Torquetenovirus viral load is associated with anti-spike antibody response in SARS-CoV-2 mRNA BNT162b2 vaccinated kidney transplant patients.

INTRODUCTION: Kidney transplant patients (KT) are at high risk for severe COVID-19 and presented attenuated antibody responses to vaccination when compared to immunocompetent individuals. Torquetenovirus (TTV) has recently gained attention as a potential surrogate marker of the net state of immunosuppression. We evaluated the association between pre-vaccination TTV viral load and anti-spike total antibody response to SARS-CoV-2 vaccination in KT. MATERIAL AND METHODS: The 114 adult KT recipients enrolled in this prospective single-center cohort study received two doses of SARS-CoV-2 mRNA BNT162b2 vaccine. Serum samples were collected immediately before vaccination at the days when patients received both the first (T0) and the second dose (T1) and 16-45 days after the second dose (T2). Primary endpoint was the development of anti-spike total antibodies after vaccination. Demographic, clinical, and laboratorial parameters were compared between patients with and without detectable SARS-CoV-2 antibodies at T2. RESULTS: Ninety-nine patients (86.8%) were naïve for SARS-CoV-2 before vaccination. Fifty-six (56.6%) patients developed anti-spike total antibodies at T2. The use of mTOR inhibitors was associated with a favorable response (p = .005); conversely, mycophenolic acid (MPA) was associated with a negative response (p = .006). In a multivariable model, the presence of TTV at T0 ≥ 3.36 log10 cp/ml was associated with unfavorable vaccine response (OR: 5.40; 95% CI: 1.47-19.80; p = .011), after adjusting for age and eGFR at T0. CONCLUSIONS: Higher TTV viral loads before vaccination are associated with reduced anti-spike total antibody response in SARS-CoV-2 mRNA BNT162b2 vaccinated KT patients. The association between TTV viral load and vaccine response may be an added-value in the optimization of vaccination regimens in KT.

JCV viruria associates with suboptimal recovery of kidney function three years after living kidney donation / Virúria por JCV se associa a recuperação subótima da função renal três anos após doação renal de doador vivo

Abstract Introduction: Few studies have investigated pre-donation factors that could affect renal recovery after living kidney donation (LKD). We retrospectively investigated the role of John Cunningham virus (JCV) infection and other pre-donation factors on the magnitude of kidney function decline after LKD. Methods: Urine JCV viral loads, glomerular filtration rate, and blood pressure were evaluated in 60 consecutive LK donors before donation. Suboptimal compensatory hypertrophy was defined as an eGFR <60% of the pre-donation eGFR. Results: LKD (40% JCV infected) were followed for 3.2±1.6 years. No association was found between age, gender, and baseline hypertension with 1st, 2nd, 3rd, and 4th years post-donation eGFR <60% of the pre-donation eGFR. Mean eGFR recovery at the 3rd year after donation was lower in JCV infected donors vs non-infected donors (61.8% vs 71.0%, p=0.006). Conclusion: We hypothesized that JCV could shift glomeruli into a hyperfiltration state before nephrectomy, modulating the magnitude of compensatory hypertrophy after donation. Conversely, JCV might curtail the ability of the remaining kidney to promote hyperfiltration. Longer follow up is needed to determine whether JCV viruria ultimately leads to lower eGFR over time or if it is a protective factor for the remaining kidney.

