Being Overweight Is Related to Faster Decline in Annual Glomerular Filtration Rate in Kidney Transplant.

Few studies have examined the relationship between non-immunological factors and glomerular filtration rate (GFR) decline in kidney transplant. Correcting these factors in native kidneys slows the progression of chronic kidney disease. The aim of this study was to analyze the association between the control of non-immunological factors and the annual decline of GFR. METHODS: A single-center, retrospective study was performed. We included 128 patients who received kidney transplants between 2000 and 2015, with at least 1-year post-transplant follow-up. Clinical records were reviewed. GFR was estimated by CKD-EPI. Three groups were defined according to the annual change in eGFR (ΔGFR 2016-1015): non-progressors (> -1 mL/min/1.73 m2), slow progressors (> -1 and < -5 mL/min/1.73 m2), and fast progressors (< -5 mL/min/1.73 m2). Percentage of achievement of KDIGO target was also analyzed. RESULTS: The mean GFR was 62.5 mL/min/1.73 m2. Glomerulonephritis was the most common cause of kidney failure (36%). When the fast progressor group was compared with the non-progressor group, they differed significantly in age-patients were younger (40 ± 12.3 vs 45 ± 13.1 years)-post-transplant body mass index (27.4 ± 5.6 vs 25.2 x ± 5.9 kg/m2), and serum uric acid, which was significantly higher (6.4 ± 1.7 vs 5.5 ± 1.58 mg/dL). There were no differences between the groups with regard to blood pressure, dyslipidemia, proteinuria, or venous bicarbonate. Target systolic blood pressure was achieved by 45% of patients. Biopsy-proven acute rejection was higher in the fast progression group, although this was not statistically significant (13 [24.5%] vs 8 [13.1%]). CONCLUSIONS: High body mass index was associated with a faster decline in glomerular filtration rate in this study. Target blood pressure <140/90 mm Hg was achieved in less than 50% of cases.

Acute Antibody-Mediated Rejection in Kidney Transplant Based on the 2013 Banff Criteria: Single-Center Experience in Uruguay.

BACKGROUND: Acute antibody-mediated rejection (AMR) diagnosis criteria have changed in recent consensus of Banff, with current evidence of C4d-negative AMR. Our objective was to evaluate incidence of AMR in renal transplantation according to Banff 2013 criteria and to examine the histological features and outcome. METHODS: This retrospective study involved all kidney transplants with histological diagnosis of acute rejection (AR) at our center between 2000 and 2014. All the biopsies with AR were re-assessed by a nephro-pathologist and classified by use of the Banff 2013 criteria. RESULTS: Of 205 kidney transplants, biopsy-proven AR was diagnosed in 25 cases (12%). Re-assessing them according to Banff 2013 criteria, AMR was diagnosed in 17 (8.3%) and represented 68% of the confirmed rejections. AMR diagnosis was performed on day 23 ± 26, with median of 11 days. From the 17 cases, 7 had concomitant T-cell-mediated rejection. All cases presented endothelial edema and acute tubular necrosis. Glomerulitis was found in 12 cases and capillaritis in 14. In 3, associated thrombotic micro-angiopathy (TMA) was found. Intimal and transmural arteritis was evidenced in 5 and 1 patient. In 2, transplant glomerulopathy was present. Seven of the 10 biopsies with C4d staining in the peri-tubular capillaries were positive. Twelve cases received plasmapheresis, 6 received gamma-globulin, and 6 received rituximab. After administration of anti-AMR therapy, 16 cases recovered renal function, reaching a serum creatinine level of 1.5 ± 0.6 mg %. Graft survival at 1 year was lower in the AMR group versus patients without AMR (81.9% vs 98.9%, log-rank test, P < .001). Risk factors for AMR were re-transplant (30% vs 7%, P = .02), HLA-DR mismatch (1.06 ± 0.65 vs 0.7 ± 0.6, P = .03), panel-reactive antibody (28% ± 33 vs 6.2 ± 13, P = .00), and delayed graft function (82% vs 30%, P = .00). CONCLUSIONS: Adapting the new Banff 2013 criteria increased the sensitivity of the diagnosis of ARM. Regarding our data, despite an adequate response to the therapy, it resulted in a worse graft survival by the first year of renal transplant.

