Effects of 1-week inpatient multidisciplinary care for chronic kidney disease prior to outpatient collaborative care.

BACKGROUND: Multidisciplinary care for Chronic Kidney Disease (CKD) has been reported to be effective in preventing deterioration of renal function and avoiding hemodialysis induction using a central venous catheter. METHODS: We included 171 patients who received dialysis at our department between October 2014 and June 2017. Patients were divided into two groups: an inpatient group who received inpatient multidisciplinary care for CKD (educational hospitalization) prior to outpatient collaborative care from their family physician and nephrologist, and a non-inpatient group who did not receive such care. We compared factors related to dialysis induction. RESULTS: There was no significant difference in eGFR between the groups at the start of observation. The mean time from the start of observation to dialysis induction (inpatient group vs. non-inpatient group; 40.8 ± 2.8 vs. 23.9 ± 3.0 months, respectively; P < 0.001) and the rate of hemodialysis induction using a central venous catheter (22.5 vs. 47.1%, respectively; P = 0.002) were significantly different between the groups. Survival analysis showed that the time to dialysis induction was significantly longer in the inpatient group (P = 0.0001). Multivariate analysis revealed that educational hospitalization (odds ratio = 0.30 [95% CI 0.13, 0.67]) was significantly associated with hemodialysis induction using a central venous catheter. CONCLUSION: Educational hospitalization prior to outpatient collaborative care is beneficial for preventing hemodialysis induction using a central venous catheter and postponing dialysis induction.

Peritoneal Dialysis-associated Peritonitis Due to Streptococcus oralis Three Weeks after Peritoneal Dialysis Initiation.

A 60-year-old man with end-stage renal disease due to nephrosclerosis had a peritoneal dialysis catheter (PD) embedded with stepwise initiation of peritoneal dialysis using Moncrief and Popovich's technique three months ago. PD was initiated three weeks after creating an exit site. He presented with abdominal pain and fever a day before admission and was diagnosed with PD-associated peritonitis caused by Streptococcus oralis. Medical consultation after admission revealed a history of wisdom tooth extraction following PD catheter placement, resulting in delayed wound healing. Transient bacteremia can occur after tooth extraction, leading to PD-associated peritonitis. Contemplating the oral milieu in patients undergoing PD is pertinent.

Hemodialysis Patient with Streptococcal Toxic Shock Syndrome and Penile Necrosis.

A 72-year-old man on hemodialysis due to diabetic nephropathy presented with a fever and penile pain. Although his physical examination was unremarkable, his general condition deteriorated. Penile necrosis was observed by evening on the same day of presentation, and the patient died the next morning. Blood cultures revealed the presence of Group G Streptococcus, leading to a diagnosis of streptococcal toxic shock syndrome (STSS). Autopsy suggested penile necrosis due to septic shock. STSS in hemodialysis patients with vascular calcification, even in the absence of calciphylaxis, can lead to severe organ damage due to ischemia.

Association among kidney function, frailty, and oral function in patients with chronic kidney disease: a cross-sectional study.

BACKGROUND: Chronic kidney disease (CKD) involves many factors that can cause frailty and oral hypofunction. We aimed to investigate the prevalence of frailty and oral hypofunction and to examine the associations among kidney function, frailty, and oral function in adults with CKD in Japan. METHODS: This cross-sectional study was conducted at two institutions. The participants included 109 patients with CKD stages 3-5 who visited outpatient clinics or were admitted for inpatient treatment. Frailty was evaluated using the Japanese version of the Cardiovascular Health Study frailty criteria. Oral function was evaluated by assessing oral motor skills [oral diadochokinesis (ODK) rate], masticatory ability, and the repetitive saliva swallowing test. The estimated glomerular filtration rate (eGFR) was used to indicate kidney function. We examined the associations among kidney function, frailty, and oral function using binomial logistic regression analysis. RESULTS: In total, 31 participants (28.4%) were classified as being frail. Univariate analysis showed that age, body mass index, eGFR, and haemoglobin level were significantly associated with frailty. ODK and swallowing function were significantly associated with frailty. Multivariate analysis revealed that frailty was significantly associated with eGFR [odds ratio (OR) 0.96, 95% confidence interval (CI) 0.92-1.00, p = 0.048] and ODK rate (OR 0.68, CI 0.47-0.98, p = 0.038). However, no significant association was found between CKD severity and masticatory or swallowing function. CONCLUSION: We found a high prevalence of frailty in patients with CKD and a significant association between frailty and oral motor skills, affecting the swallowing function of patients with nondialysis CKD. The high prevalence of frailty among patients with CKD suggests that routine assessment of frailty is necessary to prevent the development of severe complications. In addition, oral and kidney function should be carefully evaluated, and oral health education and interventions should be performed for patients with CKD.

