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1.
Genes (Basel) ; 15(6)2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38927709

RESUMO

BACKGROUND: Homozygosity for LIMS1 rs893403-GG genotype is linked to an increased risk of allograft rejection after kidney transplantation. Ischemia-reperfusion of the kidney allograft leads to long term infiltration of activated and effector-memory T lymphocytes and resulting in rejection and long-term fibrosis. However, the genotype, LIMS1 expression under ischemic conditions and the long-term histopathological relationships remain ill-defined. METHODS: We examined the impact of the recipient's LIMS1-rs893403 genotype with transplant kidney histopathology. The association of the LIMS1-rs893403 genotype and LIMS1 and GCC2 mRNA expression in ischemic donor kidneys were also examined. Recipients who underwent transplant kidney biopsy were genotyped for the LIMS1-rs893403 variant and associated deletion. Histopathological findings were compared between recipients with LIMS1 risk and non-risk genotypes. Real-time PCR and immunofluorescence staining for LIMS1 and GCC2 expression were performed in non-utilized donor kidneys. RESULTS: Demographic, clinical, and treatment characteristics and the histopathological diagnosis were similar between recipients with rs893403 GG and AA/AG genotype. The Banff tubulitis score was higher in GG recipients (n = 24) compared to AA/AG (n = 86) recipients (1.42 ± 0.65 vs. 1.12 ± 0.66, p = 0.03). Ischemic kidneys with GG showed higher LIMS1 and GCC2 mRNA expression than kidneys with AG. Kidneys with rs893403-GG had higher tubular LIMS1 and GCC2 immunohistochemical staining compared to kidneys with rs893403-AG. CONCLUSIONS: Our data supports the role of the LIMS1 locus in kidney transplant rejection, particularly in lymphocyte infiltration into the internal aspect of the tubular basement membranes. Increased LIMS1 and GCC2 expression in ischemic donor kidneys with the GG genotype require further studies.


Assuntos
Genótipo , Transplante de Rim , Túbulos Renais , Proteínas com Domínio LIM , Transplante de Rim/efeitos adversos , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Proteínas com Domínio LIM/genética , Túbulos Renais/patologia , Túbulos Renais/metabolismo , Inflamação/genética , Inflamação/patologia , Rejeição de Enxerto/genética , Rejeição de Enxerto/patologia , Polimorfismo de Nucleotídeo Único
2.
Nephron ; 148(1): 54-62, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37611544

RESUMO

BACKGROUND: Although most patients with atypical hemolytic uremic syndrome (aHUS) have variants in genes participating in alternative complement pathways, rare variants in non-complement pathway-related genes, including DGKE, INF2, MMACHC, PLG, and THBD, have also been described. CASE PRESENTATION: We report an 18-year-old male patient with renal biopsy-proven chronic thrombotic microangiopathy that raised suspicion of aHUS. Whole-exome sequencing revealed a novel pathogenic homozygous MMACHC c.484G>T (p.Gly162Trp) variant. Subsequently, clinical and laboratory findings confirmed cobalamin C (Cbl C) deficiency. Also, homozygous missense c.1112C>T PLG (p.Thr371Ile) variant was detected (it had been reported as a variant of unknown significance). However, the low serum plasminogen (PLG) activity proved the pathogenicity of c.1112C>T. Hence, the patient was diagnosed with concurrent Cbl C and PLG deficiencies. Segregation analysis revealed that the mother and father had the same heterozygous PLG and MMACHC variants. PLG variants have generally been described in aHUS patients concomitant with complement gene variants in the literature; therefore, the association between aHUS and PLG variants is controversial. The possible contribution of PLG deficiency to thrombotic microangiopathy was also discussed in this case. CONCLUSION: Non-complement-mediated aHUS is an exceptional disorder. A limited number of genes are involved in this entity. To our knowledge, this is the first aHUS patient diagnosed with both Cbl C and PLG deficiencies in the literature.


