Biochemical Clusters as Substitutes of Bone Biopsies in Kidney Transplant Patients.

Bone and mineral metabolism abnormalities are frequent in kidney transplant recipients and have been associated with cardiovascular morbidity. The primary aim of this study was to analyse the association between routine clinically available biochemical evaluation, non-routine histomorphometric bone evaluation, and vascular disease in kidney transplanted patients. A cross-sectional analysis was performed on 69 patients, 1-year after kidney transplantation. Laboratory analysis, radiography of hands and pelvis, bone biopsy, bone densitometry, and coronary CT were performed. One-year post-transplantation, nearly one-third of the patients presented with hypercalcemia, 16% had hypophosphatemia, 39.3% had iPTH levels > 150 pg/mL, 20.3% had BALP levels > 40 U/L, and 26.1% had hypovitaminosis D. Evaluation of extraosseous calcifications revealed low Adragão and Agatston scores. We divided patients into three clusters, according to laboratory results routinely used in clinical practice: hypercalcemia and hyperparathyroidism (Cluster1); hypercalcemia and high BALP levels (Cluster2); hypophosphatemia and vitamin D deficiency (Cluster 3). Patients in clusters 1 and 2 had higher cortical porosity (p = 0.001) and osteoid measurements, although there was no difference in the presence of abnormal mineralization, or low volume. Patients in cluster 2 had a higher BFR/BS (half of the patients in cluster 2 had high bone turnover), and most patients in cluster 1 had low or normal bone turnover. Cluster 3 has no differences in volume, or turnover, but 60% of the patients presented with pre-osteomalacia. All three clusters were associated with high vascular calcifications scores. Vascular calcifications scores were not related to higher bone mineral density. Instead, an association was found between a higher Adragão score and the presence of osteoporosis at the femoral neck (p = 0.008). In conclusion, inferring bone TMV by daily clinical biochemical analysis can be misleading, and bone biopsy is important for assessing both bone turnover and mineralization after kidney transplantation, although hypophosphatemia combined with vitamin D deficiency is associated with abnormal mineralization. The presence of hypercalcemia with high levels of PTH or high levels of BALP, or hypophosphatemia and vitamin D deficiency should remind us to screen vascular calcification status of patients.Clinical Research: ClinicalTrials.gov ID NCT02751099.

Liver cirrhosis requiring transplantation in the context of hepaticojejunostomy stricture after a traumatic bile duct injury.

Biliary injury secondary to trauma is frequently associated with long-term complications. Liver transplantation is rarely indicated but might be the best therapeutic option in severe or intractable cases. We report the case of a 19-year-old male referred for liver transplantation due to biliary injury after abdominal trauma. A Roux-en-Y hepaticojejunostomy was initially performed without immediate complications. Anastomotic stricture developed requiring several trials of biliary dilatation and stenting through a percutaneous approach. The presence of liver cirrhosis and the intractability of this complication culminated in the decision of liver transplantation. The authors present clinical course, complications and interventional procedures that were used in a judicious step-up approach.

Alcohol Consumption Post-Liver Transplantation: A Cross-Sectional Study.

Background: Listing patients with alcohol-associated liver disease (ALD) for liver transplant (LT) remains challenging especially due to the risk of alcohol resumption post-LT. We aimed to evaluate post-LT alcohol consumption at a Portuguese transplant center. Methods: We conducted a cross-sectional study including LT recipients from 2019 at Curry Cabral Hospital, Lisbon, Portugal. A pretested survey and a validated Portuguese translation of the Alcohol Use Disorder Identification Test (AUDIT) were applied via a telephone call. Alcohol consumption was defined by patients' self-reports or a positive AUDIT. Results: In 2019, 122 patients underwent LT, and 99 patients answered the survey (June 2021). The mean (SD) age was 57 (10) years, 70 patients (70.7%) were males, and 49 (49.5%) underwent ALD-related LT. During a median (IQR) follow-up of 24 (20-26) months post-index LT, 22 (22.2%) recipients consumed any amount of alcohol: 14 had a drink monthly or less and 8 drank 2-4 times/month. On drinking days, 18 patients usually consumed 1-2 drinks and the remainder no more than 3-4 drinks. One patient reported having drunk ≥6 drinks on one occasion. All post-LT drinking recipients were considered low risk (score <8) as per the AUDIT score (median [IQR] of 1 [1-2]). No patient reported alcohol-related problems, whether self-inflicted or toward others. Drinking recipients were younger (53 vs. 59 years, p = 0.020), had more non-ALD-related LT (72.7 vs. 44.2%, p = 0.018) and active smoking (31.8 vs. 10.4%, p = 0.037) than abstinent ones. Conclusion: In our cohort, about a quarter of LT recipients consumed alcohol early posttransplant, all with a low-risk pattern according to the AUDIT score.

