Cross-talk of inflammation and chondrocyte intracellular metabolism in osteoarthritis.

Osteoarthritis is a disease that impacts millions around the world, leading to significant financial and medical burden for patients and the healthcare system. However, no effective biomarkers or disease modifying therapeutics exist for the early identification and management of the disease. Inflammation drives chondrocytes to express extracellular matrix (ECM) degrading enzymes and interruption of this pathway is a viable target to prevent degradation of cartilage. It has been demonstrated that inflammation can alter the intracellular metabolism of chondrocytes, a process known as metabolic reprogramming. This metabolic reprogramming is critical for cartilage breakdown by shifting chondrocytes to an ECM-catabolic state and likely as a potential therapeutic target for osteoarthritis. Metabolic modulators hold the potential to reduce chondrocyte inflammatory responses and protect cartilage. In this narrative review, we explore some of the existing examples of interactions between metabolism and inflammatory pathways in chondrocytes. We summarize the impact of inflammatory stimulation on various metabolic pathways and describe several examples by which targeting of metabolism is able to modulate ECM-degrading activity of chondrocytes to protect against cartilage damage.

The improvement of ischemia/reperfusion injury by erythropoetin is not mediated through bone marrow cell recruitment in rats.

BACKGROUND: Ischemia/reperfusion (I/R) injury is a major cause of acute renal failure in kidney transplantation; however, the mechanisms of kidney damage and repair are not yet clear. So far no treatment has been effective to prevent I/R injury. In the present study we evaluated the effect of erythropoetin (EPO) in I/R injury in rats. We investigated the role of bone marrow cells (BMC) in kidney repair and the effect of EPO on BMC recruitment. MATERIALS AND METHODS: Female Sprague Dawley rats transplanted with male BMCs underwent I/R injury. In the treatment group rats received 5000 IU of EPO 30 minutes before renal ischemia. At 2 and 4 weeks after I/R, rats were humanely killed and we measured creatinine clearance (glomerular filtration rate [GFR]), proteinuria, and body weight (BW). Renal tissue was harvested for histologic and molecular analysis. Fluorescein in situ hybridization (FISH) and TUNEL were used to determined the presence of male cell chimerism and apoptosis in renal tissue. RESULTS: At 4 weeks after I/R, EPO significantly improved GFR (1.8 +/- 0.2 vs 1.2 +/- 0.14 mL/min; P < .05). No significant differences between EPO and control rats were observed in proteinuria, BW, and hemoglobin levels at 2 and 4 weeks. After death, the kidney showed only minimal tubulointerstitial changes, which were more marked in control rats. FISH analysis demonstrated a low degree of microchimerism, not significantly different between EPO and control rats. Apoptosis decreased between 2 and 4 weeks after I/R, in both EPO and control groups. CONCLUSION: EPO improved GFR and injury at 4 weeks after I/R; however, it did not enhance the recruitment of BMC.

Rapamycin reduces proteinuria and renal damage in the rat remnant kidney model.

Rapamycin is an immunosuppressive drug used to prevent acute allograft rejection in solid organ transplantation. It shows less nephrotoxicity than calcineurin inhibitors. We evaluated the effect of rapamycin in rats undergoing 5/6 nephrectomy, a model of proteinuric and progressive renal failure. Fourteen days after surgery rats were randomized either to receive rapamycin or to remain untreated (control). Rats were humanely killed on day 91; serum creatinine, creatinine clearance, and proteinuria were assessed. Renal sections were stained with periodic acid-Schiff to evaluate glomerular volume (Gv), glomerulosclerosis (GS) and tubulointerstitial damage (TIS); we evaluated GS and TIS by Sirius red staining (SR). Epithelial-to-mesenchymal transition (EMT) was assessed by immunohistochemistry. Rapamycin affected neither serum creatinine nor creatinine clearance; it reduced Gv (controls, 5.9 +/- 3.1 x 10(6); rapamycin, 1.3 +/- 0.7 x 10(6) microm(3)) and proteinuria (control, 349 +/- 146; rapamycin, 56 +/- 27 mg/24 h; P < .05); rapamycin ameliorated GS (control, 78 +/- 7; rapamycin, 36 +/- 7%; P < .05; SR: control, 13.2 +/- 3.5; rapamycin, 3.8 +/- 1.0%; P < .05), and TIS (control, 3.25 +/- 0.5; rapamycin, 1.0 +/- 0.1; P < .05; SR: control, 29 +/- 3; rapamycin, 11 +/- 3%; P < .05). Rapamycin reduced alphaSMA (control, 3.25 +/- 0.5; rapamycin, 1.0 +/- 0.1; P < .05), VIM (control, 3.5 +/- 0.6; rapamycin, 1.0 +/- 1.4; P < .05), and CD68(+) cells infiltration (control, 110 +/- 43; rapamycin, 24 +/- 1 cells; P < .05). Rapamycin slows the progression of renal damage in the rat remnant kidney and may represent a novel approach to the treatment of chronic kidney disease.

Complicaciones quirúrgicas post-trasplante renal. Estudio en 185 casos / Surgical complications after kidney transplantation. Research based on 185 cases

Objetivo: Análisis de incidencia, diagnóstico y tratamiento de complicaciones quirúrgicas en el trasplante renal. Método: Estudio retrospectivo de la incidencia de complicaciones quirúrgicas en 185 trasplantes renales únicos, revisando su diagnóstico y tratamiento. Resultados: En 185 trasplantes se producen un 27% de complicaciones quirúrgicas. Sólo un paciente perdió el injerto secundario a éstas y su mortalidad asociada fue nula. Tiempo medio de isquemia fría 20horas. Utilización de catéter doble J (19%), a criterio del cirujano. Complicaciones vasculares 3,2% (todas estenosis de arteria renal). Complicaciones urológicas 6,4% (en similar porcentaje estenosis y fístulas). Hematomas perirrenales 7%. Linfoceles 4,9%. Complicaciones peritoneales 4%. Otras 4%. Diagnóstico clínico-radiológico en la mayoría de los casos. Requirieron intervención (endo-radiológica o quirúrgica) el 14%, individualizada según el caso. Conclusiones: Nuestros resultados no difieren de los de otras grandes series publicadas. La implicación de un único equipo de cirujanos manteniendo la misma técnica vascular y de ureteroneocistostomía parece influir en nuestra baja incidencia de complicaciones. La ecografía-doppler abdominal sistemática como control en los primeros días post-trasplante contribuye al diagnóstico de las complicaciones quirúrgicas. El tratamiento inicial de elección, salvo excepciones, es endoscópico-conservador (AU)

Objective: To analyze the incidence of surgical complications its diagnosis and treatment after renal transplantation. Methods: A retrospective study measuring the incidence of surgical complications and reviewing its diagnosis and treatment in 185 renal single transplants. Results: 185 transplants, 27% had surgical complications. Only one patient lost the graft due to surgical complications and there was no associated mortality. Cold ischemia time 20 hours. Double J stenting in 19%, under surgeon’s opinion. Vascular complications 3,2% (all of them renal artery stenosis). Urological complications 6,4%. Perinephric haematoma 7%. Lymphocele 4,9%. Peritoneum related complications 4%. Other 4%. The diagnosis was clinical and radiological in most of cases. 14% needed any kind of intervention. Conclusions: Our results are similar to those reported in other recent series. Only one surgical team involved and the same technique for vascular and vesico-ureteric anastomosis probably makes lower our complications rate. Early postoperative abdominal ultrasonography contributes to the diagnosis of surgical complications. The initial treatment approach is the endoscopic-conservative one, with exceptions (AU)