Arterioureteral fistula and refractory fatal pseudo-aneurysm in a patient receiving kidney transplantation.

Arterioureteral fistula represents a rare yet consequential urological complication characterized by persistent and refractory urinary tract bleeding. Its emergence typically involves aneurysm formation, presenting significant life-threatening implications. Nonetheless, its infrequency contributes to sparse documentation of incidences in post-kidney transplant recipients, thereby fostering numerous uncertainties concerning associated risks. A 67-year-old male patient, afflicted with end-stage renal failure and a history of urinary tract infection, underwent a living donor kidney transplant four months prior. Complications involving intraoperative bleeding necessitated the prolonged placement of a ureteral stent post-surgery. Subsequently, he experienced an abrupt onset of ureteral bleeding accompanied by shock, later diagnosed via contrast-enhanced computed tomography as pseudo-aneurysm formation in the right external iliac artery proximal to the allograft renal artery anastomosis, in conjunction with a fistula formation involving the donor ureter. Despite repeated attempts at intervention with covered stenting, the aneurysm persisted and proved refractory to resolution. Tragically, seven months later, the aneurysm ruptured, culminating in the demise of the patient. Our report details a case involving perioperative complications following kidney transplantation, persistent bacteriuria, and prolonged ureteral stenting, ultimately leading to the development of an arterioureteral fistula. Despite undergoing stent graft insertion as an intervention, the patient succumbed to aneurysm rupture associated with the arterioureteral fistula. This condition, though rare, can prove fatal following kidney transplantation. Consequently, future endeavors in this domain necessitate an emphasis on optimizing risk management, refining diagnostic approaches, and devising more effective therapeutic strategies to mitigate such complications.

A case of destination therapy for post-fulminant myocarditis with myelodysplastic syndrome.

We encountered a 64-year-old woman who experienced fulminant myocarditis and underwent treatment with veno-arterial extracorporeal membrane oxygenation and Impella CP support. Subsequently, she underwent a device upgrade to Impella 5.5 and received continuous hemodiafiltration for 3 months. During mechanical circulatory support, she developed refractory anemia and thrombocytopenia, leading to a diagnosis of myelodysplastic syndrome. Following the removal of the devices, she no longer required blood transfusions. She received HeartMate 3 left ventricular assist device implantation as a destination therapy indication despite the presence of myelodysplastic syndrome. She was successfully managed by aspirin-free antithrombotic therapy without any hemocompatibility-related adverse events for 4 months after index discharge on foot. We present a patient with a unique and rare presentation, wherein HeartMate 3 was implanted and successfully managed without aspirin to prevent bleeding complications associated with myelodysplastic syndrome.

Pegylated-liposomal Doxorubicin-induced Glomerular Thrombotic Microangiopathy.

Pegylated liposomal doxorubicin (PLD) has emerged as a recent innovation within the realm of antineoplastic agents, distinguished by its incorporation of doxorubicin within the liposomal bilayer. Given the low risk of cardiotoxicity, the clinical use of PLD has been expanding. We encountered a patient who underwent extended PLD therapy for recurrent malignancy and subsequently developed PLD-associated thrombotic microangiopathy, which was diagnosed by a detailed pathophysiological assessment. This case underscores the importance of considering thrombotic microangiopathy as a potential differential diagnosis in patients presenting with unexplained hypertension and renal impairment during prolonged PLD monotherapy.

Pembrolizumab-induced Acute Tubulointerstitial Nephritis Accompanying Fanconi Syndrome and Type 1 Renal Tubular Acidosis.

Pembrolizumab, an immune checkpoint inhibitor, is used to treat a variety of refractory malignancies. However, these agents are sometimes associated with immune-related adverse events. A 71-year-old woman received pembrolizumab-integrated chemotherapy to treat her recurrent mandibular gingival cancer. Five months after stopping pembrolizumab, she developed acute tubulointerstitial nephritis associated with Fanconi syndrome and type 1 renal tubular acidosis, which resolved with steroid therapy. We experienced a case of pembrolizumab-induced Fanconi syndrome and type 1 renal acidosis. We recommend follow-up of the tubular function in addition to the renal function even after discontinuation of pembrolizumab.

