Leonardo Pazarín-Villaseñor

Kidney transplantation (KT) remains the optimal therapy for end-stage kidney disease (ESKD), yet long-term graft survival is limited by unremitting allograft dysfunction and non-immune treatment toxicities. Sterile inflammation primarily drives graft failure. This inflammatory process releases damage-associated molecular patterns (DAMPs). DAMPs activate pattern recognition receptors (PRRs), such as Toll-like receptors (TLRs) 2 and 4, from proximal tubule epithelial cells, endothelial compartments, and infiltrating myeloid lineages. PRR signaling and the release of pro-inflammatory cytokines (IL-1β, IL-18, TNF-α) promote pro-inflammatory M1 macrophage polarization and accelerate interstitial fibrosis and tubular atrophy (IFTA). While maintenance immunosuppression prevents adaptive rejection, it causes severe metabolic, cardiovascular, and oncologic complications, including post-transplant diabetes mellitus, hypertension, and malignancies. Sodium-glucose cotransporter 2 (SGLT2) inhibitors (dapagliflozin, empagliflozin, canagliflozin) have emerged as novel disease-modifying, immunomodulatory adjuncts that act independently of glycemic control. SGLT2 inhibition reactivates tubuloglomerular feedback to relieve intraglomerular hypertension, blunts hyperfiltration, and reduces tubular transport workload. This alleviates cortical hypoxia, curtails mitochondrial ROS production, and activates AMP-activated protein kinase (AMPK) to suppress NF-κB and NLRP3 inflammasome assembly. SGLT2 inhibitors downregulate TLR expression, drive a phenotypic shift toward reparative M2 macrophages, reduce proteinuria, and provide sustained volume decongestion without triggering compensatory activation of the renin–angiotensin–aldosterone system. By targeting both upstream bioenergetic strain and downstream fibrotic remodeling (YAP/TAZ axis), SGLT2 inhibitors complement standard immunosuppression to protect allograft architecture, reduce cardiovascular morbidity, and improve long-term transplant outcomes.

Obesity affects the adaptability of adipose tissue (AT), impairing its ability to regulate energy and metabolism. Obesity is associated with many metabolic disorders, including dyslipidemia, hypertension, sleep disorders, non-alcoholic liver disease, and some types of cancer. Toll-like receptors (TLRs) are important in obesity and related metabolic disorders. TLRs are pattern-recognizing receptors (PRRs) involved in the innate immune system and recognize pathogen-associated molecular patterns (PAMPs) and endogenous ligands. TLRs, especially TLR2 and TLR4, are activated by fatty acids, endotoxins, and other ligands. TLR2 and TLR4 activation triggers inflammatory responses. Chronic inflammation driven by TLR activation is a hallmark of obesity and metabolic diseases. The inflammatory response triggered by TLR activation alters insulin signaling, contributing to insulin resistance, a key feature of metabolic syndrome and type 2 diabetes. Modulation of TLR activity through lifestyle changes (diet and exercise), obesity surgery, and pharmacological agents is under study as a possible therapeutic approach to controlling obesity and its complications.

Introduction. Protein-energy wasting (PEW) is highly prevalent among patients undergoing peritoneal dialysis (PD), and it has been proposed that oxidative stress (OS) may contribute to its pathogenesis. This study was an attempt to determine the association between the presence of PEW and OS levels in PD patients. Methods. This analytical cross-sectional study involved 62 clinically stable PD patients aged >= 18 years, between September 2017 and July 2018. PEW was assessed using PEW definition criteria, 7-point Subjective Global Assessment (SGA), and Malnutrition- Inflammation Score (MIS). Redox state was evaluated through oxidants (lipoperoxides, 8-Isoprostane, nitric oxide), antioxidants (superoxide dismutase, catalase, glutathione peroxidase-GPx, total antioxidant capacity), and oxidative DNA damage [8-hydroxy2 '- deoxyguanosine-8-OHdG, 8-Oxoguanine-DNA-N-Glycosylase1(8-OHdG)]. Results. Among study participants, 38 (61.2%) were males and 24 (38.8%) were females; 22 (35.4%) had diabetes mellitus [males 15 (68.1%) and females 7 (31.8%)]. The average PD duration was 11 (4-27) months, body mass index: 23.5 +/- 4.1 kg/m2, energy intake: 1138.4 +/- 394.2 kcal/day, and protein intake: 50.2 +/- 18.5 g/day. Prevalence of PEW varied based on the assessment method used (50-88.7%). Plasma 8-OHdG levels were higher in patients with PEW evaluated by MIS (0.1 [0.1-56.4] vs. 1.8 [0.1-74.7] ng/mL, P = .028), while GPx activity was lower in the presence of PEW as measured by MIS (3.6 [3.1-7.6] vs. 2.8 [1.2-10] nmol/min/mL, P = .021). No significant differences were observed between PEW markers and remaining OS levels. Conclusions. In PD patients with PEW, assessed by MIS, 8-OHdG was significantly increased, while GPx activity was significantly low.

