Isolated arterial mucoid intimal thickening lesion in early post-transplant kidney allograft biopsies.

INTRODUCTION: Thrombotic microangiopathy (TMA) on kidney biopsy shows a variable combination of features: arterial mucoid intimal thickening, acellular closure of glomerular capillary loops, fragmented red blood cells, fibrin thrombi, and arterial fibrinoid necrosis. However, some early post-transplant kidney biopsies show only arterial mucoid intimal thickening. We aimed to elucidate the importance of this finding. METHODS: We identified 19 biopsies showing isolated arterial mucoid intimal thickening and compared them with 22 bona fide TMA biopsies identified based on the pathological findings (excluding rejection) (2011-2020). Additionally, delayed graft function (DGF) (n = 237), and no DGF (control, n = 1314) groups were included for survival analysis. RESULTS: Seven of 19 cases with isolated arterial mucoid intimal thickening showed peripheral blood schistocytes but no other systemic features of TMA. Eight patients underwent adjustments in maintenance immunosuppression (mainly calcineurin inhibitors). None of the cases progressed to full-blown TMA on consecutive biopsies. The overall and death-censored graft survival rates in this group were comparable to the DGF group, but significantly better than the TMA group (P = .005 and .04, respectively). CONCLUSIONS: Isolated arterial mucoid intimal thickening in early post-transplant biopsies may be an early/mild form of TMA, probably requiring adjustment in immunosuppressive regimen. Careful exclusion of known causes of TMA, and donor-derived arterial injury are important.

Anorexia Assessed by Simplified Nutritional Appetite Questionnaire and Association with Medication in Older Patients Undergoing Hemodialysis.

Anorexia is a common symptom in older patients undergoing hemodialysis (HD) and has become a serious problem in dialysis facilities with the aging of patients. Polypharmacy, defined as the prescription of several medications, is known to cause drug-induced anorexia. Although polypharmacy is also common in older patients undergoing HD, only a few studies have examined the association between anorexia and polypharmacy. This study used the Simplified Nutritional Appetite Questionnaire for Japanese Elderly (SNAQ-JE) to evaluate patients' appetite, and examined its association with medications. This cross-sectional study included 233 patients (aged ≥65 years) who underwent HD in October 2021. Among the 233 patients (median age, 73.0 [interquartile range (IQR), 69.0-80.5] years; men, 57.3%; median dialysis vintage, 62.0 [IQR, 30.0-122.0] months), 116 and 117 were classified into the poor (SNAQ-JE total score ≤14) and good (>14) appetite groups, respectively. Although the total number of medications prescribed was not significantly different between the two groups (p = 0.12), the number of antihypertensive drugs was significantly lower (p = 0.03), and that of sleeping medications was significantly higher (p = 0.002) in the poor appetite group. Multivariable logistic regression analysis showed that the number of sleeping medications was associated with poor appetite (odds ratio, 2.08; 95% confidence interval, 1.32-3.27; p < 0.001). The findings suggest that the number of sleeping medications is an important contributing factor to poor appetite in older patients undergoing HD. A proper and regular review of prescriptions may be necessary to improve anorexia.

Association between annual variability of potassium levels and prognosis in patients undergoing hemodialysis.

BACKGROUND: Hyperkalemia and hypokalemia are associated with mortality in patients undergoing hemodialysis. However, there are few reports on the association between potassium level fluctuations and mortality. We retrospectively investigated the association between serum potassium level variability and mortality in patients undergoing hemodialysis. METHODS: This study was conducted at a single center. Variability in serum potassium levels was evaluated using the standard deviation of potassium level from July 2011 to June 2012, and its association with prognosis was examined by following up the patients for 5 years. Serum potassium variability was assessed as the coefficient of variation, and the statistical analysis was performed after log transformation. RESULTS: Among 302 patients (mean age 64.9 ± 13.3; 57.9% male; and median dialysis vintage 70.5 months [interquartile range, IQR 34-138.3]), 135 died during the observation period (median observation period 5.0 years [2.3-5.0]). Although the mean potassium level was not associated with prognosis, serum potassium level variability was associated with prognosis, even after adjustments for confounding factors such as age and dialysis time (hazard ratio: 6.93, 95% confidence interval [Cl] 1.98-25.00, p = 0.001). After the adjustments, the coefficient of variation of potassium level in the highest tertile (T3) showed a higher relative risk for prognosis than that in T1 (relative risk: 1.98, 95% CI 1.19-3.29, p = 0.01). CONCLUSIONS: Variability in serum potassium levels was associated with mortality in patients undergoing hemodialysis. Careful monitoring of potassium levels and their fluctuations is necessary for this patient population.