Resumo Introdução Poucos estudos investigaram fatores anteriores à doação que poderiam afetar a recuperação renal após doação renal de doador vivo (LKD, do inglês Living Kidney Donation). Investigamos retrospectivamente o papel da infecção pelo vírus John Cunningham (JCV) e outros fatores de risco pré-doação na magnitude do declínio da função renal após LKD. Métodos: Cargas virais de JCV na urina, taxa de filtração glomerular e pressão arterial foram avaliadas consecutivamente em 60 doadores renais vivos antes da doação. Hipertrofia compensatória subótima foi definida como uma TFGe <60% da TFGe pré-doação. Resultados: LKD (40% infectados pelo JCV) foram acompanhados por 3,2±1,6 anos. Não foi encontrada nenhuma associação entre idade, sexo e hipertensão basal com a TFGe pós-doação no 1º, 2º, 3º e 4º anos <60% da TFGe pré-doação. A recuperação média da TFGe no 3º ano após a doação foi menor em doadores infectados pelo JCV vs doadores não infectados (61,8% vs 71,0%, p=0,006). Conclusão: Levantamos a hipótese de que o JCV pode levar os glomérulos a um estado de hiperfiltração antes da nefrectomia, modulando a magnitude da hipertrofia compensatória após a doação. Por outro lado, o JCV pode limitar a capacidade do rim remanescente de promover a hiperfiltração. É necessário um acompanhamento mais longo para determinar se a virúria por JCV leva, em última instância, a uma menor TFGe ao longo do tempo ou se é um fator de proteção para o rim remanescente.

Glycosuria in primary glomerulopathies: prevalence and prognostic significance / Glicosúria nas doenças glomerulares primárias: prevalência e significância prognóstica

Abstract Introduction: Tubular damage is common in glomerular diseases (GD). Glycosuria is a marker of tubular dysfunction and may be used to detect tubular lesion and CKD progression. The aim of this study was to evaluate the prevalence and prognostic value of glycosuria at the time of diagnosis in primary glomerulopathies (PG). Methods: We conducted a 24-month retrospective study in patients diagnosed with PG in our center between 2009 and 2020. We excluded diabetic patients, use of SGLT2 inhibitors, transplant patients, and secondary GD. Patients were divided in two groups according to their glycosuria status at diagnosis. Results: We studied 115 patients. Global prevalence of glycosuria was 10% (n=11) and membranous nephropathy (MN) had the highest prevalence (n=5, 17.9%). We found that patients with glycosuria had higher serum creatinine (2.4 vs. 1.2 mg/dL, p=0.030), higher albuminuria (4.8 vs. 1.9 g/g, p=0.004), and lower serum albumin (2.3 vs. 3.2 g/dL, p=0.021). We did not find association with histological prognostic factors. At the end of follow-up, patients with glycosuria had higher prevalence of the composite outcome of stage 5D CKD or 50% increase in basal SCr (45.5% vs. 17.3%, p=0.037). In patients with MN, results were similar but we were able to find an association of glycosuria with more severe interstitial fibrosis and tubular atrophy (25.0 vs. 0.0 %, p=0.032). Conclusion: Ten percent of our patients with PG have glycosuria. Glycosuria at the time of diagnosis was associated with more severe clinical presentation and worst renal outcome. The association with higher albuminuria suggests that tubular function has an impact on the severity and outcomes of PG.

Resumo Introdução: Danos tubulares são comuns em doenças glomerulares (DG). Glicosúria é um marcador de disfunção tubular e pode detectar lesão tubular e progressão da DRC. O objetivo deste estudo foi avaliar a prevalência e o valor prognóstico da glicosúria no diagnóstico em glomerulopatias primárias (GP). Métodos: Realizamos estudo retrospectivo de 24 meses em pacientes diagnosticados com GP em nosso centro entre 2009-2020. Excluímos pacientes diabéticos, uso de inibidores de SGLT2, pacientes transplantados e DG secundárias. Os pacientes dividiram-se em dois grupos de acordo com seu estado de glicosúria no diagnóstico. Resultados: Estudamos 115 pacientes. A prevalência global de glicosúria foi de 10% (n=11) e a nefropatia membranosa (NM) teve maior prevalência (n=5, 17,9%). Constatamos que pacientes com glicosúria apresentavam creatinina sérica mais elevada (2,4 vs. 1,2 mg/dL, p=0,030), albuminúria mais alta (4,8 vs. 1,9 g/g, p=0,004), e albumina sérica mais baixa (2,3 vs. 3,2 g/dL, p=0,021). Não encontramos associação com fatores prognósticos histológicos. Ao final do acompanhamento, pacientes com glicosúria tiveram maior prevalência do desfecho composto de DRC estágio 5D ou aumento de 50% na CrS basal (45,5% vs. 17,3%, p=0,037). Em pacientes com NM, os resultados foram semelhantes, mas encontramos uma associação de glicosúria com fibrose intersticial mais grave e atrofia tubular (25,0 vs. 0,0 %, p=0,032). Conclusão: 10% de nossos pacientes com GP têm glicosúria. A glicosúria no diagnóstico foi associada a uma apresentação clínica mais grave e pior desfecho renal. A associação com albuminúria mais elevada sugere que a função tubular tem um impacto na gravidade e nos desfechos da GP.

