Factors affecting the relationship between ionized and corrected calcium levels in peritoneal dialysis patients: a retrospective cross-sectional study.

BACKGROUND: Chronic kidney disease-mineral and bone disorder (CKD-MBD) management in patients with end-stage renal disease is important owing to the risk of cardiovascular diseases. In clinical practice, we manage patients not by monitoring the levels of biologically active ionized calcium (iCa) but by monitoring total serum calcium or corrected calcium (cCa). We previously reported that iCa/cCa ratio was different between patients with hemodialysis and those with peritoneal dialysis (PD). In PD patients, several factors are expected to affect iCa/cCa ratio. Therefore, modifying the strategy to achieve better CKD-MBD management might be necessary; however, no reports have studied this to date. Therefore, we investigated the factors influencing iCa/cCa ratio in PD patients. METHODS: This retrospective cross-sectional study examined background and laboratory data, including iCa, collected at routine outpatient visits. The patients were divided into the first, second, and third tertile of iCa/cCa ratio groups to compare patient background and laboratory data. Multiple regression analysis was used to investigate the factors influencing iCa/cCa ratio. We used multiple imputation to deal with missing covariate data. RESULTS: In total, 169 PD patients were enrolled. In PD patients with lower iCa/cCa ratio, PD duration was longer and pH was higher. Urine volume and weekly renal Kt/V were lower in the patients with lower iCa/cCa ratio than in those with higher iCa/cCa ratio. iCa/cCa ratio and weekly renal Kt/V were directly correlated (r = 0.41, p < 0.01), and weekly renal Kt/V and pH were independent factors affecting iCa/cCa ratio (t = 2.86, p < 0.01 and t = - 5.42, p < 0.01, respectively). CONCLUSIONS: iCa levels were lower in PD patients with lower residual renal function (RRF) even though their cCa levels were equal to those with maintained RRF, warranting caution in the assessment and management of CKD-MBD in PD patients.

Clinical outcome of incident peritoneal dialysis patients with diabetic kidney disease.

BACKGROUND: Although peritoneal dialysis (PD) is becoming more widespread, PD among diabetic patients carries some concerns, such as worsened glycemic control due to constant exposure to glucose and operational errors due to diabetic complications. However, several technical advances could overcome these disadvantages. We, therefore, aimed to compare technical and patient survival between diabetic and non-diabetic PD patients. METHODS: We conducted a historical cohort study of 103 patients (mean age, 57 ± 16 years; 75 males, 32 diabetic patients) who started PD between January 2011 and January 2016. Kaplan-Meier survival analysis was used to compare technical and patient survivals between diabetic and non-diabetic patients. Multivariate Cox regression analysis was used to estimate the effects of the presence of diabetes on these outcomes. RESULTS: Technical and patient survivals did not differ significantly between groups (P = 0.62, P = 0.34, respectively). In addition, presence of diabetes affected neither technical nor patient survival in multivariate analysis (hazard ratio [HR], 1.31; 95% confidence interval [CI], 0.58-2.82 and HR 0.80; 95% CI 0.22-2.68, respectively). CONCLUSIONS: Technical and patient survivals of diabetic PD patients were not inferior to those of non-diabetic PD patients. These results suggest that no hesitation is warranted in initiating PD for diabetic patients with end-stage renal disease.

Negative impact of proteinuria on circulating myeloid dendritic cells.

