Recurrence of membranous nephropathy after kidney transplantation: A multicenter retrospective cohort study.

Membranous nephropathy (MN) is a leading cause of kidney failure worldwide and frequently recurs after transplant. Available data originated from small retrospective cohort studies or registry analyses; therefore, uncertainties remain on risk factors for MN recurrence and response to therapy. Within the Post-Transplant Glomerular Disease Consortium, we conducted a retrospective multicenter cohort study examining the MN recurrence rate, risk factors, and response to treatment. This study screened 22,921 patients across 3 continents and included 194 patients who underwent a kidney transplant due to biopsy-proven MN. The cumulative incidence of MN recurrence was 31% at 10 years posttransplant. Patients with a faster progression toward end-stage kidney disease were at higher risk of developing recurrent MN (hazard ratio [HR], 0.55 per decade; 95% confidence interval [CI], 0.35-0.88). Moreover, elevated pretransplant levels of anti-phospholipase A2 receptor (PLA2R) antibodies were strongly associated with recurrence (HR, 18.58; 95% CI, 5.37-64.27). Patients receiving rituximab for MN recurrence had a higher likelihood of achieving remission than patients receiving renin-angiotensin-aldosterone system inhibition alone. In sum, MN recurs in one-third of patients posttransplant, and measurement of serum anti-PLA2R antibody levels shortly before transplant could aid in risk-stratifying patients for MN recurrence. Moreover, patients receiving rituximab had a higher rate of treatment response.

Exploring the causes of the high incidence of delayed graft function after kidney transplantation in Brazil: a multicenter study.

This retrospective multicenter (n = 18) cohort study evaluated the incidence, risk factors, and the impact of delayed graft function (DGF) on 1-year kidney transplant (KT) outcomes. Of 3992 deceased donor KT performed in 2014-2015, the incidence of DGF was 54%, ranging from 29.9% to 87.7% among centers. Risk factors (lower-bound-95%CI OR upper-bound-95%CI ) were male gender (1.066 1.2491.463 ), diabetic kidney disease (1.053 1.2961.595 ), time on dialysis (1.005 1.0071.009 ), retransplantation (1.035 1.3971.885 ), preformed anti-HLA antibodies (1.011 1.3831.892 ), HLA mismatches (1.006 1.0661.130 ), donor age (1.011 1.0171.023 ), donor final serum creatinine (sCr) (1.239 1.3171.399 ), cold ischemia time (CIT) (1.031 1.0431.056 ), machine perfusion (0.401 0.5420.733 ), and induction therapy with rabbit antithymocyte globulin (rATG) (0.658 0.8000.973 ). Duration of DGF > 4 days was associated with inferior renal function and DGF > 14 days with the higher incidences of acute rejection, graft loss, and death. In conclusion, the incidence and duration of DGF were high and associated with inferior graft outcomes. While late referral and poor donor maintenance account for the high overall incidence of DGF, variability in donor and recipient selection, organ preservation method, and type of induction agent may account for the wide variation observed among transplant centers.

Optimizing the clinical utility of sirolimus-based immunosuppression for kidney transplantation.

While calcineurin inhibitors (CNIs) are effective for preventing acute rejection in kidney transplant recipients, long-term use may cause chronic kidney injury and is associated with increased risks of cardiovascular events, cancer, and infection-associated death. Immunosuppression strategies are needed to balance risks of acute and subclinical rejection with long-term benefits of improved kidney function. Sirolimus, an inhibitor of mammalian target of rapamycin, is used for immunosuppression in kidney transplantation. Its clinical utility has evolved, over more than 15 years, including de novo sirolimus with and without concomitant CNIs and conversion from CNI-based regimens to sirolimus. Sirolimus-containing regimens are associated with preservation of good renal function, with promising characteristics for improving long-term graft and patient survival, including antiviral and anticancer effects. Based on clinical evidence, use of low-dose sirolimus in a de novo approach with tacrolimus/steroids in the immediate posttransplantation period is appropriate. A feasible alternative is a long term, CNI-free combination with mycophenolate mofetil (following CNI-to-sirolimus conversion at 3-6 months). These strategies are appropriate for a broad range of patients with various levels of immunologic risk, including those receiving expanded criteria donor kidneys or at increased risk of delayed graft function, particular challenges in Latin America and other global regions.

