Chapter 4: CKD treatment in cancer survivors, from Clinical Practice Guidelines for the Management of Kidney Injury During Anticancer Drug Therapy 2022.

Chronic kidney disease (CKD) is one of the most disabling disorders with significant comorbidity and mortality. Incidence and prevalence of CKD in cancer survivors are remarkably high in both adults and pediatric patients. The reasons for this high incidence/prevalence are multifold but kidney damage by cancer itself and cancer treatment (pharmacotherapy/surgery/radiation) are the main reasons. Since cancer survivors commonly have significant comorbidities, risk of cancer recurrence, limited physical function or life expectancy, special attentions should be paid when considering the treatment of CKD and its complications. Especially, shared decision-making should be considered when selecting the renal replacement therapies with as much information/facts/evidence as possible.

[Management of Chronic Kidney Disease in Cancer Survivors].

Chronic kidney disease(CKD)associated with cancer and its treatment affects life after cancer treatment. There is inconclusive opinion on whether CKD treatment in survivors after cancer treatment needs special care differently than in the general population with CKD. Several topics were discussed by nephrologists, urologists and medical oncologists, pediatricians, pharmaceutical specialists, and others based on the results of a literature search, and the consensus was documented in the "Clinical Practice Guidelines for the Management for Kidney Injury During Anticancer Drug Therapy, 2022". The prevalence of CKD among adult cancer survivors is reported to be 4-7%. The characteristics include(1)elderly and physically impaired patients(, 2)a high risk of cancer recurrence, and(3)frequently cancer treatment-related CKD. Although there are no cancer survivor-specific indications or contraindications in the selection of renal replacement therapy, renal transplantation is often preferred in pediatric cancer survivors. It was determined that it is not appropriate to recommend or not recommend the administration of erythropoietin stimulating agents for renal anemia in cancer survivors based on a systematic review and discussion between panelists. When used in individual cases, its application should be well examined and consideration should be given to avoiding high hemoglobin level and to monitoring for cancer development.

Seasonality of peritoneal dialysis-related peritonitis in Japan: a single-center, 10-year study.

BACKGROUND: Peritonitis is one of the major complications of peritoneal dialysis (PD). Although several reports have indicated seasonality of peritonitis, the observation periods were short, and there were no reports from Japan. Therefore, the purpose of this study was to investigate the long-term seasonality of peritonitis in a single institution in Japan. METHODS: Of 126 patients who started PD in our hospital between January 1, 2009, and December 31, 2018, 25 patients (15 men, 10 patients with diabetes) developed peritonitis with a total of 42 episodes. The median age at onset was 63 years, and the median duration from the start of PD to the onset of peritonitis was 22 months. RESULTS: The 10-year incidence of peritonitis was 0.12 episodes per patient-year. Compared with the reference season of winter (December-February), the incidence rate ratios (95% confidence interval) for spring (March-May), summer (June-August), and autumn (September-November) were 1.75 (0.65-4.75), 1.56 (0.57-4.31), and 2.42 (0.94-6.23), respectively. In addition, no seasonality of Gram-positive and Gram-negative organisms was observed. CONCLUSION: No seasonality was evident in the incidence of PD-related peritonitis in our hospital over a 10-year period. These findings suggest that the development of peritonitis in Japanese PD patients is not affected by seasonality.

Inpatient educational program delays the need for dialysis in patients with chronic kidney disease stage G5.

BACKGROUND: Inpatient educational programs (IEPs) for patients with chronic kidney disease (CKD) decrease CKD progression. However, patients with end-stage kidney disease who started dialysis during the observation period were excluded from previous studies. METHODS: After adjusting for age, sex, baseline estimated glomerular filtration rate, hemoglobin level, and the presence of diabetes mellitus using 1:1 propensity score matching (caliper width of 0.008) in the groups that did and did not receive an IEP, we compared the time period from the beginning of CKD stage G5 to the start of dialysis and patient characteristics at the start of dialysis. RESULTS: Prior to matching, 41 patients received an IEP and 260 did not. After propensity score matching, the 41 patients who received an IEP had a longer period from the beginning of stage G5 to the start of dialysis (344 vs. 257 days, P = 0.011), shorter hospitalization period upon the start of dialysis (14 vs. 18 days, P = 0.015) compared with the 41 patients who did not receive an IEP. In addition, the proportion of patients with a planned start of dialysis tended to be higher in the IEP group (95.1 vs. 83.0%, P = 0.077). CONCLUSION: An IEP may delay the start of dialysis in patients with end-stage kidney disease, contribute to better preparation of vascular access placement and the smoother start of dialysis.