Assuntos
Síndrome Hemolítico-Urêmica Atípica , Microangiopatias Trombóticas , Deficiência de Vitamina B 12 , Masculino , Humanos , Adolescente , Vitamina B 12 , Microangiopatias Trombóticas/genética , Síndrome Hemolítico-Urêmica Atípica/genética , Síndrome Hemolítico-Urêmica Atípica/diagnóstico , Proteínas do Sistema Complemento/genética , Deficiência de Vitamina B 12/complicações , Deficiência de Vitamina B 12/genética , Plasminogênio/genética , Oxirredutases
4.
Nephrology (Carlton) ; 29(1): 39-47, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37731224

RESUMO

AIM: Increased venous thrombosis and arterial embolism rates are observed in the general population during or after COVID-19. Data regarding the kidney transplant population are scarce. In this study, we aim to investigate the thrombotic complications and risk factors associated with thrombotic complications in kidney transplant patients. METHODS: This retrospective observational study included adult kidney transplant recipients diagnosed with COVID-19 between March 2020 and June 2022. The endpoint was the occurrence of thromboembolic events. RESULTS: Four hundred and sixty-nine patients were followed for a median of 10.8 months after COVID-19. Forty patients (8.5%) died. Thromboembolic complications developed in 51 (11.9%) of the surviving patients. Twenty-four patients with thromboembolic events were receiving prophylactic anticoagulation before the event. The patients with mild, moderate, and severe COVID-19 were 292, 129, and 48, respectively. Patients with moderate COVID-19 had a significantly higher percentage of thromboembolic complications than patients with mild COVID-19. Older age, prior heart disease, and moderate COVID-19 were significantly associated with thromboembolic events. The incidence of thromboembolic events after COVID-19 is 10.9 per 100 patient-year. CONCLUSION: Thromboembolic complications were observed at increased rates in kidney transplant recipients after COVID-19. Therefore, prospective and cohort studies for post-COVID-19 complications regarding the treatment modalities are urgently needed.


Assuntos
COVID-19 , Transplante de Rim , Tromboembolia , Trombose Venosa , Adulto , Humanos , Transplante de Rim/efeitos adversos , COVID-19/complicações , COVID-19/epidemiologia , Estudos Prospectivos , Tromboembolia/diagnóstico , Tromboembolia/epidemiologia , Tromboembolia/etiologia , Trombose Venosa/etiologia , Estudos Retrospectivos , Transplantados
5.
J Nephrol ; 2023 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-37947938

RESUMO

BACKGROUND: Immunoglobulin A nephropathy (IgAN) is a common primary glomerulonephropathy. There is evidence that mesangial C3 deposition plays a role in the development of the disease. The aim of this study was to examine the effect of C3 deposition on the prognosis of IgAN patients. METHOD: The study included 1135 patients with biopsy-confirmed IgAN from the database of the Turkish Nephrology Association Glomerular Diseases Working Group (TSN-GOLD). Patients were excluded from the study if they were aged < 18 or > 75 years or if C3 staining had not been performed in the immunofluorescent analysis. C3 deposition was defined as an immunofluorescence intensity of C3 ≥ 2 + within the mesangium. The primary endpoints were the development of end-stage renal disease, a 30% decrease in glomerular filtration rate compared to the basal value or an elevation in proteinuria to a nephrotic level (3.5 gr/day). RESULTS: Mesangial C3 deposition was observed in 603 (53.1%) patients. No statistically significant difference was found at baseline between the groups with and without mesangial C3 deposition, as for age, sex, BMI, proteinuria level, or the presence of hypertension. In the follow-up period with a mean duration of 78 months, no significant difference was found between the two groups regarding the primary endpoints (p = 0.43). A significant correlation between C3 deposition and segmental glomerulosclerosis (S1) according to the Oxford MEST-C classification was found (p = 0.001). CONCLUSION: Although a correlation was observed between mesangial C3 deposition and the S1 MEST-C classification, mesangial C3 deposition was not a prognostic factor in IgAN.

