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Background Peritoneal fibrosis (PF) represents a long-term complication of peritoneal dialysis (PD), affecting peritoneal membrane (PM) integrity and function. Understanding the mechanisms underlying PF development in an uremic environment aiming alternative therapeutic strategies for treating this process is of great interest. The aim of this study was to analyze the effects of tamoxifen (TAM) and recombinant BMP7 (rBMP7) in an experimental model of PF developed in uremic rats. Methods To mimic the clinical situation of patients on long-term PD, a combo model, characterized by the combination of PF and CKD with severe uremia, was developed in Wistar rats. PF was induced by intraperitoneal (IP) injections of chlorhexidine gluconate (CG), and CKD was induced by an adenine-rich diet. Uremia was confirmed by severe hypertension, increased blood urea nitrogen (BUN> 120 mg/dL) and serum creatinine levels (> 2 mg/dL). Uremic rats with PF were treated with TAM (10 mg/Kg by gavage) or BMP7 (30 μg/Kg, IP). Animals were followed up for 30 days. Results CG administration in uremic rats induced a striking increase in PM thickness, neoangiogenesis, demonstrated by increased capillary density, and failure of ultrafiltration capacity. These morphological and functional changes were blocked by TAM or rBMP7 treatment. In parallel, TAM and rBMP7 significantly ameliorated the PM fibrotic response by reducing α-SMA, extracellular matrix proteins and TGF-ß expression. TAM or rBMP7 administration significantly inhibited peritoneal Smad3 expression in uremic rats with PF, prevented Smad3 phosphorylation, and induced a remarkable up-regulation of Smad7, an intracellular inhibitor of TGFβ/Smad signaling, contributing to a negative modulation of profibrotic genes. Both treatments were also effective in reducing local inflammation, possibly by upregulating IκB-α expression in the PM of uremic rats with PF. In vitro experiments using primary peritoneal fibroblasts activated by TGF-ß confirmed the capacity of TAM or rBMP7 in blocking inflammatory mediators, such as IL-1ß expression. Conclusions In conclusion, these findings indicate important roles of TGF-ß/Smad signaling in PF aggravated by uremia, providing data regarding potential therapeutic approaches with TAM or rBMP7 to block this process. Electronic supplementary material The online version of this article (10.1186/s10020-019-0110-5) contains supplementary material, which is available to authorized users.

Cancer patients are living longer. The sequelae of cancer treatment and the role of comorbid conditions present before the diagnosis, such as CKD, have been increasingly recognized. The interface between CKD and cancer is multifaceted. CKD is frequently observed in patients with cancer, and cancer treatment contributes to CKD development and progression. In addition, CKD has been recognized as an important risk factor for cancer development and reduced specific cancer survival. In this context, an accurate evaluation of the glomerular filtration rate (GFR) during oncologic treatment is pivotal and is used to define surgery strategies, program prophylactic management of contrasted examinations, make decisions on cisplatin eligibility, and adjust drug prescriptions, particularly chemotherapy agents. Although the most commonly used equations to estimate GFR based on serum creatinine levels in clinical practice (Cockcroft-Gault, Modification of Diet in Renal Disease Study, and CKD Epidemiology Collaboration equations) have not been validated in patients with cancer in large prospective studies, there is increasingly evidence supporting the use of CKD Epidemiology Collaboration equation to assess the GFR in patients with cancer, including for the use of chemotherapy prescriptions. Many patients with cancer may have changes in nutrition status and clearance measurements such as exogenous filtration markers might be extremely useful when clinical decisions differ depending on the GFR level. Future perspectives include the advent of new serum GFR biomarkers such as cystatin C, beta-trace protein, and beta-2 microglobulin as well as the GFR assessment by measuring total kidney parenchymal volume through image examinations.

