RESUMO
INTRODUCTION: Sarcopenia and vitamin D deficiency are highly prevalent among patients undergoing haemodialysis. Although vitamin D deficiency, assessed using serum 25-hydroxyvitamin D (25(OH)D) levels, is known to be associated with sarcopenia in the general population, whether serum 25(OH)D levels are associated with sarcopenia in patients undergoing haemodialysis with suppressed renal activation of 25(OH)D remains unclear. This study aimed to examine the association between serum 25(OH)D levels and sarcopenia in patients undergoing haemodialysis. METHODS: Serum 25(OH)D level measurements and assessment of sarcopenia using the Asian Working Group for Sarcopenia criteria were conducted in 95 stable outpatients undergoing maintenance haemodialysis therapy. RESULTS: Sarcopenia was observed in 22 (23.1%) patients. In multiple logistic regression analysis, serum 25(OH)D levels were associated with sarcopenia (odds ratio [OR] 0.87, 95% confidence interval [CI] 0.77-0.99, p = 0.039) independent of traditional risk factors for sarcopenia. In multiple linear regression analyses, serum 25(OH)D levels were associated with parameters of skeletal muscle mass and strength (ß = 0.145, p = 0.046, and ß = 0.194, p = 0.020, respectively). The adjusted OR for sarcopenia was 5.60 (95% CI 1.52-20.57, p = 0.009) in the vitamin D deficiency group categorized based on the cut-off serum 25(OH)D level of 10 ng/mL. Regarding model discrimination, adding vitamin D deficiency to the traditional risk factors significantly improved the integrated discrimination improvement score (0.093, p = 0.007). CONCLUSION: Lower serum 25(OH)D levels were associated with sarcopenia independent of traditional risk factors in patients undergoing haemodialysis with suppressed vitamin D activation in the kidney. This finding implies that circulating 25(OH)D may have an important relationship with the skeletal muscle function of patients undergoing haemodialysis, and its measurement may be recommended to identify patients at high risk for sarcopenia among those undergoing haemodialysis.
Assuntos
Diálise Renal , Sarcopenia , Deficiência de Vitamina D , Vitamina D , Humanos , Sarcopenia/sangue , Sarcopenia/etiologia , Sarcopenia/epidemiologia , Sarcopenia/diagnóstico , Diálise Renal/efeitos adversos , Masculino , Feminino , Vitamina D/análogos & derivados , Vitamina D/sangue , Pessoa de Meia-Idade , Idoso , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/epidemiologia , Falência Renal Crônica/terapia , Falência Renal Crônica/sangue , Falência Renal Crônica/complicações , Estudos Transversais , Fatores de Risco , Músculo EsqueléticoRESUMO
INTRODUCTION: Sarcopenia and osteoporosis are highly prevalent among kidney transplant recipients (KTRs). Although osteoporosis is known to increase fracture risk in KTRs, it is unclear whether sarcopenia or osteosarcopenia is associated with this increased risk. Thus, we aimed to investigate the association of the coexistence of low muscle mass (LMM) and osteoporosis with the risk of fracture in long-term KTRs. METHODS: Exactly 342 stable KTRs underwent dual-energy X-ray absorptiometry and skeletal muscle mass index (SMI) measurement using bioelectrical impedance analysis. RESULTS: LMM and osteoporosis were observed in 109 (31.9%) and 93 patients (27.2%), respectively. During a follow-up period of 5.1 years, 48 (14.0%) fractures occurred. KTRs with LMM had a higher fracture risk, but this was not significant (adjusted hazard ratio [aHR] 1.82, 95% confidence interval [CI] 0.94-3.50, p = 0.073). Similar results were obtained in KTRs with osteoporosis (aHR 1.84, 95% CI 0.96-3.47, p = 0.063). We divided the KTRs into four groups according to the presence of LMM and/or osteoporosis. The cumulative incidence rates of fractures were 13.0%, 11.1%, 10.5%, and 31.3% in the KTRs without both LMM and osteoporosis, those with LMM alone, those with osteoporosis alone, and those with both, respectively. The KTRs with both LMM and osteoporosis had a 2.92fold higher risk of fractures (95% CI 1.29-6.49; p = 0.010) than those without both LMM and osteoporosis. CONCLUSION: Long-term KTRs with the coexistence of LMM and osteoporosis had an independently higher risk of fragility fractures than those without both LMM and osteoporosis. The combination of SMI and osteoporosis definitions can be used to identify KTRs with a high fracture risk.