Association between health-related hope and adherence to prescribed treatment in CKD patients: multicenter cross-sectional study.

BACKGROUND: In chronic kidney disease (CKD), patients' adherence to prescriptions for diet and for medications might depend on the degree to which they have hope that they will enjoy life, and that hope could vary with the stage of CKD. The aims of this study were to quantify both the association of CKD stage with health-related hope (HR-Hope), and the association of that hope with psychological and physiological manifestations of adherence. METHODS: This was a cross-sectional study involving 461 adult CKD patients, some of whom were receiving dialysis. The main exposure was HR-Hope, measured using a recently-developed 18-item scale. The outcomes were perceived burden of fluid restriction and of diet restriction, measured using the KDQOL, and physiological manifestations of adherence (systolic and diastolic blood pressure [BP], and serum phosphorus and potassium levels). General linear models and generalized ordered logit models were fit. RESULTS: Participants at non-dialysis stage 4 and those at stage 5 had lower HR-Hope scores than did those at stage 2 or 3 (combined). Those at non-dialysis stage 5 had the lowest scores. HR-Hope scores of participants at stage 5D were similar to those of participants at stage 4, but they were lower than the scores of participants at stage 2 or 3 (combined). Higher HR-Hope scores were associated with lower perceived burdens of fluid restriction and of diet restriction (adjusted ORs per ten-point difference were 0.82 and 0.84, respectively). Higher HR-Hope scores were associated with lower systolic BP (adjusted mean difference in systolic BP per ten-point difference in HR-Hope scores was - 1.87 mmHg). In contrast, HR-Hope scores were not associated with diastolic BP, serum phosphorus levels, or serum potassium levels. CONCLUSIONS: Among CKD patients, HR-Hope is associated with disease stage, with psychological burden, and with some physiological manifestations of adherence.

Changes in Peritoneal Transport and Peritoneal Damage in Japanese Patients Undergoing Peritoneal Dialysis Using Neutral-pH Dialysate: A Retrospective Cohort Study at Two Centers.

The effects of medium- or long-term use of neutral-pH dialysate on peritoneal transport and peritoneal damage have not been sufficiently researched.We retrospectively evaluated time-dependent changes in the dialysate-to-plasma ratio of creatinine (D/P Cr) and biomarkers of peritoneal damage in the effluent of 65 patients who underwent peritoneal dialysis (PD) with neutral-pH dialysate, including 48 who underwent medium-term PD (≥3 years) and 17 who underwent long-term PD (≥5 years).Patients who underwent medium-term PD initially had a D/P Cr of 0.59 (range: 0.53 - 0.74), nonsignificantly changing to 0.65 (range: 0.55 - 0.73), 0.67 (range: 0.56 - 0.74), and 0.67 (range: 0.62 - 0.72) after 1, 2, and 3 years respectively (p = 0.30, p = 0.26, and p = 0.19). Patients who underwent long-term PD initially had a D/P Cr of 0.57 (range: 0.52 - 0.62), nonsignificantly changing to 0.61 (range: 0.52 - 0.69), 0.64 (range: 0.54 - 0.67), 0.62 (range: 0.57 - 0.66), 0.65 (range: 0.50 - 0.72), and 0.61 (range: 0.48 - 0.7) after 1, 2, 3, 4, and 5 years respectively (p = 0.49, p = 0.31, p = 0.24, p = 0.23, and p = 0.46). After 3 years, a significant increase in effluent hyaluronan (HA) from 90 ng/mL initially (range: 66 - 121 ng/mL) to 144 ng/ mL (range: 116 - 216 ng/mL) was observed (p = 0.04).No significant change in D/P Cr was observed in patients who underwent PD with neutral-pH dialysate. However, effluent HA, which is a biomarker for peritoneal damage, increased. In patients using neutral-pH dialysate, D/P Cr cannot be a biomarker for determining PD discontinuation within 5 years, but effluent HA might be useful.

Early Postoperative Complications of Peritoneal Dialysis Catheter Surgery Conducted by Nephrologists: A Single-Center Experience Over an Eight-Year Period.