Peritoneal fibrosis (PF) represents a long-term complication of peritoneal dialysis (PD), affecting the peritoneal membrane (PM) function. Adipose tissue-derived mesenchymal stem cells (ASC) display immunomodulatory effects and may represent a strategy to block PF. The aim of this study was to analyze the effect of ASC in an experimental PF model developed in uremic rats. To mimic the clinical situation of patients on long-term PD, a combo model, characterized by the combination of PF and chronic kidney disease (CKD), was developed in Wistar rats. Rats were fed with a 0.75% adenine-containing diet, for 30 days, to induce CKD with uremia. PF was induced with intraperitoneal injections of chlorhexidine gluconate (CG) from day 15 to 30. 1×106 ASC were intravenously injected at days 15 and 21. Rats were divided into 5 groups: control, normal rats; CKD, rats receiving adenine diet; PF, rats receiving CG; CKD+PF, CKD rats with PF; CKD+PF+ASC, uremic rats with PF treated with ASC. PF was assessed by Masson trichrome staining. Inflammation- and fibrosis-associated factors were assessed by immunohistochemistry, multiplex analysis, and qPCR. When compared with the control and CKD groups, GC administration induced a striking increase in PM thickness and inflammation in the PF and CKD+PF groups. The development of PF was blocked by ASC treatment. Further, the upregulation of profibrotic factors (TGF-β, fibronectin, and collagen) and the increased myofibroblast expression observed in the CKD+PF group were significantly ameliorated by ASC. Beyond the antifibrotic effect, ASC showed an anti-inflammatory effect avoiding leucocyte infiltration and the overexpression of inflammatory cytokines (IL-1β, TNF-α, and IL-6) in the PM induced by GC. ASC were effective in preventing the development of PF in the experimental model of CKD+PF, probably due to their immunomodulatory properties. These results suggest that ASC may represent a potential strategy for treating long-term PD-associated fibrosis.

Acute kidney injury (AKI) is associated with extended hospital stays, high risks of in-hospital and long-term mortality, and increased risk of incident and progressive chronic kidney disease. Patients with urological diseases are a high-risk group for AKI owing to the coexistence of obstructive uropathy, older age, and preexistent chronic kidney disease. Nonetheless, precise data on the incidence and outcomes of postoperative AKI in urological procedures are lacking. Benign prostatic hyperplasia and prostate cancer are common diagnoses in older men and are frequently treated with surgical procedures. Whereas severe AKI after prostate surgery in general appears to be unusual, AKI associated with transurethral resection of the prostate (TURP) syndrome and with rhabdomyolysis (RM) after radical prostatectomy have been frequently described. The purpose of this review is to discuss the current knowledge regarding the epidemiology, risk factors, outcomes, prevention, and treatment of AKI associated with prostatic surgery. The mechanisms of TURP syndrome and RM following prostatic surgeries will be emphasized.

Ischemia-reperfusion injury (IRI) is a major contributor to acute kidney injury (AKI). At present, there are no effective therapies to prevent AKI. The aim of this study was to analyse whether valproic acid (VPA), a histone deacetylase inhibitor with anti-inflammatory properties, prevents renal IRI. Male Wistar rats were divided into three groups: SHAM rats were subjected to a SHAM surgery, IRI rats underwent bilateral renal ischemia for 45 min, and IRI + VPA rats were treated with VPA at 300 mg/kg twice daily 2 days before bilateral IRI. Animals were euthanized at 48 hours after IRI. VPA attenuated renal dysfunction after ischemia, which was characterized by a decrease in BUN (mg/dL), serum creatinine (mg/dL), and FENa (%) in the IRI + VPA group (39 ± 11, 0.5 ± 0.05, and 0.5 ± 0.06, resp.) compared with the IRI group (145 ± 35, 2.7 ± 0.05, and 4.9 ± 1, resp.; p < 0.001). Additionally, significantly lower acute tubular necrosis grade and number of apoptotic cells were found in the IRI + VPA group compared to the IRI group (p < 0.001). Furthermore, VPA treatment reduced inflammatory cellular infiltration and expression of proinflammatory cytokines. These data suggest that VPA prevents the renal dysfunction and inflammation that is associated with renal IRI.

The measurement of CRP levels may be a useful tool for differentiating CMV infection from the other types (bacterial or TB) of infection in kidney transplant recipients.