Prognoses of patients undergoing hemodialysis administered 23-valent pneumococcal polysaccharide versus 13-valent pneumococcal protein conjugate vaccines.

INTRODUCTION: Sequential vaccination with the 13-valent pneumococcal protein conjugate vaccine (PCV13) and 23-valent pneumococcal polysaccharide vaccine (PPSV23) is recommended for patients undergoing hemodialysis; however, evidence for the efficacy of these pneumococcal vaccines for patients undergoing hemodialysis is limited to a single dose. We aimed to evaluate the prognosis of patients undergoing hemodialysis who received vaccination with PPSV23 alone versus sequential vaccination with PCV13 and PPSV23. METHODS: Patients undergoing hemodialysis who were vaccinated with PPSV23 alone (PPSV23 group) or PCV13 followed by PPSV23 (PCV13+PPSV23 group) between 2014 and 2016 were included; the observation period was three years from the first injection. Patients who underwent hemodialysis between 2011 and 2012 were included as controls. After propensity score matching using age, sex, dialysis vintage, diabetes history, pneumonia history, and serum albumin and creatinine levels, survival analysis was performed. RESULTS: The study included 89, 71, and 319 patients in the PPSV23, PCV13+PPSV23, and control groups, respectively. After propensity score matching, the PPSV23 and control group 1 (79 patients each) and the PCV13+PPSV23 and control group 2 (61 patients each) were compared. Significant differences were observed in the survival rate between the PPSV23 group and control group 1 (p = 0.005) but not between the PCV13+PPSV23 group and control group 2. Pneumonia-related mortality in the two vaccinated groups did not differ significantly during the observation period. CONCLUSIONS: Patients who received PPSV23 had a favorable prognosis; however, no positive effect was demonstrated in the PCV13+PPSV23 group.

Parameters affecting prognosis after hemodialysis withdrawal: experience from a single center.

INTRODUCTION: Withdrawal from maintenance hemodialysis is unavoidable in some patients due to their poor general condition; however, their survival days vary depending on their health status. The factors associated with life prognosis in the terminal phase in patients undergoing hemodialysis remain unclear. METHODS: Patients who died after withdrawal from hemodialysis between 2011 and 2021 at Nagasaki Renal Center were included. Patient background data were collected, and the association between the patients' clinical features and survival duration was analyzed. RESULTS: The withdrawal group included 174 patients (79.8 ± 10.8 years old; 50.6% male; median dialysis vintage, 3.6 years). The most common reason for withdrawal (95%) was that hemodialysis was more harmful than beneficial because of the patient's poor general condition. The median time from withdrawal to death was 4 days (interquartile range, 3-10 days). Multivariable Cox proportional regression analysis showed that oral nutrition (hazard ratio (HR), 1.98; 95% confidence interval (CI), 1.12-3.50; P = 0.03), hypoxemia (HR, 2.32; 95% CI, 1.55-3.47; P < 0.01), ventilator use (HR, 0.26; 95% CI, 0.11-0.58; P < 0.01), and pleural effusion (HR, 1.54; CI, 1.01-2.37; P = 0.04) were associated with increased survival duration. In contrast, antibiotics and vasopressor administration were not associated with the survival duration. CONCLUSION: In this study, we explored the parameters affecting the survival of patients who withdrew from hemodialysis. Physicians could use our results to establish more accurate predictions, which may help the patient and their family to emotionally accept and implement the desired care plan.

Association between hospital acquired disability and post-discharge mortality in patients after living donor liver transplantation.

