Phenotypes of Mineral Bone Disorder in Chronic Kidney Disease in a Dialysis Population.

BACKGROUND: Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD) is associated with clinical outcomes. It is necessary to identify the phenotype to make clinical decisions that optimize resources and follow-up. OBJECTIVE: To determine the frequency of the CKD-MBD phenotype in dialysis patients and the associated factors. METHODS: Cross-sectional study in 440 patients, evaluated for CKD-MBD. Phenotypes show frequency of high, low or on target levels of PTH, vitamin D and phosphorus. The most common phenotype was used for comparisons. RESULTS: Age was 37.5 ± 15.8 years, 53% male, 28% were diabetic, 60% on peritoneal dialysis (PD), dialysis vintage was 12.0 months (IQR 3.0-34.3). High PTH was 58%, low vitamin D 82%, high phosphorus 39%, low calcium 50%, and vascular calcification 55%. The combination of high PTH and low vitamin D and high on-target phosphorus was 39%. Those with high PTH and low vitamin D were more likely to use PD (71 vs 51%; p <0.0001), had higher lipids: total cholesterol (159 vs. 152; p = 0.002) and triglycerides (137 vs. 123; p = 0.02), higher potassium (4.7 ± 0.7 vs. 4.9 ± 0.9 mg/dL; p = 0.04), and higher serum creatinine (11.9 ± 4.4 vs. 10.6 ± 3.7 mg/dL; p = 0.01). Predictors of the most common phenotypes were PD use, total cholesterol, and serum creatinine. CONCLUSIONS: More than one third (38%) of our sample of patients had high PTH and low vitamin D with either high or normal phosphorus. Patients with these phenotypes more frequently used PD, had higher lipids and low potassium. PD use, total cholesterol and serum creatinine were significantly associated with these phenotypes.

The Inflammatory and Oxidative Status of Newly Diagnosed Class III and Class IV Lupus Nephritis, with Six-Month Follow-Up.

Lupus nephritis (LN) is the most frequent and severe complication of systemic lupus erythematosus (SLE). A prospective cohort with a six-month follow-up was performed. Twelve SLE patients diagnosed with LN Class III, twelve NL Class IV patients, and twelve healthy control subjects (HC) were included. SLE data, renal function, oxidants, antioxidants, and inflammation were determined at baseline and six-month follow-up. During the six-month follow-up, the SLE Disease Activity Index (SLEDAI-2K) decreased in both LN Class III (20.08 ± 6.92 vs. 11.92 ± 5.87, p < 0.001) and LN Class IV (25.33 ± 6.01 vs. 13.83 ± 5.52, p < 0.001) patients. Furthermore, the values of the C4 component also increased during follow-up for LN Class III (25.36 ± 6.34 vs. 30.91 ± 9.22, p = 0.027) and LN Class IV (12.18 ± 3.90 vs. 20.33 ± 8.95, p = 0.008) groups. Regarding inflammation markers, both groups presented decreased C-reactive protein (CRP), but this was only significant for patients with LN class III (7.93 ± 1.77 vs. 4.72 ± 3.23, p = 0.006). Renal function remained stable in both groups, with no changes in eGFR. Patients with LN Class III and Class IV showed higher baseline levels for lipoperoxides (Class III p < 0.01, Class IV p < 0.1) and carbonyl groups in proteins (Class III p < 0.01, Class IV p < 0.1) compared to HC. Moreover, both groups presented lower baseline values of total antioxidant capacity (Class III p < 0.01, Class IV p < 0.1) and catalase (Class III p < 0.01, Class IV p < 0.1) compared to HCs. However, antioxidant and oxidant markers did not show significant differences between baseline values and at six months for either of the two study groups. In conclusion, patients show an imbalance in the oxidative state characterized by the increase in the oxidants LPO and protein carbonyl groups and the decrease in the activity of the antioxidant enzymes TAC and CAT compared to HC. However, the patients did not present an increase in disease activity and renal function improvement. The glomerular filtration rate did not change during the length of the study, and SLEDAI -2K, C3, and C4 improved. The early co-management between Rheumatologists and Nephrologists is essential to prevent the rapid progression of LN. It would be interesting to administer antioxidant supplements to patients with a recent diagnosis of LN and evaluate its effect in a follow-up study.

Clinical impact using low-dose mycophenolate mofetil with tacrolimus on infectious, noninfectious complications and acute rejection, in renal transplant: A single hospital experience in Mexico.