JCV viruria associates with suboptimal recovery of kidney function three years after living kidney donation.

INTRODUCTION: Few studies have investigated pre-donation factors that could affect renal recovery after living kidney donation (LKD). We retrospectively investigated the role of John Cunningham virus (JCV) infection and other pre-donation factors on the magnitude of kidney function decline after LKD. METHODS: Urine JCV viral loads, glomerular filtration rate, and blood pressure were evaluated in 60 consecutive LK donors before donation. Suboptimal compensatory hypertrophy was defined as an eGFR <60% of the pre-donation eGFR. RESULTS: LKD (40% JCV infected) were followed for 3.2±1.6 years. No association was found between age, gender, and baseline hypertension with 1st, 2nd, 3rd, and 4th years post-donation eGFR <60% of the pre-donation eGFR. Mean eGFR recovery at the 3rd year after donation was lower in JCV infected donors vs non-infected donors (61.8% vs 71.0%, p=0.006). CONCLUSION: We hypothesized that JCV could shift glomeruli into a hyperfiltration state before nephrectomy, modulating the magnitude of compensatory hypertrophy after donation. Conversely, JCV might curtail the ability of the remaining kidney to promote hyperfiltration. Longer follow up is needed to determine whether JCV viruria ultimately leads to lower eGFR over time or if it is a protective factor for the remaining kidney.

Glycosuria in primary glomerulopathies: prevalence and prognostic significance.

INTRODUCTION: Tubular damage is common in glomerular diseases (GD). Glycosuria is a marker of tubular dysfunction and may be used to detect tubular lesion and CKD progression. The aim of this study was to evaluate the prevalence and prognostic value of glycosuria at the time of diagnosis in primary glomerulopathies (PG). METHODS: We conducted a 24-month retrospective study in patients diagnosed with PG in our center between 2009 and 2020. We excluded diabetic patients, use of SGLT2 inhibitors, transplant patients, and secondary GD. Patients were divided in two groups according to their glycosuria status at diagnosis. RESULTS: We studied 115 patients. Global prevalence of glycosuria was 10% (n=11) and membranous nephropathy (MN) had the highest prevalence (n=5, 17.9%). We found that patients with glycosuria had higher serum creatinine (2.4 vs. 1.2 mg/dL, p=0.030), higher albuminuria (4.8 vs. 1.9 g/g, p=0.004), and lower serum albumin (2.3 vs. 3.2 g/dL, p=0.021). We did not find association with histological prognostic factors. At the end of follow-up, patients with glycosuria had higher prevalence of the composite outcome of stage 5D CKD or 50% increase in basal SCr (45.5% vs. 17.3%, p=0.037). In patients with MN, results were similar but we were able to find an association of glycosuria with more severe interstitial fibrosis and tubular atrophy (25.0 vs. 0.0 %, p=0.032). CONCLUSION: Ten percent of our patients with PG have glycosuria. Glycosuria at the time of diagnosis was associated with more severe clinical presentation and worst renal outcome. The association with higher albuminuria suggests that tubular function has an impact on the severity and outcomes of PG.

Primary Hyperaldosteronism: A Rare Cause of Malignant Hypertension with Thrombotic Microangiopathy in a Kidney Transplant Recipient.

