Serum pre-albumin is prognostic for all-cause mortality in patients with community-acquired and post-operative acute kidney injury.

BACKGROUND: Acute kidney injury (AKI) is a critical clinical syndrome characterised by a rapid decrease in renal filtration, with the accumulation of products of metabolism such as creatinine and urea. In recent years, the incidence of AKI has increased not only in critically ill hospitalised patients but also in community patients. Also, the prognosis of AKI is poor and treatment is limited in these populations. The increasing incidence and poor prognosis may be the reasons why more investigators are involved in epidemiological and risk factor analysis of AKI. AIMS: To investigate the effects of these risk factors on outcomes in both community-acquired and hospitalised AKI populations to provide certain guidance for clinics and to explore the prognostic value of prealbumin on all-cause mortality in patients with community-acquired and post-operative AKI. METHODS: From 2000 to 2010, 477 patients diagnosed with AKI and treated in the Department of Nephrology, Ruijin Hospital, Shanghai Jiaotong University, were enrolled in the community-acquired AKI (CA-AKI) group and 138 patients diagnosed with AKI after an operation were enrolled in the post-operative AKI (PO-AKI) group. Data were collected at AKI onset and 1 year after discharge and analysed retrospectively. RESULTS: Compared with PO-AKI patients, more patients in CA-AKI group had chronic kidney disease, obesity and hyperlipidaemia, and fewer patients had cerebrovascular disease (CVD), anaemia, shock or arrhythmia. Risks for CA-AKI were atherosclerosis, CVD, arrhythmia, multiple organ dysfunction syndrome and usage of vasoactive agents, and risks for PO-AKI were elderly, arrhythmia and requirement of renal replacement therapy. A higher level of serum PA was associated with a better outcome in the CA-AKI group (hazard ratio 0.92, 95% confidence interval 0.85-0.996) and PO-AKI group (hazard ratio 0.91, 95% confidence interval 0.84-0.99). In the CA-AKI group, the cumulative survival rate of patients with a normal PA level (PA >20 mg/dL) was higher than that among patients with a lower PA (PA ≤20 mg/dL; 95.4% vs 88.3%, P = 0.031). Similarly, in the PO-AKI group, a normal PA level was associated with a higher survival rate (74.1% vs 47.6%, P = 0.019). CONCLUSION: Serum PA may serve as a prognostic marker for CA-AKI and PO-AKI, and further research is warranted to confirm this finding.

Peritoneal dialysis outflow failure from omental wrapping diagnosed by catheterography.

Peritoneal dialysis outflow failure caused by omental wrapping is a serious complication that is difficult to diagnose noninvasively. We report a case of outflow failure in which catheterography showed several characteristics of omental wrapping: "pseudocele" formation, delayed catheter emptying, and uneven distribution of contrast in the abdominal cavity. A laparoscopic procedure was performed with identification of peritoneal adhesion and greater omental wrapping. The catheter was stripped from the omentum and repositioned in the Douglas peritoneal sac. Catheterography is a reliable, safe, noninvasive, and inexpensive alternative procedure to diagnose outflow failure caused by omental wrapping.

Angiotensin II-mediated activation of fibrotic pathways through ERK1/2 in rat peritoneal mesothelial cells.

INTRODUCTION: Peritoneal fibrosis is a common complication of peritoneal dialysis (PD) although the pathway involved is unclear. Of this article, angiotensin II (Ang II)-mediated upregulation of mitogen-activated protein kinase (MAPK) pathway as well as their downstream profibrotic genes including transforming growth factor (TGF)-beta1 and fibronectin (FN) was investigated. METHODS: Rat peritoneal mesothelial cells (RPMCs) were obtained by enzymatic digestion from the colic omentum. After incubated with Ang II, real-time PCR, ELISA, and Western blot analysis were used to determine RPMCs cellular and secretory (supernatants) levels of TGF-beta1, FN, tissue inhibitor of metalloproteinase-1 (TIMP-1), and plasminogen activator inhibitor-1 (PAI-1) as well as the phosphorylation of extracellular signal-regulated kinase (ERK1/2), p38 MAPK, and stress-activated protein kinase/c-Jun NH(2)-terminal kinase (JNK). We also determined the downstream pathways using the specific inhibitors including PD98059 (ERK1/2), SB230580 (p38 MAPK), SP600125 (JNK), and losartan [Ang II type-1 (AT1] receptor blocker). RESULTS: Ang II increased mRNA and protein levels of TGF-beta1, FN, TIMP-1, and PAI-1 in a time- and dose-dependent manner in RPMCs. Ang II induced a 1.5-2-fold increase in both mRNA and protein levels of the above molecules at 10 nmol/L. Ang II also upregulated the phosphorylation of ERK1/2 and p38 but not of JNK. Finally, inhibition of either AT1 or ERK1/2 was able to suppress Ang II-induced expression of FN. CONCLUSION: In cultured RPMCs, Ang II upregulated profibrotic signaling pathways through AT1-mediated ERK1/2 phosphorylation.

Endoplasmic reticulum stress and proteasome pathway involvement in human podocyte injury with a truncated COL4A3 mutation.

