Assessment of the Relationship Between Inflammation and Glomerular Filtration Rate.

Background: Chronic kidney disease (CKD) is a global health problem. As it progresses to end stages, renal replacement therapy is required but ultimately, the best treatment is transplantation. Decreased renal function has been associated with an inflammatory state associated to primary CKD and in kidney transplant recipients (KTRs). Objective: To establish how the serum concentrations of some cytokines, such as interleukin (IL)-2, IL-8, IL-22, IL-17α, interferon-gamma, IL-4, and transforming growth factor-ß, correlate with various CKD stages. Methods: One hundred and forty-one KTRs between the ages of 18 and 75 years were included in the study. We also included 112 live kidney donors, 37 CKD PGCKD+3, and 76 GPhealthy. Participants were grouped according to their glomerular filtration rate (GFR) and their circulating cytokine levels, previously quantified by ELISA. Results: By linear regression analysis, we established the relation of each cytokine with the GFR. Transforming growth factor-ß correlated positively with the GFR in the study population, except in healthy individuals. A negative correlation of IL-8 and IL-17α and GFR was found in all cases. Conclusions: Whether these cytokines (IL-8 and IL-17α) could be used as inflammatory biomarkers indicating CKD progression, regardless of the type of population, remains to be prospectively determined.

Contexte: L'insuffisance rénale chronique (IRC) est un problème de santé mondial. Une thérapie de remplacement rénal est nécessaire au fur et à mesure que la maladie évolue vers les stades terminaux. Mais, en définitive, le meilleur traitement reste la transplantation. La réduction de la fonction rénale a été associée à un état inflammatoire associé à l'IRC primaire; une association observée aussi chez les receveurs d'une greffe de rein. Objectif: Déterminer la façon dont les concentrations sériques de certaines cytokines, notamment IL-2, IL-8, IL-22, IL-17a, IFN-γ, IL-4 et TGF-ß, corrèlent avec divers stades de l'IRC. Méthodologie: Ont été inclus dans l'étude 141 receveurs d'une greffe rénale âgés de 18 à 75 ans, 112 donneurs vivants de rein, 37 personnes atteintes d'IRC (PGIRC+3) et 76 personnes en bonne santé (PGen santé). Les sujets ont été regroupés en fonction de leur débit de filtration glomérulaire (DFGe) et de leur taux de cytokines en circulation, quantifiés préalablement par ELISA. Résultats: Une analyse de régression linéaire a servi à établir la relation entre chaque cytokine et le DFGe. Dans la population étudiée, une corrélation positive a été observée entre TGF-ß et le DFGe, sauf chez les individus sains. Dans tous les cas, la corrélation s'est avérée négative entre le DFGe et les taux d'IL-8 et d'IL-17a. Conclusion: Il reste à déterminer prospectivement si ces cytokines (IL-8 et IL-17a) pourraient être utilisées comme biomarqueurs inflammatoires pour indiquer la progression de l'IRC, quelle que soit la population.

Systemic autoimmunity in a patient with CANDLE syndrome

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Correlation of the Glomerular Filtration Rate Measured With the Use of DTPA-Tc99m in Live Kidney Donors With Equations Based on Creatinine and Cystatin C.

BACKGROUND: Renal donation leads to a risk of developing chronic kidney disease, with an incidence of 0.47%. To evaluate for its presence, formulas based on serum creatinine are used, but up to 80% of these formulas underestimate the glomerular filtration rate (GFR) in donors. The aim of this work was to confirm the highest correlation of the GFR as measured with the use of DTPA-Tc99m with the GFR as estimated by means of the formula based on serum cystatin C (CKD-EPI creatinine-cystatin C) in healthy kidney donors. METHODS: In this observational, analytic, cross-sectional study, the GFR of kidney donors was determined ≥1 year after donation by means of DTPA gammagram and estimation with the use of conventional formulations and with cystatin C. RESULTS: Of 112 donors, 38 (34%) were included, 20 (60%) were female, with an overall average age of 40 years, 36.5 months after donation, and body mass index of 25.5 kg/m2. Correlation with the GFR as measured by means of DTPA gammagram was better with the use of CKD-EPI cystatin C (0.402; P = .020) and CKD-EPI creatinine-cystatin (0.549; P < .001) than the conventional formulas. Linear correlation with serum cystatin C was 0.825 (P < .001; 95% confidence interval, -105.3 to -63.2) for the CKD-EPI cystatin C formula, 0.77 (P < .001; -89.9 to -48.1) for the CKD-EPI creatinine-cystatin formula, and 0.525 (P = .002; -91.1 to -23.2) for DTPA-Tc99m scintigraphy. CONCLUSIONS: There is a strong correlation between estimate the GFR by equations based on cystatin C and the measurement of the GFR by DTPA-Tc99m gammagram.