Thrombotic microangiopathy (TMA) is a rare disease that presents with haemolysis and organ damage. The kidney is one of the main affected organs, and TMA is associated with serious complications and increased mortality. In transplanted patients, TMA is even less common and has a variety of possible causes, including thrombotic thrombocytopenic purpura (TTP) and haemolytic-uremic syndrome (HUS), infections, drugs, autoimmune disease, tumours, and malignant hypertension. Transplant-related causes, such as antibody-mediated rejection, calcineurin inhibitors, and viral infections, need to be considered as well. The authors report a rare case of TMA in a kidney transplant recipient, whose investigation revealed malignant hypertension secondary to primary hyperaldosteronism.

Outcomes of Living Kidney Donor Candidates and Living Kidney Recipient Candidates with JC Polyomavirus and BK Polyomavirus Viruria.

INTRODUCTION: Recent data have emerged about a protective association between JCV viruria and chronic kidney disease (CKD). Material and Methods. Single-center retrospective cohort study; 230 living kidney donors (LKD) candidates and 59 potential living kidney receptors (LKR) were enrolled. Plasma and urinary JCV and BKV viral loads were measured in all LKD candidates and in nonanuric LKR candidates. Twenty-six living kidney transplant surgeries were performed. LKR were followed in order to evaluate BKV and JCV viremia and urinary viral shedding after KT. RESULTS: In LKD candidates, JCV viruria was negatively associated with proteinuria of >200 mg/24 hours (JC viruric LKD: 12.5% vs JCV nonviruric LKD: 26.7%, p=0.021, OR:0.393; 95% CI: 0.181-0.854). In a multivariate analysis, LKD candidates with JCV viruria had a lower risk of proteinuria of >200 mg/24 hours (p=0.009, OR: 0.342, 95% CI: 0.153-0.764), in a model adjusted for age, gender, presence of hypertension, and eGFR <80 mL/min. Prevalence of JCV viruria was higher in LKD candidates when compared with LKR candidates (40.0% vs 1.7%, p < 0.001). Among the 26 LKR, 14 (53.8%) KT patients evolved with JCV viruria; 71.4% received a graft from a JCV viruric donor. CONCLUSION: Our data corroborate the recent findings of an eventual protective association between JCV viruria and kidney disease, and we extrapolated this concept to a South European population.

Preeclampsia as an Inaugural Manifestation of Primary Hyperparathyroidism: A Case Report.

Primary hyperparathyroidism is an endocrine disorder characterized by hypercalcemia and elevated or inappropriately normal levels of parathyroid hormone. The diagnosis is based on a biochemical evaluation, and a neck ultrasound is the first choice during pregnancy to access the parathyroid glands. Manifestations during pregnancy are rare and can be present with life-threatening complications, so the diagnosis is challenging. The conservative treatment is limited, and there is not enough data about its safety and efficacy during pregnancy. Surgery is the only curative treatment, and a parathyroidectomy performed during the second or third trimesters is considered safe. Recently, some authors suggested an association between primary hyperparathyroidism and preeclampsia. We describe a case of preeclampsia with severe features at 27 weeks of gestational age. The severity of the preeclampsia motivated an early termination of the pregnancy by cesarean section. During the postpartum period, the patient presented life-threatening complications, such as severe hypercalcemia and acute pancreatitis. An ultrasound exam found two parathyroid nodules, suggestive of parathyroid adenomas. The patient recovered after the pharmacological correction of the calcemia levels.