6.
Nefrología (Madrid) ; 43(6): 783-788, nov.- dec. 2023. tab, ilus
Artigo em Inglês | IBECS | ID: ibc-228016

RESUMO

Background Passenger lymphocyte syndrome (PLS) causes immune-mediated hemolysis in solid and bone marrow transplant recipients. Donor-derived antibodies against the recipient erythrocyte drive the pathogenesis. It is a rare entity in kidney transplantation, and most of the cases are self-limited. Case presentation A 36-year-old woman presented with fatigue 13 days after living donor renal transplantation. The operation was uneventful, and she was discharged with normal graft functions on the 11th day of transplantation Findings were consistent with cold agglutinin disease at her admission. However, the cold agglutinin test was negative. Eventually, she was diagnosed with PLS. Refractory intravascular hemolysis and frank hemoglobinuria were also present in the patient. Hemolysis was resistant to steroids, intravenous immunoglobulin (IVIG), and Rituximab. Because of life-threatening anemia related to refractory PLS, mycophenolate and tacrolimus were interrupted. However, hemolysis persisted. Following that, immunoadsorption (IA) treatment was obtained. Unfortunately, graft loss occurred due to rejection despite the resolution of PLS after IA. Conclusion PLS is a rare and usually self-limited entity. Our case was an atypical refractory PLS that resembled cold agglutinin disease. Also, frank hemoglobinuria was observed related to severe intravascular hemolysis. These features have not been described before in PLS, to the best of our knowledge. Additionally, IA treatment had never been reported in the literature for PLS, as far as we know. Treatment and management could be a challenge in refractory PLS. Rituximab, IVIG, and extracorporeal treatments could be beneficial. It should be borne in mind that refractory PLS can cause graft and patient loss (AU)


Antecedentes El síndrome de linfocitos pasajeros (PLS) causa hemólisis inmunomediada en receptores de trasplantes sólidos y de médula ósea. Los anticuerpos derivados del donante contra el eritrocito receptor impulsan la patogénesis. Es una entidad rara en el trasplante de riñón y la mayoría de los casos son autolimitados. Presentación del caso Una mujer de 36 años presentó fatiga 13 días después del trasplante renal de donante vivo. La operación transcurrió sin incidentes y fue dada de alta con las funciones normales del injerto el día 11 del trasplante. Los hallazgos coincidían con la enfermedad por crioaglutininas en el momento de su ingreso. Sin embargo, la prueba de crioaglutininas fue negativa. Finalmente, le diagnosticaron PLS. La paciente también presentó hemólisis intravascular refractaria y hemoglobinuria franca. La hemólisis fue resistente a los esteroides, la inmunoglobulina intravenosa (IgIV) y el rituximab. Debido a la anemia potencialmente mortal relacionada con PLS refractario, se interrumpieron el micofenolato y el tacrolimus. Sin embargo, persistió la hemólisis. A continuación, se obtuvo el tratamiento de inmunoadsorción (IA). Desafortunadamente, la pérdida del injerto ocurrió debido al rechazo a pesar de la resolución de PLS después de la IA. Conclusión El PLS es una entidad rara y generalmente autolimitada. Nuestro caso fue un PLS refractario atípico que se asemejaba a la enfermedad por crioaglutininas. Además, se observó hemoglobinuria franca relacionada con hemólisis intravascular grave. Estas características no se han descrito antes en PLS, según nuestro leal saber y entender. Además, el tratamiento IA nunca se había informado en la literatura para PLS, hasta donde sabemos. El tratamiento y el manejo podrían ser un desafío en PLS refractarios. El rituximab, la IgIV y los tratamientos extracorpóreos podrían ser beneficiosos. Debe tenerse en cuenta que los PLS refractarios pueden provocar la pérdida del injerto y del paciente (AU)


Assuntos
Humanos , Feminino , Adulto , Reação Hospedeiro-Enxerto/imunologia , Transplante de Rim/efeitos adversos , Linfócitos B/imunologia , Hemólise/imunologia , Síndrome
7.
Rev Nefrol Dial Transpl ; 43(3): 156-166, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37794855