A Clinical Diagnosis of Laminopathy without Systolic Dysfunction: When Does Nuclei Malformation Start?

Nuclear shape abnormalities in laminopathy are well known to occur in patients with cardiac systolic dysfunction. However, those in patients without systolic dysfunction are still unclear. We herein report a 42-year-old man who presented with advanced atrioventricular block without systolic dysfunction. Genetic testing identified a laminopathic mutation, c.497G>C, and an endocardial biopsy was performed. The hyperperfine structure on electron microscopy showed malformation of the nuclei, euchromatic nucleoplasm, and partial existence of heterochromatin clumps. Intrusion of heterochromatin into the nuclear fibrous lamina was observed. Cardiomyocyte nuclear shape abnormalities were observed before the progression of systolic dysfunction.

Nephrotic syndrome induced by aortic regurgitation with Takayasu arteritis: an autopsy case with long-term clinical follow-up.

Takayasu arteritis is a rare, chronic, and large-vessel vasculitis involving the aorta and its branches in a complex autoimmune reaction. Takayasu arteritis sometimes complicates aortic regurgitation and chronic kidney disease, but rarely accompanies nephrotic syndrome. We had a patient with Takayasu arteritis and concomitant aortic regurgitation. She had nephrotic syndrome that was refractory to immunosuppressive therapy but was promptly improved after surgical aortic valve replacement. In her kidney biopsy, glomeruli had mild mesangial proliferative changes without immune complex deposition. Her proteinuria remained negative until the recurrence of aortic regurgitation due to perivalvular leakage. Seventeen years after the surgery, she died suddenly. In her kidney autopsy, the arteriolar showed severe hyalinosis and the glomerulus showed mesangial proliferative changes with segmental mesangiolysis. Severe aortic regurgitation may have altered renal hemodynamics and caused glomerular lesions, resulting in nephrotic syndrome. We should be aware of the rare but critical comorbidity of nephrotic syndrome in patients with Takayasu arteritis and concomitant aortic regurgitation.

Urinary levels of cortisol but not catecholamines are associated with those of 8-hydroxy-2'-deoxyguanosine in uncomplicated primary hypertension.

OBJECTIVES: The relationships between stress hormones and oxidative DNA damage have not yet been explored in human hypertension. We investigated the associations of urinary levels of cortisol or catecholamines with those of 8-hydroxy-2'-deoxyguanosine, a marker of oxidative DNA damage in primary hypertension. METHODS: Untreated 156 primary hypertensives without apparent cardiovascular diseases were entered into the study. Following blood sampling after an overnight fast, 24-h blood pressure monitoring and 24-h urinary sampling were performed simultaneously to determine 24-h averaged values for blood pressure and urinary levels of cortisol, catecholamines and 8-hydroxy-2'-deoxyguanosine. RESULTS: Urinary cortisol significantly correlated positively with urinary 8-hydroxy-2'-deoxyguanosine in all studied participants (r = 0.334, P < 0.001). Contrary, either urinary adrenaline or urinary noradrenaline did not significantly correlate with urinary 8-hydroxy-2'-deoxyguanosine (r = 0.050, P = 0.553 or r = 0.063, P = 0.435). Additionally, the positive association of urinary cortisol with urinary 8-hydroxy-2'-deoxyguanosine remained highly significant after the adjustments for multiple confounders of oxidative stress such as age, gender, body mass index, smoking status, 24-h blood pressure, C-reactive protein and estimated glomerular filtration rate (partial r = 0.323, P < 0.001), although only approximately 10% of the variance in urinary cortisol was attributable to differences in urinary 8-OHdG (partial r2 = 0.104). Thus, our data indicate that cortisol but not catecholamines could at least partially contribute to the occurrence of oxidative DNA damage in primary hypertensives. CONCLUSION: The present study suggested the possibility that the overactivation of hypothalamic-pituitary-adrenal axis rather than sympathoadrenal system could enhance oxidative stress and attendant DNA oxidation in uncomplicated primary hypertension.

Serum Angiopoetin-2 Levels in Pediatric Patients After Fontan Operation.