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Transplante de Rim , Osteoporose , Sarcopenia , Humanos , Sarcopenia/complicações , Sarcopenia/diagnóstico , Sarcopenia/epidemiologia , Transplante de Rim/efeitos adversos , Osteoporose/complicações , Osteoporose/epidemiologia , Absorciometria de Fóton/efeitos adversos , Absorciometria de Fóton/métodos , Músculos , Densidade ÓsseaRESUMO
BACKGROUND: Although the prevalence of osteoporosis and fractures in the first 6-12 months post-renal transplantation is high, little is known about the utility of bone mineral density (BMD) to predict fractures in long-term kidney graft recipients. Lateral spine dual-energy X-ray absorptiometry (DXA) scanning is a reliable tool for measuring glucocorticoid-induced and age-related bone loss in the elderly population. However, little is known about the utility of lateral spine DXA for patients with chronic kidney diseases. This study aimed to analyze the utility of lateral spine BMD for fragility fractures in long-term kidney graft recipients. METHODS: A total of 357 stable kidney transplant recipients for a minimum of 1 year after kidney transplantation underwent DXA measurements at several sites, including the lateral spine between January 2017 and December 2018. We collected data on new incident fractures from the patients' medical records. RESULTS: The median post-transplantation time at baseline DXA measurement was 12.6 years. During the median follow-up period of 3.5 years, 41 (11.4%) fractures occurred. The lateral spine BMDs were independently associated with fractures (adjusted hazard ratio 0.076; 95% confidence interval 0.012-0.42, p = 0.003). The cumulative incidence rate of fractures was significantly higher in the lower lateral spine BMD group (< 0.471 g/cm2, optimal cut-off value by receiver operating characteristic curve) than in the higher lateral spine BMD group (23.4 vs. 7.4%, adjusted hazard ratio 4.92; 95% confidence interval 2.33-10.74, p < 0.001). CONCLUSION: Lateral lumbar spine BMD can be used to predict the risk of fragility fractures in long-term kidney graft recipients.
Assuntos
Fraturas Ósseas , Osteoporose , Fraturas por Osteoporose , Absorciometria de Fóton/efeitos adversos , Idoso , Densidade Óssea , Humanos , Rim , Vértebras Lombares/diagnóstico por imagem , Osteoporose/diagnóstico por imagem , Osteoporose/epidemiologia , Fraturas por Osteoporose/diagnóstico por imagem , Fraturas por Osteoporose/epidemiologia , Fraturas por Osteoporose/etiologiaRESUMO
BACKGROUND: In living kidney transplantation, predicting the risk of end-stage kidney disease in the organ donors though crucial remains to be resolved. Thus, any useful biomarker to predict kidney outcome would be highly desirable to safeguard donors. METHODS: This retrospective study was conducted at Nagoya Daini Red Cross Hospital to confirm whether an increase in preserved kidney volume (PKV) was a predict marker of proteinuria. A change of PKV before and 1 year after kidney donation was measured, and its association with proteinuria 3 years after the donation was analyzed. RESULTS: A total of 119 kidney donors who met the Japanese donor guideline were enrolled. The mean age was 57.4 years, 46.2% were male. The mean values of the variables before kidney donation (baseline) were: BMI levels: 23.4 kg/m2, BSA-adjusted PKV: 132.9 cm3/1.73 m2, and estimated glomerular filtration rate (eGFRave): 82.9 mL/min/1.73 m2. A positive correlation was noted between BSA-adjusted PKV and eGFRave (r = 0.61, p < 0.001). BSA-adjusted PKV increased by 19.5% 1 year after donation, and the median urine protein was 0.04 g/gCre. Linear regression analyses showed that change of PKV and BSA-adjusted PKV before the donation were significantly associated with proteinuria 3 years after donation. CONCLUSION: Change of PKV and BSA-adjusted PKV before donation is important factors for proteinuria after donation under the Japanese donor guidelines. Further studies are needed to confirm whether these factors are associated with renal survival after donation.
Assuntos
Transplante de Rim , Rim/anatomia & histologia , Doadores Vivos , Nefrectomia/efeitos adversos , Proteinúria/etiologia , Idoso , Superfície Corporal , Creatinina/urina , Seleção do Doador/normas , Feminino , Seguimentos , Taxa de Filtração Glomerular , Humanos , Japão , Rim/diagnóstico por imagem , Rim/fisiologia , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Período Pré-Operatório , Estudos Retrospectivos , Coleta de Tecidos e Órgãos/efeitos adversos , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Preemptive kidney transplantation (PEKT) incidence has recently increased in Japan. The effect of PEKT and mineral bone factors before kidney transplantation (KTx) on long-term calcium (Ca) levels remains unknown. METHODS: Eighty-one consecutive patients at Nagoya Daini Red Cross Hospital were included in this study (PEKT group with 41 patients and non PEKT group with 40 patients). Ca metabolism, including intact fibroblast growth factor 23 (iFGF23), were measured before KTx and intact parathyroid hormone (iPTH), and corrected Ca (cCa) were measured before KTx and 6 months (M), 12 M, and 24 M after KTx. RESULTS: In PEKT group, cCa levels at 24 M were higher from the baseline level. At baseline, cCa levels had a positive correlation with iFGF23 levels (r = 0.51; p < 0.001) and a negative correlation with iPTH levels (r = 0.51; p < 0.001). The cCa difference between baseline and 24 M was 0.8 ± 0.6 mg/dL in PEKT group and 0.3 ± 0.7 mg/dL in non-PEKT group (p = 0.001). A multivariate linear regression analysis showed iFGF23 and iPTH at baseline in entire groups were useful markers on calcium levels at 24 M. However, in PEKT group, both markers were found to be not associated with Ca at 24 M, whereas in non PEKT group, iPTH was the only effective marker. CONCLUSIONS: This study suggested that iFGF23 and iPTH may be useful markers of the calcium status after KTx. However, no correlation was noted in PEKT group.