BACKGROUND: Hospital-acquired disability (HAD) in patients who undergo living donor liver transplantation (LDLT) is expected to worsen physical functions due to inactivity during hospitalization. The aim of this study was to explore whether a decline in activities of daily living from hospital admission to discharge is associated with prognosis in LDLT patients, who once discharged from a hospital. METHODS: We retrospectively examined the relationship between HAD and prognosis in 135 patients who underwent LDLT from June 2008 to June 2018, and discharged from hospital once. HAD was defined as a decline of over 5 points in the Barthel Index as an activity of daily living assessment. Additionally, LDLT patients were classified into four groups: low or high skeletal muscle index (SMI) and HAD or non-HAD. Univariate and multivariate Cox proportional hazard models were used to evaluate the association between HAD and survival. RESULTS: HAD was identified in 47 LDLT patients (34.8%). The HAD group had a significantly higher all-cause mortality than the non-HAD group (log-rank: p < 0.001), and in the HAD/low SMI group, all-cause mortality was highest between the groups (log-rank: p < 0.001). In multivariable analysis, HAD was an independent risk factor for all-cause mortality (hazard ratio [HR]: 16.54; P < 0.001) and HAD/low SMI group (HR: 16.82; P = 0.002). CONCLUSION: HAD was identified as an independent risk factor for all-cause mortality suggesting that it could be a key component in determining prognosis after LDLT. Future larger-scale studies are needed to consider the overall new strategy of perioperative rehabilitation, including enhancement of preoperative physiotherapy programs to improve physical function.

Comparison of bone microstructures via high-resolution peripheral quantitative computed tomography in patients with different stages of chronic kidney disease before and after starting hemodialysis.

Chronic kidney disease (CKD) negatively affects bone strength; however, the osteoporotic conditions in patients with CKD are not fully understood. Moreover, the changes in bone microstructure between pre-dialysis and dialysis are unknown. High-resolution peripheral quantitative computed tomography (HR-pQCT) reveals the three-dimensional microstructures of the bone. We aimed to evaluate bone microstructures in patients with different stages of CKD. This study included 119 healthy men and 40 men admitted to Nagasaki University Hospital for inpatient education or the initiation of hemodialysis. The distal radius and tibia were scanned with HR-pQCT. Patient clinical characteristics and bone microstructures were evaluated within 3 months of initiation of hemodialysis (in patients with CKD stage 5 D), patients with CKD stage 4-5, and healthy volunteers. Cortical bone parameters were lower in the CKD group than in healthy controls. Tibial cortical and trabecular bone parameters (cortical thickness, cortical area, trabecular volumetric bone mineral density, trabecular-bone volume fraction, and trabecular thickness) differed between patients with CKD stage 5 D and those with CKD stage 4-5 (p < 0.01). These differences were also observed between patients with CKD stage 5 and those with CKD stage 5 D (p < 0.017), but not between patients with CKD stage 4 and those with CKD stage 5, suggesting that the bone microstructure rapidly changed at the start of hemodialysis. Patients with CKD stage 5 D exhibited tibial microstructural impairment compared with those with CKD stage 4-5. HR-pQCT is useful for elucidation of the pathology of bone microstructures in patients with renal failure.

Life prognosis and renal relapse after induction therapy in Japanese patients with proliferative and pure membranous lupus nephritis.

OBJECTIVE: We aimed to compare life prognosis and renal relapse after induction therapy in proliferative (PLN) and pure membranous LN (MLN). METHODS: We retrospectively analysed the cases of 140 of 172 patients with LN who underwent a renal biopsy at our hospital or community hospitals from 1993 to 2016. We determined the complete response (CR) rate at 12 months after the patients had started induction therapy, and we evaluated the predictive factors for CR, life prognosis and renal relapse in PLN and pure MLN. We defined PLN as International Society of Neurology and the Renal Pathology Society (ISN/RPS) Class III or IV and MLN as ISN/RPS Class V. RESULTS: The renal pathology of 99 (70.7%) patients was classified as PLN, and that of the other 41 (29.3%) patients as MLN. Fifty patients (50.5%) with PLN and 22 patients (53.7%) with MLN achieved a CR at 12 months. A multivariate analysis showed that a lower index of chronicity in PLN and a higher total haemolytic complement (CH50) level in MLN were predictive factors for achieving a CR at 12 months. A Kaplan-Meier analysis showed that the life prognosis (P = 0.93) and renal relapse (P = 0.52) were not significantly different between PLN and MLN. CONCLUSIONS: The predictive factors for a CR at 12 months post-induction therapy were index of chronicity in PLN and CH50 level in MLN. There were no significant differences in life prognosis or renal relapse between PLN and MLN in the achievement of a CR at 12 months post-induction therapy.