Ambulatory blood pressure monitoring-based analysis of long-term outcomes for kidney disease progression.

Non-dipping nocturnal blood pressure (BP) pattern is a predictor of the future decline of renal function; however, it is unclear whether it is still a risk for chronic kidney disease (CKD) patients with normal BP. To solve this question, a retrospective cohort study was conducted, and 1107 CKD patients who underwent ambulatory blood pressure monitoring (ABPM) were enrolled. We divided patients into 4 groups based on their nocturnal BP dipping pattern (dipper or non-dipper) and average 24-hour BP (hypertension or normotension). The cumulative incidence of composite renal outcomes, including a 40% reduction in eGFR, the induction of renal-replacement therapy, or death from renal causes, was analyzed. Overall, 86.1% of participants were non-dippers and 48.2% of them were normotensive. During the median follow-up period of 4.72 years, the incidence of renal composite outcomes was highest in hypertensive non-dipper patients, and was similar between normotensive dipper and non-dipper patients. Multivariate regression analysis revealed that the 24-hour systolic BP, amount of urinary protein, and hemoglobin values were associated with the incidence of renal outcomes. In conclusion, our ABPM-based analysis revealed that a non-dipping BP pattern with normotension does not predict the future incidence of composite renal outcomes in CKD patients.

Rapid weight loss with dietary salt restriction in hospitalized patients with chronic kidney disease.

Dietary salt restriction is essential for managing fluid retention in patients with chronic kidney disease (CKD). In this retrospective cohort study, we investigated weight loss from the perspective of fluid status in CKD patients during a 7-day hospitalization period while consuming a low-salt diet (5 g/day). Among 311 patients, the median weight loss (interquartile range, maximum) was 0.7 (0.0-1.4, 4.7) kg on Day 4 and 1.0 (0.3-1.7, 5.9) kg on Day 7. Patients were classified into quartiles based on pre-hospital urinary salt excretion (quartile [Q] 1, 1.2-5.7; Q2, 5.8-8.4; Q3, 8.5-11.3; Q4, 11.4-29.2 g/day). Weight loss was significantly greater in Q3 and Q4 than in Q1. The body mass index (BMI) and urinary salt excretion in the first 24 hours after admission were independently associated with rapid weight loss on Day 4 by multivariate logistic regression analysis. In conclusion, CKD patients with a high salt intake or high BMI exhibit rapid weight loss within a few days of consuming a low-salt diet. Dietary salt restriction is effective for reducing proteinuria in these patients, but long-term observation is needed to confirm the sustained effects.

Impact of salt taste dysfunction on interdialytic weight gain for hemodialysis patients; a cross-sectional study.

BACKGROUND: Little is known about salt taste dysfunction among hemodialysis (HD) patients. This study aimed to elucidate the prevalence of salt taste dysfunction and its relationship with interdialytic weight gain (IDWG) among HD patients. METHODS: A single-center cross-sectional study involving 99 maintenance HD patients was conducted in September 2015. Salt taste threshold was measured using a salt-impregnated test strip. Salt taste dysfunction was defined as a recognition threshold of ≥0.8%. IDWG was calculated as the mean value of weight gain at the beginning of each week during a 1-month period before the taste test. We performed a multivariate analysis using the standard linear regression model to investigate the association between salt taste dysfunction and IDWG. RESULTS: Among the 99 participants, 42% had a recognition threshold of 0.6%, whereas 38% had a recognition threshold of ≥1.6%. Overall, the prevalence of salt taste dysfunction was 58%. The mean (±SD) IDWG was 4.9% (±1.7%), and there was no significant difference in IDWG between the two groups with (4.9%) and without (4.8%) salt taste dysfunction (P = 0.90). A multivariate analysis indicated that salt taste dysfunction is not significantly associated with IDWG (mean difference = 0.06; 95% confidence interval = - 0.27 to 0.40). CONCLUSIONS: The prevalence of salt taste dysfunction was very high among HD patients who had a unique distribution of salt taste recognition thresholds with two peaks. We found no significant association between salt taste dysfunction and IDWG.

Normotensive non-dipping blood pressure profile does not predict the risk of chronic kidney disease progression.

