Role of High-sensitivity C-reactive Protein in Future Cardiovascular Events in Hemodialysis Patients.

BACKGROUND/AIM: The pathogenesis of cardio-vascular disease (CVD) in hemodialysis (HD) patients involves inflammation and oxidative stress. High-sensitivity C-reactive protein (hs-CRP) is an established inflammatory biomarker associated with CVD. Several studies have suggested that the inflammatory biomarker pentraxin-3 (PTX-3) and the oxidative stress-related biomarker soluble lectin-like low-density lipoprotein receptor-1 (sLOX-1) are novel biomarkers for CVD in non-HD populations. This study aimed to clarify the association of these established and novel biomarkers with future cardiovascular (CV) events in HD patients. PATIENTS AND METHODS: This was a single-center prospective cohort study that included 255 HD patients. The primary outcome was the composite of nonfatal and fatal CV events. The event-free survival rate between the two groups according to the median plasma level of each biomarker at baseline was evaluated using the Kaplan-Meier method. The risk for CV events at elevated levels of each biomarker was estimated using Cox proportional hazard model. RESULTS: We observed 44 CV events during the median follow-up period of 743 days. The event-free survival rate significantly differed between the two groups in hs-CRP but not in PTX-3 or sLOX-1. The unadjusted hazard ratio (HR) for CV events in patients with hs-CRP levels above the median was 2.63 [95% confidence interval (CI)=1.37-5.02]. The HR remained significant after adjusting for age, sex, history of CVD, and diabetes (HR=2.30; 95%CI=1.20-4.43). CONCLUSION: In HD patients, hs-CRP may have a predictable role for future CV events, whereas PTX-3 and sLOX-1 do not.

Neutrophil depletion attenuates acute renal injury after exhaustive exercise in mice.

Prolonged intense exercise induces acute renal injury; however, the precise mechanism remains unclear. We investigated the effects of neutrophil depletion in male C57BL/6J mice. Male C57BL/6J mice were divided into four groups: sedentary with control antibody; sedentary with antineutrophil antibody; exhaustive exercise with control antibody; and exhaustive exercise with antineutrophil antibody. Antineutrophil (1A8) or control antibody was administered i.p. to the mice before they ran on a treadmill. Plasma levels of creatinine and blood urea nitrogen (BUN) were measured. Renal histology was assessed 24 h after exhaustive exercise, and the concentration of kidney injury molecule (KIM)-1 was measured using an enzyme-linked immunosorbent assay. The expression levels of inflammatory cytokines were measured using qRT-PCR. Furthermore, NADPH oxidase activity and the hydrogen peroxide concentration in the kidney were measured. Immediately after exhaustive exercise, plasma BUN was significantly increased, but creatinine was not. The increase in BUN after exercise was suppressed by 1A8 treatment. The pathological changes manifested as congested and swollen glomeruli and nuclear infiltration after exhaustive exercise. These changes were suppressed by treatment with the 1A8 antibodies. The KIM-1 concentration increased after exhaustive exercise but was reduced by the 1A8 antibodies. Treatment with the 1A8 antibody also decreased exhaustive exercise-induced inflammation and reactive oxygen species levels in the kidney. These results suggest that neutrophils contribute to exercise-induced acute renal injury by regulating inflammation and oxidative stress.

Hypoxia-inducible Factor-1α Suppresses the Innate Immune Response in Cultured Human Proximal Tubular Cells.