The results of several recent studies indicate that the practice of peritoneal dialysis catheter (PDC) insertion by nephrologists is safe. However, few studies have addressed the important issue of safety in surgeries related to PD, including PDC removal and other types of surgery. In the present study, we aimed to verify whether the incidence of early postoperative complications for surgical procedures related to PD and performed by nephrologists meets the audit standards of clinical practice guidelines for peritoneal access.Between April 2008 and July 2016 at our hospital, 282 patients underwent various types of PD-related surgery conducted by 17 nephrologists. The surgery types were the Moncrief-Popovich technique (n = 74), PDC exteriorization (n = 62), conventional laparotomy insertion (n = 29), PDC removal (n = 70), partial replacement (n = 32), unroofing or cuff shaving (n = 7), and others (n = 8).Bowel perforation and significant hemorrhage did not occur at the time of PDC insertion and removal. Although peritonitis was not evident, exit-site and tunnel infection within 2 weeks of PDC insertion by conventional laparotomy or exteriorization after the Moncrief-Popovich technique occurred in 3 of 91 patients (3.3%). The PDC malfunctioned in 2 of 103 patients (1.9%) after the Moncrief-Popovich technique because of PDC occlusion with a fibrin plug. Dialysate leaks occurred in 2 of 103 patients (1.9%). Partial replacement and unroofing or cuff shaving for refractory PDC infection and other type of surgeries were not associated with serious complications.The incidence of complications after surgery related to PD was low at our institution. The incidences of complications met the audit standards in the guidelines, indicating that surgery by nephrologists is safe and effective.

Predictive Factors for Withdrawal from Peritoneal Dialysis: A Retrospective Cohort Study at Two Centers in Japan.

Peritoneal dialysis (PD) is recognized as an excellent method of dialysis because the therapy is gentle, continuous, and cost-effective. However, a large number of patients must unfortunately transfer from PD to hemodialysis because of peritonitis or fluid overload in the early phase after PD initiation. In the present study, we reviewed clinical indicators before PD initiation to try to identify predictive factors for early withdrawal from PD.For this retrospective cohort study at two hospitals between March 2003 and October 2016, we defined withdrawal from PD as the induction of combination therapy, transfer to hemodialysis, or death. Data about clinical indicators before PD induction-namely age, sex, presence of diabetes mellitus, past history of cardiovascular disease (CVD), body mass index, primary kidney disease, and blood biochemistry-were collected from medical records. The primary outcome was duration of PD until withdrawal.We analyzed 151 PD patients (median age: 62.5 years; 94 men; 74 with diabetes mellitus; median duration of PD: 30.2 months). Univariate Cox regression analysis showed that the hazard ratio (HR) for withdrawal was 1.08 [95% confidence interval (CI): 1.04 to 1.12; p < 0.001] per 1 mg/L increase in ß2-microglobulin (ß2MG), 0.65 (95% CI: 0.46 to 0.93; p = 0.02) per 1 g/dL decrease in serum albumin, and 1.07 (95% CI: 1.02 to 1.11; p = 0.01) per 1 g per gram creatinine increase in daily urinary protein excretion. Using multivariate Cox regression analysis, ß2MG (HR: 1.08; 95% CI: 1.04 to 1.12; p < 0.001) and past history of CVD (HR: 1.47; 95% CI: 1.02 to 2.13; p = 0.04) were factors predictive for withdrawal from PD. Kaplan-Meier analysis showed that the technique survival rate was significantly different in the two groups defined as having a serum ß2MG level above or below the measured median (p = 0.047).Serum ß2MG at PD initiation and past history of CVD are high-risk factors for withdrawal from PD. Special focus should be placed on the care and management of patients found to have a high risk of withdrawal at the time of PD induction.

Long-Term Prognosis of Peritoneal Dialysis Patients with a Re-embedded Catheter.