Contexto: las enfermedades renales representan un problema de salud pública en América Latina. Los programas de la especialidad de Nefrología en la región muestran una elevada heterogeneidad en su estructura curricular y las competencias del perfil profesional no están debidamente explicitadas. Objetivo: definir con claridad el perfil de egreso de la especialidad de Nefrología, precisando las competencias que debe de desarrollar el futuro nefrólogo. El presente trabajo propone un conjunto de competencias mínimas para la formación de médicos nefrólogos en la región, incorporando la metodología de construcción de competencias profesionales integradas. Metodología: al seguir el enfoque curricular de competencias profesionales integradas, el perfil de egreso se organizó y construyó a partir de la identificación de las necesidades sociales en atención de la salud en América Latina. En trabajo colegiado se identificaron las necesidades sociales de la región, las mismas que se tradujeron en necesidades de formación y, con base en ellas, se desarrollaron las competencias profesionales integradas para atenderlas, las cuales se organizaron en: competencias profesionales, técnico-instrumentales y socioculturales. Resultados: con base en las necesidades sociales identificadas, se desarrollaron y organizaron ocho competencias profesionales, cuatro técnico-instrumentales, cinco socioculturales y una transversal, a partir de las cuales se derivaron los saberes prácticos, teóricos y formativos que integrarán el programa educativo. Conclusiones: la metodología de construcción de competencias profesionales integradas, considerando los estándares internacionales, ofrece una oportunidad de definir el perfil de egreso del futuro nefrólogo, a partir de un enfoque curricular que enlaza las necesidades de atención con los contenidos de la formación de los especialistas.

End-stage renal disease (ESRD) progression is closely related to oxidative stress (OS). The study objective was to determine the oxidant and antioxidant status in peritoneal dialysis (PD) patients with type 2 diabetes mellitus (DM). An analytical cross-sectional study from the PD program was carried out with 62 patients, 22 with and 40 without DM. Lipoperoxides (LPO) levels in patients with DM, 3.74 ± 1.09 mM/L, and without DM, 3.87 ± 0.84 mM/L were found to increase compared to healthy controls (HC) 3.05 ± 0.58 mM/L (p = 0.006). The levels of the oxidative DNA damage marker (8-OH-dG) were found to be significantly increased in patients with DM, 1.71 ng/mL (0.19–71.92) and without DM, 1.05 ng/mL (0.16–68.80) front to 0.15 ng/mL (0.15–0.1624) of HC (p = 0.001). The antioxidant enzyme superoxide dismutase (SOD) activity was found to be significantly increased in patients with DM, 0.37 ± 0.15 U/mL, and without DM, 0.37 ± 0.17 compared to HC, 0.23 ± 0.05 U/mL (p = 0.038). The activity of the enzyme glutathione peroxidase (GPx) showed a significant increase (p < 0.001) in patients with DM, 3.56 ± 2.18 nmol/min/mL, and without DM, 3.28 ± 1.46 nmol/min/mL, contrary to the activity obtained in HC, 1.55 ± 0.34 nmol/min/mL. In conclusion, we found an imbalance of oxidative status in patients undergoing PD with and without DM through the significant increase in LPO oxidants and the marker of oxidative damage in DNA. The activity of the antioxidant enzymes SOD and GPx were significantly increased in patients with and without DM undergoing PD, possibly in an attempt to compensate for the deregulation of oxidants. Antioxidant enzymes could be promising therapeutic strategies as a complement to the management of chronic kidney diseases.

Early Chronic Kidney Disease (CKD) is a condition that tends to progress to End-Stage Kidney Disease (ESKD). Early diagnosis of kidney disease in the early stages can reduce complications. Alterations in renal function represent a complication of diabetes mellitus (DM). The mechanisms underlying the progression of CKD in diabetes could be associated with oxidative and inflammatory processes. This study aimed to evaluate the state of inflammation and oxidative stress (OS) on the progression of CKD in the early stages in patients with and without type 2 diabetes mellitus (T2DM). An analytical cross-sectional study was carried out in patients with CKD in early stages (1, 2, 3) with and without T2DM. The ELISA method determined the expression of pro-inflammatory cytokines IL-6 and TNF-α as well as lipoperoxides (LPO), nitric oxide (NO), and superoxide dismutase activity (SOD). Colorimetric methods determined glutathione peroxidase (GPx) and total antioxidant capacity (TAC). Patients with CKD and T2DM had significantly decreased antioxidant defenses for SOD (p < 0.01), GPx (p < 0.01), and TAC (p < 0.01) compared to patients without T2DM. Consequently, patients with T2DM had higher concentrations of oxidant markers, NO (p < 0.01), inflammation markers, IL-6 (p < 0.01), and TNF-α than patients without T2DM. CKD stages were not related to oxidative, antioxidant, and inflammatory marker outcomes in T2DM patients. Patients without T2DM presented an increase in SOD (p = 0.04) and a decrease in NO (p < 0.01) when the stage of CKD increased. In conclusion, patients with T2DM present higher levels of oxidative and inflammatory markers accompanied by a decrease in antioxidant defense. However, these oxidative status markers were associated with CKD stage progression in patients without T2DM. Thus, NO and SOD markers could help detect the early stages of CKD in patients who have not yet developed metabolic comorbidities such as T2DM.

