased 24-h protein excretion.ConclusionsWe report the first case of proteinuria and renal biopsy in a patient with FPLD4. Gene analysis demonstrated a novel heterozygous frameshift mutation in PLIN1 in this patient and her mother. Treatment with ACEI proved to be beneficial.

Renal involvement in primary Sjögren's syndrome: A retrospective study of 103 biopsy-proven cases from a single center in China.

To retrospectively investigate the features of renal involvements in patients with primary Sjögrens syndrome (pSS) with biopsy results.

The Neglected Significance of Glomerular Density as a 5-year Progression Indicator for IgA Nephropathy .

Objective To investigate whether glomerular density (GD) could be an independent prognostic factor for patients of IgA nephropathy with estimated glomerular filtration rate (eGFR) of 30 to 60 ml/min per 1.73 m2, or for patients with time-average proteinuria < 0.5 g/d. Methods A total of 173 patients with biopsy-confirmed IgA nephropathy diagnosed from January 2000 to December 2010 were included. All of these patients were followed up for more than 5 years. The endpoint was a > 30% of decline in eGFR from baseline after 5-year follow-up. The optimal cut-off value of GD was calculated by ROC curve. Kaplan-Meier method and Cox regression analysis was used for survival analysis. Results A 30% of decline in eGFR occurred in 14.5% of all patients. The optimal diagnostic cut-off value of GD was 1.99/mm2 (AUC = 0.90, sensitivity = 84.0%, specificity = 81.8%) determined by ROC curve. The low GD group (GD < 1.99 per mm2) experienced a significant increase in renal endpoint for patients with eGFR of 30 to 60 ml/min per 1.73 m2 (six patients in lower GD group, while one patient in the other group). For patients with time-average proteinuria < 0.5 g/d, the lower GD group showed a higher eGFR decline from baseline (4.5±16.7 ml/min per 1.73 m2 vs. -8.1±21.4 ml/min per 1.73 m2, P = 0.038); two patients in this group reached the endpoint, while no patients in the higher GD group did. Conclusion GD could be an independent prognostic factor for patients of IgA nephropathy with eGFR at 30 to 60 ml/min per 1.73 m2 of body surface, particularly for those with time-averaged amount of urine protein less than 0.5 g per day.