Introdução: Incluir doentes com doença hepática associada ao álcool (DHA) em lista ativa de transplante hepático (TH) é desafiante, especialmente pelo risco de recidiva de consumo de álcool pós-TH. O objetivo foi avaliar o consumo de álcool pós-TH num centro de transplantação português. Métodos: Realizamos um estudo transversal incluindo doentes submetidos a TH em 2019 no Hospital Curry Cabral, Lisboa, Portugal. Foi realizado um questionário previamente testado e uma tradução validada para o português do Alcohol Use Disorder Identification Test (AUDIT), através de uma chamada telefónica. O consumo de álcool foi definido pelo autorrelato do doente ou por um AUDIT positivo. Resultados: Durante 2019, 122 doentes foram submetidos a TH e 99 responderam ao questionário (junho de 2021). A idade média (SD) foi de 57 (10) anos, 70 doentes (70,7%) eram do sexo masculino e 49 (49,5%) foram submetidos a TH relacionado com DHA. Com uma mediana (IQR) de follow-up de 24 (20­26) meses após o TH-índex, 22 (22,2%) doentes admitiram algum consumo de álcool: 14 beberam mensalmente ou menos e oito beberam 2­4 vezes/mês. Nos dias em que bebiam, 18 consumiam normalmente 1­2 bebidas e os restantes não mais do que 3­4 bebidas. Um doente reportou o consumo de ≥6 bebidas em uma ocasião. Todos os doentes transplantados com consumo alcoólico pós-TH foram considerados de baixo risco (pontuação >8) de acordo com o AUDIT (mediana [IQR] de 1 [1­2]). Nenhum doente reportou problemas relacionados com o álcool, tanto autoinfligido como a terceiros. Os indivíduos transplantados com consumo alcoólico eram mais jovens (53 vs. 59 anos, p = 0,020), o motivo de TH era mais frequentemente não relacionado com DHA (72,7 vs. 44,2%, p = 0,018) e apresentavam mais tabagismo ativo (31,8 vs. 10,4%, p = 0,037) quando comparado com os abstinentes. Conclusão: Na nossa coorte, cerca de um quarto dos doentes transplantados hepáticos consumiram álcool no período pós-transplante precoce, todos com um padrão de baixo risco, de acordo com o AUDIT.

The Impact of Donor Risk Index, Recipients' and Operative Characteristics on Post Liver Transplant One-Year Graft Failure: A Cohort Analysis.

Background and Aims: The donor risk index (DRI) quantifies donor-related characteristics potentially associated with increased risk of early graft failure. We aimed to assess the impact of the DRI, recipient and perioperative factors on post liver transplant (LT) outcomes. Methods: This was a single-center retrospective cohort study including all adult (≥18 years) patients who underwent LT from 01/2019 to 12/2019 at Curry Cabral Hospital, Lisbon, Portugal. Primary endpoint was 1-year graft failure post LT. Associations were studied with logistic regression. Results: A total of 131 cadaveric donor LT procedures were performed in 116 recipients. Recipients' median (IQR) age was 57 (47-64) years and 101/131 (77.1%) were males. Cirrhosis was the underlying etiology in 95/131 (81.2%) transplants. Based on 8 predefined donors' characteristics, median (IQR) DRI was 1.96 (1.67-2.16). Following adjustment for MELDNa score pre LT and SOFA score (adjusted odds ratio [aOR], 95% confidence interval [CI] = 0.91 [0.56-1.47]) or lactate (aOR [95% CI] = 2.76 [0.71-10.7]) upon intensive care unit (ICU) admission post LT, DRI was not associated with 1-year graft failure. However, higher SOFA score (aOR [95% CI] = 1.20 [1.05-1.37]) or lactate (aOR [95% CI] = 1.27 [1.10-1.46]) upon ICU admission post LT were independently associated with higher odds of 1-year graft failure. Conclusions: In a recent cohort of patients who underwent LT, DRI, despite being high, was not associated with 1-year graft failure, but SOFA score or lactate upon ICU admission post LT were.