The lack of a decrease in nocturnal blood pressure is a risk factor for the progression of chronic kidney disease (CKD); however, it currently remains unknown whether it is a risk factor in normotensive CKD patients. We conducted a retrospective cohort study and enrolled 676 CKD patients who underwent ambulatory blood pressure monitoring (ABPM). According to their nocturnal blood pressure dipping pattern (>10%: dipper or <10%: non-dipper) and average 24-h systolic blood pressure (>130/80 mmHg: hypertension or <130/80 mmHg: normotension), patients were divided into four groups. The estimated glomerular filtration rate (eGFR) decline over 2 years and relevant clinical parameters were analyzed among groups. Among all participants, 82.7% were non-dippers and half of them were normotensive. The eGFR decline was the most rapid in hypertensive non-dipper patients (4.73 ± 0.45 ml/min/1.73 m2/2 years), and was not significantly different between normotensive non-dipper (1.31 ± 0.49 ml/min/1.73 m2/2 years) and dipper patients (1.69 ± 0.80 ml/min/1.73 m2/2 years). A multivariate regression analysis revealed that the amount of urinary protein (95% confidence interval (CI): 1.51-2.63), 24-h systolic blood pressure (95% CI 1.13-1.45), and eGFR (95% CI 1.02-1.44) were associated with a rapid eGFR decline. We conclude that, according to the ABPM-based analysis, a non-dipping blood pressure pattern in normotensive CKD patients does not predict the risk of a rapid decline in eGFR. This suggests that the control of blood pressure, rather than its circadian rhythm, is essential for the preservation of eGFR.

Extranodal NK/T-cell Lymphoma, Nasal Type Accompanied by PR3-ANCA-associated Glomerulonephritis.

A 62-year-old man exhibiting nasal obstruction and glomerulonephritis with proteinase 3-antineutrophil cytoplasmic antibodies (PR3-ANCAs) was diagnosed with extranodal NK/T-cell lymphoma, nasal type (ENKL) with infiltration of neutrophils with apoptosis. Chemoradiotherapy reduced the tumor, improved the renal function, and decreased the PR3-ANCA levels. ANCA-positivity is observed in immunoinsufficient diseases, in which neutrophils lead to apoptosis and translocate intracellular granules, such as PR3, to the cell surface, triggering the production of ANCAs. In our case, the PR3-ANCA production was derived from the expression of PR3 on the cell surface of apoptotic neutrophils. This is the first report on ENKL describing the mechanism of ANCA development.

Lower blood pressure and risk of cisplatin nephrotoxicity: a retrospective cohort study.

BACKGROUND: The pathophysiological mechanisms of cisplatin nephrotoxicity include the reduction of renal blood flow, as well as tubular epithelial cell toxicity. The objective of this study was to investigate the influence of lower blood pressure and decreased food intake on the incidence of cisplatin nephrotoxicity. METHODS: We conducted a retrospective cohort study at a university hospital between 2011 and 2012. We identified hospitalized adult patients with head and neck cancer, esophageal cancer, or gastric cancer, who received intravenous cisplatin administration. The primary outcome was the incidence of cisplatin nephrotoxicity defined as the increase in serum creatinine after cisplatin administration more than 1.5 times from baseline. RESULTS: The study participants included 182 patients, in whom we observed a total of 442 cycles of cisplatin chemotherapy. The incidence of cisplatin nephrotoxicity was observed in 41 of 182 cycles with initial administration. Multivariate logistic regression analysis showed that systolic blood pressure was independently associated with cisplatin nephrotoxicity (adjusted odds ratio 0.75, 95% confidence interval 0.57 to 0.95 for each 10 mmHg). The use of renin-angiotensin system (RAS) inhibitors was also associated with cisplatin nephrotoxicity (3.39, 1.30 to 8.93). Among quartiles of systolic blood pressure in all cycles of chemotherapy, the incidence of nephrotoxicity in the lower blood pressure group was significantly higher than that in the higher blood pressure group for patients taking non-solid food (P = 0.037), while there was no significant difference for patients taking solid food (P = 0.67). CONCLUSIONS: Lower blood pressure and the use of RAS inhibitors were associated with the incidence of cisplatin nephrotoxicity, and lower blood pressure had a greater influence on nephrotoxicity in patients who could not take solid food. Discontinuation of antihypertensive medication including RAS inhibitors before cisplatin chemotherapy should be considered, which may be beneficial for patients with lower blood pressure.