Upon peritoneal dialysis (PD) discontinuation in frail patients, we have re-embedded the catheter and left it subcutaneously buried. However, we have not evaluated the long-term prognosis of those patients after the procedure or the complications associated with buried catheters. We therefore aimed to clarify the long-term prognosis of patients with a re-embedded catheter and to identify any associated complications.The outcomes of 10 patients having a catheter that was re-embedded between February 2010 and May 2016 were assessed by interviewing the patients or their families (when possible), and by reviewing medical records.Catheter re-embedding to reduce the surgical burden was elected by 7 patients, and 3 patients underwent re-embedding because they wanted to resume PD in the future. By the time of the interviews, 6 patients had already died of causes that were unrelated either to the buried catheter or infection. No abnormality was found in any buried catheter. A re-embedded catheter was later externalized to resume PD in 1 of the 4 patients who survived.Catheter re-embedding is safe and allows for PD resumption at the terminal stage of dialysis.

Correlation Between Near-Vision Acuity and the Incidence of Peritoneal Dialysis-Related Infections.

Peritoneal dialysis (PD)-related infections (PDIs) such as peritonitis, exit-site infection, and tunnel infection are serious complications affecting patients on PD. Because patients with diabetes (DM) and of older age have increased in number in Japan, the number of patients with visual impairment is estimated also to have increased. Near vision is necessary for performing proper PD daily care. However, no studies have reported whether visual impairment is likely to increase the risk of PDIs.Our study included 31 PD patients (16 men, 15 women; mean age: 61.5 ± 11.8 years; mean PD duration: 27.3 ± 20.3 months; 38.7% with DM; 54.8% wearing glasses) who performed their own PD care. At our facility and related facilities, we used a standard near-vision test chart, which classifies vision into 12 grades, from 0.1 (poor) to 1.5 (clear), to assess near-vision binocular visual acuity in those patients between March 2015 and September 2015. In addition, we retrospectively examined the medical records of the patients to determine their history of PDIs. We then evaluated the correlation between near-vision acuity and the incidence of PDIs.Mean measured near-vision acuity was 0.61 ± 0.29, and we observed no significant difference in the visual acuity of patients with and without DM (0.55 ± 0.31 vs. 0.63 ± 0.26 respectively, p = 0.477). In addition, we observed no significant difference in the incidence of PDIs between patients with and without DM (1.298 ± 1.609 per year vs. 1.164 ± 0.908 per year respectively, p = 0.804). We did not find a correlation between near-vision acuity and the incidence of PDIs (r = -0.071, p = 0.795).

Association Between Residual Kidney Function and Visit-to-Visit Blood Pressure Variability in Peritoneal Dialysis Patients.

Visit-to-visit blood pressure (BP) variability has recently been recognized as an important risk factor for decline of residual kidney function (RKF) in patients with chronic kidney disease. However little is known about the impact of visit-to-visit BP variability on RKF in peritoneal dialysis (PD) patients. We retrospectively studied the association between RKF and visit-to-visit BP variability in 42 patients who started on PD between February 2006 and March 2012. Residual kidney function was defined as the mean of the urea and creatinine clearances in the patients. Visit-to-visit BP variability was defined as the average real variability of BP measurements taken during 12 consecutive visits after the start of PD. A significant association between the slope of RKF after the start of PD and the visit-to-visit variability of systolic BP was evident (r = -0.353, p = 0.022). On multiple regression analysis, the association was significant (p = 0.024) after adjustments for possible confounders (proteinuria, estimated glomerular filtration rate, and mean systolic BP). Decline in RKF was significantly associated with visit-to-visit BP variability in PD patients. The results suggest that RKF can be better maintained by reducing visit-to-visit BP variability.

Using a Peritoneal Dialysis Access Simulator in Surgical Training for Nephrologists.

In Japan, peritoneal dialysis (PD) catheter insertion has been performed by both nephrologists and surgeons. However, nephrologists have fewer opportunities to train in the insertion procedure. We therefore used a PD access simulator to provide training in this operative technique for nephrologists. A PD access simulator developed by Terumo Medical Corporation was used for the training. The simulator uses a mannequin made of acrylic resin. The abdominal wall of a pig is attached to the abdominal area, and a plastic bag represents the abdominal cavity. The simulator enables the surgical procedure to be performed from skin incision to PD catheter insertion. Between October 2011 and December 2013, 3 supervising doctors used the simulator to guide 17 nephrologists with no experience through a PD catheter insertion. One-on-one training was provided in a single 2- or 3-hour session. In a questionnaire survey after the training, trainees gave high marks to the handling of surgical instruments, the environment of the operating room, and the surgical guidance during training. However, the supervising doctors required the ability to respond flexibly, because trainees had individual differences in skills. The PD access simulator might be useful for providing guided training in operative technique for PD catheter insertion.