Association between the psoas muscle index and hospitalization for pneumonia in patients undergoing hemodialysis.

BACKGROUND: Although muscle mass loss and pneumonia are common and crucial issues in hemodialysis (HD) patients, few reports have focused on their association, which remains unclear. This study assessed the association between skeletal muscle mass and the incidence of pneumonia in HD patients using the psoas muscle index (PMI). METHODS: This retrospective study included 330 patients on HD who were treated at a single center between July 2011 and June 2012. The observation period was between July 2011 and June 2021. Demographic, clinical, and HD data were collected, and the associations between PMI and hospitalization due to bacterial pneumonia were evaluated using Cox proportional hazards models adjusted for patients' background data. Additionally, the correlation between patient characteristics and PMI was evaluated using multivariable linear regression. RESULTS: Among 330 patients (mean age, 67.3 ± 13.3; 56.7% male; median dialysis vintage 58 months, (interquartile range [IQR] 23-124), 79 were hospitalized for pneumonia during the observation period (median observation period was 4.5 years [IQR 2.0-9.1]). The multivariable Cox proportional analysis, which was adjusted for age, sex, dialysis vintage, diabetes mellitus, and stroke history and considered death as a competing risk, indicated that decreased PMI/(standard deviation) was closely associated with the development of pneumonia (hazard ratio: 0.67, 95% confidence interval: 0.47-0.95, p = 0.03). CONCLUSIONS: Skeletal muscle mass was associated with the development of pneumonia in patients on HD and could be a useful marker for the risk of pneumonia.

Lower serum calcium and pre-onset blood pressure elevation in cerebral hemorrhage patients undergoing hemodialysis.

BACKGROUND: Asymptomatic blood pressure (BP) elevation may be associated with cerebral hemorrhage (CH); however, few studies have investigated this association. We aimed to evaluate BP elevation before CH in hemodialysis (HD) patients and elucidate its associated factors. METHODS: We reviewed HD patients treated for CH at our hospital between 2008 and 2019 (CH group). The control group comprised HD patients treated at Nagasaki Renal Center between 2011 and 2012. Data were obtained from medical records and three consecutive HD charts, made immediately before CH. HD1 was the session closest to onset, followed by HD2 and HD3. Systolic and mean BP were evaluated at the beginning of HD, and factors associated with BP elevation were investigated. RESULTS: The CH and control groups included 105 and 339 patients, respectively. Systolic and mean BP at HD1 were significantly higher than those at baseline (HD2 + HD3) in the CH group by 5 and 3 mmHg, respectively (P < 0.001). Multiple linear regression analysis showed that lower calcium levels were significantly associated with BP elevation in the CH group (P < 0.05). The CH group was sub-divided by June 2013; the latter group had lower calcium levels (9.2 mg/dL) and a marked systolic BP difference from baseline (+ 10 mmHg) compared with the former (9.5 mg/dL and - 4 mmHg). CONCLUSION: Asymptomatic BP elevation was observed in HD patients before CH; this elevation was associated with lower serum calcium levels and observed more frequently in the recent era. The precise mechanism underlying this effect remains unknown.