BACKGROUND/AIM: Retinoic acid-inducible gene (RIG)-I like receptors (RLRs) are expressed on renal proximal tubular epithelial cells (RPTECs) in viral nephropathy, indicating the presence of RLR-mediated innate immune responses in RPTECs. Hypoxia is also known to affect innate immunity. This study investigated the effects of hypoxia, and hypoxia-inducible factor (HIF) on innate immunity in RPTECs. MATERIALS AND METHODS: Primary human RPTECs were cultured under normoxic or hypoxic conditions and treated with a synthetic analog of double-stranded RNA (polyIC). The expression levels of RIG-I and MDA5, as RLRs, and IFNß, IL6, and TNFα, as inflammatory mediators were evaluated using quantitative reverse transcription-polymerase chain reaction, western blotting, and lactate dehydrogenase activity (LDH) assays. To further investigate the role of hypoxia, a small interfering RNA was used to knockdown HIF1α. RESULTS: Under normoxic conditions, polyIC increased RIG-I, MDA5, and IFNß mRNA expression in RPTECs by, 9.4±0.4-, 10.8±0.5-, and 4.0±0.1-fold, respectively, compared to control, and by 5.4±0.1-, 7.4±0.1-, and 2.4±0.3-fold, respectively, under hypoxic conditions, the rate of increase was lower than that under normoxic conditions (p<0.01). Protein expression showed a similar trend. Under hypoxic conditions, polyIC treatment with HIF1α knockdown in RPTECs increased RIG-I, MDA5, and IFNß mRNA expression by 3.1±0.5-, 2.9±0.4-, and 6.1±0.4-fold, respectively, and cytotoxicity, demonstrated by LDH assay, was increased compared to that without knockdown (all p<0.01). CONCLUSION: Hypoxia suppresses polyIC-induced RLRs mediated innate immune responses in RPTECs via HIF1α.

Dietary Intake of Polyunsaturated Fatty Acids and Diabetic Nephropathy: Cohort Analysis of the Tsugaru Study.

BACKGROUND/AIM: Diabetic nephropathy (DN) is the leading cause of end-stage renal failure and its incidence continues to increase. To decrease this, a countermeasure from an early stage is required. This is a DN stage 2 observation study that analyzed the results of a concurrent dietary survey in the Tsugaru study and discussed the relationship between dietary intake of n-3 fatty acid and DN. PATIENTS AND METHODS: Patients with stage 2 DN and aged 20 years or older in the Tsugaru region of Aomori Prefecture were enrolled. We examined the association between urinary albumin excretion (UAE) at enrollment and 36 months later and n-3PUFA intake obtained from a dietary survey. RESULTS: Of the 317 subjects at enrollment, 234 were followed for 36 months, of whom 123 were able to complete the dietary survey. After 36 months of follow-up of these 123 subjects, 28 were in remission and 18 had progressed. Correlations between UAE at 36 months and each of the parameters were examined and UAE at enrollment showed a positive correlation (r=0.4224, p<0.001); correlations between eicosapentaenoic acid (EPA)/arachidonic acid (AA), EPA+docosahexaenoic acid/AA, and n-6/n-3 and UAE at 36 months were weak. As shown by multiple regression analysis, the factor influencing UAE after 36 months was UAE at enrollment. CONCLUSION: Concerning the relationship between fatty acid intake balance and UAE, the previously reported renoprotective effect of n-3 fatty acids could not be demonstrated.

Relationship Between Cardiovascular Events and Serum Lipid and Plasma Fatty Acid Profile in Maintenance Hemodialysis Patients With Diabetic Mellitus.