Assuntos
Cálcio/sangue , Fatores de Crescimento de Fibroblastos/sangue , Transplante de Rim , Hormônio Paratireóideo/sangue , Insuficiência Renal Crônica/sangue , Adulto , Idoso , Biomarcadores/sangue , Feminino , Fator de Crescimento de Fibroblastos 23 , Humanos , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Período Pré-Operatório , Insuficiência Renal Crônica/cirurgia , Estudos Retrospectivos , Fatores de TempoRESUMO
BACKGROUND: The aim of the present study was to clarify the prevalence of immunosuppressive drug use and outcomes in elderly and non-elderly patients with primary membranous nephropathy (MN) in nationwide real-world practice in Japan. PATIENTS AND METHODS: Between 2009 and 2010, 374 patients with primary nephrotic syndrome were enrolled in the cohort study (The Japan Nephrotic Syndrome Cohort Study, JNSCS), including 126 adult patients with MN. Their clinical characteristics were compared with those of nephrotic patients with primary MN registered in a large nationwide registry (The Japan Renal Biopsy Registry, J-RBR). Outcomes and predictors in the elderly (≥ 65 years) and non-elderly groups were identified. RESULTS: Similar clinical characteristics were observed in JNSCS patients and J-RBR patients (n = 1808). At the early stage of 1 month, 84.1% of patients were treated with immunosuppressive therapies. No significant differences were observed in therapies between age groups. However, elderly patients achieved complete remission (CR) more frequently than non-elderly patients, particularly those treated with therapies that included corticosteroids. No significant differences were noted in serum creatinine (sCr) elevations at 50 or 100%, end-stage kidney disease, or all-cause mortality between age groups. Corticosteroids were identified as an independent predictor of CR (HR 2.749, 95%CI 1.593-4.745, p = 0.000) in the multivariate Cox's model. sCr levels, hemoglobin levels, immunosuppressants, clinical remission, and relapse after CR were independent predictors of sCr × 1.5 or × 2.0. CONCLUSION: Early immunosuppressive therapy including corticosteroids for primary MN showed better remission rates in elderly patients in a nationwide cohort study.
Assuntos
Corticosteroides/uso terapêutico , Glomerulonefrite Membranosa/tratamento farmacológico , Imunossupressores/uso terapêutico , Adulto , Fatores Etários , Idoso , Creatinina/sangue , Feminino , Glomerulonefrite Membranosa/sangue , Glomerulonefrite Membranosa/complicações , Hemoglobinas/metabolismo , Humanos , Japão , Falência Renal Crônica/etiologia , Masculino , Pessoa de Meia-Idade , Mortalidade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Recidiva , Sistema de Registros , Indução de Remissão , Fatores de Risco , Resultado do TratamentoRESUMO
BACKGROUND: Despite recent advances in immunosuppressive therapy for patients with primary nephrotic syndrome, its effectiveness and safety have not been fully studied in recent nationwide real-world clinical data in Japan. METHODS: A 5-year cohort study, the Japan Nephrotic Syndrome Cohort Study, enrolled 374 patients with primary nephrotic syndrome in 55 hospitals in Japan, including 155, 148, 38, and 33 patients with minimal change disease (MCD), membranous nephropathy (MN), focal segmental glomerulosclerosis (FSGS), and other glomerulonephritides, respectively. The incidence rates of remission and relapse of proteinuria, 50% and 100% increases in serum creatinine, end-stage kidney disease (ESKD), all-cause mortality, and other major adverse outcomes were compared among glomerulonephritides using the Log-rank test. Incidence of hospitalization for infection, the most common cause of mortality, was compared using a multivariable-adjusted Cox proportional hazard model. RESULTS: Immunosuppressive therapy was administered in 339 (90.6%) patients. The cumulative probabilities of complete remission within 3 years of the baseline visit was ≥ 0.75 in patients with MCD, MN, and FSGS (0.95, 0.77, and 0.79, respectively). Diabetes was the most common adverse events associated with immunosuppressive therapy (incidence rate, 71.0 per 1000 person-years). All-cause mortality (15.6 per 1000 person-years), mainly infection-related mortality (47.8%), was more common than ESKD (8.9 per 1000 person-years), especially in patients with MCD and MN. MCD was significantly associated with hospitalization for infection than MN. CONCLUSIONS: Patients with MCD and MN had a higher mortality, especially infection-related mortality, than ESKD. Nephrologists should pay more attention to infections in patients with primary nephrotic syndrome.