Urinary Liver-Type Fatty Acid-Binding Protein Predicts Residual Renal Function Decline in Patients on Peritoneal Dialysis

BACKGROUND Liver-type fatty acid-binding protein (L-FABP) is a predictive marker for the early detection of acute kidney injury; however, less is known about how useful it is for predicting residual renal function (RRF) decline in patients on peritoneal dialysis (PD). MATERIAL AND METHODS The study subjects were 35 patients on PD who underwent multiple peritoneal equilibration tests (PETs) between October 2011 and October 2019. Urinary L-FABP levels were analyzed with enzyme-linked immunosorbent assay. The relationship between baseline clinical data, including urinary L-FABP levels and the subsequent annual rate of renal Kt/V decline, was investigated. RESULTS The median follow-up duration was 11 months and the rate of renal Kt/V decline was 0.29/y. Compared with outcomes in the group with renal Kt/V preservation, renal Kt/V decline was associated with both high daily levels of urinary protein excretion (0.60 g/d [range, 0.50-0.87] vs. 0.36 g/d [range, 0.19-0.48]; P=0.01) and high daily levels of urinary L-FABP excretion (111.2 mg/d [range, 76.1-188.6] vs. 61.5 mg/d [range, 35.7-96.0]; P=0.002). Multiple logistic regression analysis showed that only high daily levels of urinary L-FABP excretion were independently associated with renal Kt/V decline (odds ratio 1.03, 95% confidence interval 1.00-1.05; P=0.001). Furthermore, higher daily levels of urinary L-FABP excretion were significantly correlated with the higher annual rate of renal Kt/V decline (r=0.71, P<0.001). CONCLUSIONS We demonstrated that daily levels of urinary L-FABP are associated with RRF decline in patients on PD. The results of the present study indicate that assessment of urinary L-FABP levels may help predict RRF decline in patients on PD.

Transplantation of a kidney with a heterozygous mutation in the SLC22A12 (URAT1) gene causing renal hypouricemia: a case report.

BACKGROUND: Renal hypouricemia (RHUC) is a genetic disorder caused by mutations in the SLC22A12 gene, which encodes the major uric acid (UA) transporter, URAT1. The clinical course of related, living donor-derived RHUC in patients undergoing kidney transplantation is poorly understood. Here, we report a case of kidney transplantation from a living relative who had an SLC22A12 mutation. After the transplantation, the recipient's fractional excretion of UA (FEUA) decreased, and chimeric tubular epithelium was observed. CASE PRESENTATION: A 40-year-old man underwent kidney transplantation. His sister was the kidney donor. Three weeks after the transplantation, he had low serum-UA, 148.7 µmol/L, and elevated FEUA, 20.8% (normal: < 10%). The patient's sister had low serum-UA (101.1 µmol/L) and high FEUA (15.8%) before transplant. Suspecting RHUC, we performed next-generation sequencing on a gene panel containing RHUC-associated genes. A heterozygous missense mutation in the SLC22A12 gene was detected in the donor, but not in the recipient. The recipient's serum-UA level increased from 148.7 µmol/L to 231.9 µmol/L 3 months after transplantation and was 226.0 µmol/L 1 year after transplantation. His FEUA decreased from 20.8 to 11.7% 3 months after transplantation and was 12.4% 1 year after transplantation. Fluorescence in situ hybridization of allograft biopsies performed 3 months and 1 year after transplantation showed the presence of Y chromosomes in the tubular epithelial cells, suggesting the recipient's elevated serum-UA levels were owing to a chimeric tubular epithelium. CONCLUSIONS: We reported on a kidney transplant recipient that developed RHUC owing to his donor possessing a heterozygous mutation in the SLC22A12 (URAT1) gene. Despite this mutation, the clinical course was not problematic. Thus, the presence of donor-recipient chimerism in the tubular epithelium might positively affect the clinical course, at least in the short-term.

IgM monoclonal gammopathy with heavy-and-light-chain amyloidosis resembling fibrillary glomerulonephritis determined by tandem mass spectrometry: a case report.

