Baseline characteristics and evolution of Brazilian patients with atypical hemolytic uremic syndrome: first report of the Brazilian aHUS Registry.

Background: Atypical hemolytic uremic syndrome (aHUS) is an ultra-rare disease. Therefore, studies involving large samples are scarce, making registries powerful tools to evaluate cases. We present herein the first analysis of the Brazilian aHUS Registry (BRaHUS). Methods: Analysis of clinical, laboratory, genetic and treatment data from patients inserted in the BRaHUS, from 2017 to 2020, as an initiative of the Rare Diseases Committee of the Brazilian Society of Nephrology. Results: The cohort consisted of 75 patients (40 adults and 35 pediatric). There was a predominance of women (56%), median age at diagnosis of 20.7 years and a positive family history in 8% of cases. Renal involvement was observed in all cases and 37% had low C3 levels. In the <2 years of age group, males were predominant. Children presented lower levels of hemoglobin (P = .01) and platelets (P = .003), and higher levels of lactate dehydrogenase (LDH) (P = .004) than adults. Genetic analysis performed in 44% of patients revealed pathogenic variants in 66.6% of them, mainly in CFH and the CFHR1-3 deletion. Plasmapheresis was performed more often in adults (P = .005) and 97.3% of patients were treated with eculizumab and its earlier administration was associated with dialysis-free after 3 months (P = .08). Conclusions: The cohort of BRaHUS was predominantly composed of female young adults, with renal involvement in all cases. Pediatric patients had lower hemoglobin and platelet levels and higher LDH levels than adults, and the most common genetic variants were identified in CFH and the CFHR1-3 deletion with no preference of age, a peculiar pattern of Brazilian patients.

The Kinetics of Anti-HLA Antibodies in the First Year after Kidney Transplantation: In Whom and When Should They Be Monitored?

The impact of the kinetics of the anti-HLA antibodies after KTx on the occurrence of acute rejection as well as the better time-point to monitor anti-HLA Abs after transplantation is not completely defined. This prospective study followed 150 patients over 12 months after transplantation. Serum IgG anti-HLA Abs were detected by single antigen beads after typing donors and recipients for loci A, B, C, DR, and DQ. Before KTx, 89 patients did not present anti-HLA Abs and 2% developed "de novo" Abs during the 1st year, 39 patients were sensitized without DSAs, and 13% developed DSA after surgery; all of them presented ABMR. Sensitized patients presented higher acute rejection rates (36.4% versus 13.5%, p < 0.001), although 60% of the patients did not present ABMR. Patients, in whom DSA-MFI decreased during the first two weeks after surgery, did not develop ABMR. Those who sustained their levels presented a rate of 22% of ABMR. 85% of patients developed ABMR when MFIs increased early after transplantation (which occurred in 30% of the DSA positive patients). In the ABMR group, we observed an iDSA-MFI sharp drop on the fourth day and then an increase between the 7th and 14th POD, which suggests DSA should be monitored at this moment in sensitized patients for better ABMR prediction.

Use of Thymoglobulin® (antithymocyte immunoglobulin) in renal transplantation: practical guide.

The combination of immunosuppressive drugs is part of the treatment regimen of patients undergoing kidney transplantation (RT). Thymoglobulin®, a rabbit immunoglobulin directed against human thymocytes, is the most commonly agent used for induction therapy in RT in the US. In Brazil, Thymoglobulin® is approved by ANVISA for the use in patients who underwent kidney transplantation and despite being widely used, there are controversies regarding the drug administration. We prepared a systematic review of the literature, evaluating studies that used Thymoglobulin® for induction and for acute rejection treatment in patients undergoing RT. The review used the computadorized databases of EMBASE, LILACS and MedLine. Data were extracted from the studies concerning general features, methodological characteristics and variables analyzed in each study. From the results, a practical guide was prepared analyzing various aspects on the use of Thymoglobulin® in patients submitted to RT.