Introdução: O índice de risco do dador (DRI) quantifica as características relacionadas com o dador potencialmente associadas com risco acrescido de falência precoce do enxerto. Procurou-se avaliar o impacto do DRI e factores relacionados com os receptores e cirurgia nos resultados clínicos após transplante hepático (LT). Materiais e Métodos: Estudo coorte retrospectivo de centro único incluindo todos os doentes adultos (≥18 anos) que receberam LT entre 01/2019 e 12/2019 no Hospital Curry Cabral, Lisboa, Portugal. O endpoint primário foi a falência do enxerto após um ano do LT. As associações foram estudadas com regressão logística. Resultados: Um total de 131 transplantes de dadores cadavéricos foram realizados em 116 receptores. A idade mediana (IQR) destes foi 57 (47­64) anos e 101/131 (77.1%) eram homens. A cirrose foi a etiologia subjacente em 95/131 (81.2%) transplantes. Com base nas 8 características dos dadores predefinidas, o DRI mediano (IQR) foi 1.96 (1.67­2.16). Após ajuste para o score MELDNa pre LT e o score SOFA (odds ratio ajustado [aOR], intervalo de confiança 95% [CI] = 0.91 [0.56­1.47]) ou o lactato (aOR [95% CI] = 2.76 [0.71­10.7]) após admissão na unidade de cuidados intensivos (ICU) pós LT, o DRI não se associou com a falência do enxerto um ano depois do LT. Contudo, um maior score SOFA (aOR [95% CI] = 1.20 [1.05­1.37]) ou lactato (aOR [95% CI] = 1.27 [1.10­1.46]) após admissão na ICU depois do LT associaram-se independentemente com a falência do enxerto um ano depois do LT. Conclusões: Num coorte recente de doentes submetidos a LT, o DRI, apesar de alto, não se associou com a falência precoce do enxerto precoce. Contudo, o score SOFA ou lactato após admissão na ICU depois do LT associaram-se com a falência precoce do enxerto.

Acute interstitial nephritis due to dolutegravir: The first case reported / Nefritis intersticial aguda por dolutegravir: primer caso notificado

Kidney disease is frequent in HIV-patients. We present a case of a 44-year-old woman, with known uncontrolled HIV infection and chronic kidney disease due to HIV-associated nephropathy. After starting dolutegravir, the patient developed eosinophilia and worsening kidney function. A kidney biopsy confirmed the diagnosis of acute interstitial nephritis. Given the time relation with dolutegravir introduction, it was deemed the culprit medication. Dolutegravir was stopped, and corticosteroids were initiated, with moderate improvement in renal function. To our knowledge, this is the first reported case of acute interstitial nephritis to dolutegravir, which should raise awareness of previously undocumented renal effects of antiretroviral therapy. (AU)

La enfermedad renal es frecuente en pacientes con VIH. Presentamos el caso de una mujer de 44 años, con infección por VIH no controlada conocida y enfermedad renal crónica por nefropatía asociada al VIH. Después de comenzar con dolutegravir, el paciente desarrolló eosinofilia y empeoramiento de la función renal. Una biopsia de riñón confirmó el diagnóstico de nefritis intersticial aguda. Dada la relación temporal con la introducción de dolutegravir, se consideró al medicamento el culpable. Se interrumpió el tratamiento con dolutegravir y se iniciaron corticosteroides, con una mejoría moderada de la función renal. Hasta donde sabemos, este es el primer caso notificado de nefritis intersticial aguda por dolutegravir, lo que debería crear conciencia sobre los efectos renales previamente indocumentados de la terapia antirretroviral. (AU)

Fibrosis of Peritoneal Membrane, Molecular Indicators of Aging and Frailty Unveil Vulnerable Patients in Long-Term Peritoneal Dialysis.

Peritoneal membrane status, clinical data and aging-related molecules were investigated as predictors of long-term peritoneal dialysis (PD) outcomes. A 5-year prospective study was conducted with the following endpoints: (a) PD failure and time until PD failure, (b) major cardiovascular event (MACE) and time until MACE. A total of 58 incident patients with peritoneal biopsy at study baseline were included. Peritoneal membrane histomorphology and aging-related indicators were assessed before the start of PD and investigated as predictors of study endpoints. Fibrosis of the peritoneal membrane was associated with MACE occurrence and earlier MACE, but not with the patient or membrane survival. Serum α-Klotho bellow 742 pg/mL was related to the submesothelial thickness of the peritoneal membrane. This cutoff stratified the patients according to the risk of MACE and time until MACE. Uremic levels of galectin-3 were associated with PD failure and time until PD failure. This work unveils peritoneal membrane fibrosis as a window to the vulnerability of the cardiovascular system, whose mechanisms and links to biological aging need to be better investigated. Galectin-3 and α-Klotho are putative tools to tailor patient management in this home-based renal replacement therapy.