Assuntos
Glomerulonefrite Membranosa/tratamento farmacológico , Glomerulosclerose Segmentar e Focal/tratamento farmacológico , Falência Renal Crônica/epidemiologia , Nefrose Lipoide/tratamento farmacológico , Síndrome Nefrótica/tratamento farmacológico , Proteinúria/etiologia , Adulto , Idoso , Doenças Cardiovasculares/epidemiologia , Estudos de Coortes , Creatinina/sangue , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/epidemiologia , Feminino , Seguimentos , Glomerulonefrite Membranosa/complicações , Glomerulonefrite Membranosa/mortalidade , Glomerulosclerose Segmentar e Focal/complicações , Hospitalização/estatística & dados numéricos , Humanos , Hipoglicemiantes/uso terapêutico , Imunossupressores/uso terapêutico , Incidência , Infecções/mortalidade , Japão/epidemiologia , Falência Renal Crônica/mortalidade , Masculino , Pessoa de Meia-Idade , Nefrose Lipoide/complicações , Nefrose Lipoide/mortalidade , Síndrome Nefrótica/complicações , Recidiva , Indução de RemissãoRESUMO
BACKGROUND: Posttransplant anemia may be a major determinant of chronic allograft nephropathy. However, the impact of correcting anemia on graft function remains controversial. METHODS: A 3-year follow-up of an open-label, multicenter, randomized controlled trial involving kidney transplantation recipients examined whether sustained maintenance of target hemoglobin (Hb) concentrations at a high level (12.5-13.5 g/dL, n = 64) with either darbepoetin alfa or epoetin beta pegol would slow the graft function decline rate as the primary efficacy endpoint, compared with maintenance of a low Hb concentration (10.5-11.5 g/dL, n = 63). RESULTS: The mean blood pressures in the two groups were well controlled throughout the study. In the high Hb group, mean Hb concentrations increased to >12 g/dL at 3 months, reaching the target range at 18 months. At the end of this study (36 months), the mean Hb concentration was 12.8 ± 0.7 g/dL in the high Hb group and 11.5 ± 1.2 g/dL in the low Hb group. The decline rate of the estimated glomerular filtration (eGFR) rate was considerably greater in the low Hb group (ΔeGFR, -5.1 ± 9.5 mL/min/1.73 m2) than in the high Hb group (-1.0 ± 8.4 mL/min/1.73 m2) (P = 0.02). Of note, only a few high Hb patients developed cardiovascular events and returned to hemodialysis, but the low Hb patients did not. CONCLUSION: This prospective study suggests that correcting anemia to the target Hb level range (12.5-13.5 g/dL) slows renal function deterioration by >3 years in the chronic phase of allograft nephropathy.
Assuntos
Hematínicos/uso terapêutico , Hemoglobinas/análise , Falência Renal Crônica/cirurgia , Transplante de Rim , Adulto , Aloenxertos , Anemia/sangue , Anemia/complicações , Pressão Sanguínea , Progressão da Doença , Eritropoetina/sangue , Feminino , Seguimentos , Humanos , Rim/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Diálise Renal , Resultado do TratamentoRESUMO
BACKGROUND: The lack of high-quality clinical evidences hindered broad consensus on optimal therapies for primary nephrotic syndromes. The aim of the present study was to compare prevalence of immunosuppressive drug use in patients with primary nephrotic syndrome across 6 regions in Japan. METHODS: Between 2009 and 2010, 380 patients with primary nephrotic syndrome in 56 hospitals were enrolled in a prospective cohort study [Japan Nephrotic Syndrome Cohort Study (JNSCS)], including 141, 151, and 38 adult patients with minimal change disease (MCD), membranous nephropathy (MN), and focal segmental glomerulosclerosis (FSGS), respectively. Their clinical characteristics were compared with those of patients registered in a large nationwide registry of kidney biopsies [Japan Renal Biopsy Registry (J-RBR)]. The regional prevalence of use of each immunosuppressive drug was assessed among adult MCD, MN, and FSGS patients who underwent immunosuppressive therapy in the JNSCS (n = 139, 127, and 34, respectively). Predictors of its use were identified using multivariable-adjusted logistic regression models. RESULTS: The clinical characteristics of JNSCS patients were comparable to those of J-RBR patients, suggesting that the JNSCS included the representatives in the J-RBR. The secondary major immunosuppressive drugs were intravenous methylprednisolone [n = 33 (24.6%), 24 (19.7%), and 9 (28.1%) in MCD, MN, and FSGS, respectively] and cyclosporine [n = 25 (18.7%), 62 (50.8%), and 16 (50.0%), respectively]. The region was identified as a significant predictor of use of intravenous methylprednisolone in MCD and MN patients. CONCLUSION: Use of intravenous methylprednisolone for MCD and MN differed geographically in Japan. Its efficacy should be further evaluated in a well-designed trial.
Assuntos
Glomerulosclerose Segmentar e Focal/tratamento farmacológico , Imunossupressores/uso terapêutico , Síndrome Nefrótica/tratamento farmacológico , Adulto , Idoso , Biópsia , Estudos de Coortes , Feminino , Glomerulonefrite Membranosa/tratamento farmacológico , Humanos , Rim/patologia , Masculino , Pessoa de Meia-Idade , Nefrose Lipoide/tratamento farmacológicoRESUMO
Apolipoprotein A-I amyloidosis is a rare, autosomal dominant disorder of APOA-1 gene characterized by the deposition of apolipoprotein A-I in various organs and can be classified into either hereditary or nonhereditary form in the absence of a family history. Renal disease caused by Apolipoprotein A-I amyloidosis commonly manifested as slowly progressive renal function impairment without heavy proteinuria. Apolipoprotein A-I-related amyloidosis of kidney is of pathogenetic interest because the renal failure is due to peritubular and interstitial amyloid deposits without glomerular deposits. Tubulointerstitial lesion of amyloid deposits was diagnosed in half of carriers of APOA1 gene mutation, only 13% of patients progressed to renal failure requiring hemodialysis or kidney transplantation. Recurrence of apolipoprotein A-I-related amyloidosis after kidney transplantation is very rare. We report a case of a 63-year-old Japanese female without a family history of kidney and/or liver disease who showed slowly progressive renal graft dysfunction without overt proteinuria. Graft biopsy revealed characteristic Congo red stain positive amyloid deposits localized in the renal interstitial area. No glomerular, vascular and tubular amyloid deposits were noted. Laser microdissection-liquid chromatography tandem mass spectrometry-based proteomic analysis elucidated the type of amyloidosis as apolipoprotein A-I amyloidosis. Genetic analysis of DNA sequence study revealed two novel APOA1 gene mutations of Leu202Arg and Lys262Asn. This is a first and very rare case report of the recurrence of non-familial hereditary apolipoprotein A-I amyloidosis in Japanese transplant recipient.