BACKGROUND: A decrease in absolute numbers (abs.) of circulating dendritic cells (DCs) and recruitment into target organs has been reported, but whether the level of proteinuria associates with circulating DC abs. has not been clarified. METHODS: We conducted a cross-sectional study of 210 patients with kidney disease aged 21-96 years who were admitted to our hospital for kidney biopsy in 2007-2010. For accuracy, the level of proteinuria was thoroughly measured by 24-h urine collection from patients in their admitted condition. The abs. of total DCs (tDCs), myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) was measured by three-color fluorescence-activated cell sorting (FACS). Patients were divided into four groups based upon the quartile of each DC abs. and one-way ANOVA, and multivariable-adjusted regression analyses were performed. RESULTS: Quantile analysis showed that the level of daily proteinuria decreased with increasing blood mDC abs., with mean proteinuria levels (g/day) of 2.45, 1.68, 1.68, 1.10 for those in mDC abs. quartiles ≤ 445, < 686, < 907, ≥ 907 cells/102 µL (p = 0.0277), respectively. Multivariate-adjusted regression analysis revealed that the mDC abs. was negatively associated with proteinuria (95% CI - 57.0 to - 8.5) and positively associated with male gender (95% CI 66.2-250.5). Independent associations were also shown between pDCs abs. and estimated glomerular filtration rate (eGFR) (95% CI 0.14-2.67) and C-reactive protein (95% CI - 49.4 to - 9.9) and between tDCs abs. and male gender (95% CI 54.5-253.6) and C-reactive protein (95% CI - 80.5 to - 13.4). CONCLUSION: We first reported that circulating mDC abs. has a negative association with the level of proteinuria.

Interventional nephrology: current status and clinical impact in Japan.

BACKGROUND: Current status and clinical significance of interventional nephrology has not been reported from Japan. METHODS: Questionnaires were mailed twice to the directors of all 534 Japanese certificated nephrology training institutions in 2014. The main questions were current performance, categorized annual procedure volume and managers of peritoneal dialysis (PD) access, vascular access (VA) surgery, endovascular intervention, and kidney biopsy. Frequencies of nephrologist involvement between high volume center and low volume center and association between the level of nephrologists' involvement to each procedure and annual procedure volume were examined. RESULTS: 332 (62.2%) institutions answered performance of all procedures and 328 (61.4%) institutions answered all procedure volume. Kidney biopsy, VA surgery, endovascular intervention and PD access surgery were performed by any doctors in 94.2, 96.3, 88.4, and 76.2% and each involvement of nephrologist was 93.9, 54.1, 53.1 and 47.6%, respectively. Cochran-Armitage analyses demonstrated significant increases in all 4 procedure volume with greater management by nephrologists (p < 0.01). Nephrologists involvement to VA surgery associated with procedure volume increase in not only VA surgery, but also PD catheter insertion (p < 0.01) and kidney biopsy (p < 0.05). And nephrologists involvement to PD catheter insertion also associated with surgical volume increase in both VA surgery (p < 0.01) and endovascular intervention (p < 0.05). CONCLUSIONS: Main manager of all 4 procedures was nephrologist in Japan. Each procedure volume increased as nephrologists become more involved. Acquisition of one specific procedure by nephrologist associated with increase not only in this specific procedure volume, but also the other procedure volume.

Beneficial Effect of Intradialytic Electrical Muscle Stimulation in Hemodialysis Patients: A Randomized Controlled Trial.

Many hemodialysis (HD) patients cannot perform self-administered exercise training for their muscle wasting, weakness, and sarcopenia. Electrical muscle stimulation (EMS) has the advantages of easy application, and minimal risks for these patients. This study aimed to evaluate the effects of intradialytic EMS. This was a prospective, open-label, randomized controlled trial. Twenty-nine HD patients were randomly assigned to either the EMS group or the control (no training) group, and 13 patients in each group were eventually analyzed. The EMS group received intradialytic EMS over an 8-week period. Measurement of isometric knee extensor strength using a handheld dynamometer, evaluation of the quadriceps cross-sectional area (CSA) using magnetic resonance imaging (MRI), the Timed Up & Go Test (TUG) for physical function assessment, the Japanese version of the Short Form-8 Health Survey (SF-8), and blood tests were performed before and after the intervention period. The primary and secondary outcomes were improvement of quadriceps muscle strength and size, respectively. The EMS group demonstrated significant improvement compared with the control group in terms of knee extensor strength (right: 22.3 ± 12.8 vs. -10.8 ± 22.3 N, P < 0.001; left: 26.1 ± 29.7 vs. -8.3 ± 18.7 N, P < 0.001), quadriceps CSA at three positions, 25, 50, and 75% of the segment length from the greater trochanter to the inferior border of the lateral epicondyle of the femur (25% right: EMS group 1.7 ± 2.0 vs. Control group -0.4 ± 1.8cm2 , P = 0.05; 25% left: EMS group 1.3 ± 1.1 vs. Control group -0.6 ± 1.8cm2 , P = 0.01; 50% right: EMS group 2.0 ± 2.2 vs. Control group -0.7 ± 1.9cm2 , P = 0.004; 50% left: EMS group 2.7 ± 2.1 vs. Control group -0.7 ± 1.6cm2 , P = 0.001; 75% right: EMS group 1.8 ± 2.2 vs. Control group -0.7 ± 1.5cm2 , P = 0.003; 75% left: EMS group 2.1 ± 1.9 vs. Control group -0.4 ± 1.5cm2 , P = 0.003); and TUG time (-0.8 ± 0.6 vs. 0.2 ± 0.5s, P < 0.001). The EMS group showed improvement after intervention in all components of SF-8, but these were not statistically significant. EMS could be an effective exercise training tool for HD patients with either muscle wasting, weakness, or sarcopenia.