Contexto: la procalcitonina (PCT) podría ser útil en la evaluación de la función del injerto renal (IR) en el postrasplante inmediato, ya que sus niveles se incrementan posterior a la elevación de citocinas inflamatorias (IL-6, TNF-?) durante eventos de disfunción renal. Objetivo: determinar la asociación de la PCT sérica con la función del injerto renal en el periodo postrasplante inmediato. Metodología: cohorte retrospectiva de septiembre del 2018 a abril del 2019 en la División de Nefrología y Trasplantes, del Centro Médico Nacional de Occidente (CMNO), del Instituto Mexicano del Seguro Social (IMSS). Se incluyeron 62 receptores de trasplante renal de donante vivo (DV) y fallecido (DF) con determinación de PCT en los primeros 7 días del TR y el registro de eventos de disfunción temprana del injerto (DTI), fueron comparados con pacientes sin DTI (sDTI). Resultados: los receptores con DTI presentaron niveles más altos de PCT (13,90, 3,90, 1,22 ng/mL) comparado con el grupo sin DTI (0,32, 0,31 y 0,22 ng/ml) en los días 1, 3 y 5 respectivamente; p < 0,05. Conclusiones: la PCT es un marcador biológico asociado a DTI en el postrasplante renal inmediato.

Oxidative stress (OS) is implicated as a unifying factor between chronic kidney diseases and cardiovascular diseases. The objective of the study was to compare the oxidant and antioxidant status in patients with PD according to the state of DM. Lipoperoxides (LPO), 8-isoprostanes (8-IP) and nitric oxide (NO) were determined as oxidants and the activity of superoxide dismutase (SOD) and total antioxidant capacity (TAC) as antioxidants in patients with DM and without DM (No-DM). We included 35 patients with DM, 42 No-DM patients and 10 healthy people as a control group (HC). Patients with DM were older (p<0.0001), had higher BMI (p<0.0001), high glucose levels (p<0.0001) and more hypertension (p<0.0001). It was found that LPO levels increased in patients with DM and No-DM vs. HC (p<0.0001). There was a decrease in the levels of 8-IP in DM and No-DM compared to HC (p<0.0001). The levels of NO in patients with DM and No-DM decreased significantly compared to the HC group with 197.97±34.20 μM (p<0.0001). The activity of the SOD enzyme in patients with DM and No-DM was found to be increased compared to the HC group (p<0.0001). The levels of TAC in HC were 2.62±0.17 mM and decreased in patients with DM and No-DM (p<0.0001).

Multi-frequency bio-impedance analysis (BIA) accurately evaluates body composition. To assess nutritional status and its relationship with body mass index (BMI) or with BIA-obtained phase angle in patients with end-stage renal disease (ESRD) on hemodialysis. BMI, BIA and dialysis malnutrition score (DMS) were assessed in 99 patients on hemodialysis (43.6 ± 17.2 years of age, 58.8% males). Multivariate linear regression analysis was used to determine BMI and phase angle independent associations with DMS. Malnutrition risk (DMS > 13) showed a gradual increase among patients with normal BMI and phase angle (44.4%), low BMI (45.8%), low phase angle (64.0%), and in those with both parameters at abnormal ranges (68.0%). The phase angle was the only variable that was independently associated with patient nutritional status (standardized coefficient beta -0.372, p < 0.001), accounting for 13.8% of DMS variation. Phase angle is inversely and independently associated with malnutrition risk in patients with ESRD, which suggests that BIA-assessed body composition might be better than BMI in the clinical assessment of patients with ESRD.

The prevalence of end-stage renal disease (ESRD) has increased globally to 10% due to diabetes mellitus, hypertension, and stroke. When chronic kidney disease (CKD) maintenance therapy fails, patients require renal replacement therapy (RRT) to survive, such as peritoneal dialysis (PD), hemodialysis, and renal transplantation. The most common therapy in Mexico is PD because it is a feasible, low-cost, and easy-to-perform procedure; however, fluid overload is a frequent condition in patients with this RRT modality. The usual adverse comorbidities in patients with PD are cardiovascular diseases (CVD) associated to atherosclerosis, uremia, inflammation, and oxidative stress. Fluid overload is intimately associated to hypertension, left ventricular hypertrophy, heart failure, and worsening of kidney failure, leading to increased hospital admissions, higher cardiovascular mortality, and reduced life expectancy. Two main pathologies are involved in the deterioration of both heart and kidney functions, namely, cardiorenal syndrome and uremic cardiomyopathy. Along with these phenomena, patients in PD with rapid peritoneal transport have reduced ultrafiltration, increased glucose absorption, and albumin loss in the dialysate, which lead to overhydration, hypertension, dyslipidemia, and malnutrition. This review focuses on the clinical, physiological, and biochemical mechanisms involved in fluid overload of patients with CKD undergoing PD.