RESUMO

Objectives: Prophylactic acid suppression with proton pump inhibitors or H2 receptor antagonists is often administered after kidney transplantation. The Association of proton pump inhibitors or H2 receptor antagonists with acute rejection, hypomagnesemia, and graft loss in kidney transplant recipients is not well established. Material and Methods: We performed a retrospective cohort study of 302 kidney transplant recipients at one center (57% male; mean age 35.5±11.2 years) with more than 6 months post-transplant follow-up. Recipients were grouped according to gastric acid prophylaxis: only proton pump inhibitors (n=179), only H2 receptor antagonists (n=42), proton pump inhibitors and H2 receptor antagonists (n=55), and nonusers (n=26). The primary outcome was biopsy-proven acute rejection. Graft loss and hypomagnesemia were defined as secondary outcomes. Results: Nonusers were younger and mostly under steroid-free immunosuppression compared to other study groups (p=0.030 and p=0.009, respectively). The primary outcome was similar across study groups (p=0.266). Kaplan-Meier analyses also demonstrated similar 10-year graft survival rates: 95.5% for proton pump inhibitors, 97.6% for H2 receptor antagonists, 100% for proton pump inhibitors/H2 receptor antagonists, and 96.2% for nonusers (p=0.275). Conclusions: The use of proton pump inhibitors is not associated with acute rejection or graft loss but may cause mild hypomagnesemia in kidney transplant recipients.

9.
J Nephrol ; 36(9): 2507-2517, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37665527

RESUMO

BACKGROUND: Percutaneous kidney biopsy is a fundamental procedure in nephrology. Although pregnancy is not a contraindication, a careful risk-benefit assessment is mandatory in pregnancy. We aimed to evaluate safety and diagnostic accuracy of percutaneous kidney biopsy in pregnancy in a single-center retrospective study. METHODS: Percutaneous kidney biopsy was performed in 19 pregnant patients. Demographics, estimated glomerular filtration rates, serum albumin levels, and proteinuria levels at the time of biopsy were evaluated. Biopsy-related complications, diagnoses, and treatments during the follow-up were analyzed. In addition, delivery success, preeclampsia, early delivery, low birth weight rates, and long-term outcomes of the patients were retrieved and analyzed. RESULTS: Mean patient age was 27 (range 16-41) years. Median gestational week at kidney biopsy was 20th. All but one biopsies were diagnostic. Median gestational week of delivery was 35 (range 23-39) gestational weeks. Preterm delivery (< 37 gestational weeks) and low birth weight (< 2500 mg) occurred in 73.7% and 52.6% of cases, respectively. Median weight at birth was 2500 mg. The incidence of preeclampsia was 57.9%. Overall 89.5% of the children survived. Median post-biopsy follow-up was 64 months. Maternal mortality was not observed during the follow-up period. End stage kidney disease developed in one patient. The results of percutaneous kidney biopsy led to therapeutic decisions in 73.7% of cases. CONCLUSIONS: Although percutaneous kidney biopsy is not frequently performed during pregnancy, it is relatively safe and usually diagnostic, and may guide further follow-up.


Assuntos
Pré-Eclâmpsia , Nascimento Prematuro , Gravidez , Recém-Nascido , Criança , Feminino , Humanos , Adolescente , Adulto Jovem , Adulto , Pré-Eclâmpsia/diagnóstico , Estudos Retrospectivos , Biópsia/efeitos adversos , Rim/patologia
10.
Curr Transplant Rep ; 10(3): 110-116, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37743976

RESUMO

Purpose of review: To review the current studies and guidelines on the risk of adverse pregnancy outcomes in female kidney donors. Recent findings: Living kidney donors include a significant amount of young women of child-bearing age. Safety and possible risks of pregnancy after donation are a concern for female kidney donor candidates. Many current studies indicate a higher risk of preeclampsia in women after kidney donation. Considering the increasing number of living kidney donors, the maternal outcomes of living kidney donation is an active area of research. Summary: Guidelines and consensus statements on the risk of pregnancy in living kidney donors recommend close monitoring of blood pressure, weight gain, and proteinuria during pregnancy. Current studies indicate an increased risk of hypertensive disorders of pregnancy in living kidney donors. Counseling and informing donor candidates about the possible risks is important.