Proteomic analysis of whole glomeruli in patients with IgA nephropathy using microsieving.

BACKGROUND: To promote understanding of immunoglobulin A nephropathy (IgAN) pathophysiology, we tried to elucidate glomerular protein profiles in IgAN, using microsieving that we established recently to isolate glomeruli from renal biopsy samples and proteomic approaches. METHODS: Glomeruli were isolated from renal biopsy samples of patients with IgAN (n = 5) and with minimal change nephrotic syndrome (MCNS; n = 5) using microsieving. Proteins extracted from the isolated glomeruli were separated by 2-dimensional differential gel electrophoresis (2D-DIGE). Proteins with different amounts between the two groups were identified by mass spectrometry. One of the identified proteins, α-actinin-4 (ACTN4), was further analyzed by Western blotting, RT-polymerase chain reaction (PCR), and immunohistochemistry. RESULTS: By 2D-DIGE, 72 out of the detected 1,170 protein spots showed significantly different intensity between the two groups (p < 0.05). Thirty-four out of the 72 protein spots showed more than 1.5-fold or less than 1/1.5-fold intensity, out of which 16 protein spots were successfully identified. No microbial protein was identified. ACTN4 molecules with a low molecular weight of approximately 77 kDa were found to increase in the IgAN group. Lack of an N-terminal part of ACTN4 was demonstrated by Western blotting. No defect of mRNA for ACTN4 was evidenced by RT-PCR. Predominant existence of ACTN4 in capillary walls of glomeruli of IgAN patients was demonstrated by immunohistochemistry in glomerular sections of patients with IgAN. CONCLUSION: Use of microsieving enabled us to biochemically analyze glomerular proteins in renal biopsy samples from patients with glomerular diseases. With this method, we demonstrated skewed glomerular protein profiles in IgAN.

Subcutaneous pathway diversion for peritoneal dialysis catheter salvage.

Peritoneal dialysis (PD) catheter-related infection is still is the most troublesome problem for continuation of PD without the need to switch to hemodialysis. We have been performing subcutaneous pathway diversion (SPD) as a surgical treatment for refractory exit-site and tunnel infection (ESTI). To clarify the efficacy and safety of SPD, we conducted a retrospective study. From August 2008 to August 2013, 30 SPDs were performed in 26 patients (16 men, 10 women; mean age: 58 +/- 13 years; 54% with diabetes; mean body mass index: 23.9 +/- 3.5 kg/ m2). The reasons for the SPDs were ESTI in 25 patients, and outer cuff extrusion in 1 patient. All patients resumed PD immediately after SPD, and the duration of hospitalization was 11.7 +/- 10.1 days. After SPD, one patient experienced a dialysate leak, and another patient experienced a mild subcutaneous hematoma. Another 4 patients developed exit-site infection (ESI) and underwent a second SPD. Of those 4 patients, 3 presented with another ESI unrelated to the first episode, and all developed an ESI after 6 months or more. The remaining 20 patients experienced no such complications. Furthermore, catheter survival after SPD was 17.4 +/- 13.4 months. To eradicate ESTTI we suggest that SPD, which does not require catheter removal or interruption of PD, is useful compared with the unroofing technique or catheter removal.

The first case report of peritoneal dialysis related peritonitis caused by Microbacterium paraoxydans.

Peritonitis is still the major complication associated with peritoneal dialysis (PD). Microbacterium spp., a type of coryneform bacteria, is an environmental bacterium isolated from soil, waste water and animals. Human infection is rare, and only few cases have so far been reported in immunocompromised hosts, such as PD patients. Microbacterium paraoxydans, one type of Microbacterium spp. was identified for the first time in 2003. Only two cases of infection of Microbacterium paraoxydans have so far been reported. We herein report the first case of PD-related peritonitis caused by Microbacterium paraoxydans, which was identified by a sequence determination of the 16S rRNA gene. Based on the results of antibiotic sensitivity, the intravenous administration of erythromycin (EM) and oral administration of sulfamethoxazole/trimethoprim (ST) were selected, and PD was interrupted. EM administration was stopped after a total of 14 days. ST was administered for a total of 21 days, and later PD was resumed. Thereafter, no recurrence or relapse of peritonitis without removal of the PD catheter was observed. Microbacterium spp. exhibits multidrug resistance and such an infection is refractory in many cases. We assume that both accurate species identification and the use of antibiotic sensitivity tests are essential to effectively treat this kind of infection.