BACKGROUND/AIM: Cardiovascular disease (CVD) is a frequent complication in hemodialysis (HD) patients, especially when the underlying disease is diabetes mellitus (DM). In this study, we investigated cardiovascular events and lipid and fatty acid profile in maintenance HD patients with diabetic kidney disease (DKD). PATIENTS AND METHODS: The subjects were 123 patients undergoing HD at Oyokyo Kidney Research Institute Hirosaki Hospital, who were considered to have DKD as the underlying cause of dialysis induction. Among these patients, the lipid and fatty acid profile were examined in two groups, CVD group (n=53) and non-CVD group (n=70), according to the presence or absence of a history of cardiovascular events (coronary artery disease, stroke, arteriosclerosis obliterans, valvular disease, and aortic disease). For serum lipid profile, the levels of total-cholesterol (T-C), triglycerides (TG), high density lipoprotein-cholesterol (HDL-C), and low density lipoprotein-cholesterol (LDL-C) were measured, and for fatty acid balance, 24 fractions of fatty acid composition in plasma total lipids were measured. These markers were compared between the CVD and non-CVD groups. RESULTS: The levels of T-C and TG were significantly lower in the CVD group compared with the non-CVD group (147.7±36.9 mg/dl vs. 159.2±35.6 mg/dl, p<0.05, 120.2±65.7 mg/dl vs. 143.8±124.4 mg/dl, p<0.05). In the plasma fatty acid composition, alpha-linolenic acid (ALA) and docosapentaenoic acid (DPA) were significantly lower in the CVD group compared with the non-CVD group (0.74±0.26 wt% vs. 0.84±0.31 wt%, p<0.05; 0.61±0.21 wt% vs. 0.70±0.30 wt%, p<0.05). CONCLUSION: Abnormal fatty acid balance, especially low levels of ALA and DPA, rather than serum lipids, are more likely the factors associated with cardiovascular events in maintenance HD patients with underlying DKD.

Valacyclovir-associated acute kidney injury and encephalopathy in an elderly woman with normal kidney function: a case report.

A 72-year-old Japanese woman was treated by 3000 mg/day of valacyclovir for the herpes zoster in her left back. She had been treated as hypertension with no renal insufficiency. In two days, she visited an emergency room of a regional stroke care center with dysarthria, dexterity disorder and gait disturbance. Neither head CT nor MRI found intracranial lesions, then, laboratory tests revealed that her serum creatinine level was 4.63 mg/dL. She was transferred and admitted to our hospital on the following day and received hemodialysis under the diagnosis of AKI due to acyclovir accompanied with encephalopathy. Afterward, her serum concentration of acyclovir revealed as 44 µg/mL, which is extremely high. Her neurological symptom disappeared in parallel with the decrease of serum concentration of acyclovir. She received 3 sessions of hemodialysis and discharged on the 8th day of admission with almost normal renal function and no neurological sequela.

Pulmonary surfactants and the respiratory-renal connection in steroid-sensitive nephrotic syndrome of childhood.

Steroid-sensitive nephrotic syndrome (SSNS) in childhood is usually due to minimal change disease (MCD). Unlike many glomerular conditions, SSNS/MCD is commonly precipitated by respiratory infections. Of interest, pulmonary inflammation releases surfactants in circulation which are soluble agonists of SIRPα, a podocyte receptor that regulates integrin signaling. Here, we characterized this pulmonary-renal connection in MCD and performed studies to determine its importance. Children with SSNS/MCD in relapse but not remission had elevated plasma surfactants and urinary SIRPα. Sera from relapsing subjects triggered podocyte SIRPα signaling via tyrosine phosphatase SHP-2 and nephrin dephosphorylation, a marker of podocyte activation. Further, addition of surfactants to MCD sera from patients in remission replicated these findings. Similarly, nasal instillation of toll-like receptor 3 and 4 agonists in mice resulted in elevated serum surfactants and their binding to glomeruli triggering proteinuria. Together, our data document a critical pulmonary-podocyte signaling pathway involving surfactants and SIRPα signaling in SSNS/MCD.

Macrophage Depletion Attenuates Acute Renal Damage after Exhaustive Exercise in Mice.