Angiopoietin-2 is associated with chronic inflammation and angiogenesis, but its activity after Fontan operation in pediatric patients remains uncertain. We compared serum angiopoietin-2 levels in pediatric patients after Fontan operation versus those with congenital heart disease as a control group. A total of 185 patients (median age 7 [3 to 12] years, 106 males) were included, consisting of 140 in the Fontan group and 45 in the control group. Serum angiopoietin-2 levels were significantly higher in the Fontan group (7,670 vs 2,351 pg/ml, p <0.001). In the Fontan group, a serum angiopoietin-2 level ≥3.9 of common logarithm was an independent risk factor for death or Fontan-related adverse events with an adjusted hazard ratio of 6.25 (95% confidence interval 1.64 to 23.9, p = 0.007). In preoperative variables, desaturation was independently associated with increased serum angiopoietin-2 levels after Fontan operation (p = 0.047). In conclusion, serum angiopoietin-2 levels were elevated in the pediatric phase after Fontan operation. In Fontan patients, a higher serum angiopoietin-2 level was an independent risk factor for death or Fontan-related adverse events. The clinical implication of measuring and monitoring serum angiopoietin-2 levels in this cohort requires further investigation.

Prognostic Impact of the Increase in Cardiac Troponin Levels during Tafamidis Therapy in Patients with Transthyretin Cardiac Amyloidosis.

BACKGROUND: Recent clinical trials have demonstrated that tafamidis (Pfizer Inc., New York, NY, USA) reduced all-cause mortality and the number of cardiovascular hospitalizations compared with placebo in patients with transthyretin cardiac amyloidosis. However, the optimal surrogate markers during tafamidis treatment remain unknown. METHODS: Consecutive patients with transthyretin cardiac amyloidosis who received tafamidis in our institute between May 2019 and December 2022 were retrospectively evaluated. The prognostic impact of an increase in troponin I levels during tafamidis therapy was evaluated. RESULTS: A total of 18 patients (median age 77 years, 84% male) were included. For 14-month tafamidis therapy on median, cardiac troponin I levels increased in five patients. The cumulative incidence of all-cause hospitalization was significantly higher in the troponin-increased group than in the others (100% versus 33%, p < 0.0001). Troponin increase was independently associated with the cumulative incidence of all-cause hospitalization with an adjusted hazard ratio of 5.14 (95% confidence interval 1.02-25.9, p = 0.048). CONCLUSIONS: The increase in cardiac troponin levels may be a reasonable surrogate marker of response to tafamidis therapy in patients with transthyretin cardiac amyloidosis.

Novel Scoring System to Risk Stratify Patients Receiving Durable Left Ventricular Assist Device From J-MACS Registry Data.

BACKGROUND: Recently, destination therapy (DT) was approved in Japan, and patients ineligible for heart transplantation may now receive durable left ventricular assist devices (LVADs). Several conventional risk scores are available, but a risk score that is best to select optimal candidates for DT in the Japanese population remains unestablished.Methods and Results: A total of 1,287 patients who underwent durable LVAD implantation and were listed for the Japanese registry for Mechanically Assisted Circulatory Support (J-MACS) were eligible for inclusion. Finally, 494 patients were assigned to the derivation cohort and 487 patients were assigned to the validation cohort. According to the time-to-event analyses, J-MACS risk scores were newly constructed to predict 3-year mortality rate, consisting of age, history of cardiac surgery, serum creatinine level, and central venous pressure to pulmonary artery wedge pressure ratio >0.71. The J-MACS risk score had the highest predictability of 3-year death compared with other conventional scores in the validation cohort, including HeartMate II risk score and HeartMate 3 risk score. CONCLUSIONS: We constructed the J-MACS risk score to estimate 3-year mortality rate after durable LVAD implantation using large-scale multicenter Japanese data. The clinical utility of this scoring to guide the indication of DT should be validated in the next study.

Prognostic Impact of Polypharmacy following Trans-Catheter Aortic Valve Replacement.