BACKGROUND: Collagen type IV (COL4)-related nephropathy includes a variety of kidney diseases that occur with or without extra-renal manifestations caused by COL4A3-5 mutations. Previous studies revealed several novel mutations, including three COL4A3 missense mutations (G619R, G801R, and C1616Y) and the COL4A3 chr:228172489delA c.4317delA p.Thr1440ProfsX87 frameshift mutation that resulted in a truncated NC1 domain (hereafter named COL4A3 c.4317delA); however, the mutation mechanisms that lead to podocyte injury remain unclear. This study aimed to further explore the mutation mechanisms that lead to podocyte injury. METHODS: Wild-type (WT) and four mutant COL4A3 segments were constructed into a lentiviral plasmid, then stably transfected into human podocytes. Real-time polymerase chain reaction and Western blotting were applied to detect endoplasmic reticulum stress (ERS)- and apoptosis-related mRNA and protein levels. Then, human podocytes were treated with MG132 (a proteasome inhibitor) and brefeldin A (a transport protein inhibitor). The human podocyte findings were verified by the establishment of a mus-Col4a3 knockout mouse monoclonal podocyte using clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9) technology. RESULTS: Our data showed that COL4A3 mRNA was significantly overexpressed in the lentivirus stably transfected podocytes. Moreover, the COL4A3 protein level was significantly increased in all groups except the COL4A3 c.4317delA group. Compared to the other test groups, the COL4A3 c.4317delA group showed excessive ERS and apoptosis. Podocytes treated with MG132 showed remarkably increased intra-cellular expression of the COL4A3 c.4317delA mutation. MG132 intervention improved higher ERS and apoptosis levels in the COL4A3 c.4317delA group. Mouse monoclonal podocytes with COL4A3 chr:82717932insA c.4852insA p.Arg1618ThrfsX4 were successfully acquired; this NC1-truncated mutation suggested a higher level of ERS and relatively remarkable level of apoptosis compared to that of the WT group. CONCLUSIONS: We demonstrated that excessive ERS and ERS-induced apoptosis were involved in the podocyte injury caused by the NC1-truncated COL4A3 mutation. Furthermore, proteasome pathway intervention might become a potential treatment for collagen type IV-related nephropathy caused by a severely truncated COL4A3 mutation.

Biomarkers to detect membranous nephropathy in Chinese patients.

Anti-M-type phospholipase A2 receptor (anti-PLA2R) is a widely accepted biomarker for clinical idiopathic membranous neurophathy (IMN). However, its ability to differentiate between IMN and secondary MN (SMN) is controversial. The objective of this study was to assess clinical MN biomarkers in blood, tissue and urine samples from Chinese patients. In total, 195 MN patients and 70 patients with other glomerular diseases were prospectively enrolled in the study. Participants were followed up for average of 17 months (range 3-39 months). Anti-PLA2R and anti-THSD7A (thrombospondin type-1 domain-containing 7A) were detected only in MN patient sera and not in controls. Serum anti-THSD7A and THSD7A-positive biopsies were detected in 1/18 and 2/18 PLA2R-negative MN cases, respectively. PLA2R and THSD7A were detected in 72.27% and 40% of SMN cases, respectively. While serum positivity for both anti-PLA2R and anti-THSD7A at the time of renal biopsy was specific to MN patients, neither antigen could discriminate between primary and secondary MN. We also found that high urinary levels of retinol binding protein (RBP) predicted poor proteinuria outcomes in study participants. Patients with low or medium urinary RBP levels achieved remission more frequently than those with high RBP.

[A study on urine microglobulin change after interventional therapy of renal artery in patients with coronary heart disease].

OBJECTIVE: To evaluate the urine microglobulin change after interventional therapy in patients with renal artery stenosis. METHODS: According to the results of renal artery angiography, 69 consecutive patients with coronary heart disease were divided into 2 groups, including 44 patients with severe renal artery stenosis RAS (luminal narrowing > 70%, group I) and 25 patients with atherosclerotic lesion in renal artery (luminal narrowing > 50% but < 70%, group II). The urine alpha(1), beta(2)-microglobulin (alpha(1), beta(2)-MG) were measured respectively. The successful procedural rates, rates of complication, serum creatitine and the urine alpha(1), beta(2)-MG 3 months after procedure were also recorded. The acute results and long-term follow-up outcomes were compared between the 2 groups. RESULTS: Urine alpha(1)-MG [(5.2 +/- 2.5) microg/L vs (3.0 +/- 2.7) microg/L, P > 0.001] and beta(2)-MG [(377 +/- 173) microg/L vs (202 +/- 184) microg/L, P > 0.001] were significantly higher in group I than in group II. However, the urine alpha(1)-MG of the 2 groups did not exceed the normal range (<6 microg/L). The urine beta(2)-MG [(237 +/- 187) microg/L vs (377 +/- 173) microg/L, P > 0.01] 3 months after stenting procedure in group I were significantly decreased. There were no significance change in urine alpha(1)-MG in group I and both the microglobulins in group II during follow-up. There was significant difference in improvement of blood pressure between the 2 groups (62.5% vs 9.1%, P > 0.01). As compared with group II, group I patients had more re-admission (22.5% vs 9.1%), renal failure (5% vs 0) and higher mortality (5% vs 0). However, these measurements did not differ significantly. Multivariate analysis revealed that persistent elevation of urine beta(2)-MG was an independent predictor of severe events (including re-admission and renal failure) after renal artery stenting (OR = 3.01, 95% CI 1.01 - 8.95, P = 0.036). CONCLUSIONS: Severe RAS causes damage of tubular reabsorption. Renal artery stenting improves tubular function, but in patients with persistent elevation of beta(2)-MG, the rates of re-admission and renal failure remain high.