Exhaustive exercise is known to induce acute renal damage. However, the precise mechanisms remain unclear. We investigated the effects of macrophage depletion on exhaustive exercise-induced acute renal damage. Male C57BL/6 J mice were divided into four groups: sedentary with control liposome (n=8), sedentary with clodronate liposome (n=8), exhaustive exercise with control liposome (n=8), and exhaustive exercise with clodronate liposome (n=8). Mice were treated with clodronate liposomes or control liposomes intraperitoneally for 48 h before undergoing exhaustive exercise. Renal function and renal histology were tested at 24 h. The expression levels of kidney injury molecule (KIM)-1 and inflammatory cytokines in kidney tissues were measured by quantitative RT-PCR, and KIM-1 concentration was semi-quantified by immunostaining. As a result, exhaustive exercise increased macrophage infiltration into the kidney. However, clodronate reduced it. Although exhaustive exercise resulted in an increase in KIM-1 mRNA expression levels and concentration, injection of clodronate liposome reduced it. In addition, TUNEL positive apoptotic cells were increased after exercise, but significantly reduced by clodronate. Clodronate liposome treatment also decreased the mRNA expression levels of inflammatory cytokines (TNF-α, IL-1ß, and IL-6) in the kidney after exhaustive exercise. These results suggest that macrophages play a critical role in increasing renal damage by regulating inflammation.

Nintedanib-Induced Renal Thrombotic Microangiopathy.

Nintedanib is a unique tyrosine kinase inhibitor used to suppress fibrosis in patients with idiopathic pulmonary fibrosis (IPF). Nintedanib has been shown to suppress multiple processes of fibrosis, thereby reducing the rate of lung function decline in patients with IPF. Since vascular endothelial growth factor is one of this agent's targets, nephrotoxicity, including renal thrombotic microangiopathy (TMA), is a possible major adverse effect. However, only 2 previous cases of nintedanib-induced renal TMA have been published. Our patient was an 83-year-old man with IPF. As adverse effects including liver enzyme level elevation, diarrhoea, anorexia, and nephrotoxicity developed, the nintedanib dosage was reduced after 9 months. The digestive symptoms resolved promptly, but the proteinuria and reduced kidney function remained. Although the kidney injury had improved to some extent, we performed a percutaneous renal biopsy. The biopsy revealed typical TMA findings such as microaneurysms filled with pale material, segmental double contours of glomerular basement membranes, and intracapillary foam cells. After discontinuation of nintedanib, the patient's nephrotoxicity improved. Nintedanib-induced renal TMA is reversible and is possibly dose-dependent. Here, we report the clinical course of our case and review the characteristics of nintedanib-induced renal TMA.

Rivaroxaban attenuates cardiac hypertrophy by inhibiting protease-activated receptor-2 signaling in renin-overexpressing hypertensive mice.

Rivaroxaban (Riv), a direct factor Xa (FXa) inhibitor, exerts anti-inflammatory effects in addition to anticoagulation. However, its role in cardiovascular remodeling is largely unknown. We tested the hypothesis that Riv attenuates the progression of cardiac hypertrophy and fibrosis induced by continuous activation of the renin-angiotensin system (RAS) in renin-overexpressing hypertensive transgenic (Ren-Tg) mice. We treated 12-week-old male Ren-Tg and wild-type (WT) mice with a diet containing Riv (12 mg/kg/day) or a regular diet for 4 weeks. After this, FXa in plasma significantly increased in Ren-Tg mice compared with WT mice, and Riv inhibited this increase. Left ventricular wall thickness (LVWT) and the area of cardiac fibrosis evaluated by Masson's trichrome staining were greater in Ren-Tg mice than in WT mice, and Riv decreased them. Cardiac expression levels of the protease-activated receptor (PAR)-2, tumor necrosis factor-α, transforming growth factor (TGF)-ß1, and collagen type 3 α1 (COL3A1) genes were all greater in Ren-Tg mice than in WT mice, and Riv attenuated these increases. To investigate the possible involvement of PAR-2, we treated Ren-Tg mice with a continuous subcutaneous infusion of 10 µg/kg/day of the PAR-2 antagonist FSLLRY for 4 weeks. FSLLRY significantly decreased LVWT and cardiac expression of PAR-2, TGF-ß1, and COL3A1. In isolated cardiac fibroblasts (CFs), Riv or FSLLRY pretreatment inhibited the FXa-induced increase in the phosphorylation of extracellular signal-regulated kinases. In addition, Riv or FSLLRY inhibited FXa-stimulated wound closure in CFs. Riv exerts a protective effect against cardiac hypertrophy and fibrosis development induced by continuous activation of the RAS, partly by inhibiting PAR-2.