Dynamics of anti-human leukocyte antigen antibodies after renal transplantation and their impact on graft outcome.

The purpose of this study was to sequentially monitor anti-HLA antibodies and correlate the results with antibody-mediated rejection (AMR), graft survival (GS), and graft function (GF). We collected sera from 111 kidney transplant recipients on transplant days 0, 7, 14, 30, 60, 90, 180, and 360 and analyzed PRA levels by ELISA. DSAs were analyzed by single-antigen beads in rejecting kidneys. At pre-transplant, 79.3% of the patients were non-sensitized (PRA = 0%) and 20.7% were sensitized (PRA > 1%). After transplant, patients were grouped by PRA profile: no anti-HLA antibodies pre- or post-transplant (group HLApre-/post-; n = 80); de novo anti-HLA antibodies post-transplant (group HLApre-/post+; n = 8); sensitized pre-transplant/increased PRA post-transplant (group HLApre+/post↑; n = 9); and sensitized pre-transplant/decreased PRA post-transplant (group HLApre+/post↓; n = 14). De novo anti-HLA antibodies were detected at 7-180 d. In sensitized patients, PRA levels changed within the first 30 d post-transplant. Incidence of AMR was higher in HLApre-/post+ and HLApre+/post↑ than in HLApre-/post-, and HLApre+/post↓ (p < 0.001) groups. One-yr death-censored GS was 36% in group HLApre+/post↑, compared with 98%, 88% and 100% in groups HLApre-/post-, HLApre-/post+, and HLApre+/post↓, respectively (p < 0.001). Excluding first-year graft losses, GF and GS were similar among the groups. In conclusion, post-transplant antibody monitoring can identify recipients at higher risk of AMR.

Antibody-mediated rejection (AMR) after pancreas and pancreas-kidney transplantation.

Antibody-mediated rejection (AMR) requires specific diagnostic tools and treatment and is associated with lower graft survival. We prospectively screened C4d in pancreas (n = 35, in 27 patients) and kidney (n = 33, in 21 patients) for cause biopsies. Serum amylase and lipase, amylasuria, fasting blood glucose (FBG) and 2-h capillary glucose (CG) were also analysed. We found that 27.3% of kidney biopsies and 43% of pancreatic biopsies showed C4d staining (66.7% and 53.3% diffuse in peritubular and interacinar capillaries respectively). Isolated exocrine dysfunction was the main indication for pancreas biopsy (54.3%) and was followed by both exocrine and endocrine dysfunctions (37.1%) and isolated endocrine dysfunction (8.6%). Laboratorial parameters were comparable between T-cell mediated rejection and AMR: amylase 151.5 vs. 149 U/l (P = 0.075), lipase 1120 vs. 1288.5 U/l (P = 0.83), amylasuria variation 46.5 vs. 61% (P = 0.97), FBG 69 vs. 97 mg/dl (P = 0.20) and 2-h CG maximum 149.5 vs. 197.5 mg/dl (P = 0.49) respectively. Amylasuria values after treatment correlated with pancreas allograft loss (P = 0.015). These data suggest that C4d staining should be routinely investigated when pancreas allograft dysfunction is present because of its high detection rate in cases of rejection.

Alpha-hydroxy acids: unapproved uses or indications.

Alpha-hydroxy acids have been used for rejuvenation since ancient times, and now there are several on the market. Depending on the concentration, some have been shown to be effective as peeling agents and for rejuvenation. Glycolic acid and lactic acid are the alpha-hydroxy acids most frequently used in cosmetics, although there are many others used in combination. Some of the most striking advances in dermatology have followed the off-label use of drugs, which is widespread and unavoidable, but a well founded scientific approach to an individual patient's pathology must be emphasized as the number of products, regimens, and adjuncts increases exponentially in the cosmetic field. In this article the authors review some unapproved uses of alpha-hydroxy acids. More published data on the scientific value of these off-label indications that proves whether they are effective or not is needed.