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2.
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
3.
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
6.
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.

7.
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
8.
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.

9.
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.

10.
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
11.
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
13.
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
14.
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
15.
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
16.
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.

17.
Am J Nephrol ; 53(8-9): 628-635, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36349757

RESUMO

INTRODUCTION: Data to guide the evaluation of living-related donor candidates for kidney transplant recipients with Alport syndrome (AS) spectrum are limited. We aimed to examine a cohort of living-related donors to recipients with AS and compare their outcomes with a control group to improve understanding of the clinical course and outcomes of living donation in this context. METHODS: Living donors (LDs) of AS recipients and propensity score-matched control LDs without any family history of AS (control group) were followed for major cardiac events, death, post-donation estimated glomerular filtration rate (eGFR), and proteinuria. RESULTS: There were 31 LDs (48.4% male), in whom relationship to AS recipient included mother (45.2%), father (32.3%), sibling (16.1%), grandparent (3.2%), and uncle (3.2%). Long-term outcomes over 10.0 (IQR, 3.0-15.0) years were evaluated in 25 and 25 LDs from study and control groups, respectively. During follow-up, 5 LDs (20.0%) in study group developed major cardiac event (acute coronary ischemia [n = 4] and severe congestive heart failure [n = 1]) after 5.5 (IQR, 4.5-10.3) years, whereas only 2 (8.0%) LDs in control group developed major cardiac events (p = 0.221). New-onset hypertension was higher in study group (56.0%) compared to the control group (16.0%) (p = 0.003). Three donors in study and 2 donors in control group who developed new-onset hypertension died during follow-up (p = 0.297). Major cardiac event rate was significantly higher in donors who developed hypertension after donation (0 vs. 28.0%, p < 0.001). There were no differences between study groups regarding last eGFR and proteinuria levels (p = 0.558 and p = 0.120, respectively). DISCUSSION/CONCLUSION: Although the risk of kidney disease can be minimized by careful donor evaluation, our findings suggest that hypertension risk after the donation is higher than expected in related donors of recipients with AS.


Assuntos
Hipertensão , Transplante de Rim , Nefrite Hereditária , Masculino , Humanos , Feminino , Nefrite Hereditária/epidemiologia , Transplante de Rim/efeitos adversos , Pontuação de Propensão , Doadores Vivos , Rim , Taxa de Filtração Glomerular , Proteinúria/epidemiologia , Proteinúria/etiologia , Hipertensão/epidemiologia , Hipertensão/etiologia , Nefrectomia
18.
BMC Nephrol ; 23(1): 264, 2022 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-35870899

RESUMO

BACKGROUND: Glomerular endotheliosis is the pathognomonic glomerular lesion in pre-eclampsia that has also been described in those taking tyrosine kinase inhibitors for cancer treatment. Ibrutinib is a Bruton's tyrosine kinase inhibitor used to treat chronic lymphocytic leukemia (CLL). We report the first known case of glomerular endotheliosis on kidney biopsy in a patient on ibrutinib monotherapy. CASE PRESENTATION: The patient presented with acute on chronic kidney disease, proteinuria, low C3 and C4 and a high rheumatoid factor titer. A kidney biopsy was performed to confirm a preliminary diagnosis of membranoproliferative glomerulonephritis (MPGN), the most common glomerular disease in patients with CLL. Unexpectedly, the kidney biopsy showed pre-eclampsia-like lesions on light and electron microscopy: occlusion of glomerular peripheral capillary lumens by swollen reactive endothelial cells. Findings of glomerulonephritis were not seen, and there were no specific glomerular immune deposits by immunofluorescence or electron microscopy. CONCLUSIONS: CLL is known to cause glomerular lesions, mainly MPGN. There is increasing evidence that ibrutinib, a major treatment for CLL, can cause kidney disease, but the precise pathology is not characterized. We present a patient with CLL on ibrutinib with signs of glomerular endotheliosis. Based on the absence of CLL-induced kidney pathologies typically seen on the kidney biopsy and the non-selectivity of ibrutinib, we attributed the glomerular endotheliosis to ibrutinib. In pre-eclampsia, increased soluble fms-like tyrosine kinase 1 (sFlt1) levels induce endothelial dysfunction by decreasing vascular endothelial growth factor (VEGF). Ibrutinib has been demonstrated to have non-selective tyrosine kinase inhibition, including inhibition of VEGF receptor (VEGFR) and epidermal growth factor receptor (EGFR). VEGFR and EGFR inhibitors have recently been described in the literature to cause hypertension, proteinuria, and glomerular endotheliosis. Kidney biopsy should be performed in CLL patients on ibrutinib that present with acute kidney injury (AKI) or proteinuria to determine whether the clinical picture is attributable to the disease itself or a complication of the therapy.