Kidney Disease in Ankylosing Spondylitis: a case series and review of the literature / Doença Renal na Espondilite Anquilosante: uma série de casos e revisão da literatura

Abstract Background Kidney disease is a rare manifestation of ankylosing spondylitis (AS) and its pathological alterations remain poorly described. The aim of this study was to investigate the clinical presentation and pathological alterations on kidney biopsy of AS patients and review and discuss the current literature on the issue. Methods: We retrospectively studied the clinical presentation and kidney pathological alterations of 15 Caucasian AS patients submitted to kidney biopsy between October 1985 and March 2021. Results: Patients were predominantly male (66.7%) with median age at the time of kideney biopsy of 47 years [IQR 34 - 62]. Median serum creatinine at presentation was 1.3 mg/dL [IQR 0.9 - 3] and most patients also had either proteinuria (85.7%) and/or hematuria (42.8%). The most common indication for kidney biopsy was nephrotic syndrome (33.3%), followed by acute or rapidly progressive kidney injury (20%) and chronic kidney disease of unknown etiology (20%). Chronic interstitial nephritis (CIN) (n=3) and AA amyloidosis (n=3) were the most common diagnosis. Others included IgA nephropathy (IgAN) (n=2), focal segmental glomerulosclerosis (n=2), membranous nephropathy (n=1), and immune complex-mediated membranoproliferative glomerulonephritis (IC-MPGN)(n=1). Conclusions: We present one of the largest series of biopsy-proven kidney disease in Caucasian AS patients. We found a lower prevalence of IgAN than previously reported in Asian cohorts. We found a higher prevalence of CIN and a lower prevalence of AA amyloidosis than that described in previous series of Caucasian patients. We also present the first case of AS-associated IC-MPGN.

Resumo Antecedentes: A doença renal é uma manifestação rara de espondilite anquilosante (EA) e as suas alterações patológicas permanecem pouco descritas. O objetivo deste estudo foi investigar a apresentação clínica e alterações patológicas na biópsia renal de doentes com EA bem como rever e discutir a literatura atual sobre o assunto. Métodos: Estudamos retrospectivamente a apresentação clínica e alterações patológicas renais de 15 doentes caucasianos com EA submetidos a biópsia renal entre Outubro de 1985 e Março de 2021. Resultados: Os doentes eram predominantemente homens (66,7%) com idade mediana no momento da biópsia de 47 anos [IIQ 34 - 62]. A creatinina sérica mediana na apresentação foi de 1,3 mg/dL [IIQ 0,9 - 3] e a maioria dos pacientes apresentava também proteinúria (85,7%) e/ou hematúria (42,8%). A indicação mais comum para biópsia renal foi a síndrome nefrótica (33,3%), seguida de lesão renal aguda ou rapidamente progressiva (20%) e doença renal crónica de etiologia desconhecida (20%). A Nefrite intersticial crónica (NIC) (n=3) e a amiloidose AA (n=3) foram os diagnósticos mais comuns. Outros incluíram nefropatia por IgA (NIgA) (n=2), glomeruloesclerose segmentar focal (n=2), nefropatia membranosa (n=1) e glomerulonefrite membranoproliferativa mediada por imunocomplexos (GNMP-IC) (n=1). Conclusões: Apresentamos uma das maiores séries de doenças renais comprovadas por biópsia em doentes caucasianos com EA. Encontramos uma prevalência de NIgA menor do que a relatada anteriormente em coortes asiáticas. Encontramos uma maior prevalência de NIC e uma prevalência menor de amiloidose AA do que a descrita em séries anteriores de pacientes caucasianos. Também apresentamos o primeiro caso de GNMP-IC associada à EA.

Urinary Sediment Microscopy and Correlations with Kidney Biopsy: Red Flags Not To Be Missed.