Yellow fever disease in a renal transplant recipient: Case report and literature review.

Yellow fever (YF) is a viral disease, with clinical presentation among immunosuppressed patients not fully understood. YF vaccination (YFV), a live vaccine, is contraindicated in patients receiving immunosuppressive treatment due to the risk of developing the disease after vaccination. We report a case of a 50-year-old male recipient who presented wild-type YF five years after a deceased donor kidney transplant. He lived in a YF endemic area and inadvertently received YFV. One day after YFV, the patient presented nausea, vomiting, fever, diarrhea, polyarthralgia, thrombocytopenia, and increased levels of liver function enzymes. The serological test was compatible with YF disease, and quantitative viral load confirmed the diagnosis of wild-type YF. The patient received supportive care for twelve days, with hospital discharge in good clinical condition and stable renal function. One month after discharge, the patient developed de novo donor-specific anti-HLA antibodies (DSA) and histological evidence of endothelial lesion, with a diagnosis of acute antibody-mediated rejection (AMR), treated with plasmapheresis and human IVIg therapy. Six months after therapy, he presented normal renal function with a reduction of DSA MFI. In the reported case, we observed a clinical wild-type YF diagnosed even after YF vaccine administration, with good clinical outcome. De novo DSA and AMR occurred after the recovering of disease, with an adequate response to therapy and preserved allograft function. We reviewed the published literature on YF and YFV in solid organ transplantation.

Immunization in end stage renal disease: The perception of waiting list patients.

BACKGROUND: The number of patients with chronic kidney disease is increasing worldwide, as well as the number of patients in kidney transplant waiting lists. In order to prevent infections related to immunosuppressive therapy, immunization guidelines for CKD patients before transplantation have been proposed. The aim of the present study was to evaluate adherence to immunization in a cohort of CKD patients in transplant waiting list and their renal replacement therapy clinics. METHODS: CKD patients older than 18 years old, receiving renal replacement therapy longer than 12 months and included in kidney transplant waiting list at University of Campinas (Unicamp) were enrolled. RESULTS: From February 2014 to December 2015, 105 patients fulfilled the inclusion criteria. Complete hepatitis B vaccination was observed in 73% and influenza vaccine in 67%. None of the other vaccine protocols reached 50% of coverage. Patients receiving immunization at primary health units presented higher coverage for diphtheria, tetanus (dT), measles, mumps, rubella (MMR), and hepatitis B vaccines, while patients immunized at renal replacement therapy clinics showed higher prevalence of pneumococcus (pneumo23). CONCLUSION: The low rates of immunization could reflect the RRT's clinics knowledge about the vaccines guidelines and its application on daily care. We suggest an integration between transplant center and RRT clinics, through lectures, periodic checking of vaccination cards, and easy to follow guidelines in order to provide a better vaccine coverage and to obtain higher immunization rates.

Oral Glucose Tolerance Test as a Risk Marker for Developing Post-Transplant Diabetes Mellitus.