Assuntos
Adenina , Glomerulonefrite Membranoproliferativa , Nefropatias , Leucemia Linfocítica Crônica de Células B , Piperidinas , Adenina/efeitos adversos , Adenina/análogos & derivados , Idoso de 80 Anos ou mais , Células Endoteliais , Receptores ErbB , Glomerulonefrite Membranoproliferativa/induzido quimicamente , Glomerulonefrite Membranoproliferativa/diagnóstico , Humanos , Hipertensão , Rim/patologia , Nefropatias/induzido quimicamente , Nefropatias/diagnóstico , Leucemia Linfocítica Crônica de Células B/complicações , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Masculino , Piperidinas/efeitos adversos , Proteinúria/complicações , Fator A de Crescimento do Endotélio Vascular , Receptor 1 de Fatores de Crescimento do Endotélio Vascular
19.
J Clin Apher ; 37(4): 376-387, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35535432

RESUMO

BACKGROUND: Primary focal segmental glomerulosclerosis (FSGS) treatment is based on immunosuppressive therapies. Since refractory disease is common, alternative methods are emerging. One of these methods is plasmapheresis with intravenous cyclosporine and corticosteroids, and it could be an option in post-transplant recurrent FSGS. We retrospectively investigated the efficacy of this combined treatment in adult patients with refractory primary FSGS. METHODS: Seven refractory primary FSGS patients were included. Demographics, estimated glomerular filtration rates, serum albumin levels, urine protein/creatinine ratios, and previous treatments were evaluated. Also, complications and remission rates were assessed. RESULTS: Median patient age was 23 years. Median duration of diagnosis was 2 years. Median number of plasmapheresis sessions was 14. Five of seven patients (71.4%, one complete, four partial remissions) were responders after the protocol. Changes in serum albumin levels and proteinuria after protocol were statistically significant (P = 0.018 and P = 0.018, respectively). eGFR levels did not change statistically (P = 0.753). Median follow-up duration after the treatment was 17 months. However, two patients experienced disease relapse (28.5%). End-stage kidney disease was developed in two patients. Sustained remission rate was 42.8% during follow-up (One complete and two partial remissions). Also, 42.8% of patients experienced catheter infections. Catheter-associated thrombosis that required surgery was observed in a patient. CONCLUSIONS: Plasmapheresis combined with intravenous cyclosporine and corticosteroids could be an option in refractory primary FSGS. High response rates after this protocol were encouraging. However, the relapsing disease was observed after the cessation of apheresis. Also, complications of the protocol could limit the applicability.


Assuntos
Ciclosporinas , Glomerulosclerose Segmentar e Focal , Transplante de Rim , Adulto , Glomerulosclerose Segmentar e Focal/terapia , Humanos , Terapia de Imunossupressão , Transplante de Rim/efeitos adversos , Plasmaferese/métodos , Recidiva , Estudos Retrospectivos , Albumina Sérica , Resultado do Tratamento , Adulto Jovem
20.
Clin Kidney J ; 15(5): 999-1006, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35498893

RESUMO

Background: In this study, we evaluated 3-month clinical outcomes of kidney transplant recipients (KTR) recovering from COVID-19 and compared them with a control group. Method: The primary endpoint was death in the third month. Secondary endpoints were ongoing respiratory symptoms, need for home oxygen therapy, rehospitalization for any reason, lower respiratory tract infection, urinary tract infection, biopsy-proven acute rejection, venous/arterial thromboembolic event, cytomegalovirus (CMV) infection/disease and BK viruria/viremia at 3 months. Results: A total of 944 KTR from 29 different centers were included in this study (523 patients in the COVID-19 group; 421 patients in the control group). The mean age was 46 ± 12 years (interquartile range 37-55) and 532 (56.4%) of them were male. Total number of deaths was 8 [7 (1.3%) in COVID-19 group, 1 (0.2%) in control group; P = 0.082]. The proportion of patients with ongoing respiratory symptoms [43 (8.2%) versus 4 (1.0%); P < 0.001] was statistically significantly higher in the COVID-19 group compared with the control group. There was no significant difference between the two groups in terms of other secondary endpoints. Conclusion: The prevalence of ongoing respiratory symptoms increased in the first 3 months post-COVID in KTRs who have recovered from COVID-19, but mortality was not significantly different.

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