BACKGROUND: Urinary sediment is a noninvasive laboratory test that can be performed by an automated analyzer or manually by trained personnel. Manual examination remains the diagnostic standard because it excels at differentiating isomorphic from dysmorphic red blood cells and identifying other urinary particles such as renal tubular epithelial cells (RTECs), lipids, crystals, and the composition of casts. This study aimed to investigate the prevalence of a complete profile of urinary sediment particles and its associations with histologic lesions on kidney biopsy, regardless of diagnosis. METHODS: This was a single-center, observational retrospective study of 131 patients who had contemporary manual urinary sediment evaluation and kidney biopsy. A comprehensive set of urinary particles and histologic lesions were quantified, and their associations were analyzed. RESULTS: In our samples, we found an elevated frequency of findings suggestive of proliferative kidney disease and a low frequency of particles evoking urologic damage. The association of histologic lesions and urinary particles was explored with a multivariate model. We identified urinary sediment characteristics that independently correlated with the presence of some histologic lesions: urinary lipids with mesangial expansion (OR=2.86; 95% confidence interval [95% CI], 1.3 to 6.3), mesangial hypercellularity (OR=2.44; 95% CI, 1.06 to 5.58), and wire loops and/or hyaline deposits (OR=2.89; 95% CI, 1.13 to 7.73); Urinary renal tubular epithelial cells with endocapillary hypercellularity (OR=3.17; 95% CI, 1.36 to 7.39), neutrophils and/or karyorrhexis (OR=4.51; 95% CI, 1.61 to 12.61), fibrinoid necrosis (OR=4.35; 95% CI, 1.48 to 12.74), cellular/fibrocellular crescents (OR=5.27; 95% CI, 1.95 to 14.26), and acute tubular necrosis (OR=2.31; 95% CI, 1.08 to 4.97). CONCLUSIONS: In a population of patients submitted to kidney biopsy, we found that the presence of some urinary particles (renal tubular epithelial cells, lipids, and dysmorphic erythrocytes), which are seldom reported by automated analyzers, is associated with active proliferative histologic lesions. In this regard, manual urinary sediment evaluation may help to shape the indications for performing a kidney biopsy.

Kidney Disease in Ankylosing Spondylitis: a case series and review of the literature.

BACKGROUND: Kidney disease is a rare manifestation of ankylosing spondylitis (AS) and its pathological alterations remain poorly described. The aim of this study was to investigate the clinical presentation and pathological alterations on kidney biopsy of AS patients and review and discuss the current literature on the issue. METHODS: We retrospectively studied the clinical presentation and kidney pathological alterations of 15 Caucasian AS patients submitted to kidney biopsy between October 1985 and March 2021. RESULTS: Patients were predominantly male (66.7%) with median age at the time of kideney biopsy of 47 years [IQR 34 - 62]. Median serum creatinine at presentation was 1.3 mg/dL [IQR 0.9 - 3] and most patients also had either proteinuria (85.7%) and/or hematuria (42.8%). The most common indication for kidney biopsy was nephrotic syndrome (33.3%), followed by acute or rapidly progressive kidney injury (20%) and chronic kidney disease of unknown etiology (20%). Chronic interstitial nephritis (CIN) (n=3) and AA amyloidosis (n=3) were the most common diagnosis. Others included IgA nephropathy (IgAN) (n=2), focal segmental glomerulosclerosis (n=2), membranous nephropathy (n=1), and immune complex-mediated membranoproliferative glomerulonephritis (IC-MPGN)(n=1). CONCLUSIONS: We present one of the largest series of biopsy-proven kidney disease in Caucasian AS patients. We found a lower prevalence of IgAN than previously reported in Asian cohorts. We found a higher prevalence of CIN and a lower prevalence of AA amyloidosis than that described in previous series of Caucasian patients. We also present the first case of AS-associated IC-MPGN.

Acute interstitial nephritis due to dolutegravir: The first case reported.

Kidney disease is frequent in HIV-patients. We present a case of a 44-year-old woman, with known uncontrolled HIV infection and chronic kidney disease due to HIV-associated nephropathy. After starting dolutegravir, the patient developed eosinophilia and worsening kidney function. A kidney biopsy confirmed the diagnosis of acute interstitial nephritis. Given the time relation with dolutegravir introduction, it was deemed the culprit medication. Dolutegravir was stopped, and corticosteroids were initiated, with moderate improvement in renal function. To our knowledge, this is the first reported case of acute interstitial nephritis to dolutegravir, which should raise awareness of previously undocumented renal effects of antiretroviral therapy.