INTRODUCTION: The incidence of post-transplant diabetes mellitus (PTDM) can reach 30% during the first 6 months after kidney transplantation (KT), increasing the risk of graft failure and mortality. There is no well-established biomarker for predicting PTDM occurrence. This study evaluated the association between the abnormal 2-hour oral glucose tolerance test (OGTT) and the PTDM incidence. METHODS: A retrospective single-center study, including adult kidney transplant recipients from deceased donors, was performed between March 2021 and June 2022. EXCLUSION CRITERIA: age <18 years; pretransplant diabetes mellitus (DM); death with a functioning graft; loss of follow-up and/or graft failure before 6 months post-transplant. The results of pretransplant OGTT, fasting (FPG), and afternoon plasma glucose levels at hospitalization and FPG in the first, second, and third months post-transplant were evaluated. For analysis, patients were grouped according to the PTDM diagnosis: PTDM and non-PTDM. RESULTS: From 164 KT performed in the period, 50 (30%) were included, most male (n = 34, 68%), with a mean age of 48.3 ± 12.5 years. Nine patients (18%) developed PTDM, 44% between 3 and 6 months. General characteristics and immunosuppressive therapy were similar between the groups. The mean FPG in the pretransplant OGTT was significantly higher in the PTDM group compared with the non-PTDM group (85.7 ± 7.9 vs 79.1 ± 8.2, P = .03). The number of patients classified as impaired glucose tolerance (IGT) on the pre-transplant OGTT was significantly higher in the PTDM group. CONCLUSION: IGT in the pretransplant OGTT was associated with PTDM cases in kidney transplant recipients without a previous diagnosis of DM.

Post-transplant diabetes mellitus: risk factors and outcomes in a 5-year follow-up.

Introduction: Kidney transplantation is associated with an increased risk of posttransplant diabetes mellitus (PTDM), impacting recipient and graft survivals. The incidence of PTDM ranges from 15% to 30%, with most cases occurring in the first year post-transplant. Some clinical and laboratory characteristics pre- and post-transplant may be associated with a higher PTDM incidence in a more extended follow-up period. This study aimed to analyze the prevalence of PTDM among renal transplant recipients without previous DM diagnosis during a five-year post-transplant follow-up, as well as clinical and laboratory characteristics associated with a higher incidence of PTDM during this period. Material and methods: Single-center retrospective cohort including kidney transplant recipients older than 18 years with a functioning graft over six months of follow-up between January and December 2018. Exclusion criteria were recipients younger than 18 years at kidney transplantation, previous diabetes mellitus diagnosis, and death with a functioning graft or graft failure within six months post-transplant. Results: From 117 kidney transplants performed during the period, 71 (60.7%) fulfilled the inclusion criteria, 18 (25.3%) had PTDM diagnosis, and most (n=16, 88.9%) during the 1st year post-transplant. The need for insulin therapy during the hospital stay was significantly higher in the PTDM group (n=11, 61.1% vs. n=14, 26.4%, PTDM vs. non-PTDM). Other PTDM risk factors, such as older age, high body mass index, HLA mismatches, and cytomegalovirus or hepatitis C virus infections, were not associated with PTDM occurrence in this series. During 5-year post-transplant follow-up, the graft function remained stable in both groups. Conclusion: The accumulated incidence of PTDM in this series was similar to the reported in other studies. The perioperative hyperglycemia with the need for treatment with insulin before hospital discharge was associated with PTDM.

Analysis of Factors Related to the Success of Pediatric Kidney Transplantation: A 35 Years Experience.

BACKGROUND: Despite the significant improvement results over the past 20 years, pediatric kidney transplantation remains a challenge. Chronic rejection, thrombosis, and recurrence of the primary disease are frequent causes of graft loss that have been little studied. Therefore, our objective is to analyze factors related to a better prognosis, which can be used to improve future strategies to allow higher pediatric transplant success rates. METHODS: A retrospective cohort study with patients under 15 years old submitted for kidney transplantation at the Hospital das Clínicas da UNICAMP between January 1, 1987, and January 1, 2022. Age, patient weight, time and type of dialysis, use of anticoagulation, complications, ischemia time, and donor weight were analyzed and related to graft loss. The significance level adopted for the statistical tests was 5%. RESULTS: One hundred ninety-two medical records were anaThe mean follow-up time was 11 years, and the mean graft duration was ration 8.5 years. The main causes of graft loss were chronic dysfunction, thrombosis, and acute cellular rejection. Thrombosis presented significantly with the donor's body mass index and second transplantation. There was no correlation between the analyzed variables and chronic dysfunction or acute cellular rejection. DISCUSSION: Thrombosis remains the main cause of early graft loss, followed by acute cellular rejection. Measures such as thrombophilia screening and thromboprophylaxis have been proposed to improve results. However, they are still not standardized. CONCLUSION: The main causes of graft loss were chronic dysfunction, thrombosis, and acute cellular rejection. Only the thrombosis was related to the donor's body mass index and a second transplantation.