Hematopoietic Stem Cell Transplantation Nephropathy Associated with Chronic Graft-versus-Host Disease without Extrarenal Involvement.

A 30-year-old woman with myelodysplastic syndrome underwent allogeneic hematopoietic stem cell transplantation (HSCT) derived from her HLA-matched sister six years previously. She received preconditioning total body irradiation with renal shielding and was subsequently administered cyclosporin A (CyA) as prophylaxis against graft-versus-host disease (GVHD). Four months after HSCT, asymptomatic proteinuria and glomerular hematuria developed during CyA tapering without obvious extrarenal involvements of GVHD, and persisted for six years. A renal biopsy revealed endothelial injury in the glomeruli, and the deposition of C4d was detected diffusely on glomerular capillaries and focally on peritubular capillaries, suggesting that nephropathy involved antibody- or complement-associated immune reactions.

A Japanese Family Suffering from Familial Juvenile Hyperuricemic Nephropathy due to a Rare Mutation of the Uromodulin Gene.

We report the case of a Japanese family suffering from familial juvenile hyperuricemic nephropathy (FJHN) due to a rare missense mutation of the uromodulin (UMOD) gene. An 18-year-old male presented with gout, hyperuricemia, and stage 3 chronic kidney disease. Mostly, FJHN is caused by a mutation altering the cystine residue of UMOD/Tamm-Horsfall protein. However, in the present case, a T688C mutation was identified in exon 4, resulting in amino acid substitution with arginine replacing tryptophan at position 230 (Trp230Arg). This mutation was also found in his brother and father with the same phenotype, indicating autosomal dominant inheritance. The affected amino acid was conserved in 200 healthy Japanese controls. Therefore, mutation T688C most likely causes rare structural and/or functional abnormalities in UMOD/Tamm-Horsfall protein.

[Case of lupus nephritis complicated with hemophagocytic syndrome].

A 27-year-old woman was referred to our hospital because of pancytopenia and nephritic syndrome in November, 2008. The findings of physical and laboratory examinations showed systemic lupus erythematosus (SLE). Diffuse proliferative lupus nephritis(group IV-G(A))was confirmed by renal biopsy. After combined therapy with prednisolone, intravenous cyclophosphamide pulse and mizoribine, proteinuria decreased from 13.0 g/day to 2.0 g/day and the serum complement level recovered to the normal level. However, she visited our hospital again for management of bleeding tendency in July 2009. She was diagnosed as hemophagocytic syndrome (HPS), with pancytopenia, high ferritin, high LDH level and hemophagocytosis in the bone marrow. She was treated effectively with steroid pulse therapy, but relapsed with HPS after two weeks. Although her child caught a cold, the case did not show any sign or symptom of infection, such as the common cold. However, we diagnosed her HPS as infection-associated hemophagocytic syndrome (IAHS) because she was not in the active phase of SLE at the onset of hemophagocytosis and the laboratory findings showed elevation of her serum ferritin and LDH. Therefore, we considered that her infectious sign may have been concealed by immunosuppressive therapy with prednisolone for SLE. It is very difficult to distinguish between IAHS and autoimmune-associated hemophagocytic syndrome (AAHS)in autoimmune diseases, but the differential diagnosis is necessary to treat the HPS. Here, we report an important case of HPS complicated with SLE. This case may attract interest particularly in the management of HPS-complicated autoimmune disease. Therefore, we report it with a review of the literature.

The kinase Pyk2 is involved in renal fibrosis by means of mechanical stretch-induced growth factor expression in renal tubules.

Unilateral ureteral obstruction is a well-established experimental model of progressive renal fibrosis. We tested whether mechanical stretch and subsequent renal tubular distension might lead to renal fibrosis by first studying renal tubular epithelial cells in culture. We found that mechanical stretch induced reactive oxygen species that in turn activated the cytoplasmic proline-rich tyrosine kinase-2 (Pyk2). This kinase is abundantly expressed in tubular epithelial cells where it is activated by several stimuli. Using mice with deletion of Pyk2 we found that the expression of transforming growth factor-ß1 induced by mechanical stretch in renal tubular epithelial cells was significantly reduced. The expression of connective tissue growth factor was also reduced in the Pyk2(-/-) mice. We also found that expression of connective tissue growth factor was independent of transforming growth factor-ß1, but dependent on the Rho-associated coiled-coil forming protein kinase pathway. Thus, Pyk2 may be an important initiating factor in renal fibrosis and might be a new therapeutic target for ameliorating renal fibrosis.