Eosinophilic arthritis-A case report.

Eosinophilic arthritis is characterized by arthritis, eosinophilia, normal laboratory findings, unresponsiveness to nonsteroidal anti-inflammatory drugs and favorable response to corticosteroids. We diagnosed a female patient with this rare disease.

PolyIC Induces Retinoic Acid-inducible Gene-I and Melanoma Differentiation-associated Gene 5 and Modulates Inflammation in Podocytes.

BACKGROUND/AIM: Viral infection often exacerbates proteinuria, which has been suggested to be due to antiviral responses of podocytes. We examined the effect of polyinosinic-polycytidylic acid (polyIC) on the expression of retinoic acid-inducible gene-I (RIG-I) and melanoma differentiation-associated gene 5 (MDA5) in differentiated human podocytes in culture. MATERIALS AND METHODS: The podocytes were treated with 2 ng/ml to 500 µg/ml of polyIC for 3 to 36 h, and also transfected with siRNA against RIG-I and MDA5. F-actin staining was performed to assess actin reorganization. RESULTS: PolyIC induced the expression of RIG-I and MDA5 in dose- and time-dependent manner, accompanied with interferon-ß (IFN-ß) and interleukin-6 (IL-6) up-regulation and actin reorganization. Temporal knockdown of RIG-I by siRNA decreased IFN-ß expression, while MDA5 siRNA inhibited IFN-ß and IL-6 expression. Actin reorganization was attenuated by RIG-I and MDA5 knockdown. CONCLUSION: RIG-I and MDA5 may play a role in the antiviral responses of podocytes.

Peritoneal Dialysis with Marked Pneumoperitoneum.

Pneumoperitoneum, the presence of free air within the peritoneal cavity, is often caused by the perforation of gas-containing viscus and commonly requires surgical treatment. However, in patients with peritoneal dialysis, free air is commonly seen on X-ray. We present the case of a patient with peritoneal dialysis with marked pneumoperitoneum. A 75-year-old Japanese male with end-stage renal disease due to antineutrophil cytoplasmic antigen-associated vasculitis had been receiving continuous ambulatory peritoneal dialysis for 9 years. He had a poor appetite and general malaise without abdominal pain or fever. These symptoms gradually worsened, and he was hospitalized. At the time of admission, chest X-ray revealed bilateral free air in the abdomen. Subsequent computed tomography of the abdomen revealed marked pneumoperitoneum. Peritonitis due to perforation of the digestive tract was considered; however, the absence of abdominal pain, fever, and turbidity of dialysis drainage indicated that peritonitis was unlikely. Insufficient air venting during continuous ambulatory peritoneal dialysis bag replacement was suspected. The bag was carefully changed, resulting in a gradual decrease in the free air. We encountered a patient with continuous ambulatory peritoneal dialysis who had significant free air in the abdominal cavity in the absence of peritonitis. The source of the air was determined to be the dialysis bag due to insufficient venting during replacement. This case underscores the importance of instructing patients with continuous ambulatory peritoneal dialysis on the thorough removal of air from the bag during replacement.

Survey on attitudes toward brain-dead and living donor transplantation in medical students: a cross-sectional study in Japan.

BACKGROUND: Although a shortage in organ donation is a critical problem in Japan, understanding of and attitude toward organ transplantation in medical students have not been sufficiently reported. METHODS: Between 2013 and 2018, we surveyed 702 medical students in the fifth-year clinical training in our urology department. The survey concerned (1) knowledge of Japanese transplantation law, which was amended in 2010, and (2) whether the respondents had an organ donor card and had agreed to be a brain-dead donor or a living donor in kidney transplantation with specific reasons for their choices. RESULTS: All 702 students answered the survey. Of 657 students who provided valid answers to the first section, 402 (61%) recognized the amendment to the Japanese transplantation law, and only 11 (1.7%) fully understood its contents. Of 702 students, 194 (28%) had a donor card, 384 (55%) agreed to be a brain-dead donor, and 529 (75%) agreed to be a living donor in kidney transplantation. As the specific reasons for their choices, only a few medical students wrote reasons based on their medical standpoint, and more students wrote emotional reasons. CONCLUSIONS: The understanding of and attitude toward organ transplantation were not remarkably high in the fifth-year medical students in Japan. To solve the donor shortage problem, education about organ transplantation may need to be more effective.