Risk factors for encapsulating peritoneal sclerosis: Analysis of a 36-year experience in a University Hospital.

AIM: Encapsulating peritoneal sclerosis (EPS) is a rare but serious complication that occurs in peritoneal dialysis (PD) therapy. The present study aimed to identify the risk factors, especially peritonitis and biocompatible PD fluid. METHODS: The study included 703 patients who received PD between January 1980 and March 2015 at two centres. The patients were divided into two groups: those who had developed EPS (EPS group: n = 44) and those who had no documentary evidence of EPS (non-EPS group: n = 659). The independent risks of EPS were determined by univariate and multivariate logistic models. RESULTS: Encapsulating peritoneal sclerosis occurred in 44/703 (6.3%) patients between January 1980 and March 2015. In multivariate logistic models of risk factors correlated with EPS, dialysate to plasma creatinine ratio (D/P Cr) by peritoneal equilibration test (PET) and history of peritonitis were risk factors for EPS development (P < 0.01, respectively) in addition to PD duration. Especially, total duration of peritonitis, defined by period between onset and resolution of peritonitis, was an important risk factor for EPS development in patients with a history of peritonitis. Receiver operating characteristic (ROC) curve analysis revealed that cut-off point for EPS development was 36 days. Moreover, biocompatible PD fluid contributed to decreased EPS development. CONCLUSION: Both the longer duration of peritonitis and higher D/P Cr, as well as the longer PD duration, were risk factors for EPS development. Furthermore, use of biocompatible PD fluid contributed to the decrease in EPS development.

The differences in acid-base status and the calcium parathyroid axis between peritoneal dialysis and hemodialysis.

BACKGROUND: Several guidelines have set the target levels of serum Ca, phosphorus, and parathyroid hormone (PTH) for better management of chronic kidney disease-mineral and bone disorders (CKDMBD) in dialysis patients. Although serum ionized Ca (iCa) is a biologically active component, corrected Ca (cCa) is used in clinical settings. However, the association between iCa and cCa is affected by acid-base status. We investigated the difference in acid-base and the calcium-parathyroid status between hemodialysis (HD) and peritoneal dialysis (PD). METHODS: The markers associated with CKD-MBD were measured in 142 patients receiving chronic dialysis (69 on PD and 73 on HD). RESULTS: Serum bicarbonate levels were significantly higher in the PD group than in the HD group (26.6 ± 2.8 vs. 22.9 ± 2.0 mEq/L, p < 0.01). The serum iCa levels and the iCa/cCa ratio were significantly lower in the PD group than in the HD group (iCa 1.07 ± 0.08 vs. 1.14 ± 0.08 mmol/L, p < 0.01; iCa/cCa ratio 45.5 ± 3.1% vs. 49.7 ± 3.2%, p < 0.01). The cCa levels were significantly higher in the PD group than in the HD group (9.4 ± 0.4 vs. 9.1 ± 0.4 mg/dL, p < 0.01). Intact PTH levels were significantly higher in the PD group than in the HD group (220 (40 - 581) vs. 133 (30 - 666) pg/mL, p < 0.01). CONCLUSIONS: We found that PD patients had lower iCa and higher PTH levels despite higher cCa levels as compared to HD patients. These results suggested that the assessment of both Ca and PTH should be different between PD and HD.