Assuntos
Amiloidose/genética , Amiloidose/cirurgia , Apolipoproteína A-I/genética , Nefropatias/genética , Nefropatias/cirurgia , Transplante de Rim/efeitos adversos , Mutação , Amiloidose/diagnóstico , Biópsia , Cromatografia Líquida , Análise Mutacional de DNA , Feminino , Predisposição Genética para Doença , Hereditariedade , Humanos , Nefropatias/diagnóstico , Microscopia Eletrônica , Pessoa de Meia-Idade , Fenótipo , Proteômica/métodos , Recidiva , Espectrometria de Massas em Tandem , Resultado do TratamentoRESUMO
The effectiveness of desensitization with rituximab in ABO-incompatible renal transplantation (ABO-I) has been widely reported. However, ABO-I outcomes are still worse than those of ABO-identical or ABO-compatible renal transplantation (ABO-Id/C). We retrospectively examined the outcomes in consecutive living donor ABO-Id/C (n = 412) and ABO-I (n = 205) cases to elucidate the causes of inferiority in ABO-I. ABO-I cases included recipients treated with rituximab (RIT, n = 131), splenectomy (SPX, n = 21), or neither because of low anti-A/B antibody titers (NoR/S, n = 53). Graft survival, infection, and de novo HLA antibody production were compared for ABO-I and ABO-Id/C, followed by stratification into RIT and NoR/S groups. Propensity score-based methods were employed to limit selection bias and potential confounders. Overall graft survival for ABO-I was significantly lower than that for ABO-Id/C (92.8% vs 97.2% after 5 years, P = .0037). Graft loss due to infection with ABO-I was significantly more frequent than that with ABO-Id/C, whereas acute antibody-mediated rejection (AMR) caused no graft failure in ABO-I recipients. Stratified analysis demonstrated significantly higher infection risk with RIT than with NoR/S. Safe reduction or avoidance of rituximab in desensitization protocols might contribute to further improvement of ABO-I outcome.
Assuntos
Sistema ABO de Grupos Sanguíneos/imunologia , Linfócitos B/imunologia , Incompatibilidade de Grupos Sanguíneos/imunologia , Sobrevivência de Enxerto/imunologia , Falência Renal Crônica/cirurgia , Transplante de Rim/métodos , Rituximab/uso terapêutico , Adulto , Linfócitos B/efeitos dos fármacos , Feminino , Seguimentos , Taxa de Filtração Glomerular , Sobrevivência de Enxerto/efeitos dos fármacos , Humanos , Imunossupressores/uso terapêutico , Testes de Função Renal , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Cuidados Pré-Operatórios , Prognóstico , Estudos Retrospectivos , Fatores de RiscoRESUMO
BACKGROUND: Deceased organ donations are rare in Japan, with most kidney transplants performed from a limited number of living donors. Researchers have thus developed highly successful ABO-incompatible transplantation procedures, emphasizing preoperative desensitization and postoperative immunosuppression. A recent open-label, single-arm, multicenter clinical study prospectively examined the efficacy and safety of rituximab/mycophenolate mofetil desensitization in ABO-incompatible kidney transplantation without splenectomy. METHODS: Mycophenolate mofetil and low dose steroid were started 28 days pretransplant, followed by two doses of rituximab 375 mg/m2 at day -14 and day -1, and postoperative immunosuppression with tacrolimus or ciclosporin and basiliximab. The primary endpoint was the non-occurrence rate of acute antibody-mediated rejection. Patient survival and graft survival were monitored for 1 year posttransplant. RESULTS: Eighteen patients received rituximab and underwent ABO-incompatible kidney transplantation. CD19-positive peripheral B cell count decreased rapidly after the first rituximab infusion and recovered gradually after week 36. The desensitization protocol was tolerable, and most rituximab-related infusion reactions were mild. No anti-A/B antibody-mediated rejection occurred with this series. One patient developed anti-HLA antibody-mediated rejection (Banff 07 type II) on day 2, which was successfully managed. Patient and graft survival were both 100 % after 1 year. CONCLUSION: Our desensitization protocol was confirmed to be clinically effective and with acceptable toxicities for ABO-I-KTx (University Hospital Medical Information Network Registration Number: UMIN000006635).