Natriuretic peptides in acute kidney injury - A sojourn on parallel tracks?

OBJECTIVE: The focus of this review was to elicit the mechanistic logic of the experimental and clinical study designs of natriuretic peptides (NP) in acute kidney injury (AKI) and to understand their respective outcomes. METHODS: Online search of PubMed and manual review of articles. Randomized trials, observational and physiologic studies of NPs and AKI were extracted. Rationale, design and study outcomes were analyzed. RESULTS: In experimental models of AKI, infusion of NP prevented post-ischemic fall in renal blood flow (RBF) or improvement in RBF, GFR, diuresis and natriuresis and demonstrated anti-inflammatory properties. NPs were most effective in the early stages of AKI, also in established phase of AKI but their effectiveness were limited to the time of infusion. Hypotension was a major side-effect. Based on these observations, preliminary clinical studies were performed which demonstrated improved urine output, RBF and GFR and reduced need for dialysis. However, randomized, controlled trials failed to demonstrate improvement in dialysis-free survival in different cohorts and study designs. Although NPs reduced the incidence of AKI in the postoperative period in cardiac surgery, it was not associated with improved long-term survival. In contrast to randomized trials, meta-analysis reported favorable results. CONCLUSIONS: Reasons for the divergence of experimental and clinical outcomes of NPs in AKI are discussed in this review article.

Henoch-Schönlein Nephritis Manifesting with Purpura 15 years after Diagnosis of IgA Nephropathy.

Henoch-Schönlein nephritis or immunoglobulin A (IgA) vasculitis is characterized by purpura, arthralgia, abdominal pain, and glomerulonephritis with glomerular IgA deposition. Notably, the presence of purpura is essential to diagnose this disease. We report the case of a patient in whom proteinuria and haematuria were detected during screening tests and he was diagnosed with IgA nephropathy at 20 years of age. Corticosteroids were administered for 7 years and were subsequently tapered. At 35 years of age, he noticed purpura on his lower extremities and was diagnosed with anaphylactoid purpura. Following the appearance of purpura, urinalysis revealed an increase in urinary protein levels from 0.7 g/g creatinine (Cr) to 1.4 g/gCr, and his serum Cr levels increased from 1.1 mg/dL to 1.35 mg/dL. Two months later purpura subsided, and his urinary protein level and serum Cr level were restored to the former levels. Although the cause remains unknown, an interval may occasionally be observed between the appearance of purpura and urinary abnormalities. However, to our knowledge to date, a 15-year interval is the longest interval, in such cases, reported in the literature.

Rivaroxaban, a Direct Factor Xa Inhibitor, Ameliorates Hypertensive Renal Damage Through Inhibition of the Inflammatory Response Mediated by Protease-Activated Receptor Pathway.

