Infectious complications in adult patients with idiopathic minimal change nephrotic syndrome undergoing immunosuppressive therapy.

BACKGROUND: Patients with idiopathic minimal change nephrotic syndrome (MCNS) undergoing immunosuppressive therapy are susceptible to infectious complications. Study specifically focusing on adult population's infectious complications is lacking. METHODS: We retrospectively collected 101 adult patients with biopsy-proven idiopathic MCNS and analysed for the infectious complications. Published literatures were also reviewed aiming to evaluate the feasibility of prophylactic antibiotic treatment. RESULTS: Infectious complications developed in 17 of 101 (16.8%) patients, with pneumonia (n = 4), cellulitis/fasciitis (n = 4) and urinary tract infection (UTI) (n = 4) being the dominant diseases, and Gram-negative bacilli the main cause. AKI stage ≥2 (Hazard ratio = 6.1; 95% CI: 1.2-31.9, p = 0.031) and non-remission by treatment (Hazard ratio = 4.4; 95% CI: 1.2-15.6, p = .023) were the two independent risk factors relevant to developing infectious complications. Review of 16 published literatures and our data showed that even no prophylactic antibiotic therapy, only one case of Pneumocystis jirovecii pneumonia developed among the 1787 accumulative cases of MCNS. In contrast, 16 (44%) of acute flare cases were reported among the 36 patients with positive hepatitis B surface antigen that did not receive antiviral prophylactic therapy. CONCLUSIONS: Advanced acute kidney injury and non-remission by treatment are the risk factors toward developing infectious complications in adult MCNS undergoing immunosuppressive therapy. It appears unnecessary to use prophylactic antibiotic for Pneumocystis jirovecii pneumonia or other bacterial infections, while screening and prophylactic therapy for hepatitis B and latent tuberculosis are critical for patients in prevalent area.

Kidney bioengineering by using decellularized kidney scaffold and renal progenitor cells.

Patients with end-stage renal disease often need dialysis to maintain their lives because of donor organ shortage. The creation of a transplantable graft to permanently replace kidney function would overcome the organ shortage problem and the morbidity associated with immunosuppression. In the present study, we decellularized rat kidneys by the perfusion of detergent, yielding acellular scaffolds with the vascular, uretic, as well as cortical and medullary architecture. To regenerate the functional organ, we seeded tubular epithelial cells and mouse kidney progenitor cells from the ureter together with endothelial cells and mouse kidney progenitor cells from the renal artery. The renal constructs from seeded cells were cultured in a whole-organ bioreactor. After 3 months of organ culture, the seeded cells formed renal tubules, grew in the glomeruli, and some mouse kidney progenitor cells were also scattered in the interstitium. We tested the function of the bioengineered kidney with standardized perfusate in vitro. The bioengineered kidney not only produced urine but also reabsorbed albumin, glucose, and calcium. We conclude that seeded cell-based bioengineering of kidneys with physiological secreting and reabsorbing properties is possible and holds therapeutic promise.

Evaluation of the association of Wnt signaling with coronary artery calcification in patients on dialysis with severe secondary hyperparathyroidism.

BACKGROUND: Patients with end-stage renal disease have a higher risk of death from cardiovascular events, which can be mainly attributed to coronary artery calcification (CAC). Wnt signaling is involved in vascular development and may play a role in vascular calcification. This study aimed to evaluate CAC prevalence in patients on dialysis with severe secondary hyperparathyroidism (SHPT) and identify CAC risk factors. METHODS: The study is a retrospective analysis of the severe hyperparathyroidism registration study that prospectively recruited patients on dialysis with severe SHPT who were candidates for parathyroidectomy, from October 2013 to May 2015. CAC and bone mineral density (BMD) were measured. Demographic and clinical data including calcium, phosphorus, alkaline phosphatase, intact parathyroid hormone, Dickkopf-related protein 1 (DKK1), and sclerostin levels were analyzed. CAC scores were reported in Agatston units (AU). RESULTS: A total of 61 patients were included in this study. No CAC, mild CAC (<100 AU), moderate CAC (>100 AU), and severe CAC (>400 AU) were observed in 4.9%, 11.4%, 14.8%, and 68.9% of patients, respectively. DKK1 and sclerostin were not associated with CAC. In univariate analysis, CAC was significantly correlated with age, sex (male), total cholesterol, and intravenous pulse calcitriol (p<0.05). CAC was not inversely correlated with the BMD, T scores, or Z scores of the femoral neck (p>0.05). In multivariate analysis, the stepwise forward multiple linear regression revealed that CAC was associated with age, male sex and intravenous pulse calcitriol (p<0.05). Furthermore, serum sclerostin was positively correlated with the BMD of the femoral neck but negatively associated with intact parathyroid hormone (p<0.05). Serum sclerostin was significantly associated with severely low bone mass with Z-scores<-2.5 of the femoral neck, even when adjusted for serum intact parathyroid hormone, vitamin D status, dialysis pattern, sex, and DKK-1 (p<0.05). CONCLUSIONS: The patients on dialysis with severe SHPT have a high prevalence of vascular calcification. Although the Wnt signaling pathway could play a role in hyperparathyroid bone disease, CAC may be mainly due to the treatment modality rather than the Wnt signaling pathway associated bone metabolism in patients on dialysis with severe SHPT.