[A case of glomerulopathy associated with the vascular endothelial growth factor inhibitor bevacizumab].

The patient was a 73-year-old Japanese female diagnosed with stage IIIc primary peritoneal cancer. After undergoing total hysterectomy and bilateral oophorectomy, she received regimens consisting of paclitaxel (PTX) and carboplatin (CBDCA). She subsequently developed recurrence four years after the disease onset and was treated with PTX, CBDCA and the vascular endothelial growth factor (VEGF) inhibitor bevacizumab (Bev). Although clinical remission was maintained with the administration of Bev monotherapy every three weeks, proteinuria was detected six months later, and gradually increased. The findings of a renal biopsy showed diffuse wrinkling and double contouring of the glomerular tufts under light microscopy, although no immune complex deposition was observed on immunostaining. Additionally, electron microscopy showed hypertrophy of glomerular endothelial cells and widening of the subendothelial spaces. These histopathological findings were fully consistent with those of reported patients treated with VEGF inhibitors. The proteinuria attenuated following the initiation of treatment with losartan. Therefore, the administration of renoprotective therapy contributed to the patient's ability to continue the anticancer regimen with Bev in this case.

Estimation of salt intake from spot urine samples in patients with chronic kidney disease.

BACKGROUND: High salt intake in patients with chronic kidney disease (CKD) may cause high blood pressure and increased albuminuria. Although, the estimation of salt intake is essential, there are no easy methods to estimate real salt intake. METHODS: Salt intake was assessed by determining urinary sodium excretion from the collected urine samples. Estimation of salt intake by spot urine was calculated by Tanaka's formula. The correlation between estimated and measured sodium excretion was evaluated by Pearson´s correlation coefficients. Performance of equation was estimated by median bias, interquartile range (IQR), proportion of estimates within 30% deviation of measured sodium excretion (P30) and root mean square error (RMSE).The sensitivity and specificity of estimated against measured sodium excretion were separately assessed by receiver-operating characteristic (ROC) curves. RESULTS: A total of 334 urine samples from 96 patients were examined. Mean age was 58 ± 16 years, and estimated glomerular filtration rate (eGFR) was 53 ± 27 mL/min. Among these patients, 35 had CKD stage 1 or 2, 39 had stage 3, and 22 had stage 4 or 5. Estimated sodium excretion significantly correlated with measured sodium excretion (R = 0.52, P < 0.01). There was apparent correlation in patients with eGFR <30 mL/min (R = 0.60, P < 0.01). Moreover, IQR was lower and P30 was higher in patients with eGFR < 30 mL/min. Estimated sodium excretion had high accuracy to predict measured sodium excretion, especially when the cut-off point was >170 mEq/day (AUC 0.835). CONCLUSIONS: The present study demonstrated that spot urine can be used to estimate sodium excretion, especially in patients with low eGFR.

Association between lipid profile and residual renal function in incident peritoneal dialysis patients.

INTRODUCTION: Residual renal function (RRF) is one of the most crucial factors in the management of peritoneal dialysis (PD). The aim of this study was to evaluate the association between lipid profile and preservation of RRF among incident PD patients. METHODS: This retrospective cohort study investigated 113 patients (male, 72%; age, 59 ± 14 years) who initiated PD between 2006 and 2017. We investigated the relationships between high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) at PD initiation and change in renal Kt/V during the first year after PD initiation. RESULTS: Alterations in renal Kt/V during the first year after PD initiation correlated negatively with HDL-C at PD initiation but not with LDL-C. On multivariate analysis, HDL-C at PD initiation was independently associated with a change in renal Kt/V during the first year after PD initiation. CONCLUSION: These results suggest the importance of lipid management among incident PD patients for the preservation of RRF.

Comparison of peritoneal function within the first 1 year of peritoneal dialysis between diabetic and non-diabetic patients.