11.
Curr Transplant Rep ; 10(3): 117-125, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37720696

RESUMO

Purpose of review: We review the key principles of kidney paired donation (KPD) and discuss the status and unique considerations for KPD in developing countries. Recent findings: Despite the advantages of KPD programs, they remain rare among developing nations, and the programs that exist have many differences with those of in developed countries. There is a paucity of literature and lack of published data on KPD from most of the developing nations. Expanding KPD programs may require the adoption of features and innovations of successful KPD programs. Cooperation with national and international societies should be encouraged to ensure endorsement and sharing of best practices. Summary: KPD is in the initial stages or has not yet started in the majority of the emerging nations. But the logistics and strategies required to implement KPD in developing nations differ from other parts of the world. By learning from the KPD experience in developing countries and adapting to their unique needs, it should be possible to expand access to KPD to allow more transplants to happen for patients in need world-wide.

12.
Turk J Med Sci ; 53(2): 526-535, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37476885

RESUMO

BACKGROUND: We compared long-term outcomes after kidney transplantation (KTx) in patients with and without congenital anomalies of the kidney and urinary tract (CAKUT). METHODS: KTx recipients (KTRs) with CAKUT in 1980-2016 were identified; their hard copy and electronic medical records were reviewed and compared to a propensity-score-matched control group (non-CAKUT) from the same period. The primary outcomes were graft loss or death with a functioning graft; secondary outcomes included posttransplant urinary tract infections (UTIs) and biopsy-proven rejection (BPR). RESULTS: : We identified 169 KTRs with CAKUT and 169 matched controls. Median follow-up was 132 (IQR: 75.0-170.0) months. UTIs were more common in CAKUT patients compared to non-CAKUT group (20.7% vs 10.7%; p = 0.01). Rates of BPR were similar between the two groups. In Kaplan-Meier analysis, 10-year graft survival rates were significantly higher in the CAKUT group than in the non-CAKUT group (87.6% vs 69.2%; p < 0.001), while patient survival rates were similar. In multivariate Cox regression analyses, CAKUT (HR: 0.469; 95% CI: 0.320-0.687; p < 0.001) and PRA positivity before transplantation (HR: 3.756; 95% CI: 1.507-9.364; p = 0.005) predicted graft loss. DISCUSSION: Graft survival in KTRs with CAKUT appears superior to KTRs without CAKUT. Transplant centers should develop multidisciplinary educational and social working groups to support and encourage CAKUT patients with kidney failure to seek for transplants.


Assuntos
Transplante de Rim , Infecções Urinárias , Sistema Urinário , Humanos , Transplante de Rim/efeitos adversos , Rim/cirurgia , Sistema Urinário/cirurgia , Infecções Urinárias/epidemiologia , Estudos de Casos e Controles
13.
Balkan Med J ; 40(3): 182-187, 2023 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-36960943

RESUMO

Background: Treatment using direct-acting antivirals provides high rates of sustained virologic response and a favorable safety profile for patients with chronic hepatitis C virus infection. However, data on the efficacy of direct-acting antivirals in kidney transplant recipients are still limited. Aims: To evaluate the safety and efficacy of fixed-dose sofosbuvir/ledipasvir combination in kidney transplant recipients. Study Design: Retrospective, observational, single-center study. Methods: Data of 29 kidney transplant recipients who received a fixed-dose safety and efficacy of fixed-dose sofosbuvir/ledipasvir combination for 12 or 24 weeks with or without ribavirin were analyzed. The primary outcome was SVR12, which was defined as undetectable HCV-RNA levels 12 weeks after the treatment. Secondary outcomes were graft function, proteinuria, and calcineurin inhibitor trough level variability. Results: The predominant hepatitis C virus genotype was 1b (n = 19, 65.6%). All patients achieved SVR12. No graft failures nor deaths were reported during the study period. Throughout and after the treatment, the levels of aspartate aminotransferase [21 (range: 18-29.5) to 16 (range: 14-20) U/l, p < 0.001] and alanine aminotransferase [22 (range: 15-34) to 14 (range: 12-17.5) U/l, p < 0.001] improved significantly, unlike bilirubin, hemoglobin, and platelet levels. Renal function remained stable. Dose adjustments for calcineurin inhibitors were required. Serious adverse events were not observed. Conclusion: Safety and efficacy of fixed-dose sofosbuvir/ledipasvir combination was effective and safe in kidney transplant recipients with hepatitis C virus. However, cautious monitoring of trough levels of calcineurin inhibitorss is needed due to potential drug-drug interactions during the treatment episode.