Effects of one-hour discussion on the choice of dialysis modality at the outpatient clinic: A retrospective cohort study using propensity score matching.

BACKGROUND: The aim of present study was to evaluate the effects of one-hour discussion on the choice of dialysis modality at the outpatient clinic. METHODS: Charts of consecutive patients who had started maintenance dialysis from May 2013 to April 2021 were retrospectively reviewed. Characteristics at the start of dialysis were compared between patients participated and not participated in the discussion. RESULTS: Of the 620 incident dialysis patients, 128 patients had participated in the discussion. After propensity score matching (1:1), 127 patients who participated in the discussion tended to have fewer urgent hospitalizations (13.4% vs. 21.3%, p = 0.068). In addition, more patients who initiated peritoneal dialysis (PD) (30.7% vs. 9.4%, p < 0.001). On multivariate analysis, participation in the discussion (OR 4.81, 95% CI 2.807-8.24; p < 0.001) was related to PD initiation. CONCLUSION: One-hour discussion on the choice of dialysis modality may increase PD initiations and decrease the number of urgent hospitalizations.

A multi-institutional, observational study of outcomes after catheter placement for peritoneal dialysis in Japan.

BACKGROUND: This multi-institutional, observational study examined whether the outcomes after peritoneal dialysis (PD) catheter placement in Japan meet the audit criteria of the International Society for Peritoneal Dialysis (ISPD) guideline and identified factors affecting technique survival and perioperative complications. METHODS: Adult patients who underwent first PD catheter placement for end-stage kidney disease between April 2019 and March 2021 were followed until PD withdrawal, kidney transplantation, transfer to other facilities, death, 1 year after PD start or March 2022, whichever came first. Primary outcomes were time to catheter patency failure and technique failure, and perioperative infectious complications within 30 days of catheter placement. Secondary outcomes were perioperative complications. Appropriate statistical analyses were performed to identify factors associated with the outcomes of interest. RESULTS: Of the total 409 patients, 8 who underwent the embedded catheter technique did not have externalised catheters. Of the 401 remaining patients, catheter patency failure occurred in 25 (6.2%). Technical failure at 12 months after PD catheter placement calculated from cumulative incidence function was 15.3%. On Cox proportional hazards model analysis, serum albumin (hazard ratio (HR) 0.44; 95% confidence interval (CI) 0.27-0.70) and straight type catheter (HR 2.14; 95% CI 1.24-3.69) were the independent risk factors for technique failure. On logistic regression analysis, diabetes mellitus was the only independent risk factor for perioperative infectious complications (odds ratio 2.70, 95% CI 1.30-5.58). The occurrence rate of perioperative complications generally met the audit criteria of the ISPD guidelines. CONCLUSION: PD catheter placement in Japan was proven to be safe and appropriate.

Physical activity is associated with serum albumin in peritoneal dialysis patients.

The incidence of metabolic syndrome is about 50% in peritoneal dialysis (PD) patients. The positive association of metabolic syndrome with lower physical activity (PA) has been reported in the general population, but the effect of PA in PD patients has not been clarified. The purpose of the present study was to evaluate PA in PD patients and to clarify the correlations between PA and various clinical parameters in PD patients. We assessed 38 PD patients (22 men; age: 63.9 +/- 10.8 years; body mass index: 24.0 +/- 3.9; 15 with diabetes) who had been treated with PD at least for 3 months. We defined PA as the average number of steps per day measured using a pedometer for 1 month. Blood biochemical findings and dialysis adequacy were measured as clinical parameters. Of the 38 patients, only 11 (29%) reached the steps per day of healthy individuals. In addition, steps per day were significantly correlated with serum albumin (r = 0.45, p = 0.01), C-reactive protein (r = -0.33, p = 0.04), and age (r = -0.34, p = 0.04). Multiple regression analysis showed that serum albumin was the only variable that significantly correlated with steps per day (beta = 0.42, p = 0.01). Our study showed that PA declines significantly in PD patients, which might correlate with malnutrition-inflammation-atherosclerosis syndrome.