The aim of this study was to compare the changes in peritoneal function and residual renal function in the first year between diabetic and non-diabetic patients receiving peritoneal dialysis (PD). We extracted 73 incident PD patients (male, 73%; age, 59 ± 15 years) from a previous cohort, and investigated the changes in PD-related parameters, including the dialysate to plasma ratio of creatinine (D/P Cr) and Kt/V. D/P Cr increased in non-diabetics, whereas it did not change significantly in diabetic patients. These differences were more pronounced among icodextrin users. On multivariate analysis, the presence of diabetes was independently associated with the changes in D/P Cr. On the contrary, there was no significant difference in the changes of renal Kt/V between the two groups. A higher peritoneal solute transport rate at the start of PD in diabetics was attenuated within 1 year. Icodextrin is thought to have an important role through improving body fluid status.

Effect of diabetes on incidence of peritoneal dialysis-associated peritonitis.

BACKGROUND: Several reports on patients with diabetes mellitus (DM) treated by peritoneal dialysis (PD) have shown a higher risk of PD-associated peritonitis compared to non-DM (NDM) patients. The aim of this study was to investigate the incidence of PD-associated peritonitis in DM patients. METHODS: We divided all patients who received PD at a single center between January 1980 and December 2012 into three groups according to era: Period 1 (n = 43, 1980-1993); Period 2 (n = 123, 1994-2004); and Period 3 (n = 207, 2005-2012). We investigated incidences of PD-associated peritonitis between patients with and without DM. RESULTS: In Periods 1 and 2, incidence of PD-associated peritonitis was higher in the DM group than in the NDM group (P<0.05). However, no difference according to presence of DM was seen in Period 3. Multivariate Cox regression analysis revealed DM as a risk factor for incidence of PD-associated peritonitis in Periods 1 and 2, but not in Period 3 (hazard ratio [HR], 2.49; 95% confidence interval [CI], 1.15 to 5.23; HR, 2.36; 95%CI, 1.13 to 4.58; and HR, 0.82; 95%CI, 0.41 to 1.54, respectively). Furthermore, the peritonitis-free period was significantly shorter in the DM group than in the DM group in Periods 1 and 2, whereas no significant difference was seen in Period 3 (P<0.01, P<0.01 and P = 0.55, respectively). Moreover, a significant interaction was seen between diabetes and study period, and became less pronounced during Period 3(P<0.01). CONCLUSIONS: The increased risk of peritonitis in diabetics reported in previous periods has not been evident in recent years.

33 Years of Peritoneal Dialysis-Associated Peritonitis: A Single-Center Study in Japan.

Peritoneal dialysis-associated peritonitis (PD-associated peritonitis) could influence the outcome of PD patients, including technique survival. Although the use of the twin-bag system has decreased the incidence of peritonitis, the effects of biocompatible PD solutions are controversial. Additionally, since both infection-causing microorganisms and antimicrobial therapies have changed over time, the duration of treatment of peritonitis (the duration of peritonitis) seems to have changed. The study included 527 patients who received PD between January 1980 and December 2012 at a single center. We divided patients undergoing PD into three groups according to the type of PD system used, namely single-bag and conventional PD solutions (S+C group, N = 145), twin-bag and conventional PD solutions (T+C group, N = 171) and twin-bag and biocompatible PD solutions (T+B group, N = 211), and analyzed PD-associated peritonitis incidences. Incidences of PD-associated peritonitis (times per patient-months) and peritonitis-free time were 1/59.4, 1/70.6 and 1/103.1, and 52, 97, and 100 months for the S+C, T+C and T+B groups, respectively. The duration of peritonitis, has thus, become dramatically shorter in recent years. Streptococcus sp. were associated with shortest and fungi with longest durations of peritonitis. Staphylococcus sp. and Pseudomonas aeruginosa were predominant in the S+C group. The twin-bag system has made a greater contribution to reductions in PD-associated peritonitis than biocompatible PD solutions. Furthermore, changes in microorganisms, antimicrobial therapies, patient education and improved PD system devices have presumably affected the reduction in the duration of peritonitis.