BACKGROUND: Polypharmacy in elderly patients with various comorbidities is associated with mortality and morbidity. However, the prognostic impact of polypharmacy in patients with severe aortic stenosis receiving trans-catheter aortic valve replacement remains unknown. METHODS: Patients with severe aortic stenosis who received trans-catheter aortic valve replacement between 2015 and 2022 and were followed up at our institute following index discharge were included in this retrospective study. The impact of polypharmacy, which was defined as medication numbers ≥10 at index discharge, upon 2-year all-cause death was investigated. RESULTS: A total of 345 patients (median age 85 [83, 89] years old, 99 (29%) men) were included. Median medication number was 9 (7, 10) at the index discharge and 88 (26%) were classified as receiving polypharmacy. Frailty index, including mini-mental state examination and CSHA score, were not significantly different between those with and without polypharmacy (p > 0.05 for both). Polypharmacy was associated with higher 2-year cumulative mortality with an adjusted hazard ratio of 21.4 (95% confidence interval, 6.06-74.8, p < 0.001). As a sub-analysis, the number of cardiovascular medications was not associated with 2-year mortality (hazard ratio 1.12, 95% confidence interval 0.86-1.48, p = 0.46), whereas a higher number of non-cardiovascular medications was associated with an incremental increase in 2-year mortality with a hazard ratio of 1.39 (95% confidence interval, 1.15-1.63, p < 0.001). CONCLUSIONS: In elderly patients with severe aortic stenosis, polypharmacy was associated with worse short-term survival following trans-catheter aortic valve replacement. Prognostic implication of aggressive intervention to decrease the amount of medication among those receiving TAVR requires further prospective studies.

Implication of serum growth differentiation factor-15 level in patients with renal diseases.

BACKGROUND: The synthesis of growth differentiation factor-15 (GDF-15) is induced by inflammation, hypoxia, and oxidative stress and is receiving great interest as a predictive biomarker for cardiovascular disease. However, its detailed impact on patients with renal disease remains uncertain. METHODS: Patients who underwent renal biopsy for evaluation of renal disease between 2012 and 2017 in our institute were prospectively included. Serum GDF-15 levels were measured and its association with baseline characteristics and its impact on the 3-year composites of renal prognosis (composites of > 1.5 folds of serum creatinine and renal replacement therapy) were investigated. RESULTS: A total of 110 patients (64 [42, 73] years old, 61 men) were included. The median serum GDF-15 level at baseline was 1885 (998, 3496) pg/mL. A higher serum GDF-15 level was associated with comorbidities including diabetes mellitus, anemia, renal impairment, and pathologic features including crescent formation, hyaline degeneration, and interstitial fibrosis (p < 0.05 for all). Serum GDF-15 level was a significant predictor of 3-year composite renal outcomes with an odds ratio per 100 pg/mL of 1.072 (95% confidence interval 1.001-1.103, p = 0.036) after adjustment for potential confounders. CONCLUSIONS: Serum GDF-15 levels were associated with several renal pathological features and renal prognosis in patients with renal diseases.

Prognostic impact of renal sinus fat accumulation in patients with chronic kidney disease.

BACKGROUND: Obesity is associated with the development and progression of chronic kidney disease (CKD). In the general population, the amount of renal sinus fat was associated with hypertension and renal impairment. However, its impact upon those with CKD remains uncertain. METHODS: We prospectively included CKD patients who underwent renal biopsy and simultaneously measured their renal sinus fat volume. The association between the percentage of renal sinus fat volume, which was adjusted by kidney volume, and renal outcomes was investigated. RESULTS: A total of 56 patients (median 55 years old, 35 men) were included. Among baseline characteristics, age and visceral fat volume were positively correlated with the percentage of renal sinus fat volume (p < 0.05). The percentage of renal sinus fat volume was associated with hypertension (p < 0.01) and tended to be associated with max glomerular diameter (p = 0.078) and urine angiotensinogen creatinine ratio (p = 0.064) after adjustment with several clinical factors. The percentage of renal sinus fat volume was significantly associated with a future > 50% decline in estimated glomerular filtration rate (p < 0.05). CONCLUSIONS: Among those with CKD who required renal biopsy, the amount of renal sinus fat was associated with poor renal outcomes accompanied by systemic hypertension.