The burden of coronary heart disease in simultaneous pancreas-kidney transplantation: coronary angiography as a diagnostic method for all? - a retrospective study / O peso da doença arterial coronariana no transplante de pâncreas-rim simultâneo: angiografia coronária como método diagnóstico para todos? - um estudo retrospectivo

Abstract Introduction: Type 1 diabetes mellitus is associated with an increased risk of coronary artery disease, which is frequently asymptomatic. This risk increases significantly in those with nephropathy. In selected patients, simultaneous pancreas-kidney transplantation is the renal and pancreatic replacement therapy of choice, as it increases longevity and stabilizes diabetic complications. Despite essential, universal screening protocols are still controversial for coronary artery disease in this population. Methods: We retrospectively analysed 99 simultaneous pancreas-kidney recipients from our centre from 2011 to 2018 and selected 77 patients who underwent coronary angiography during the pre-transplant evaluation. Our aim was to identify potential risk factors associated with significant lesions on coronary angiography. Results: Almost half of our cohort of 77 candidates submitted to coronary angiography had coronary artery disease. Of these, nearly 30% underwent revascularization, although only one of them reported symptoms of myocardial ischemia. In a univariate analysis, the presence of smoking habits was the only risk factor for coronary artery disease. We also found that 20 or more years of type 1 diabetes mellitus was significantly associated with the presence of coronaropathy. Discussion: Selection of diabetic candidates with acceptable cardiac risk before simultaneous pancreas-kidney transplantation is imperative. Given the impact of a correct diagnosis and a low procedural risk, we defend the routine use of coronary angiography as the initial screening method for coronary artery disease in this population. Particularly care must be taken in evaluating asymptomatic patients with long-term type 1 diabetes mellitus and smokers.

Resumo Introdução: O diabetes mellitus tipo 1 está associado ao risco aumentado de doença arterial coronariana, que é frequentemente assintomática. Este risco aumenta significativamente em pessoas com nefropatia. Em pacientes selecionados, o transplante de pâncreas- rim simultâneo é a terapia substitutiva, renal e pancreática, de escolha, pois aumenta a longevidade e estabiliza complicações diabéticas. Apesar de essenciais, protocolos de triagem universais ainda são controversos para doença arterial coronariana nesta população. Métodos: Analisamos retrospectivamente 99 receptores de pâncreas-rim simultâneo de nosso centro, de 2011 a 2018, e selecionamos 77 pacientes que realizaram angiografia coronária durante avaliação pré-transplante. Nosso objetivo foi identificar fatores de risco potenciais associados a lesões significativas na angiografia coronária. Resultados: Quase metade de nossa coorte de 77 candidatos submetidos à angiografia coronária apresentou doença arterial coronariana. Destes, quase 30% foram submetidos à revascularização, embora apenas um tenha relatado sintomas de isquemia miocárdica. Em uma análise univariada, a presença do hábito de fumar foi o único fator de risco para doença arterial coronariana. Também descobrimos que 20 ou mais anos de diabetes mellitus tipo 1 estavam significativamente associados à presença de coronariopatia. Discussão: A seleção de candidatos diabéticos com risco cardíaco aceitável antes do transplante de pâncreas-rim simultâneo é imperativa. Dado o impacto de um diagnóstico correto e baixo risco de procedimento, defendemos o uso rotineiro da angiografia coronária como método de triagem inicial para doença arterial coronariana nesta população. Deve-se ter um cuidado especial na avaliação de pacientes assintomáticos com diabetes mellitus tipo 1 de longa duração e fumantes.

Improvement of Mineral and Bone Disorders After Renal Transplantation.

BACKGROUND: Posttransplant mineral and bone diseases are causes of fractures, and their association with cardiovascular events is being studied. METHODS: We analyzed the evolution of biochemical, histological, and imaging parameters pre- and 1 y post-renal transplantation in 69 patients and correlated mineral and bone findings with coronary calcifications. At inclusion and after 12 mo, clinical data and echocardiographic findings were recorded, and laboratory evaluations, radiography of the pelvis and hands, and bone biopsy were performed. Noncontrast cardiac computed tomography was performed during the second evaluation. RESULTS: Serum levels of fibroblast growth factor 23 and sclerostin decreased in all patients, parathyroid hormone levels decreased in 89.8% of patients, bone alkaline phosphatase levels decreased in 68.1% of patients, and alpha-Klotho levels increased in 65.2% of patients. More than half of the patients presented with renal osteodystrophy at both biopsies, but histological findings improved: a significant transition from high to normal or low turnover and no significant differences in volume, mineralization defect, or cortical porosity at the 2 evaluations. Alpha-Klotho, sclerostin, and bone alkaline phosphatase shifts affect bone changes. Neither echocardiographic findings nor vascular calcification scores differed between the 2 points. Both the pretransplant period (dialysis vintage, sclerostin, and low bone volume at baseline) and the maintenance of abnormalities in the posttransplant period (high turnover posttransplant) were the most reliable predictors of the severity of the coronary calcification percentile. CONCLUSIONS: Renal transplantation improved bone and mineral abnormalities. The pretransplant period determines the severity of calcification.