Experience and Security of the Hand-Assisted Laparoscopic Nephrectomy of a Living Donor in a Public Health Center.

BACKGROUND: Hand-assisted laparoscopic nephrectomy (HALDN) is currently the procedure of choice for obtaining living donor kidneys for transplantation. In our institution, it has been the standard procedure for 5 years. Previous studies have shown the same function of the graft as that obtained by open surgery, with a lower rate of bleeding and no differences in complications. We sought to demonstrate the experience and safety of HALDN compared with open donor nephrectomy in healthy donors for kidney transplantation. METHODS: A retrospective analytical observational study was conducted, reviewing the records of the living donors for kidney transplant undergoing open donor nephrectomy or HALDN in our center from March 1, 2009, to March 1, 2016. Renal function was assessed by the estimated glomerular filtration rate by the Modification of Diet in Renal Disease method before and after donation, as well as bleeding (mL), and complications (according to Clavien), performing a comparative analysis between the two techniques using parametric or nonparametric tests. RESULTS: A total of 179 living donor nephrectomies were performed during the study period-31 open donor nephrectomy (17.3%) and 148 HALDN (82.7%)-without relevant baseline differences, except for creatinine. HALDN has a shorter surgical time (156,473 ± 87.75 minutes vs 165,484 ± 69.95 minutes) and less bleeding (244.59 ± 416.08 mL vs 324.19 ± 197.986 mL) and a shorter duration of hospital stay (3.74 ± 1.336 days vs 4.75 ± 1.226 days). There were no significant differences in surgical complications at 30 days, or graft loss reported; there were 3 conversions (1.7%) from the HALDN to the open technique. There were no differences in renal function in the donors or recipients at the 5th day or the month after surgery. CONCLUSIONS: Laparoscopic nephrectomy has replaced open surgery as the gold standard for living kidney donors. HALDN is a safe and feasible procedure when compared with open donor nephrectomy, achieving a shorter surgical time with less bleeding, and no difference in the number of complications. This procedure lowers costs by decreasing the duration of the hospital stay, making is feasible to perform it at any institution with appropriately trained personnel.

Correlation of the Renal Cortex Volume With the Glomerular Filtration Rate in Live Donors for Renal Transplantation.

INTRODUCTION: As a pretransplantation evaluation, renal function is determined by the glomerular filtration rate (GFR) with the use of renal scintigraphy (RS) and the estimated glomerular filtration rate (eGFR). To date, there are few studies that correlate renal cortex volume with eGFR determined with renal gammagram (GR) and eGFR by equations (Cockroft-Gault, Modification of Diet in Renal Disease, and Chronic Kidney Disease Epidemiology Collaboration equation) in Latin American living donors. AIM: This study sought to determine whether there is correlation of the volume of the renal cortex by Herts equation with the GFR determined with renal gammagram (GFR-GR). PATIENTS AND METHODS: This was an analytical, observational, and cross-sectional study. A review of the donor charts from January 1, 2014, to December 1, 2014, with a complete clinical file, kidney measurements, predonation tomography volume, and eGFR by different formulas and by renal scintigraphy. RESULTS: Thirty-three donors were included, 51.5% male and 48.5% female. The mean age was 38.58 ± 10 years, with an average volume of 127.83 ± 28.30 mL, with diethylenetriamine-pentaacetate (DTPA) of 54.80 ± 7.13 mL/min/1.73 m2 in the donated kidney. Spearman correlation showed the best association with the Herts equation (r = 0.346) reaching significance (P = .049) when comparing the different equations against the GFR with DTPA. Using the Bland-Altman method, the lowest variability and best significance was verified with the same equation compared to the other formulas (P = .0002). CONCLUSIONS: There is no consensus regarding which is the best formula for calculating the GFR of both kidneys. Of the different formulas, the one that best correlated with the GFR was the Herts method, which uses the volume of the kidney.

Peripheral Blood Regulatory T Cells Are Diminished in Kidney Transplant Patients With Chronic Allograft Nephropathy.