O hiperparatiroidismo primário é um distúrbio endócrino caraterizado pela elevação do cálcio sérico associada a níveis de paratormona elevados ou inapropriadamente normais. O diagnóstico é baseado em análises bioquímicas, e, na gravidez, o exame de imagem de primeira linha é a ecografia cervical. É uma doença rara na gravidez, e pode se apresentar com complicações ameaçadoras de vida, pelo que o seu diagnóstico é desafiante. O tratamento médico disponível é limitado, havendo poucos dados relativos à sua eficácia e segurança na gravidez. A cirurgia é o único tratamento curativo, e pode ser realizada no segundo ou terceiro trimestres. Tem sido descrita uma relação entre hiperparatiroidismo primário e pré-eclâmpsia. Apresenta-se um caso de uma grávida de 27 semanas com pré-eclâmpsia com critérios de gravidade, o que obrigou ao término da gravidez por cesariana. Verificou-se agravamento clínico no período pós-parto, com aparecimento de complicações graves, tais como hipercalcemia grave e pancreatite aguda. Ecograficamente, constataram-se duas massas paratiróideias sugestivas de adenomas da paratiroide. A doente recebeu tratamento médico, e teve melhora apenas após a correção dos níveis de cálcio sérico.

Preeclampsia as an inaugural manifestation of primary hyperparathyroidism: A case report / Pré-eclâmpsia como manifestação inaugural de hiperparatiroidismo primário: Um caso clínico

Abstract Primary hyperparathyroidism is an endocrine disorder characterized by hypercalcemia and elevated or inappropriately normal levels of parathyroid hormone. The diagnosis is based on a biochemical evaluation, and a neck ultrasound is the first choice during pregnancy to access the parathyroid glands. Manifestations during pregnancy are rare and can be present with life-threatening complications, so the diagnosis is challenging. The conservative treatment is limited, and there is not enough data about its safety and efficacy during pregnancy. Surgery is the only curative treatment, and a parathyroidectomy performed during the second or third trimesters is considered safe. Recently, some authors suggested an association between primary hyperparathyroidism and preeclampsia. We describe a case of preeclampsia with severe features at 27 weeks of gestational age. The severity of the preeclampsiamotivated an early termination of the pregnancy by cesarean section. During the postpartum period, the patient presented life-threatening complications, such as severe hypercalcemia and acute pancreatitis. An ultrasound exam found two parathyroid nodules, suggestive of parathyroid adenomas. The patient recovered after the pharmacological correction of the calcemia levels.

Resumo O hiperparatiroidismo primário é umdistúrbio endócrino caraterizado pela elevação do cálcio sérico associada a níveis de paratormona elevados ou inapropriadamente normais. O diagnóstico é baseado em análises bioquímicas, e, na gravidez, o exame de imagem de primeira linha é a ecografia cervical. É uma doença rara na gravidez, e pode se apresentar com complicações ameaçadoras de vida, pelo que o seu diagnóstico é desafiante. O tratamento médico disponível é limitado, havendo poucos dados relativos à sua eficácia e segurança na gravidez. A cirurgia é o único tratamento curativo, e pode ser realizada no segundo ou terceiro trimestres. Tem sido descrita uma relação entre hiperparatiroidismo primário e pré-eclâmpsia. Apresenta-se um caso de uma grávida de 27 semanas com pré-eclâmpsia com critérios de gravidade, o que obrigou ao término da gravidez por cesariana. Verificou-se agravamento clínico no período pós-parto, com aparecimento de complicações graves, tais como hipercalcemia grave e pancreatite aguda. Ecograficamente, constataram-se duas massas paratiróideias sugestivas de adenomas da paratiroide. A doente recebeu tratamento médico, e teve melhora apenas após a correção dos níveis de cálcio sérico.

Osmotic Demyelination Syndrome in a Patient with Hypokalemia but No Hyponatremia.

Osmotic demyelination syndrome (ODS) is characterized by loss of myelin in various parts of the central nervous system. It is mainly caused by a rapid correction of hyponatremia, although other factors that may cause rapid rise in serum osmolality can also be associated with its development. Its prognosis is poor and the recovery rate is unknown. The authors report a rare case of a patient with multiple risk factors for ODS, without hyponatremia, who developed ODS and surprisingly recovered. This case report highlights the importance of recognizing risk factors for the development of ODS, even if the main one is not present.