The impact of preservation solutions for static cold storage on kidney transplantation outcomes: Results of a Brazilian nationwide multicenter study.

This study evaluated the current practices of selecting cold storage preservation solutions in Brazil and their impact on delayed graft function (DGF) incidence and 1-year outcomes in kidney transplant recipients. A retrospective cohort study was conducted, including 3,134 brain-dead deceased donor kidney transplants performed between 2014 and 2015 in 18 Brazilian centers. The most commonly used preservation solution was Euro-collins (EC, 55.4%), followed by Histidine-tryptophan-ketoglutarate (HTK, 30%) and Institut Georges Lopez (IGL-1, 14.6%). The incidence of DGF was 54.4%, with 11.7% of patients requiring dialysis for more than 14 days, indicating prolonged DGF. Upon adjusting for confounding variables, HTK demonstrated a significantly lower risk of DGF than EC (OR 0.7350.82500.926), as did IGL-1 (OR 0.6050.7120.837). Similar protective effects were observed for prolonged DGF when comparing HTK (OR 0.4780.5990.749) and IGL-1 (OR 0.4780.6810.749) against EC. No significant association was found between preservation solutions and 1-year death-censored graft survival. In conclusion, EC was the most frequently used cold storage perfusion solution, demonstrating a higher incidence and duration of DGF compared with HTK and IGL-1, but with no impact on 1-year graft survival.

Recurrent Membranoproliferative Glomerulonephritis After Kidney Transplantation: Risk Factors and Impact on Graft Survival.

BACKGROUND Membranoproliferative glomerulonephritis (MPGN) is an uncommon cause of end-stage renal disease (ESRD). Recurrence rates after transplantation range from 11.8% to 18.9% after 5 and 15 years, respectively. This study aimed to assess the risk factors of MPGN recurrence after kidney transplantation and its impact on graft survival. MATERIAL AND METHODS This was a single-center retrospective cohort, including renal transplant recipients older than 18 years, with a diagnosis of MPGN in native kidneys. Data were obtained from medical records during the first 5-year post-transplant follow-up. Primary endpoints were graft function and survival. Secondary endpoints were MPGN recurrence risk factors and these cases' clinical, laboratory, and histological features. RESULTS Twenty-eight patients were included; the majority male (60.7%), with a mean age of 24.0±9.4 years. At MPGN native diagnosis, all patients presented proteinuria, with C3 consumption in 42.9%. Histological analysis showed 13 (42.9%) MPGN type I and 5 (17.9%) type II, with no cases of type III. MPGN recurrence occurred in 7 (25.0%) patients; 85.7% were male, 57.1% were recipients from a living donor, all presenting nephrotic syndrome and hematuria, with C3 consumption in 71.4%. The graft function was similar between the groups. Two (28.6%) patients progressed to graft failure in the recurrence group, and 1 died with a functioning graft. CONCLUSIONS The MPGN recurrence rate was 25%, most of them recipients of kidneys from living donors. Nephrotic syndrome and C3 consumption were frequent at recurrence. The graft function was similar between the groups, and the 5-year graft survival rate in the recurrence group was higher than in other studies.

IgA nephropathy and kidney transplantation according to the Oxford classification.