BACKGROUND: Our aim in this study was to assess peripheral blood CD4+CD25+FOXP3+ regulatory T cell (Treg) levels in patients with chronic allograft nephropathy (CAN) 1 year after kidney transplantation. METHODS: Twelve renal transplant patients with an initial onset of CAN, 12 patients with chronic kidney disease (CKD) stage G5 on dialysis, and 13 healthy control individuals were evaluated regarding the proportion of Tregs in their peripheral blood via flow cytometry. RESULTS: The renal transplant patients with CAN had a significantly lower proportion of Tregs than the hemodialysis CKD patients and healthy controls (P < .0001). In contrast, the hemodialysis CKD patients showed higher levels of Tregs than the renal transplant patients with CAN and the healthy controls (P < .0001). CONCLUSION: The high level of peripheral blood Tregs in the hemodialysis CKD patients suggests a chronic inflammatory state. However, the low frequency of Tregs in the peripheral blood from the renal transplant patients with CAN suggests an unfavorable prognosis for allograft immune tolerance.

Cardiac Remodeling in Structure and Function Six Months After Kidney Transplantation.

BACKGROUND: Cardiovascular disease accounts for 35% to 50% of the causes of mortality in chronic kidney disease. The majority of patients in substitution therapy in Mexico are subdialyzed owing to limited economic resources. This produces more cardiac deterioration than described in the statistics and has a direct impact on the prognosis of kidney transplantation. The aim of this work was to demonstrate and to quantify the improvement in the echocardiographic parameters 6 months after renal transplantation in patients with stable renal function. METHODS: This was an observational, analytic, prospective study of 23 patients with chronic kidney disease who received transplants in 2016 and had a glomerular filtration rate ≥80 mL/min (Chronic Kidney Disease-Epidemiology Collaboration) 6 months after transplantation. RESULTS: Echocardiographic results showed an increase in the left ventricular ejection fraction from 57.17 ± 10.46% to 64.09 ± 9.8%, an increase in the right ventricular ejection fraction from 0.56 ± 0.09% to 0.60 ± 0.08% and a reduction of the pulmonary arterial systolic pressure from 44.57 ± 13.88 mm Hg to 39.74 ± 11.04 mm Hg. There were also decreases in mitral regurgitation from 1.0 to 0.43, tricuspid insufficiency from 1.35 to 0.43, pulmonary insufficiency from 0.48 to 0.04, and aortic insufficiency from 0.35 to 0.04, all of these significant with P < .05. CONCLUSIONS: There was a significant improvement in cardiovascular function in our population 6 months after transplantation, despite the fact that renal transplantation is performed with greater cardiac deterioration than described in patients in other countries.

E6/E7 oncogenes in epithelial suprabasal layers and estradiol promote cervical growth and ear regeneration.

Tissue growth is a common characteristic of carcinogenesis and regeneration. Here we show that suprabasal expression of human papillomavirus (HPV)16 E6/E7 oncogenes in Tg(K6b-E6/E7) mice, similar to that observed in HPV-infected human tissue, and estradiol increased cervical epithelium growth and ear-hole closure efficiency. Oncogenes in combination with estradiol had a significant contribution to the proliferation of suprabasal cells of cervical epithelium that correlated with an increased expression of keratin genes. Remarkably, long-term treatments with estradiol resulted in evident cellular and tissue abnormalities indicative of a precancerous phenotype. Regenerating ear epithelium of transgenic mice also showed increased suprabasal cell proliferation and expression of keratin genes. Unexpectedly, we observed higher ear regeneration efficiency in adult than in young female mice, which was further increased by E6/E7 oncogenes. Supporting a role of estradiol in this phenomenon, ovariectomy and treatment with an estrogen receptor inhibitor caused a significant reduction in regenerative capacity. Our data suggest that Tg(K6b-E6/E7) mice are unique to mimic the initial stages of HPV-mediated cervical carcinogenesis, and ear regeneration could facilitate the elucidation of mechanisms involved.

Specific Antigens by Federal Entity in Patients at the Transplant Unit of Specialities Hospital, National Medical Center Twenty-First Century, Mexico.