Evidence supporting a starting dose of 2 g/day of mycophenolate mofetil (MMF) in combination with tacrolimus (TAC) for renal transplantation (RT) is still limited, but maintaining a dose of <2 g could result in worse clinical outcomes in terms of acute rejection (AR). This study aimed to determine the association between AR and infectious and noninfectious complications after RT with a dose of 1.5 g vs 2 g of MMF. A prospective cohort study was performed with a 12-month follow-up of recipients of RT from living donors with low (1.5 g/day) or standard (2 g/day) doses of MMF. The association between adverse effects and complications and doses of MMF was examined using Cox proportional hazard models, and survival free of AR, infectious diseases, and noninfectious complications was evaluated using the Kaplan-Meier test. At the end of the follow-up, the incidence of infectious diseases was 52% versus 50% (P = .71) and AR was 5% versus 5% (P = .86), respectively. The survival rate free of gastrointestinal (GI) complications requiring medical attention was higher in the low-dose group than in the standard-dose dose (88% vs 45%, respectively; P < .001). The use of 1.5 g/day of MMF confers a reduction in GI complications without an increase in infectious diseases or the risk of AR.

Procalcitonina sérica como marcador de la función del injerto en el postrasplante renal inmediato

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-ß) 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 antes del séptimo día del TR y el registro de eventos de disfunción temprana del injerto (DTI), 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.

Background Procalcitonin (PCT) could be useful for evaluation of the renal allograft (RG) in the immediate post-transplant since its levels increase after elevation of the inflammatory cytokines (IL-6, TNF-ß) during events of renal failure. Purpose Our objective was to determine the association of serum PCT with the function of the RG in the immediate post-transplant. Methodology A retrospective cohort from September 2018- April 2019 in the National Western Medical Center of the Mexican Social Security Institute (IMSS), was performed. Sixty-two recipients of living donor (LD) and deceased donor (DD) renal transplant (RT) with PCT evaluation before the seventh days of RT were included; and, events of early renal allograft failure (EAF) were recorded and compared to patients no EAF (nEAF). Results The recipients with EAF presented with higher PCT levels (13.90, 3.90, 1.22 ng/mL) compared to the nEAF group (0.32, 0.31, and 0.22 ng/ml) on days 1, 3, and 5, respectively (p < 0.05). Conclusions The PCT is a biological marker associated with EAF in the immediate post-transplant.

Mycetoma by Actinomadura madurae in the central nervous system: Renal transplant receptor disease.

The mycetoma is a granulomatous chronic disease, subcutaneous disease is the common presentation, very few cases are reported affecting central nervous system, but there are not cases in Renal Transplant (RT).

The Effect of Enalapril, Losartan, or Not Antihypertensive on the Oxidative Status in Renal Transplant Recipients.

The clinical and biochemical improvement observed in kidney transplant (RT) recipients is remarkable. The correct functioning of the allograft depends on various factors such as the donor's age, the alloimmune response, the ischemia-reperfusion injury, arterial hypertension, and the interstitial fibrosis of the allograft, among others. Antihypertensive drugs are necessary for arterial hypertension patients to avoid or reduce the probability of affecting graft function in RT recipients. Oxidative stress (OS) is another complex pathophysiological process with the ability to alter posttransplant kidney function. The study's objective was to determine the effect of the administration of Enalapril, Losartan, or not antihypertensive medication on the oxidative state in RT recipients at the beginning of the study and one year of follow-up. All patients included in the study found significant overexpression of the oxidative damage marker to DNA and the antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx). In contrast, it was found that the determination of the total antioxidant capacity decreased significantly in the final determination at one year of follow-up in all the patients who ingested Enalapril and Losartan. We found dysregulation of the oxidative state characterized mainly by oxidative damage to DNA and a significant increase in antioxidant enzymes, which could suggest a compensatory effect against the imbalance of the oxidative state.

The Influence of Sevelamer Hydrochloride and Calcium Carbonate on Markers of Inflammation and Oxidative Stress in Hemodialysis at Six Months of Follow-Up.