INTRODUCTION: IgA nephropathy (IgAN) is the most common glomerular disease globally, and its susceptibility and the risk for the development of end-stage kidney disease are related to genetic and environmental factors. IgAN recurrence after kidney transplantation is relatively common, impacting graft function and survival. This study evaluated the risk factors and the clinical, laboratory, and histological characteristics of post-transplant IgAN recurrence based on the Oxford classification. MATERIAL AND METHODS: Retrospective single-center cohort study including kidney transplant recipients with biopsy-proven pre-transplantation IgAN, with analysis of risk factors and clinical, laboratory, and histological characteristics of the IgAN recurrence cases. RESULTS: 53 patients fulfilled the inclusion criteria and were included in the study. The majority was male, white, eutrophic, with a mean age of 27 ± 9 years at IgAN diagnosis. Systemic arterial hypertension and proteinuria were frequent in the pretransplant period. Four recipients (7.5%) presented IgAN recurrence in a period of 6 to 122 months post-transplant. According to the Oxford classification, they had high scores of mesangial hypercellularity and segmental glomerulosclerosis in the native kidney biopsies and there was mesangial hypercellularity in all analyzed graft biopsies. None of these patients had received induction immunosuppression and all of them presented graft failure in the follow-up. CONCLUSIONS: In this series, there was a high prevalence of mesangial hypercellularity and segmental glomerulosclerosis on native kidney biopsies, and mesangial hypercellularity occurred in all IgAN recurrence graft biopsies. Despite the lower incidence of recurrence of IgAN post-transplant compared to previous reports, progression to graft loss was of 100%.

Sugar, salt, immunity and the cause of primary hypertension.

Despite its discovery more than 150 years ago, the cause of primary hypertension remains unknown. Most studies suggest that hypertension involves genetic, congenital or acquired risk factors that result in a relative inability of the kidney to excrete salt (sodium chloride) in the kidneys. Here we review recent studies that suggest there may be two phases, with an initial phase driven by renal vasoconstriction that causes low-grade ischemia to the kidney, followed by the infiltration of immune cells that leads to a local autoimmune reaction that maintains the renal vasoconstriction. Evidence suggests that multiple mechanisms could trigger the initial renal vasoconstriction, but one way may involve fructose that is provided in the diet (such as from table sugar or high fructose corn syrup) or produced endogenously. The fructose metabolism increases intracellular uric acid, which recruits NADPH oxidase to the mitochondria while inhibiting AMP-activated protein kinase. A drop in intracellular ATP level occurs, triggering a survival response. Leptin levels rise, triggering activation of the sympathetic central nervous system, while vasopressin levels rise, causing vasoconstriction in its own right and stimulating aldosterone production via the vasopressin 1b receptor. Low-grade renal injury and autoimmune-mediated inflammation occur. High-salt diets can amplify this process by raising osmolality and triggering more fructose production. Thus, primary hypertension may result from the overactivation of a survival response triggered by fructose metabolism. Restricting salt and sugar and hydrating with ample water may be helpful in the prevention of primary hypertension.

Prognostic role of renal replacement therapy among hospitalized patients with heart failure in the Brazilian national public health system.

Introduction: Data on patients hospitalized with acute heart failure in Brazil scarce. Methods: We performed a cross-sectional, retrospective, records-based study using data retrieved from a large public database of heart failure admissions to any hospital from the Brazilian National Public Health System (SUS) (SUS Hospital Information System [SIHSUS] registry) to determine the in-hospital all-cause mortality rate, in-hospital renal replacement therapy rate and its association with outcome. Results: In total, 910,128 hospitalizations due to heart failure were identified in the SIHSUS registry between April 2017 and August 2021, of which 106,383 (11.7%) resulted in in-hospital death. Renal replacement therapy (required by 8,179 non-survivors [7.7%] and 11,496 survivors [1.4%, p < 0.001]) was associated with a 56% increase in the risk of death in the univariate regression model (HR 1.56, 95% CI 1.52 -1.59), a more than threefold increase of the duration of hospitalization, and a 45% or greater increase of cost per day. All forms of renal replacement therapy remained independently associated with in-hospital mortality in multivariable analysis (intermittent hemodialysis: HR 1.64, 95% CI 1.60 -1.69; continuous hemodialysis: HR 1.52, 95% CI 1.42 -1.63; peritoneal dialysis: HR 1.47, 95% CI 1.20 -1.88). Discussion: The in-hospital mortality rate of 11.7% observed among patients with acute heart failure admitted to Brazilian public hospitals was alarmingly high, exceeding that of patients admitted to North American and European institutions. This is the first report to quantify the rate of renal replacement therapy in patients hospitalized with acute heart failure in Brazil.