BACKGROUND: Fibrillary glomerulonephritis (FGN) is distinguished from amyloidosis by thicker fibrils and the lack of staining with histochemical dyes typically reactive with amyloid. However, congophilic FGN has been proposed recently and adding laser microdissection followed by mass spectrometry (LMD/MS) to conventional pathological methods would be helpful to diagnose FGN. Here, we report a patient initially diagnosed with FGN whose final pathological diagnosis was changed to immunoglobulin heavy-and-light-chain amyloidosis (AHL) after LMD/MS. CASE PRESENTATION: A 75-year-old male developed nephrotic syndrome. Protein electrophoresis showed IgM κ type M proteinemia and he was diagnosed with IgM monoclonal gammopathy. A renal biopsy was performed and pathological examination showed marked periodic acid-Schiff-positive enlargement of the mesangial region and silver stain positivity, but weak direct fast scarlet staining. Immunofluorescence analysis showed monoclonal deposition of IgM-κ chain in the glomerulus. Under electron microscopy, the fibrils were about 20 nm in diameter, which was thicker than typical amyloid fibrils. Based on these findings, the patient was diagnosed with FGN. Although cyclophosphamide and prednisolone were administered, his renal function deteriorated and progressed to end stage renal disease requiring maintenance hemodialysis. As congophilic FGN has been recognized since 2018, Congo red staining and LMD/MS were performed. The Congo red staining was positive and LMD/MS results indicated that this was a case of AHL. CONCLUSIONS: We reported a case of µ and κ chain AHL resembling FGN requiring LMD/MS for definitive diagnosis. Since FGN and amyloidosis exhibit pathological findings, even if Congo red staining is positive, LMD/MS needs to be considered in cases atypical pathological findings, such as silver stain positivity or thicker fibrils.

Association between serum calcium levels and prognosis, hematoma volume, and onset of cerebral hemorrhage in patients undergoing hemodialysis.

BACKGROUND: High serum calcium levels should be avoided in patients on hemodialysis (HD) because they can induce cardiovascular diseases and worsen the patient's prognosis. In contrast, low serum calcium levels worsen the prognosis of patients with cerebral hemorrhage in the general population. So far, whether serum calcium levels in patients on HD are associated with cerebral hemorrhage remains unknown. This study aimed to reveal the association between serum calcium and cerebral hemorrhage in patients on HD, including in-hospital death, volume of hematoma, and onset of cerebral hemorrhage. METHODS: This cross-sectional case-control study included 99 patients on HD with cerebral hemorrhage at a single center between July 1, 2007 and December 31, 2017. Controls included 339 patients on HD at a single HD center between July 1, 2011 and June 30, 2012. Data on serum calcium level, patient demographics, and comorbid conditions were collected, and associations between cerebral hemorrhage and subsequent death were evaluated by multivariate logistic regression analysis. Further, the association of these backgrounds and hematoma volume was evaluated by multiple regression analysis. RESULTS: Of the 99 patients, 32 (32%) died from cerebral hemorrhage. The corrected serum calcium level (odds ratio [OR], 2.49; 95% confidence interval [CI], 1.43-4.35; P < 0.001) and antiplatelet drug use (OR, 3.95; 95% CI, 1.50-10.4; P = 0.005) had significant effects on the prognosis. Moreover, the corrected serum calcium (P = 0.003) and antiplatelet drug use (P = 0.01) were significantly correlated with hematoma volume. In the patients, the corrected serum calcium level (OR, 1.54; 95% CI, 1.07-2.22; P = 0.02) was associated with the onset of cerebral hemorrhage, as was pre-hemodialysis systolic blood pressure (per 10 mmHg) (OR, 1.40; 95% CI, 1.23-1.59; P < 0.001). CONCLUSIONS: Although the precise mechanisms remain unknown, a high serum calcium level is associated with cerebral hemorrhage in patients on HD. Thus, we should pay attentions to a patient's calcium level.

Detection of Splicing Abnormalities and Genotype-Phenotype Correlation in X-linked Alport Syndrome.