BACKGROUND: The study of the kidney transplant involves understanding the immunologic basis, such as histocompatibility and the genetic basis of a population. In Mexico, the study of the genetic basis has led to a genetic map by federal entities. METHODS: We performed an HLA study with 1,276 kidney transplant patients (recipients and donors) in the Hospital of the National Medical Center Twenty-First Century, determining HLA class I (A, B, and Cw) and class II (DRß1 and DQß1) antigens with the use of SSOP-PCR. A descriptive analysis was conducted with measures of central tendency (mean, SD). RESULTS: Of 1,276 HLA patients studied, we obtained 2,552 results for each class by the composition of the 2 haplotypes, and for HLA-Cw we processed 796 patients, for a total of 1,592 antigens for this class. We found antigens specific to each federal entity, and it was found that the Federal District had the highest number of specific antigens (10) followed by Morelos (7), Querétaro and Mexico State (3 each), and Tamaulipas, Aguascalientes, Michoacán, Guerrero, Puebla, and Oaxaca (1 each). CONCLUSIONS: The genetic map allows us to know proportions of antigens in every state in the center and south of Mexico owing to the diversity and area of influence of the National Medical Center XXIst Century, as well as the wide number of patients. Furthermore, there are still preserved proportionally distinct genetic roots in every entity.

Lack of Association Between Elevated Urinary Levels of Interleukin-10 and Interferon Gamma With the Presence of Inflammation in Kidney Transplant Recipients.

INTRODUCTION: A lot of evidence has demonstrated the importance of different cytokines in acute renal rejection. Previous studies have examined the presence or absence of interleukin (IL)-10 in related immunopathologic rejection grafts as well as other interleukins. Studies in human transplantation show elevated levels of IL-10 and gamma interferon (INF-γ) in inflammation and rejection. OBJECTIVE: The objective of this study was to demonstrate the lack of association of elevated urinary levels of IL-10 and IFN in the presence of active inflammation. METHODS: An observational, descriptive, cross-sectional study conducted in transplant recipients at 12 months of follow-up after renal transplantation. In those who were held biopsy after renal transplantation at one year follow-up, or allograft dysfunction, we also measured IL-10 and INF-γ in the urine. The following were considered as variables: age, body mass index (BMI), gender, transplant type, creatinine, chronic kidney disease epidemiology collaboration equation, (CKD-EPI), modification of diet in renal disease study equation (MDRD), Banff classification, and levels of IL-10 and INF-γ. Statistical analysis was performed calculating a sample size of 25 patients, with an alpha bias of 0.05%, yielding measures of central tendency and determining no association between levels of IL-10 and INF-γ with the presence of rejection using SPSS 21.0 program. RESULTS: A total of 50 patients, 34 (68%) males, 16 (32%) females, with an average 31.7 ± 9.9 years, weight of 64.91 ± 13.84 kg, size 1.60 ± 0.10 m and 24.97 ± 4.07 BMI were included,39 (78%) living donor and 11 (22%) cadaveric. Twenty-six (52%) showed inflammation in the biopsy and 24 (48%) showed none. Mean creatinine was 1.81 ± 1.5, and the estimated glomerular filtration rate (eGFR) was 55.27 ± 22.46, 65.76 ± 26.7. (MDRD and CKD-EPI, respectively). No statistical difference was found in the levels of IL-10 and IFN-γ using analysis of variance. (ANOVA; P = .467 and P = .063, respectively) Based on Banff, the inflammation on biopsy score was 2.78 ± 2.84. There was statistical significance (P < .05) with respect to the Cr and eGFR by different equations. There were no significant interactions between cytokine levels and more than 1 factor. (as indicated by P < .2). DISCUSSION AND CONCLUSIONS: No significant differences were observed in the level of interleukins in patients with and without inflammation, denoting an adequate immunosuppression in most of these patients. Determination of inflammatory cytokines in urine could be used as a determinant of a good immunosuppression status, rather than as an early marker of rejection.

Correlation of Allograft Weight to Recipient Body Weight Index on Renal Function in Kidney Transplantation.