Assuntos
Hepatite C Crônica , Transplante de Rim , Humanos , Sofosbuvir/efeitos adversos , Antivirais/farmacologia , Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/complicações , Hepacivirus/genética , Estudos Retrospectivos , Resultado do Tratamento , Quimioterapia Combinada , Genótipo
15.
J Nephrol ; 36(4): 979-986, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36808609

RESUMO

BACKGROUND: Atypical hemolytic syndrome (aHUS) and C3 glomerulopathy (C3G) are complement-mediated rare diseases with excessive activation of the alternative pathway. Data to guide the evaluation of living-donor candidates for aHUS and C3G are very limited. The outcomes of living donors to recipients with aHUS and C3G (Complement disease-living donor group) were compared with a control group to improve our understanding of the clinical course and outcomes of living donation in this context. METHODS: Complement disease-living donor group [n = 28; aHUS(53.6%), C3G(46.4%)] and propensity score-matched control-living donor group (n = 28) were retrospectively identified from 4 centers (2003-2021) and followed for major cardiac events (MACE), de novo hypertension, thrombotic microangiopathy (TMA), cancer, death, estimated glomerular filtration rate (eGFR) and proteinuria after donation. RESULTS: None of the donors for recipients with complement-related kidney diseases experienced MACE or TMA whereas two donors in the control group developed MACE (7.1%) after 8 (IQR, 2.6-12.8) years (p = 0.15). New-onset hypertension was similar between complement disease and control donor groups (21.4% vs 25%, respectively, p = 0.75). There were no differences between study groups regarding last eGFR and proteinuria levels (p = 0.11 and p = 0.70, respectively). One related donor for a recipient with complement-related kidney disease developed gastric cancer and another related donor developed a brain tumor and died in the 4th year after donation (2, 7.1% vs none, p = 0.15). No recipient had donor-specific human leukocyte antigen antibodies at the time of transplantation. Median follow-up period of transplant recipients was 5 years (IQR, 3-7). Eleven (39.3%) recipients [aHUS (n = 3) and C3G (n = 8)] lost their allografts during the follow-up period. Causes of allograft loss were chronic antibody-mediated rejection in 6 recipients and recurrence of C3G in 5. Last serum creatinine and last eGFR of the remaining patients on follow up were 1.03 ± 038 mg/dL and 73.2 ± 19.9 m/min/1.73 m2 for aHUS patients and 1.30 ± 0.23 mg/dL and 56.4 ± 5.5 m/min/1.73 m2 for C3G patients. CONCLUSION: The present study highlights the importance and complexity of living related-donor kidney transplant for patients with complement-related kidney disorders and motivates the need for further research to determine the optimal risk-assessment for living donor candidates to recipients with aHUS and C3G.


Assuntos
Síndrome Hemolítico-Urêmica Atípica , Hipertensão , Nefropatias , Microangiopatias Trombóticas , Humanos , Projetos Piloto , Via Alternativa do Complemento , Estudos Retrospectivos , Pontuação de Propensão , Rim , Nefropatias/complicações , Proteínas do Sistema Complemento , Hipertensão/complicações , Proteinúria/complicações
16.
Nephrol Dial Transplant ; 38(5): 1327-1336, 2023 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-36542475