Successful Pregnancies in Kidney Transplant Recipients: Experience of the National Kidney Transplant Program From Uruguay.

BACKGROUND: Renal transplantation increases the possibilities of pregnancy in women of reproductive age. The course of pregnancy was analyzed retrospectively in patients with kidney or kidney-pancreas transplant, surveying maternal-fetal or renal graft complications and the relation with pre-pregnancy renal function. METHODS: A cohort that includes all the kidney transplant recipients who went through pregnancy in Uruguay in a period of 28 years is described. Forty pregnancies in 32 patients were registered; the average time between the kidney transplant and the beginning of the gestation period was 47 months. From the total gestations, 10 abortions, 1 neonatal death, and 1 fetal demise were registered. From the remaining pregnancies, we highlight prematurity (18/29) and low birth weight (14/21). Twenty-nine in 30 pregnancies ended in cesarean section; in 8 of 30, pre-eclampsia diagnosis was performed. Acute rejection was diagnosed in 2 of 30 pregnancies, both undergoing their first post-transplant year. RESULTS: Two patients required dialysis throughout the pregnancy because of progress into severe renal insufficiency. Higher obstetric perinatal morbidity and renal function deterioration was related to lower pre-pregnancy glomerular filtration rate (GFR). CONCLUSIONS: A successful pregnancy is possible in transplant recipients, yet there are risks of prematurity, low birth weight, and abortion. A lower GFR before pregnancy was associated with poorer maternal and perinatal results as shown in the different series.

Development of the National Kidney Transplantation Program in Uruguay.

The first kidney transplantation (KT) in Uruguay was performed in 1969. We report the rates of KT and survival of patients and grafts up to December 2014. The country has a surface of 176,215 km(2) and a population of 3,286,314 inhabitants (18.6 inhabitants per km(2)). Till December 31, 2014, 1,940 KT have been performed in Uruguay (41.8 pmp that year); 90.4% of them were from cadaveric donors (CD). Median age of recipients (R) was 44 ± 14 years; R older than 55 years increased from 0 to 27% during the period. Our pre-emptive KT program started in 2007. Optimal donors (D) decreased from 65.2% to 35.5%, and D older than 45 years old increased from 9% to 37%. Trauma as cause of death decreased from 49% to 32% and stroke as cause of death increased from 25% to 39%. Patient survival rates at 1, 5, and 8 years were 93%, 87%, and 78%, respectively for KT performed between 1980 and 1989; they were 98%, 93%, and 89%, respectively, for KT performed between 1990 and1999; they were 97%, 91%, and 90%, respectively, for KT performed between 2000 and 2010. In December 2013, there were 1098 patients pmp in renal replacement therapy, 758 pmp in dialysis, and 340 pmp (30.9%) with a functioning graft. Our national KT program is mainly based (90.6%) on cadaveric donation. Epidemiological changes in the characteristics of R and D followed the changes in aging that occurred in the general population and the dialysis population. The survival rates from patients and kidneys are similar to those reported by the European and the American registries.

Clinical spectrum of cutaneous manifestations in renal and renopancreatic recipients in two centers in Uruguay.

Uruguay, with a total population of 3,345,000 inhabitants, is the Latin American country with the second highest number of renal replacement therapies. Long-term immunosuppressant therapy is essential for graft survival but results in reduced immunosurveillance, leading to an increased risk of complications. A variety of dermatological manifestations and a large increase in nonmelanoma skin cancers have been reported in this population. The purpose of this study was to evaluate the frequency and clinical spectrum of cutaneous manifestations in renal and renopancreatic recipients in 2 reference centers in Uruguay. Two hundred and six renal or renopancreatic recipients between 21 and 77 years old were evaluated between September 2009 and September 2011. A total of 206 dermatoses were observed; 60% of the patients had at least 1 cutaneous manifestation. The most frequent dermatoses were cutaneous side effects due to immunosuppressive treatment (40.6%), followed by infections (26.1%), miscellaneous causes (18.9%), and malignant and premalignant lesions (14.4%). Transplant recipients represent a high-risk dermatological population. Physicians in transplant units should be aware of the importance of dermatological screening in order to promote early detection of skin cancer.