Background An enhanced renin-angiotensin system causes hypertensive renal damage. Factor Xa not only functions in the coagulation cascade but also activates intracellular signaling through protease-activated receptors ( PAR ). We investigated the effects of rivaroxaban, a factor Xa inhibitor, on hypertensive renal damage in hypertensive mice overexpressing renin (Ren-TG). Methods and Results The 12- to 16-week-old Ren-TG and wild-type mice were orally administered with or without 6 or 12 mg/kg of rivaroxaban for 1 or 4 months. Plasma factor Xa was significantly increased in the Ren-TG compared with the wild-type mice and was reduced by 12 mg/kg of rivaroxaban ( P<0.05). Urinary albumin excretion (UAE) was higher in the nontreated 8-month-old Ren-TG than in the wild-type mice (69.6±29 versus 20.1±8.2 µg/day; P<0.01). Treatment with 12 mg/kg of rivaroxaban for 4 months decreased the UAE to 38.1±13.2 µg/day ( P<0.01). Moreover, rivaroxaban treatment attenuated histologic changes of glomerular hypertrophy, mesangial matrix expansion, effacement of the podocyte foot process, and thickened glomerular basement membrane in the Ren-TG. The renal expression of PAR -2 was increased in the Ren-TG, but was inhibited with rivaroxaban treatment. In vitro study using the human podocytes showed that the expressions of PAR -2 and inflammatory genes and nuclear factor--κB activation were induced by angiotensin II stimulation, but were inhibited by rivaroxaban. PAR -2 knockdown by small interfering RNA also attenuated the PAR -2-related inflammatory gene expressions. Conclusions These findings indicate that rivaroxaban exerts protective effects against angiotensin II-induced renal damage, partly through inhibition of the PAR -2 signaling-mediated inflammatory response.

The Role of Uric Acid in Acute Kidney Injury.

Studies have demonstrated the presence of a strong association between serum uric acid (SUA) and acute kidney injury (AKI) consistently across several disease models. Exposure to SUA at different time periods and concentrations has reliably resulted in AKI whether assessed by conventional or novel biomarkers or by kinetic estimated glomerular filtration rate (KeGFR) engineered for non-steady dynamic states. In experimental models, moderate hyperuricemia was associated with an absence of intrarenal crystals, manifestation of tubular injury, macrophage infiltration, and increased expression of inflammatory mediators that were attenuated with uric acid lowering therapy with rasburicase, a recombinant urate oxidase. In a pilot clinical trial, treatment with rasburicase was associated with a decreased incidence of AKI and evidence for less renal structural injury. Lowering SUA also improved KeGFR and estimated glomerular filtration rate in 2 separate studies. SUA has also been linked to diabetic nephropathy, hypertension, cardiovascular disease, chronic kidney disease, metabolic syndrome, and their mechanisms of action share many common traits. In this article, we explore the evidence for the causal role of SUA in AKI using Bradford Hill criteria as a guideline with data integration from related fields.

Impact of distance between donor and recipient hospitals on cadaveric kidney transplantation outcomes.

BACKGROUND: The impact of distance between donor and recipient hospitals on outcomes in cadaveric kidney transplantations is unknown. We investigated the association between inter-hospital distance and outcomes in cadaveric kidney transplantations in Japan. METHODS: We retrospectively analyzed 363 cadaveric kidney transplantations between 2002 and 2017 in Japan. Inter-hospital distance, graft transport time, total ischemic time (TIT), and graft survival were compared between our hospital and national transplantation cohort in Japan. Estimated glomerular filtration rate (eGFR) 1 month and 1 year after transplantation was compared between cadaveric and living-donor kidney transplantations in our hospitals. Additionally, inter-hospital distances among the seven geographical regions in Japan were assessed. RESULTS: There were 12 and 351 cadaveric kidney transplantations at our hospital and in Japan, respectively. Mean inter-hospital distance at our hospital (217 ± 121 km) was significantly longer than that of the national cohort (53 ± 80 km; P < 0.001). Mean TIT and graft survival for our hospital and national cohort were 539 ± 200 min and 91% and 491 ± 193 min and 81%, respectively. Mean eGFRs 1 year after cadaveric and living-donor transplantations at our hospitals were comparable (47 ± 16 vs. 47 ± 15 mL/min/1.73 m2). The comparison among seven regions in Japan indicated a regional difference in inter-hospital distance with an association between area (km2) and inter-hospital distance (km). CONCLUSIONS: Despite the longer inter-hospital distance at our hospital, TIT and transplant outcomes were acceptable in our cases. In addition, geographical inequity in graft allocation in Japan was suggested.