BACKGROUND: X-linked Alport syndrome (XLAS) is a progressive hereditary nephropathy caused by mutations in the COL4A5 gene. Genotype-phenotype correlation in male XLAS is relatively well established; relative to truncating mutations, nontruncating mutations exhibit milder phenotypes. However, transcript comparison between XLAS cases with splicing abnormalities that result in a premature stop codon and those with nontruncating splicing abnormalities has not been reported, mainly because transcript analysis is not routinely conducted in patients with XLAS. METHODS: We examined transcript expression for all patients with suspected splicing abnormalities who were treated at one hospital between January of 2006 and July of 2017. Additionally, we recruited 46 males from 29 families with splicing abnormalities to examine genotype-phenotype correlation in patients with truncating (n=21, from 14 families) and nontruncating (n=25, from 15 families) mutations at the transcript level. RESULTS: We detected 41 XLAS families with abnormal splicing patterns and described novel XLAS atypical splicing patterns (n=14) other than exon skipping caused by point mutations in the splice consensus sequence. The median age for developing ESRD was 20 years (95% confidence interval, 14 to 23 years) among patients with truncating mutations and 29 years (95% confidence interval, 25 to 40 years) among patients with nontruncating mutations (P=0.001). CONCLUSIONS: We report unpredictable atypical splicing in the COL4A5 gene in male patients with XLAS and reveal that renal prognosis differs significantly for patients with truncating versus nontruncating splicing abnormalities. Our results suggest that splicing modulation should be explored as a therapy for XLAS with truncating mutations.

Pathological Characteristics of Periodontal Disease in Patients with Chronic Kidney Disease and Kidney Transplantation.

Chronic kidney disease (CKD) is recognized as an irreversible reduction of functional nephrons and leads to an increased risk of various pathological conditions, including cardiovascular disease and neurological disorders, such as coronary artery calcification, hypertension, and stroke. In addition, CKD patients have impaired immunity against bacteria and viruses. Conversely, kidney transplantation (KT) is performed for patients with end-stage renal disease as a renal replacement therapy. Although kidney function is almost normalized by KT, immunosuppressive therapy is essential to maintain kidney allograft function and to prevent rejection. However, these patients are more susceptible to infection due to the immunosuppressive therapy required to maintain kidney allograft function. Thus, both CKD and KT present disadvantages in terms of suppression of immune function. Periodontal disease is defined as a chronic infection and inflammation of oral and periodontal tissues. Periodontal disease is characterized by the destruction of connective tissues of the periodontium and alveolar bone, which may lead to not only local symptoms but also systemic diseases, such as cardiovascular diseases, diabetes, liver disease, chronic obstructive pulmonary disease, and several types of cancer. In addition, the prevalence and severity of periodontal disease are significantly associated with mortality. Many researchers pay special attention to the pathological roles and clinical impact of periodontal disease in patients with CKD or KT. In this review, we provide information regarding important modulators of periodontal disease to better understand the relationship between periodontal disease and CKD and/or KT. Furthermore; we evaluate the impact of periodontal disease on various pathological conditions in patients with CKD and KT. Moreover, pathogens of periodontal disease common to CKD and KT are also discussed. Finally, we examine the importance of periodontal care in these patients. Thus, this review provides a comprehensive overview of the pathological roles and clinical significance of periodontal disease in patients with CKD and KT.

Periodontal Disease in Patients Receiving Dialysis.

Chronic kidney disease (CKD) is characterized by kidney damage with proteinuria, hematuria, and progressive loss of kidney function. The final stage of CKD is known as end-stage renal disease, which usually indicates that approximately 90% of normal renal function is lost, and necessitates renal replacement therapy for survival. The most widespread renal replacement therapy is dialysis, which includes peritoneal dialysis (PD) and hemodialysis (HD). However, despite the development of novel medical instruments and agents, both dialysis procedures have complications and disadvantages, such as cardiovascular disease due to excessive blood fluid and infections caused by impaired immunity. Periodontal disease is chronic inflammation induced by various pathogens and its frequency and severity in patients undergoing dialysis are higher compared to those in healthy individuals. Therefore, several investigators have paid special attention to the impact of periodontal disease on inflammation-, nutrient-, and bone metabolism-related markers; the immune system; and complications in patients undergoing dialysis. Furthermore, the influence of diabetes on the prevalence and severity of manifestations of periodontal disease, and the properties of saliva in HD patients with periodontitis have been reported. Conversely, there are few reviews discussing periodontal disease in patients with dialysis. In this review, we discuss the available studies and review the pathological roles and clinical significance of periodontal disease in patients receiving PD or HD. In addition, this review underlines the importance of oral health and adequate periodontal treatment to maintain quality of life and prolong survival in these patients.

Podocyte foot process width is a prediction marker for complete renal response at 6 and 12 months after induction therapy in lupus nephritis.