[Frequency of diagnosis and clinic presentation of glomerulopathies in Uruguay]. / Frecuencia de diagnóstico y de presentación clínica de las glomerulopatías en el Uruguay.

UNLABELLED: The Uruguayan Registry of Glomerulopathies began its activity in 1974 and since 1985 is a national registry. The aim of this report is to analyze the incidence and the variations in frequencies of the histological diagnosis and clinical presentation during the 1980-2003 period. PATIENTS AND METHODS: From the 2,058 patients with renal biopsy in the whole period, we analyzed the histological diagnosis and the following data has been collected when the patients were registered: age, gender, clinical syndrome, proteinuria, hematuria, serum creatinine, blood pressure and time from the first symptom. Four periods of registry entry were considered: 1980-1989, 1990-1994, 1995-1999 and 2000-2003. Chi-square and Student test for independent samples were used to evaluate the differences among the variables frequencies in the four periods. RESULTS: The incidence of registered glomerulopathies per million population (pmp) increased from 13 (1980-1989) to 43 (2000-2003). In the 2000-2003 period, the incidences pmp were: primary glomerulopathy (PG), 25.3 and secondary glomerulopathy, 14.2. The highest incidences pmp were: focal and segmental glomeruloesclerosis (FSGS) 6.4; vasculitis 5.4; lupus nephritis 4.6; minimal change disease (MCD) 4.6; IgA nephropathy (IgAN) 4.5; and membranous nephropathy (MN) 4.0. The most frequent PG were the FSGS (29.3%) and the MCID (19.6%). The FSGS frequency decreased from 36.3% in 1995-1999 to 19.1% in 2000-2003. The IgAN frequency increased from 5.2% in 1980-1989 to 17.5% in 2000-2003. Nephrotic syndrome was the most frequent clinical presentation; its frequency was over 30% in the four periods. Asymptomatic urinary abnormality frequency increased from 14.0% in 1980-1989 to 22.7% in 2000-2003. The frequency of serum creatinine under 1.5 mg/dl, increased from 42.2% in 1980-1989 to 67.2% in 2000-2003 (p = 0.001). The frequency of serum creatinine over 6.0 mg/dl, decreased from 19.3% in 1990-1994 to 7.2% in 2000-2003. The percentage of patients referred since the first month of the apparent onset of the disease increased from 24.0% in 1980-1989 to 40.1% in 2000-2003 (p < 0.001). CONCLUSIONS: In Uruguay, the incidence of glomerulopathies with histological diagnosis has increased and the frequency of the different types has changed. Several indicators seem to show that the reference of patients to the nephrologist tended to be earlier in the last years.

Angiotensin II stimulation of renal epithelial cell Na/HCO3 cotransport activity: a central role for Src family kinase/classic MAPK pathway coupling.

Angiotensin II (AII) plays an important role in renal proximal tubular acidification via the costimulation of basolateral Na/HCO3 cotransporter (NBC) and apical Na/H exchanger (NHE) activities. These effects are mediated by specific G protein-coupled AII receptors, but their corresponding downstream effectors are incompletely defined. Src family tyrosine kinases (SFKs) contribute to the regulation of both transport activities by a variety of stimuli and are coupled to classic mitogen-activated protein kinase (MAPK) pathway activation in this cell type. We therefore examined these signaling intermediates for involvement in AII-stimulated NBC activity in cultured proximal tubule cells. Subpressor concentrations of AII (0.1 nM) increased NBC activity within minutes, and this effect was abrogated by selective antagonism of AT1 angiotensin receptors, SFKs, or the classic MAPK pathway. AII directly activated Src, as well as the proximal (Raf) and distal (ERK) elements of the classic MAPK module, and the activation of Src was prevented by AT1 receptor antagonism. An associated increase in basolateral membrane NBC1 content is compatible with the involvement of this proximal tubule isoform in these changes. We conclude that AII stimulation of the AT1 receptor increases NBC activity via sequential activation of SFKs and the classic MAPK pathway. Similar requirements for SFK/MAPK coupling in both cholinergic and acidotic costimulation of NBC and NHE activities suggest a central role for these effectors in the coordinated regulation of epithelial transport by diverse stimuli.