Assuntos
Sistema ABO de Grupos Sanguíneos/imunologia , Incompatibilidade de Grupos Sanguíneos/tratamento farmacológico , Dessensibilização Imunológica/métodos , Rejeição de Enxerto/prevenção & controle , Histocompatibilidade/efeitos dos fármacos , Imunossupressores/administração & dosagem , Transplante de Rim , Rituximab/administração & dosagem , Adolescente , Adulto , Idoso , Incompatibilidade de Grupos Sanguíneos/diagnóstico , Incompatibilidade de Grupos Sanguíneos/imunologia , Incompatibilidade de Grupos Sanguíneos/mortalidade , Dessensibilização Imunológica/efeitos adversos , Dessensibilização Imunológica/mortalidade , Esquema de Medicação , Quimioterapia Combinada , Feminino , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/mortalidade , Sobrevivência de Enxerto/efeitos dos fármacos , Antígenos HLA/imunologia , Humanos , Imunossupressores/efeitos adversos , Isoanticorpos/imunologia , Japão , Transplante de Rim/efeitos adversos , Transplante de Rim/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Rituximab/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
AIMS: The aim of the study was to clarify the relationship between serum ferritin and infectious risks. METHODS: We evaluated all hospital admissions due to infections, clinical biomarkers and nutrition status in 129 incident Japanese dialysis patients during a median follow-up of 38 months. RESULTS: Kaplan-Meier analysis revealed that the period without infections requiring hospitalization was significantly shorter in ferritin > median (82.0 ng/ml) group than in the ferritin < median group (log-rank test 4.44, p = 0.035). High ferritin was associated with significantly increased relative risk of hospitalization for infection (Cox hazard model 1.52, 95% CI 1.06-2.17). The number of hospitalization days was gradually longer in patients with high ferritin levels and malnutrition. CONCLUSION: Although serum ferritin levels were low, and doses of iron administered to dialysis patients in Japan are generally lower than in Western countries, an elevated ferritin level was associated with increased risk of infection, particularly in patients with poor nutritional status.
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Ferritinas/sangue , Hospitalização/estatística & dados numéricos , Infecções/etiologia , Desnutrição/complicações , Idoso , Estudos de Coortes , Ferritinas/efeitos adversos , Seguimentos , Humanos , Japão , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Estudos Prospectivos , Diálise Renal/efeitos adversos , Fatores de RiscoRESUMO
The clinicopathological context of rejection after kidney transplantation was well recognized. Banff conferences greatly contributed to elucidate the pathogenesis and to establish the pathologic criteria of rejection after kidney transplantation. The most important current problem of renal transplantation is de novo donor-specific antibody (DSA) production leading chronic rejection and graft loss. Microvascular inflammation is considered as a reliable pathological marker for antibody-mediated rejection (AMR) in the presence of DSA. Electron microscopic study allowed us to evaluate early changes in peritubular capillaries in T-lymphocyte mediated rejection and transition to antibody-mediated rejection. Severe endothelial injuries with edema and activated lymphocyte invaded into subendothelial space with early multi-layering of peritubular capillary basement membrane suggest T-lymphocyte mediated rejection induce an unbounded chain of antibody-mediated rejection. The risk factors of AMR after ABO-incompatible kidney transplantation are important issues. Anti-ABO blood type antibody titre of IgG excess 32-fold before transplant operation is the only predictable factor for acute AMR. Characteristics of chronic active antibody-mediated rejection (CAAMR) are one of the most important problems. Light microscopic findings and C4d stain of peritubular capillary and glomerular capillary are useful diagnostic criteria of CAAMR. Microvascular inflammation, double contour of glomerular capillary and thickening of peritubular capillary basement are good predictive factors of the presence of de novo DSA. C4d stain of linear glomerular capillary is a more sensitive marker for CAAMR than positive C4d of peritubular capillary. Early and sensitive diagnostic attempts of diagnosing CAAMR are pivotal to prevent chronic graft failure.
Assuntos
Rejeição de Enxerto/patologia , Transplante de Rim/efeitos adversos , Rim/ultraestrutura , Aloenxertos , Biópsia , Capilares/imunologia , Capilares/ultraestrutura , Rejeição de Enxerto/imunologia , Humanos , Imunidade Humoral , Isoanticorpos/imunologia , Rim/irrigação sanguínea , Rim/imunologia , Microscopia Eletrônica , Valor Preditivo dos Testes , Fatores de Risco , Resultado do TratamentoRESUMO
BACKGROUND: Vitamin D deficiency is common among patients with chronic kidney disease (CKD). However, the benefits of vitamin D supplementation versus vitamin D receptor activator (VDRA) administration have yet to be established. Recently, an association between activated vitamin D and cardiovascular factors was reported. To evaluate the benefits of VDRA in advanced CKD, we analyzed the association between VDRA administration and the prevalence of pulmonary congestion. METHODS: This retrospective, cross-sectional analysis included patients initiated on dialysis between October 2011 and September 2013 at 17 Japanese institutions. Data from 952 participants were analyzed using a multivariate logistic regression model and a linear regression model. We also analyzed subgroup data for groups classified by selection of peritoneal dialysis or hemodialysis. RESULTS: Of the 952 participants, 303 patients received VDRA. VDRA administration was associated with a low prevalence of pulmonary congestion in the multivariate logistic regression model (odds ratio [OR], 0.64; 95 % confidence interval [CI], 0.44-0.94; P = 0.02). There was no significant association between VDRA administration and systolic blood pressure, diastolic blood pressure, or pulse pressure. Subgroup analysis revealed a tendency that VDRA administration was associated with low prevalence of pulmonary congestion in both groups. CONCLUSIONS: In this study, VDRA administration was associated with a low prevalence of pulmonary congestion in patients initiated on dialysis. Appropriate VDRA administration may prevent pulmonary congestion.