RESUMO

BACKGROUND: Data on use of interleukin (IL)-1 blockers in kidney transplant recipients (KTRs) with familial Mediterranean fever (FMF) are very limited. We aimed to evaluate the efficacy and safety of anakinra and canakinumab in the transplantation setting. METHODS: In this retrospective cohort study, we included KTRs who suffered from AA amyloidosis caused by FMF and treated with anakinra or canakinumab (study group, n = 36). Using propensity score matching, we selected 36 patients without FMF or amyloidosis from our database of 696 KTRs as the control group. Primary outcomes were patient and graft survival. Biopsy-confirmed graft rejection, changes in estimated glomerular filtration rate (eGFR), high-sensitivity CRP (hsCRP), erythrocyte sedimentation rate (ESR), proteinuria and number of monthly attacks were secondary outcomes. RESULTS: All KTRs with FMF began IL-1 blocker therapy with anakinra and nine (25%) were switched to canakinumab. Overall death was more frequent in the study group (19.4% vs 0%) (P = .005); however, overall graft loss was comparable between study (27.8%) and control groups (36.1%) (P = .448). Five- and 10-year graft survival rates were significantly higher in the study group (94.4% and 83.3%, respectively) than in the control group (77.8% and 63.9%, respectively) (P = .014 and P < .001, respectively). Rejections were numerically lower in study group (8.3% vs 25%), but it did not reach to statistical significance (P = .058). When compared with the pre-treatment period, with IL-1 blockers, the number of attacks per month (P < .001), and eGFR (P = .004), hsCRP (P < .001) and ESR (P = .026) levels were lower throughout the follow-up, whereas proteinuria levels were not. CONCLUSIONS: Anakinra and canakinumab are effective in KTRs suffering from FMF; however, the mortality rate may be of concern.


Assuntos
Febre Familiar do Mediterrâneo , Transplante de Rim , Humanos , Febre Familiar do Mediterrâneo/complicações , Febre Familiar do Mediterrâneo/tratamento farmacológico , Estudos de Coortes , Colchicina , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Transplante de Rim/efeitos adversos , Interleucina-1 , Estudos Retrospectivos , Proteína C-Reativa , Pontuação de Propensão , Proteinúria/complicações
17.
Clin Rheumatol ; 42(2): 597-606, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36502441

RESUMO

Heme oxygenase-1 (HMOX-1) is an enzyme that regulates heme degradation. Antiinflammatory, antioxidant, and cytoprotective effects of HMOX-1 were also described. It is encoded by the HMOX1 gene, and biallelic mutations cause HMOX-1 deficiency, which is a rare chronic multisystemic inflammatory disorder. This inflammatory status could lead to the development of secondary AA-type amyloidosis theoretically. Here, we report a 30-year-old male with AA-type renal amyloidosis due to a chronic inflammatory condition of unknown origin. Paternal consanguinity and dysmorphic features raised suspicion of a rare genetic disorder. Clinical exome sequencing (CES) confirmed the HMOX-1 deficiency diagnosis related to homozygous missense G139V mutation. To the best of our knowledge, our patient is the eleventh HMOX-1 deficiency case in the literature. Also, HMOX-1 deficiency-related systemic AA-type amyloidosis has not been reported before.


Assuntos
Amiloidose , Insuficiência Renal , Masculino , Humanos , Adulto , Heme Oxigenase-1/genética , Amiloidose/complicações , Amiloidose/genética , Amiloidose/diagnóstico , Insuficiência Renal/complicações , Proteína Amiloide A Sérica
18.
Ther Apher Dial ; 27(3): 428-434, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36201223

RESUMO

INTRODUCTION: We compared the outcomes associated with plasma exchange (PE), double filtration plasmapheresis (DFPP), or immunoadsorption (IA) in the treatment of late antibody mediated rejection (AMR). METHODS: Sixty-nine kidney transplantation (KTx) recipients with late AMR were retrospectively categorized according to management with PE (n = 30), DFPP (n = 22) or IA (n = 17). Allograft loss was compared across treatment groups by Kaplan-Meier analysis and Cox regression. RESULTS: Study groups were similar regarding age, sex, donor type, kidney function, donor specific antibodies, and post-KTx follow-up time. Five-year graft survival trended higher with IA (70.6%) compared to PE (36.7%) and DFPP (27.3%) (p = 0.06). In multivariate Cox regression, baseline eGFR (HR per ml/min/1.73 m2 [95% CI]; 0.96 [0.94-0.99]), rituximab use (HR [95% CI]; 0.42 [0.21-0.84]), interstitial inflammation (i) (HR [95% CI]; 2.05 [1.13-3.69]), and transplant glomerulopathy (cg) (HR [95% CI]; 1.46 [1.13-1.87]) were associated with graft loss. CONCLUSION: These results motivate the need for continued assessment of rituximab and plasmapheresis in larger studies.