Use of uric acid-lowering agents limits experimental cyclosporine nephropathy.

BACKGROUND: Hyperuricemia frequently complicates cyclosporine (CsA) therapy. Previous studies have shown that hyperuricemia exacerbates interstitial and vascular lesions in the cyclosporine model. We tested the hypothesis that normalization of uric acid could prevent the development of cyclosporine toxicity. METHODS: CsA nephropathy was induced by administering CsA (15 mg/kg/day) for 7 weeks to rats on a low salt diet (CsA group). The effect of preventing hyperuricemia was determined by concomitant treatment with a xanthine oxidase inhibitor, allopurinol (CsAALP), or with a uricosuric, benzbromarone (CsABENZ), in drinking water. Control groups included vehicle-treated rats. RESULTS: CsA-treated rats developed mild hyperuricemia with arteriolar hyalinosis, tubular atrophy, striped interstitial fibrosis, increased cell proliferation and decreased VEGF expression. Treatment with allopurinol or benzbromarone limited renal disease, with reduced interstitial fibrosis, cell proliferation, macrophage infiltration, osteopontin expression and arteriolar hyalinosis, in association with restoration of VEGF expression. Both drugs provided comparable protection. CONCLUSIONS: An increase in uric acid exacerbates CsA nephropathy in the rat. Concomitant treatment with allopurinol or benzbromarone reduced the severity of renal disease. The similar protection observed with both drugs suggests that the effect is associated more with lowering uric acid levels than the antioxidant effect of allopurinol.

Anemia in chronic renal disease: evaluation of inflammatory activity on erythropoiesis and iron metabolism in patients not submitted to dialysis treatment.

BACKGROUND: Inflammatory activity is one of the factors involved in the physiopathology of anemia in patients with chronic kidney disease (CKD). The majority of studies on anemia, inflammation, and disturbances of iron metabolism have focused on patients in end-stage renal failure and dialysis therapy. However, anemia and inflammation are present in patients in previous stages of renal failure. The objective of this study was to evaluate the possible influence of inflammatory activity on erythropoiesis and iron metabolism in CKD patients without dialytic treatment. METHODS: 114 CKD adult patients were studied. Patients with anemia (n = 72) were compared with those without anemia (n = 46). Anemic patients were classified as renal anemia (n = 46) or iron deficiency anemia (n = 26). In addition the total group was analyzed according to the degree of renal dysfunction. Iron status, erythropoiesis activity (soluble transferrin receptor and erythropoietin determinations), and inflammatory activity (C-reactive protein, interleukin-6, interleukin-lp, and neopterin determinations) were measured using commercial kits. Reticulocyte hemoglobin content (Ret-Y) was also determined. RESULTS: Interleukin-6, interleukin-li, and neopterin concentrations were higher in the anemic group when compared with those without anemia and controls. There was no difference in C-reactive protein values between CKD with and without anemia, although both of them had showed elevated levels when compared with controls. Ret-Y values were lower in iron deficiency anemia when compared with renal anemia and controls. An inverse correlation between interleukin-6 and hemoglobin (r = -0.4287, p= 0.0002) was observed only in the renal anemia group. It was observed that anemia has a tendency to worsen as renal function deteriorates. Reticulocyte count was lower and neopterin concentrations were higher in more advanced renal failure stages. CONCLUSIONS: Inflammatory factors contribute to anemia in renal patients in all stages of renal failure. High levels of neopterin in CKD patients suggest that neopterin contributes to impaired erythropoietin production and anemia in CKD patients.