Morphological change that includes diffuse effacement of podocyte foot processes is correlated with proteinuria in patients with lupus nephritis (LN). We collected the data of clinico-pathological parameters and assessed foot process width (FPW) as an index of podocyte effacement in 73 patients with LN who had undergone renal biopsy. The multivariate analysis revealed that female gender (OR: 5.288; 95%CI: 1.197-37.29; p = .0267) and FPW (OR = 0.999, 95%CI = 0.997-0.999, p = .0150) were significantly predictive of a complete renal response (CR) at 6 months, while lymphocyte counts (OR = 1.002; 95%CI = 1.001-1.003, p = .0028) and FPW (OR = 0.998, 95%CI = 0.996-0.999, p = .0027) were significantly predictive of CR at 12 months. The cut-off point determined by the Classification and Regression Trees algorithm showed that FPW <908.3 nm provides the best performance for predicting patients who achieve CR at 12 months. A smaller FPW appears to be a predictive factor for CR at 6 and 12 months after induction therapy.

Serum Endocan as a Predictive Marker for Decreased Urine Volume in Peritoneal Dialysis Patients.

BACKGROUND Endocan is expressed in vascular endothelial cells, and its expression is enhanced following endothelial injury via inflammatory cytokines. Subsequently, endocan is secreted into the circulation. Thus, serum endocan levels are considered a marker of endothelial injury. However, to the best of our knowledge, no data on the serum endocan levels in peritoneal dialysis (PD) patients are available. MATERIAL AND METHODS This study included 21 PD patients who underwent peritoneal equilibration test (PET) more than once between 2011 and 2015. Serum samples were collected from each patient, and the 24-h urine volume was measured at the time of PET. Serum endocan levels were measured using enzyme-linked immunosorbent assay (ELISA) at the time of the first PET, and their relationship with clinical data or the extent of urine volume decline (mL/year) was analyzed retrospectively. RESULTS Serum endocan levels were positively correlated with proteinuria level, serum creatinine level, serum tumor necrosis factor (TNF)-α level, ß2-microglobulin level, and PD drainage volume, but not with urine volume at baseline. The extent of decline in urine volume was significantly associated with serum endocan level, proteinuria level, serum creatinine level, and serum TNF-α level at baseline in a simple linear regression analysis. Moreover, multiple linear regression analysis showed that the serum endocan level and proteinuria level at baseline were independent predictors for the extent of decline in urine volume. CONCLUSIONS The results of this study indicate that serum endocan level and proteinuria level may be useful predictive markers for decreased urine volume in PD patients.

Curcumin ameliorates nephrosclerosis via suppression of histone acetylation independent of hypertension.

BACKGROUND: Although histone acetylation, an epigenetic modification, has been reported to be related to the progression of various diseases, its involvement in nephrosclerosis is unclear. METHODS: Dahl salt-sensitive rats were used as a model of nephrosclerosis in this study. The rats were divided into three groups: (i) normal-salt diet group, (ii) high-salt diet group (HS), and (iii) HS administered daily with curcumin, a histone acetyltransferase inhibitor (HS+C). At 6 weeks after the treatment, the kidneys were dissected. Morphologic changes were assessed by Masson's trichrome staining. The number of macrophages, fibroblasts and the cells expressing acetylated histone H3 at Lys 9 (H3K9) were assessed by immunohistochemistry. RESULTS: Although both HS and HS+C rats revealed a marked increase in systolic blood pressure, serum creatinine was increased only in HS rats at 6 weeks. In the HS rats, nephrosclerosis was induced, accompanying a significant accumulation of macrophages and fibroblasts. The inflammation and fibrosis was markedly suppressed in the HS+C group. The level of histone acetylation at Lys 9 was enhanced in the HS rats, whereas curcumin administration suppressed the histone acetylation. Moreover, in the HS rats, interleukin-6 gene expression was associated with acetylated H3K9, as revealed by chromatin immunoprecipitation assay. CONCLUSIONS: Our results suggested that curcumin ameliorates nephrosclerosis via suppression of histone acetylation, independently of hypertension.