Assuntos
Transplante de Rim , Humanos , Rituximab , Estudos Retrospectivos , Anticorpos , Plasmaferese/métodos , Rejeição de Enxerto , Sobrevivência de Enxerto
19.
Nephron ; 147(5): 272-280, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36183694

RESUMO

INTRODUCTION: There are not enough data on the post-CO-VID-19 period for peritoneal dialysis (PD) patients affected from COVID-19. We aimed to compare the clinical and laboratory data of PD patients after COVID-19 with a control PD group. METHODS: This study, supported by the Turkish Society of Nephrology, is a national, multicenter retrospective case-control study involving adult PD patients with confirmed COVID-19, using data collected from April 21, 2021, to June 11, 2021. A control PD group was also formed from each PD unit, from patients with similar characteristics but without COVID-19. Patients in the active period of COVID-19 were not included. Data at the end of the first month and within the first 90 days, as well as other outcomes, including mortality, were investigated. RESULTS: A total of 223 patients (COVID-19 group: 113, control group: 110) from 27 centers were included. The duration of PD in both groups was similar (median [IQR]: 3.0 [1.88-6.0] years and 3.0 [2.0-5.6]), but the patient age in the COVID-19 group was lower than that in the control group (50 [IQR: 40-57] years and 56 [IQR: 46-64] years, p < 0.001). PD characteristics and baseline laboratory data were similar in both groups, except serum albumin and hemoglobin levels on day 28, which were significantly lower in the COVID-19 group. In the COVID-19 group, respiratory symptoms, rehospitalization, lower respiratory tract infection, change in PD modality, UF failure, and hypervolemia were significantly higher on the 28th day. There was no significant difference in laboratory parameters at day 90. Only 1 (0.9%) patient in the COVID-19 group died within 90 days. There was no death in the control group. Respiratory symptoms, malnutrition, and hypervolemia were significantly higher at day 90 in the COVID-19 group. CONCLUSION: Mortality in the first 90 days after COVID-19 in PD patients with COVID-19 was not different from the control PD group. However, some patients continued to experience significant problems, especially respiratory system symptoms, malnutrition, and hypervolemia.


Assuntos
COVID-19 , Insuficiência Cardíaca , Falência Renal Crônica , Diálise Peritoneal , Adulto , Humanos , Pessoa de Meia-Idade , COVID-19/epidemiologia , Estudos Retrospectivos , Estudos de Casos e Controles , Turquia/epidemiologia , Diálise Renal , Diálise Peritoneal/efeitos adversos , Insuficiência Cardíaca/etiologia
20.
Nefrologia (Engl Ed) ; 2022 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-36517356

RESUMO

BACKGROUND: Passenger lymphocyte syndrome (PLS) causes immune-mediated hemolysis in solid and bone marrow transplant recipients. Donor-derived antibodies against the recipient erythrocyte drive the pathogenesis. It is a rare entity in kidney transplantation, and most of the cases are self-limited. CASE PRESENTATION: A 36-year-old woman presented with fatigue 13 days after living donor renal transplantation. The operation was uneventful, and she was discharged with normal graft functions on the 11th day of transplantation Findings were consistent with cold agglutinin disease at her admission. However, the cold agglutinin test was negative. Eventually, she was diagnosed with PLS. Refractory intravascular hemolysis and frank hemoglobinuria were also present in the patient. Hemolysis was resistant to steroids, intravenous immunoglobulin (IVIG), and Rituximab. Because of life-threatening anemia related to refractory PLS, mycophenolate and tacrolimus were interrupted. However, hemolysis persisted. Following that, immunoadsorption (IA) treatment was obtained. Unfortunately, graft loss occurred due to rejection despite the resolution of PLS after IA. CONCLUSION: PLS is a rare and usually self-limited entity. Our case was an atypical refractory PLS that resembled cold agglutinin disease. Also, frank hemoglobinuria was observed related to severe intravascular hemolysis. These features have not been described before in PLS, to the best of our knowledge. Additionally, IA treatment had never been reported in the literature for PLS, as far as we know. Treatment and management could be a challenge in refractory PLS. Rituximab, IVIG, and extracorporeal treatments could be beneficial. It should be borne in mind that refractory PLS can cause graft and patient loss.

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