The burden of coronary heart disease in simultaneous pancreas-kidney transplantation: coronary angiography as a diagnostic method for all? - a retrospective study.

INTRODUCTION: Type 1 diabetes mellitus is associated with an increased risk of coronary artery disease, which is frequently asymptomatic. This risk increases significantly in those with nephropathy. In selected patients, simultaneous pancreas-kidney transplantation is the renal and pancreatic replacement therapy of choice, as it increases longevity and stabilizes diabetic complications. Despite essential, universal screening protocols are still controversial for coronary artery disease in this population. METHODS: We retrospectively analysed 99 simultaneous pancreas-kidney recipients from our centre from 2011 to 2018 and selected 77 patients who underwent coronary angiography during the pre-transplant evaluation. Our aim was to identify potential risk factors associated with significant lesions on coronary angiography. RESULTS: Almost half of our cohort of 77 candidates submitted to coronary angiography had coronary artery disease. Of these, nearly 30% underwent revascularization, although only one of them reported symptoms of myocardial ischemia. In a univariate analysis, the presence of smoking habits was the only risk factor for coronary artery disease. We also found that 20 or more years of type 1 diabetes mellitus was significantly associated with the presence of coronaropathy. DISCUSSION: Selection of diabetic candidates with acceptable cardiac risk before simultaneous pancreas-kidney transplantation is imperative. Given the impact of a correct diagnosis and a low procedural risk, we defend the routine use of coronary angiography as the initial screening method for coronary artery disease in this population. Particularly care must be taken in evaluating asymptomatic patients with long-term type 1 diabetes mellitus and smokers.

Dialysis Initiation in Patients With Chronic Coronary Disease and Advanced Chronic Kidney Disease in ISCHEMIA-CKD.

Background In participants with concomitant chronic coronary disease and advanced chronic kidney disease (CKD), the effect of treatment strategies on the timing of dialysis initiation is not well characterized. Methods and Results In ISCHEMIA-CKD (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches-Chronic Kidney Disease), 777 participants with advanced CKD and moderate or severe ischemia were randomized to either an initial invasive or conservative management strategy. Herein, we compare the proportion of randomized participants with non-dialysis-requiring CKD at baseline (n=362) who initiated dialysis and compare the time to dialysis initiation between invasive versus conservative management arms. Using multivariable Cox regression analysis, we also sought to identify the effect of invasive versus conservative chronic coronary disease management strategies on dialysis initiation. At a median follow-up of 23 months (25th-75th interquartile range, 14-32 months), dialysis was initiated in 18.9% of participants (36/190) in the invasive strategy and 16.9% of participants (29/172) in the conservative strategy (P=0.22). The median time to dialysis initiation was 6.0 months (interquartile range, 3.0-16.0 months) in the invasive group and 18.2 months (interquartile range, 12.2-25.0 months) in the conservative group (P=0.004), with no difference in procedural acute kidney injury rates between the groups (7.8% versus 5.4%; P=0.26). Baseline clinical factors associated with earlier dialysis initiation were lower baseline estimated glomerular filtration rate (hazard ratio [HR] associated with 5-unit decrease, 2.08 [95% CI, 1.72-2.56]; P<0.001), diabetes (HR, 2.30 [95% CI, 1.28-4.13]; P=0.005), hypertension (HR, 7.97 [95% CI, 1.09-58.21]; P=0.041), and Hispanic ethnicity (HR, 2.34 [95% CI, 1.22-4.47]; P=0.010). Conclusions In participants with non-dialysis-requiring CKD in ISCHEMIA-CKD, randomization to an invasive chronic coronary disease management strategy (relative to a conservative chronic coronary disease management strategy) is associated with an accelerated time to initiation of maintenance dialysis for kidney failure. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01985360.