Impact of urine cyclic AMP relative to plasma arginine vasopressin on response to tolvaptan in patients with chronic kidney disease and heart failure.

BACKGROUND: The clinical utility of tolvaptan in chronic kidney disease (CKD) patients with heart failure remains uncertain. The level of urine cyclic adenosine monophosphate (AMP) relative to plasma arginine vasopressin (AVP) indicates the residual function of the collecting ducts in response to AVP stimulation and might be a key to predicting response of tolvaptan. METHODS: CKD patients who were hospitalized to treat their congestive heart failure refractory to conventional loop diuretics were considered to receive tolvaptan and included in this prospective study. The impact of urine cyclic AMP/plasma AVP ratio for prediction of response to tolvaptan, which was defined as any increase in urine volume at day 7 from day 0, was investigated. RESULTS: A total of 30 patients (median 75 years old, 24 men, and median estimated glomerular filtration rate 14.4 mL/min/1.73 m2) were included. As compared to baseline, urine volume increased at day 7 in 17 responders, whereas urine volume decreased at day 7 in 13 non-responders. Baseline urine cyclic AMP/plasma AVP ratio distributed between 0.25 and 4.01 with median 1.90. The urine cyclic AMP/plasma AVP ratio was a significant predictor of response to tolvaptan, which was adjusted for 6 potential confounders with a cutoff of 1.24. CONCLUSIONS: Baseline urine cyclic AMP/plasma AVP ratio is an independent predictor of response to tolvaptan in advanced CKD patients with heart failure. CLINICAL TRIAL REGISTRATION: UMIN000022422.

Malignant Hypertension and Bilateral Primary Aldosteronism.

Malignant hypertension triggers incremental renin activity, whereas primary aldosteronism suppresses such activity. We encountered a patient with malignant hypertension refractory to multiple anti-hypertensive agents. Repeated neurohormonal assessments, instead of a single one, eventually uncovered trends in an incremental aldosterone concentration, ranging from 221 up to 468 pg/mL, with a decline in the renin activity from 2.3 to <0.2 ng/mL/h. Adrenal venous sampling confirmed bilateral aldosterone secretion. Following the diagnosis of bilateral primary aldosteronism, we initiated a mineralocorticoid receptor antagonist, which improved his blood pressure. Repeated neurohormonal assessments are encouraged to correctly diagnose underlying primary aldosteronism with malignant hypertension.

Impact of Goreisan upon aquaporin-2-incorporated aquaresis system in patients with congestive heart failure.

We often encounter patients with congestive heart failure refractory to conventional diuretics therapy, and Kampo Goreisan is receiving great concern to mediate body water balance particularly for such a cohort. However, its detailed biological mechanism remains uncertain. We had two hospitalized patients with congestive heart failure receiving tolvaptan. Following the administration of Goreisan, both urine cyclic adenosine monophosphate concentration and urine aquaporin-2 concentration decreased, accompanied by incremental diluted urine volume. Although further studies are warranted to establish therapeutic strategy, Goreisan might be a promising therapeutic tool for those with congestive heart failure refractory to conventional diuretics including tolvaptan, via pleiotropic effects including suppression of aquaporin-incorporated water reabsorption system.

Impact of the elevated angiopoietin-2 levels during Impella support on the short-term prognosis.

Elevated serum angiopoietin-2 levels in patients with acute myocardial infarction-related cardiogenic shock with and without intra-aortic balloon pump as well as acute decompensated heart failure are associated with short-term mortality. However, its prognostic impact in patients with cardiogenic shock supported by Impella-incorporated mechanical circulatory support (MCS) remains unknown. Patients who received temporary MCS (Impella alone or Impella and veno-arterial extracorporeal membrane oxygenation) in our institute between August 2018 and January 2022 were included in this prospective study. The serum levels of angiopoietin-2 were measured just before and following the initiation of temporary MCS therapy. Association between the levels of serum angiopoietin-2 and 30-day mortality was investigated. A total of 38 patients (median 72 years old, 63% men) were included. The median levels of serum angiopoetin-2 tended to decrease from baseline to 4 days following the initiation of temporary MCS from 5.2 (3.3, 10.5) ng/mL to 4.8 (2.7, 6.8) ng/mL (p = 0.132). A higher angiopoietin-2 (> 6.8 ng/mL) following the initiation of temporary MCS was associated with higher 30-day mortality (89.7% versus 44.4%, p = 0.0048) with an odds ratio 18.946 (95% confidence interval 1.624-218.695, p = 0.018) adjusted for potential confounders. A higher serum angiopoietin-2 level following the initiation of Impella-incorporated temporary MCS, instead of baseline angiopoetin-2 level, was associated with higher short-term mortality.