Assuntos
Edema Pulmonar/epidemiologia , Receptores de Calcitriol/agonistas , Insuficiência Renal Crônica/terapia , Deficiência de Vitamina D/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Edema Pulmonar/etiologia , Análise de Regressão , Diálise Renal , Insuficiência Renal Crônica/complicações , Estudos Retrospectivos , Deficiência de Vitamina D/complicaçõesRESUMO
BACKGROUND: Recently, preemptive kidney transplantation (PKT) has increased in Japan; however, the effects of PKT on calcium (Ca) and phosphorus (Pi) metabolism are poorly understood. METHODS: Thirty-two consecutive patients were enrolled in this study at Nagoya Daini Red Cross Hospital. Fifteen patients were in the PKT group and 17 patients were in the non-PKT group. Parameters of Ca and Pi metabolism, including fibroblast growth factor (FGF) 23 and intact parathyroid hormone, were measured before transplantation and 1, 3, and 24 weeks after transplantation. RESULTS: FGF 23 decreased dramatically in both groups after transplantation; however, FGF 23 before transplantation and at 1 and 3 weeks after transplantation was significantly lower in the PKT group than in the non-PKT group (p < 0.05). Although iPTH levels were higher in the PKT group than in the non-PKT group before transplantation, these levels were lower in the PKT group at 24 weeks after transplantation (p < 0.05). Corrected Ca was lower at 24 weeks in the PKT group (p < 0.05), whereas Pi was lower in the non-PKT group at 1 and 3 weeks (p < 0.05), but not significantly different at 24 weeks. Multivariate linear regression analysis revealed that FGF 23 before transplantation was the strongest predictor of Ca and Pi disorders in early post-transplant recipients. CONCLUSIONS: This study suggests that PKT has beneficial effects on Ca and Pi metabolism and pre-transplant FGF 23 levels are a good marker of post-transplant Ca and Pi metabolism disorders.
Assuntos
Fatores de Crescimento de Fibroblastos/sangue , Hipercalcemia/sangue , Hipofosfatemia/sangue , Transplante de Rim/efeitos adversos , Hormônio Paratireóideo/sangue , Adulto , Cálcio/metabolismo , Feminino , Fator de Crescimento de Fibroblastos 23 , Humanos , Hipercalcemia/etiologia , Hipofosfatemia/etiologia , Transplante de Rim/métodos , Masculino , Pessoa de Meia-Idade , Fósforo/metabolismo , Período Pós-Operatório , Valor Preditivo dos Testes , Estudos Prospectivos , Fatores de Tempo , Vitamina D/análogos & derivados , Vitamina D/sangue , Adulto JovemRESUMO
BACKGROUND: With the recent increase in renal transplantations in Japan, accurate assessment of renal function is required. METHODS: This study included 73 patients who had undergone renal transplantation at Nagoya Daini Red Cross Hospital at least 6 months previously and had stable renal function for >3 months. Glomerular filtration rates (GFRs) were measured by inulin clearance (mGFR) and compared with estimated cystatin C-based GFRs (eGFRcys), estimated creatinine-based GFRs (eGFRcre) and their average values (eGFRave). RESULTS: mGFR was 43.3 ± 14.1 mL/min/1.73 m(2), eGFRcre was 39.6 ± 11.7, eGFRcys was 56.0 ± 17.1, and eGFRave was 47.8 ± 13.7 mL/min/1.73 m(2). Serum cystatin C was 1.39 ± 0.37 mg/L and serum creatinine was 1.58 ± 0.51 mg/dL. The correlation coefficients between mGFR and eGFRcre, eGFRcys, and eGFRave were 0.768, 0.831, and 0.841, respectively (P < 0.001, for all).The intraclass correlation coefficients were 0.754, 0.816, and 0.840, respectively (P < 0.001, for all).The mean differences between measured and estimated GFR values were 3.74 mL/min/1.73 m(2) with a root-mean square error (RMSE) of 9.06 for eGFRcre, +12.64 with RMSE of 9.48 for eGFRcys, and +4.45 with RMSE of 7.86 for eGFRave. Bland-Altman plots showed that eGFRcys overestimated GFR values compared with mGFR values in most cases and that eGFRave overestimated GFR values in 53 of 73 cases, whereas eGFRcre underestimated the values in 53 of 73 cases. CONCLUSION: eGFRave may be the best marker to estimate kidney function in Japanese renal transplant recipients with mildly reduced or normal kidney function.