Patients with end-stage renal disease (ESRD) present alterations in mineral and bone metabolism. Hyperphosphatemia in ESRD is considered an independent risk factor for cardiovascular disease (CVD), increasing morbidity, and mortality. Sevelamer hydrochloride is a calcium-free, non-absorbable phosphate-chelating polymer. Calcium carbonate chelator is helpful in controlling serum phosphate levels. There is insufficient information on the influence of sevelamer hydrochloride and calcium carbonate on the behavior of oxidative stress (OS) markers and inflammation in patients on hemodialysis (HD). A randomized open clinical trial was carried out on patients to evaluate sevelamer hydrochloride and calcium carbonate influence at 6 months of study follow-up. Levels of oxidants (LPO, NO, and 8-isoprostanes), antioxidants (SOD and TAC), oxidative DNA damage (8-OHdG and hOGG1), pro-inflammatory cytokines (IL-6 and TNF-α), and inflammation markers (ferritin and C-reactive protein) were measured with colorimetric and ELISA methods. We found a significant increase in oxidants LPO and NO, and antioxidants SOD and TAC, and downregulation of IL-6 and TNF-α. Ferritin decrease at 6 months follow-up in the sevelamer hydrochloride group. Increase in C-reactive protein was found in the group of patients treated with calcium carbonate. In conclusion, we found an oxidative state imbalance with increase in LPO and NO oxidants. The activity of the antioxidant enzymes (SOD and TAC) was also found to increase, suggesting a compensatory effect in the face of increase in oxidants. The same phenomenon was observed with increase in the oxidative damage marker to DNA and the increase in the DNA repair enzyme, suggesting a compensatory effect. Pro-inflammatory cytokines were predominantly downregulated by TNF-α in the group that ingested sevelamer hydrochloride in the final determination at 6 months of follow-up. Serum ferritin levels decreased significantly at the end of follow-up in patients on HD in the sevelamer hydrochloride group. The management of hyperphosphatemia with sevelamer hydrochloride appears to have obvious anti-inflammatory and antioxidant benefits.

Impact of transplantation on neutrophil extracellular trap formation in patients with end-stage renal disease: A single-center, prospective cohort study.

ABSTRACT: Increased neutrophil extracellular trap (NET) formation associates with high cardiovascular risk and mortality in patients with end-stage renal disease (ESRD). However, the effect of transplantation on NETs and its associated markers remains unclear. This study aimed to characterize circulating citrullinated Histone H3 (H3cit) and Peptidyl Arginase Deiminase 4 (PAD4) in ESRD patients undergoing transplantation and evaluate the ability of their neutrophils to release NETs.This prospective cohort study included 80 healthy donors and 105 ESRD patients, out of which 95 received a transplant. H3cit and PAD4 circulating concentration was determined by enzyme-linked immunosorbent assay in healthy donors and ESRD patients at the time of enrollment. An additional measurement was carried out within the first 6 months after transplant surgery. In vitro NET formation assays were performed in neutrophils isolated from healthy donors, ESRD patients, and transplant recipients.H3cit and PAD4 levels were significantly higher in ESRD patients (H3cit, 14.38 ng/mL [5.78-27.13]; PAD4, 3.22 ng/mL [1.21-6.82]) than healthy donors (H3cit, 6.45 ng/mL [3.30-11.65], P < .0001; PAD4, 2.0 ng/mL [0.90-3.18], P = .0076). H3cit, but not PAD4, increased after transplantation, with 44.2% of post-transplant patients exhibiting high levels (≥ 27.1 ng/mL). In contrast, NET release triggered by phorbol 12-myristate 13-acetate was higher in neutrophils from ESRD patients (70.0% [52.7-94.6]) than healthy donors (32.2% [24.9-54.9], P < .001) and transplant recipients (19.5% [3.5-65.7], P < .05).The restoration of renal function due to transplantation could not reduce circulating levels of H3cit and PAD4 in ESRD patients. Furthermore, circulating H3cit levels were significantly increased after transplantation. Neutrophils from transplant recipients exhibit a reduced ability to form NETs.

Humoral Acute Rejection in a Kidney Transplant Recipient with Idiopathic Thrombocytopenic Purpura.

A 47-year-old male was diagnosed with chronic kidney disease (CKD) in 2011; idiopathic thrombocytopenic purpura (ITP) was also diagnosed in 2011 refractory to medical treatment and finally treated with splenectomy (2017) without relapses since that date, 5 blood transfusions, and 4 platelet apheresis in 2017. Renal transplant from a living related donor (brother), ABO compatible, crossmatch were negative, sharing 1 haplotype. Donor-specific anti-HLA antibody was negative. Graft function was stable until the 5th day and graft biopsy on the 6th day; thrombotic microangiopathy (TMA), C4D negative and inflammatory infiltration of polymorphonuclear leukocytes inside peritubular capillary, and anti-MICA antibodies were positive. The treatment used were plasmapheresis, intravenous immunoglobulin, and rituximab. Serum creatinine began to decrease since the 14th day, and by day 33, post-RT graft function was restored.