Possible prevention of dialysis-requiring congestive heart failure by angiotensin-II receptor blockers in non-dialysis Japanese patients with Stage 5 chronic kidney disease.

BACKGROUND: Preventive medications for dialysis-requiring congestive heart failure (CHF) in non-dialysis Japanese patients with Stage 5 chronic kidney disease (CKD) are unknown. Our aim was to explore which CKD medication was associated with a reduced prevalence of dialysis-requiring CHF in non-dialysis Japanese patients with Stage 5 CKD. METHODS: The present multicenter, retrospective, cross-sectional study examined the association between CKD medications and the prevalence of dialysis-requiring CHF in non-dialysis Japanese patients with Stage 5 CKD. RESULTS: There were 1536 Japanese Stage 5 CKD patients who satisfied our inclusion criteria. We had 309 (20.1%) patients whom had developed dialysis-requiring CHF and 940 patients (60.8%) whom had been using angiotensin-II receptor blockers (ARBs) before initiating dialysis. In our multivariate analysis, only ARB use was significantly associated with a lower risk of CHF (Odds ratio (OR): 0.680, 95% confidence interval (CI): 0.516-0.897; p = 0.0064), of the CKD treatments examined in this study. CONCLUSIONS: We found that ARB use during the pre-dialysis period is associated with a lower prevalence of CHF in the non-dialysis Japanese patients with Stage 5 CKD, suggesting a possible prevention of dialysis-requiring CHF by ARBs, in non-dialysis Japanese patients with Stage 5 CKD.

Risk factors for encapsulating peritoneal sclerosis in long-term peritoneal dialysis: a retrospective observational study.

Encapsulating peritoneal sclerosis (EPS) is a serious complication that occurs in patients with long-term peritoneal dialysis (PD). Investigation of risk factors that contribute to EPS in patients on long-term PD therapy is needed. In a retrospective, observational study, data were collected for 107 patients treated with PD therapy for more than 5 years. Fifty cases of EPS were compared with 57 cases of non-EPS. To evaluate the impact of PD-associated peritonitis in EPS, univariate and multivariate logistic regression models were applied. Episodes of peritonitis, number of peritonitis episodes and the duration of peritonitis were included as explanatory variables in addition to previously reported risk factors. D/P Cr and serum ß2MG levels in the EPS and non-EPS groups were: 0.82 ± 0.10 and 0.67 ± 0.12 (P < 0.01), and 33.8 ± 8.54 and 29.2 ± 8.18 mg/L (P < 0.01), respectively. Episodes of peritonitis, number of peritonitis episodes and the duration of peritonitis was 68% and 42% (P < 0.01), 1.80 ± 2.19 and 0.75 ± 1.07 times (P < 0.01), and 18.1 ± 15.3 and 10.2 ± 4.90 days (P < 0.01), in the EPS and non-EPS groups, respectively. Furthermore, multivariate logistic regression models demonstrated that both D/P Cr and the duration of peritonitis were independently associated with EPS (P < 0.01 and P < 0.05, respectively). In patients on long-term PD therapy, D/P Cr and the duration of peritonitis are independently associated with EPS. Earlier treatment to promote an early recovery from PD-associated peritonitis could be critical in preventing EPS.

Fungal granulomatous interstitial nephritis presenting as acute kidney injury diagnosed by renal histology including PCR assay.

We describe two cases of fungal granulomatous interstitial nephritis (GIN) presenting as acute kidney injury (AKI). Increased serum creatinine was detected in Patient 1 after chemotherapy for pharyngeal cancer and in Patient 2 after steroid pulse therapy for bronchial asthma. Renal histology of both patients revealed GIN. Polymerase chain reaction (PCR)-based detection of fungal DNA sequences from kidney tissue demonstrated Trichosporon laibachii and Candida albicans, respectively. When AKI occurs in an immunocompromised host, differential diagnosis of fungal interstitial nephritis should be considered. Furthermore, PCR-based detection of fungal DNA sequences from renal specimens can be useful for rapid diagnosis.