Assuntos
Povo Asiático , Creatinina/sangue , Cistatina C/sangue , Taxa de Filtração Glomerular , Nefropatias/diagnóstico , Transplante de Rim/efeitos adversos , Rim/fisiopatologia , Modelos Biológicos , Transplantados , Adulto , Biomarcadores/sangue , Estudos Transversais , Feminino , Humanos , Inulina , Japão/epidemiologia , Nefropatias/sangue , Nefropatias/etnologia , Nefropatias/fisiopatologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
Recurrence of native kidney disease following kidney transplantation affects between 10% and 20% of patients, and accounts for up to 8% of graft failures. In a considerable number of recipients with transplant glomerulopathy, it is impossible to distinguish between recurrent and de novo types. An accurate estimate of the incidence of recurrence is difficult due to limitations in the diagnosis of recurrent glomerulonephritis. De novo glomerular lesions may be misclassified if histological confirmation of the patient's native kidney disease is lacking. Asymptomatic histological recurrence in renal allografts may be missed if protocol biopsies are not available. Studies based on protocol biopsy are pivotal to accurately estimate the incidence of recurrence. Many factors are known to influence recurrence of kidney disease after transplantation, including the type and severity of the original disease, age at onset, interval from onset to end-stage renal disease, and clinical course of the previous transplantation. Early recognition of recurrence is possible in several glomerular diseases. Factors such as the existence of circulating permeability factors, circulating urokinase receptor and anti-phospholipase A2 receptor antibody, as well as disorders of complement regulatory proteins like factor I mutation and factor H mutation factors are expected to be useful predictors of recurrence. Peculiar clinical course of atypical haemolytic uremic syndrome after kidney transplantation is an informative sign of recurrent glomerular disease. These factors play pivotal roles in the development of recurrence of certain types of glomerulopathies. Understanding the pathogenesis of recurrent glomerulonephritis is critical to optimize prevention as well as treat individual cases of recurrent glomerulonephritis. Subclinical recurrence of IgA nephropathy after kidney transplantation is well recognized. Only protocol biopsies of clinically silent recipient can provide the accurate prevalence of recurrent IgA nephropathy. The study of recurrent glomerulonephritis will contribute not only to improving long-term graft survival, but also to clarifying the pathogenesis of glomerulonephritis. Protocol biopsy is one the most effective methods for elucidating the pathogenesis of recurrent glomerulonephritis.
Assuntos
Glomerulonefrite/patologia , Glomerulonefrite/cirurgia , Falência Renal Crônica/patologia , Falência Renal Crônica/cirurgia , Transplante de Rim/efeitos adversos , Biópsia , Humanos , Recidiva , Medição de RiscoRESUMO
IgA nephropathy (IgAN) is recurrent after transplantation; however, its time of recurrence is unpredictable. To date, factors influencing IgAN recurrence have not been elucidated. We present a case of a 23-year-old man with end-stage renal disease (ESRD) who underwent living-related ABO-identical pre-emptive kidney transplantation (PEKT) using his 57-year-old mother as a donor. IgAN started when the patient was 19 years old, and renal biopsy revealed the usual pathological findings of IgAN. In spite of steroid therapy including steroid pulse and tonsillectomy, the patient developed nephrotic syndrome and progressed to ESRD in 4 years. Protocol biopsy on day 19 following PEKT revealed active recurrent IgAN. Nephrotic-range proteinuria and mild deterioration of kidney function developed regardless of strong immunosuppressive therapy such as steroid pulse, double filtration plasmapheresis and rituximab. We report a case of refractory IgAN that recurred 19 days after transplantation. This case is considered of value to elucidate factors leading to active IgAN recurrence.
Assuntos
Glomerulonefrite por IGA/patologia , Glomerulonefrite por IGA/cirurgia , Transplante de Rim/efeitos adversos , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/patologia , Anticorpos Monoclonais Murinos/uso terapêutico , Glomerulonefrite por IGA/tratamento farmacológico , Humanos , Fatores Imunológicos/uso terapêutico , Falência Renal Crônica/patologia , Falência Renal Crônica/cirurgia , Masculino , Plasmaferese , Complicações Pós-Operatórias/tratamento farmacológico , Recidiva , Rituximab , Adulto JovemRESUMO
A 51-year-old woman received an ABO blood type-incompatible renal transplant. She was administered rituximab and basiliximab and underwent plasma exchanges for induction therapy, followed by administration of tacrolimus, mycophenolate mofetil and methylprednisolone as maintenance immunosupression therapy. A planned renal biopsy 2 years after transplantation revealed infiltration of plasma cells in the renal interstitium, although there was no 'storiform' fibrosis surrounding these cells. There were also no findings of rejection, BK virus nephropathy, or atypical plasma cells. Immunohistochemical stainings showed a large number of IgG4-positive plasma cells, most of which expressed kappa-type light chains. A CT scan showed a mass at the renal hilum. The serum IgG4 level was high. Based on these findings, the patient was suspected of having IgG4-related kidney disease. Nine months after the biopsy, her serum creatinine level increase to 1.56 mg/dL and the dose of methylprednisolone was therefore increased to 16 mg/day. Three months after this increase in steroid, a CT scan showed the hilum mass had disappeared. A follow-up biopsy 5 months later showed that infiltration of plasma cells in the renal interstitium had decreased markedly, although focal and segmental severely fibrotic lesions with IgG4-positive plasma cells were observed. Serum IgG4 levels decreased immediately after the increase in steroid dose and remained <100 mg/dL despite a reduction in methylprednisolone to 6 mg/day. Serum creatinine levels also remained stable at around 1.6 mg/dL. To our knowledge, this is the first report of IgG4-positive plasma cell-rich tubulointerstitial nephritis mimicking IgG4-related kidney disease after kidney transplantation.