The Alteration of Pro-inflammatory Cytokines and Oxidative Stress Markers at Six-Month Post-living Kidney Donation.

Donors have a higher risk of developing chronic kidney disease than the general population. Some mechanisms mediated by pro-inflammatory cytokines and oxidative stress may be involved as risk factors. The objective of the study was to evaluate the behavior of pro-inflammatory cytokines and oxidative stress markers in living renal donors with a 6-month follow-up. A single prospective cohort was performed in 88 renal donors. At the end of the follow-up, the levels of lipoperoxides, 6.52 ± 1.12 mM, and 8-isoprostanes, 63.75 ± 13.28 pg/mL, were lower than before donation, 10.20 ± 3.95 mM (p < 0.001) and 67.54 ± 9.64 pg/mL (p = 0.026), respectively. Initial levels of nitric oxide (NO), 356.09 ± 59.38 µM increased at the end of the follow-up, 467.08 ± 38.74 µM (p < 0.001). It was observed in the final determination of donors decreased activity of antioxidant enzymes superoxide dismutase (SOD), 0.74 ± 0.57 U/L and glutathione peroxidase (GPx), 556.41 ± 80.37 nmol, in comparison with the levels obtained in the initial determination, 1.05 ± 0.57 U/L (p < 0.001) and 827.93 ± 162.78 nmol (p < 0.001), respectively. The pro-inflammatory cytokines, Tumor necrosis factor alpha and interleukin-6 showed no differences at 6 months after donation. The enzyme oxoguanine glycosylase (hOGG1) responsible for repairing oxidative damage to DNA, showed a decrease in its concentration at the end of the study in donor men, 0.40 ± 0.21 ng/mL compared to the initial levels, 0.55 ± 0.32 ng/mL (p = 0.025). The marker, 8-hydroxy-2-deoxyguanosine (8-OHdG) exhibited an increase in donor men at the final determination 2.28 ± 1.99 ng/mL, compared to the concentration before donation, 1.72 ± 1.96 ng/mL (p < 0.001). We found significant changes in the markers of the oxidative state with increased NO and 8-OHdG, as well as a significant decrease in the antioxidant defenses SOD, GPx, and in the DNA repair enzyme in living renal donors after 6 months of follow-up.

Diagnosis and clinical implications of vascular calcification of chronic kidney disease in Mexico / Diagnóstico e implicaciones clínicas de la calcificación vascular de la enfermedad renal crónica en México

Vascular calcification (VC), it is a clinical condition highly associated to Chronic Kidney Disease (CKD), CKD patients had as a primary death cause, the cardiovascular disease (CVD), among many non-traditional factors for CKD appears VC. The pathogenesis of VC it´s multifactorial and it´s in short terms a change of muscle vessels cells to a bone cell; this transformation it´s close related to Chronic Kidney Disease-Bone Metabolism Disorder (CKD-BMD), Vitamin D, phosphorus, calcium and parathyroid hormone are close related to VC. The diagnosis of VC can be done by different methods from Electron Beam Computed Tomography to plain X ray studies; there are many scores base on plain X ray studies that can predict mortality in patients with VC. In our setting there is scarce information regarding VC in dialysis patients, the available information show a higher frequency (~50%) and severe; predictors to the VC in our setting are: age, serum HDL and alkaline phosphatase. It is necessary in the primary care setting the evaluation of VC in order to prevent it appearing. There is not an effective treatment to VC so it´s necessary search for strategies to prevent it.

La calcificación vascular es un problema asociado a la ERC, los pacientes con ERC tienen como primera causa de muerte la enfermedad cardiovascular (ECV); entre los múltiples factores de riesgo no tradicionales de ECV se encuentra la calcificación vascular (CV). La patogenia de la CV es multifactorial, y se puede resumir en un cambio en el fenotipo de las células del músculo liso vascular, dicho cambio es a volverse células de tipo óseo. El diagnóstico de la CV puede llevarse a cabo mediante varios métodos, desde la tomografía computarizada por emisión de electrones (EBCT), hasta métodos como las placas simples de rayos X. En el caso de nuestro país hay pocos estudios que hayan evaluado la CV de pacientes en diálisis, donde la frecuencia es muy alta (~50%) y desafortunadamente grave; los predictores de presencia de CV que han sido evaluados en nuestro medio son: la edad, las concentraciones séricas de HDL y las concentraciones de fosfatasa alcalina. Es necesario que en el primer nivel de atención se evalúe la presencia de CV con el objeto de prevenir el desarrollo y agravamiento de los pacientes. Aunque no existe un tratamiento efectivo para el manejo de la CV es necesario buscar medidas de prevención en su desarrollo.