Initial report of percutaneous left atrial appendage closure in hemodialysis patients with atrial fibrillation and high risk of bleeding in Japan.

In the countries like Japan where anticoagulation is not recommended in hemodialysis patients, the feasibility of percutaneous left atrial appendage closure (LAAC) in hemodialysis patients with non-valvular atrial fibrillation (NVAF) accompanying high risks of thromboembolic stroke and bleeding remains unknown. Peri-procedural and 45-day clinical outcomes following LAAC using WATCHMAN system, which were performed in our institute between Jun 2020 and April 2022 according to the Japanese Circulation Society guidelines, were retrospectively compared between those with and without hemodialysis. 118 patients (median 79 years, 81 men) consisting of 25 hemodialysis patients and 93 non-hemodialysis patients were included. CHADS score was 3 (2, 4) in the hemodialysis patients and 3 (2, 4) in the non-hemodialysis patients (p = 0.98). HAS-BREAD score was 4 (3, 5) in the hemodialysis patients and 3 (2, 3) in the non-hemodialysis patients (p < 0.001). All procedures were successful, except for a non-hemodialysis patient with a larger left atrial appendage. There were no major complications during index hospitalization and 45-day observational period, except for a hemodialysis patient with suspected bleeding and a non-hemodialysis patient who died due to cardiac amyloidosis. LAAC seems to be feasible in hemodialysis patients with high risks of thromboembolic events and bleedings.

Initial experience of hypoxia-inducible factor prolyl hydroxylase inhibitors in patients with heart failure and renal anemia.

Hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitors might improve renal anemia maintaining fewer cardiovascular complications. However, its safety and efficacy, as well as its impact on inflammatory biomarkers, in heart failure patients remain unknown. We initiated HIF-PH inhibitors in 13 patients with chronic heart failure and renal anemia (median age 77 years, median estimated glomerular filtration rate 24.9 mL/min/1.73m2) between September 2021 and February 2022. There were no drug-related complications, except for a patient who had a headache and hot flash, resulting in discontinuation of HIF-PH inhibitor at 3 months. Among 10 patients who continued HIF-PH inhibitors for over 3 months, hemoglobin levels increased significantly (median from 9.6 g/dL to 10.7 g/dL, p = 0.004) and hepcidin-25 levels tended to decrease (median from 11.5 ng/mL to 3.0 ng/mL, p = 0.294) at 3-month follow-up. In conclusion, HIF-PH inhibitors might be safe and effective for the treatment of renal anemia in patients with chronic heart failure.

Clinical insight of remote dielectric sensing-guided congestive heart failure management in outpatient clinic.

Management of congestion by assessing the degree of systemic/pulmonary congestion and adjusting the dose of diuretics is of great importance to improve mortality and morbidity in patients with congestive heart failure, whereas it is sometimes challenging particularly in the outpatient clinic, where careful and daily assessment of congestion is impossible. We had a patient with congestive heart failure due to cardiac amyloidosis, whose congestion was successfully managed by referencing repeated non-invasive quantification of pulmonary congestion using a recently-introduced remote dielectric sensing system as well as appropriate adjustment of diuretics doses at once per month outpatient clinic. Remote dielectric sensing might be a promising supportive tool to guide the management of congestion in the outpatient clinic. Learning objective: Remote dielectric sensing system, which is a novel non-invasive wearable device to quantify the degree of pulmonary congestion easily and quickly within a minute, would be a promising supportive tool to guide titration of the dose of diuretics in patients with congestive heart failure in outpatient clinic follow up.