BACKGROUND: The function of renal transplant grafts can be modified by many factors. In one study of graft weight/weight of the recipient, it was concluded to avoid renal transplantation in patients with kidneys with a low ratio between the graft and recipient weight (<2.5 g/kg). OBJECTIVE: The objective of this study was to describe the association between renal allograft weight and renal function 1 month after renal transplantation in the Mexican population. MATERIAL AND METHODS: We studied patients who underwent transplantation from living or cadaveric donors with 1 month of follow-up with a functioning graft. An observational, retrospective, analytic study from January 1, 2014 to November 1, 2014 was conducted. Graft weight, donor weight, recipient weight, age, donor gender, recipient creatinine, and renal function were recorded. RESULTS: A total of 88 patients were included: 35 women (39.8%) and 53 men (60.2%). Sixty (68%) received kidneys from living donors and 28 (31.8%) from deceased donors. Mean recipient body mass index (BMI) was 24.7 (±2.6). Mean graft weight was 152 g (±33.9). Creatinine at 1 month post-transplantation was 1.6 mg/dL (±2.0). Using a linear regression model cold ischemia time was related to serum creatinine at 1 month post-transplantation (P = .020). Using multivariate analysis, significance was observed with respect to these indexes and recipient renal function. Recipient gender also was related and showed statistical significance (P = .015). CONCLUSIONS: Renal graft function depends on many factors including the amount of functional renal mass and nephrons required according to the recipient's weight. The donor kidney weigt (DKW) / receptor body weigt (RBW) index should be considered as selection criteria of donors.

Creation of a solid organ transplant program in an underdeveloped country: Mexico's General Hospital transplantation program.

BACKGROUND: With a population of >112 million persons, all Mexicans are entitled to receive medical care by the state and more than half have limited access to healthcare. From January 1985 to March 2009, 40 renal transplants were performed from living donors with a high percentage of complications. In April 2009, a new Solid Organ Transplantation Program was started; herein, we present this enterprise to the international community and briefly present a perspective on the Mexican transplant situation. MATERIALS AND METHODS: We performed a retrospective chart review of kidney and liver transplant recipients from April 2009 to November 2011, including demographic features, immunosuppression, complications as well as initial and 1 month function. RESULTS: We performed 68 kidney (59 living and 9 deceased donors) and 5 liver transplants (cadaveric donors). The kidney transplant recipients were 73.5% males and showed an overall mean age of 29.77 years (range, 18-60). The donor mean age was 34.08 years. Mean recipient creatinine pretransplant was 13.32 mg/dL, while at day 5 it was 2.33 and at month one, 1.32 mg/dL. Five grafts were lost (7.3%): 4 due to death with a functioning graft and 1 due to acute pyelonephritis. Five patients experienced delayed graft function Basiliximab induction was required in all but one who received thymoglobulin owing to a high panel reactive antibody. Maintenance therapy included a calcineurin inhibitor, mycophenolate mofetil (MMF), and prednisone. Liver transplant recipients were 83.6% women. The etiologies were alcoholic cirrhosis (n = 2), primary billiary cirrhosis (n = 1) and hepatitis C virus infection (n = 2). Complications included: reperfusion syndrome (n = 1), convulsive crisis (medication; n = 1), acute respiratory distress syndrome (n = 1), and death (n = 1). Their Model for End-Stage Liver Disease scopes were 10-21. After basiliximab induction, they had maintenance therapy with tacrolimus, MMF, and steroids. The donor mean age was 26.2 years. All survivors show normal liver function tests currently. CONCLUSIONS: From 1985 to 2009, 40 kidney transplants were performed, with multiple complications including donor deaths. Our current results were comparable to international standards, with <15% complication rate.

Parameters of Doppler ultrasound at five days posttransplantation as predictors of histology and renal function at one year.

INTRODUCTION: In our center, a Doppler ultrasound (DU) is performed at 5 days after transplantation. The normal upper limit of flow velocity (FV) in the renal artery is 200-250 cm/s. The resistance index (RI) is considered elevated when >0.8. Elevation of the RI can be shown in all the forms of graft dysfunction. OBJECTIVE: The objective of this study was to evaluate the capacity of the DU to predict the prognosis of graft function and histological damage at 1 year. METHODS: We examined a retrospective cohort of patients undergoing renal transplantation between January 2004 and May 2007. The renal function was evaluated with serum creatinine measurements and glomerular filtration rate (GFR) estimates by the quadratic Modification of Diet in Renal Disease study equation. The biopsy specimen was evaluated according to the Banff 1997 classification. RESULTS: The overall average age was 35 years, and 58% of the subjects were men. Eight cases (25.8%) showed abnormal DU. The Delta among those with normal DU was -0.94 versus 0.27 +/- 0.39 with abnormal DU (P < .005). There was no significance as far as the biopsy at 1 year. CONCLUSIONS: Renal DU allows physicians to suspect complications at the first posttransplantation year. It shows a tendency to elevated blood pressure, as well as increased deterioration of renal function over the first year.