Sexual and Reproductive Health Assessment in a Group of Female Renal Transplant Recipients.

BACKGROUND: Fertility and sexual health are impaired in individuals with chronic kidney disease and can be restored after a successful renal transplant. This is a single-center prospective study about the sexual and reproductive health (including contraceptive methods and gynecologic cancer screening) in renal transplant recipients. METHODS: Female renal transplant recipients, aged 18 to 49 years at transplant, were interviewed about their gynecologic history, sexual health, and use of contraceptive methods. RESULTS: Ninety-one patients fulfilled the inclusion criteria. The majority of women maintained menstrual cycles during dialysis therapy, being almost 60% of the women in an irregular rhythm. Pregnancies were reported for 51 women, 20% after transplant, and associated with low-weight newborns. The incidence of spontaneous abortion was 12.5%. Thirty-one patients were denied contraceptive methods due to the vasectomy of the partner (n = 16) or the belief that they would not become pregnant (n = 15). The most common contraceptive method was a condom, and the use of an intrauterine device was rare. Gynecologic assessment and cancer screening were out-of-date in almost one-third of patients. CONCLUSIONS: In this study, the majority of women were from low-income areas and had low levels of education. Despite access to public universal health care, adherence to yearly screening tests and use of contraceptive methods were lower than expected.

De Novo Membranous Nephropathy Associated With Antibody-Mediated Rejection in Kidney Transplant Recipients.

BACKGROUND: Membranous nephropathy (MN) is a rare autoimmune disease that can develop a persistent nephrotic syndrome and end-stage kidney disease, with a recurrence rate of 30% to 40% after kidney transplant. METHODS: Retrospective case series of membranous nephropathy observed in a cohort of kidney transplant recipients with donor-specific anti-human leukocyte antigen antibodies and biopsy-proven antibody-mediated rejection (AMR). RESULTS: We report 4 cases of membranous nephropathy associated with AMR. MN was diagnosed 10 to 92 months posttransplant, associated with de novo donor-specific antibodies, specific to class I in 2 cases, and class II in another 2. All cases presented typical morphology of membranous nephropathy, with subepithelial deposits with spikes at electron microscopy. Immunostaining for immunoglobulin G4 was negative in all cases, and podocyte-expressed M-type phospholipase A2 receptor was detected in glomerular basement membrane of 3 cases. Biopsy specimens from patients with longer follow-up showed more intense microvascular inflammation and chronic injury markers, possibly because of subclinical immunologic injury. AMR therapy included immunoglobulin 2g/kg in 3 patients, isolated or associated with plasmapheresis. One patient was not treated because of an active disseminated infection. Two patients remain with functioning grafts and under antiproteinuric therapy. Two grafts were lost, 1 because of chronic failure and the other because of death secondary to infection. Despite treatment, donor-specific antibodies remain detectable in a 6-month follow-up. CONCLUSIONS: De novo MN is a rare manifestation associated with AMR in kidney transplant recipients. The occurrence of podocyte-expressed M-type phospholipase A2 receptor in de novo MN suggests antibody-mediated activation, despite the use of maintenance immunosuppression.

The Mycophenolate-based Immunosuppressive Regimen Is Associated With Increased Mortality in Kidney Transplant Patients With COVID-19.