The Oxidative and Inflammatory State in Patients with Acute Renal Graft Dysfunction Treated with Tacrolimus.

Objective. To determine the oxidative stress/inflammation behavior in patients with/without acute graft dysfunction (AGD) with Tacrolimus. Methods. Cross-sectional study, in renal transplant (RT) recipients (1-yr follow-up). Patients with AGD and without AGD were included. Serum IL-6, TNF-α, 8-isoprostanes (8-IP), and Nitric Oxide (NO) were determined by ELISA; C-reactive protein (CRP) was determined by nephelometry; lipid peroxidation products (LPO) and superoxide dismutase (SOD) were determined by colorimetry. Results. The AGD presentation was at 5.09 ± 3.07 versus 8.27 ± 3.78 months (p < 0.001); CRP >3.19 mg/L was found in 21 versus 19 in the N-AGD group (p = 0.83); TNF-α 145.53 ± 18.87 pg/mL versus 125.54 ± 15.92 pg/mL in N-AGD (p = 0.64); IL-6 2110.69 ± 350.97 pg/mL versus 1933.42 ± 235.38 pg/mL in N-AGD (p = 0.13). The LPO were higher in AGD (p = 0.014): 4.10 ± 0.69 µM versus 2.41 ± 0.29 µM; also levels of 8-IP were higher in AGD 27.47 ± 9.28 pg/mL versus 8.64 ± 1.54 pg/mL (p = 0.01). Serum levels of NO in AGD were lower 138.44 ± 19.20 µmol/L versus 190.57 ± 22.04 µmol/L in N-AGD (p = 0.042); antioxidant enzyme SOD activity was significantly diminished in AGD with 9.75 ± 0.52 U/mL versus 11.69 ± 0.55 U/mL in N-AGD (p = 0.012). Discussion. Patients with RT present with a similar state of the proinflammatory cytokines whether or not they have AGD. The patients with AGD showed deregulation of the oxidative state with increased LPO and 8-IP and decreased NO and SOD.

The Beneficial Effects of Renal Transplantation on Altered Oxidative Status of ESRD Patients.

Renal transplantation (RT), has been considered the best therapeutic option for end stage renal disease (ESRD). Objective. To determine the effect of RT on the evolution of oxidative DNA status. Methods. Prospective cohort (N = 50 receptors of RT); genotoxic damage, 8-hydroxy-2'-deoxyguanosine (8-OHdG), and DNA repair enzyme, human 8-oxoguanine-DNA-N- glycosylase-1 (hOGG1); and antioxidants, superoxide dismutase (SOD) and glutathione peroxidase (GPx), were evaluated. Results. Before RT, 8-OHdG were significantly elevated (11.04 ± 0.90 versus 4.73 ± 0.34 ng/mL) compared to healthy controls (p = 0.001), with normalization after 6 months of 4.78 ± 0.34 ng/mL (p < 0.001). The same phenomenon was observed with hOGG1 enzyme before RT with 2.14 ± 0.36 ng/mL (p = 0.01) and decreased significantly at the end of the study to 1.20 ng/mL (p < 0.001) but was higher than controls, 0.51 ± 0.07 ng/mL (p < 0.03). Antioxidant SOD was elevated at 24.09 ± 1.6 IU/mL versus healthy controls (p = 0.001) before RT; however, 6 months after RT it decreased significantly to 16.9 ± 1.6 IU/mL (p = 0.002), without achieving the levels of healthy controls (p = 0.01). The GPx, before RT, was significantly diminished with 24.09 ± 1.6 IU/mL versus healthy controls (39.0 ± 1.58) (p = 0.01), while, in the final results, levels increased significantly to 30.38 ± 3.16 IU/mL (p = 0.001). Discussion. Patients with ESRD have important oxidative damage before RT. The RT significantly reduces oxidative damage and partially regulates the antioxidant enzymes (SOD and GPx).