BACKGROUND: The chronic use of immunosuppressive drugs is a key risk factor of death because of coronavirus disease 2019 (COVID-19) in kidney transplant recipients (KTRs), although no evident association between the class of immunosuppressive and outcomes has been observed. Thus, we aimed to compare COVID-19-associated outcomes among KTRs receiving 3 different immunosuppressive maintenance regimes. METHODS: This study included data from 1833 KTRs with COVID-19 diagnosed between March 20 and April 21 extracted from the national registry before immunization. All patients were taking calcineurin inhibitor associated with mycophenolate acid (MPA, n = 1258), azathioprine (AZA, n = 389), or mammalian targets of rapamycin inhibitors (mTORi, n = 186). Outcomes within 30 and 90 d were assessed. RESULTS: Compared with patients receiving MPA, the 30-d (79.9% versus 87.9% versus 89.2%; P < 0.0001) and 90-d (75% versus 83.5% versus 88.2%; P < 0.0001) unadjusted patient survivals were higher in those receiving AZA or mTORi, respectively. Using adjusted multivariable Cox regression, compared with patients receiving AZA, the use of MPA was associated with a higher risk of death within 30 d (adjusted hazard ratio [aHR], 1.70; 95% confidence interval [CI], 1.21-2.40; P = 0.003), which was not observed in patients using mTORi (aHR, 0.78; 95% CI, 0.45-1.35; P = 0.365). At 90 d, although higher risk of death was confirmed in patients receiving MPA (aHR, 1.46; 95% CI, 1.09-1.98; P = 0.013), a reduced risk was observed in patients receiving mTORi (aHR, 0.59; 95% CI, 0.35-0.97; P = 0.04) compared with AZA. CONCLUSIONS: This national cohort data suggest that, in KTRs receiving calcineurin inhibitor and diagnosed with COVID-19, the use of MPA was associated with higher risk of death, whereas mTORi use was associated with lower risk of death.

Evaluation of Trypanosoma cruzi parasitic load by real-time PCR and blood culture in long-term kidney transplant recipients.

INTRODUCTION: Acute Chagas disease involving reactivation can occur after organ transplant, and follow-up by direct parasitological or molecular methods is essential for monitoring the parasitic load in such patients. In contrast, there is a little data on the parasitic load in long-term organ recipients. In this study, we examined the parasitic load in long-term kidney transplant patients and assessed the possibility of late Chagas disease reactivation. METHODOLOGY: Blood cultures and real-time PCR were used to assess the parasitic load in four immunosuppressed patients who underwent kidney transplants (between 1996 and 2014) and were also treated for parasites. RESULTS: There were no positive blood culture or real-time PCR results in Chagas disease patients who received kidney transplants. The real-time PCR presented detection limit of 0.1 parasite equivalent/mL. The time interval between the transplant and sample collection varied from one to 19 years. CONCLUSIONS: No parasites were detected in the evaluated patients. The use of benznidazole and immunosuppressive therapy may have contributed to control the T. cruzi infection. In transplanted patients with Chagas disease, the use of methods such real-time PCR and blood culture can monitor the parasitic load and prevent disease reactivation.

Twin pregnancy after kidney transplantation: case report and systematic review.

BACKGROUND: Kidney transplantation is associated with fertility restoration in more than 50% of women with chronic kidney disease. Pregnancy after transplantation may affect women's health and fetal development, with higher rates of abortion, fetal growth restriction, and neonatal deaths. Twin pregnancy is a condition of high-risk for adverse maternal and perinatal outcomes, and its occurrence in women with previous kidney transplantation is rare. CASE: 32-year-old woman, recipient of living donor kidney transplantation, with a history of one pregnancy prior to transplantation, with current normal allograft function and no use of contraceptive method. At ten weeks of amenorrhea, ultrasound investigation showed a dichorionic diamniotic twin pregnancy. The following evaluation showed Chiari type II features in one fetus, and no detectable abnormality in the other one. There was appropriate blood pressure control with no need for an antihypertensive drug, and renal function remained normal without proteinuria. Calcium and a low dose of acetylsalicylic acid were used as preeclampsia prophylaxis. At 33 weeks of gestation, she presented premature rupture of membranes with spontaneous preterm labor. A cesarean section was performed due to the breech presentation of the first fetus. The patient persisted with normal graft function and without graft rejection during follow-up. DISCUSSION AND CONCLUSION: Twin pregnancies after kidney transplantation are rare, and it is most frequently associated with preterm birth. We reported a successful twin pregnancy after kidney transplantation, with good perinatal and maternal outcomes, and without graft rejection or dysfunction.