[Case of peritubular capillary dominant intravascular large B-cell lymphoma (PTC dominant IVLBCL) successfully treated with chemotherapy].

A 72-year-old woman developed common cold-like symptoms, diarrhea, a staggering gait, and persistent anorexia from the beginning of May 2009. In the middle of May, her general fatigue worsened, and she was transported to our hospital by ambulance. Abdominal CT showed bilateral renal enlargement, and her general condition and renal function rapidly deteriorated. The soluble interleukin-2 receptor (sIL-2R) level was elevated to 5,928 U/mL, and gallium scintigraphy showed a weak uptake in both kidneys. We considered the possibility of malignant lymphoma, and performed a renal biopsy, which showed no glomerular abnormalities, but disclosed the accumulation of large, atypical lymphoid cells with a high N/C ratio and dark chromatin in peritubular capillaries (PTC). On immunohistochemical staining, these atypical cells were found to be CD5(+), CD20 (+/-), CD10(-), CD3(-), and CD7(-), leading to a diagnosis of intravascular large B-cell lymphoma (IVLBCL). Since gallium scintigraphy showed no uptake in other organs, and examination of the cerebrospinal fluid and bone marrow revealed no tumor cells, the patient was considered to have kidney-limited IVLBCL. Chemotherapy was started immediately, which resulted in an improved general condition. Although her renal function deteriorated sufficiently to require dialysis, she was weaned from dialysis. After treatment with chemotherapy, the enlarged kidneys returned to the normal size. Subsequently, she has been receiving chemotherapy intermittently, and has remained free of recurrence. In general, IVLBCL mainly involving the kidney is difficult to diagnose antemortem, and is sometimes found at autopsy. We suggest that bilateral renal enlargement with renal failure of unknown origin should raise the suspicion of malignant lymphoma requiring a prompt renal biopsy. Cases of LBCL in which lymphoma cells fill PTC, as in this patient, have rarely been reported. We believe that this case is extremely valuable in understanding the pathogenesis of intravascular lymphoma invading the kidney; therefore, we report it with a review of the literature.

[Case of fanconi syndrome positive for anti-M2 antibodies revealed by severe hypokalemia and multiple bone fracture].

A 38-year-old female developed pain in the right leg in 2006. In 2007, the diagnosis of femoral head necrosis was made based on MR images, and femoral head prosthetic replacement was performed. In April 2009, she visited a local hospital for low back pain, and was referred to our department due to electrolyte abnormalities on hemanalysis. Since marked hypokalemia (K=2.5 mEq/L), hypophosphatemia, hyperchloric metabolic acidosis, proteinuria, and urinary blood sugar suggested Fanconi syndrome, she was admitted for close examination. Bone survey showed a marked decrease in the amount of bone particularly in the four limbs and fracture at the proximal 1/3 of the left ulnar bone. In the lumbar spine, scoliosis and vertebral deformity were observed. Since impaired P re-absorption and unselected aminoaciduria and osteomalacia were also present, the diagnosis of Fanconi syndrome was made. On admission, ventricular tachycardia developed due to hypokalemia, requiring immediate electrolyte correction. For differentiation from acquired Fanconi syndrome, various examinations were performed. No apparent cause was found except for the positive antimitochondrial antibody-M2 (anti-M2). In this case, no data suggested liver dysfunction, and subsequent liver biopsy also showed no significant pathological findings pointing to PBC. We encountered a patient with Fanconi syndrome positive for anti-M2. This case may attract interest, particularly in the mechanism of nephropathy due to anti-M2, and therefore, this case is reported with a literature review.

Plasma S100A12 levels and peripheral arterial disease in end-stage renal disease.

BACKGROUND: S100A12 is an endogenous ligand of the receptor for advanced glycation end products (RAGE). Plasma S100A12 levels are high in end-stage renal disease (ESRD) patients undergoing maintenance hemodialysis (HD). Peripheral arterial disease (PAD) is common in HD patients and is associated with increased cardiovascular morbidity and mortality rates in this population. To date, however, no study has specifically assessed the relationship between plasma S100A12 and PAD in HD patients. METHODS: We conducted a cross-sectional study of 152 HD patients in our affiliated hospital. We investigated PAD history and patient characteristics and quantified plasma S100A12 levels in all participants. RESULTS: HD patients with PAD (n = 26; 21.9 [13.6-33.4] ng/ml) showed significantly higher plasma S100A12 levels than HD patients without PAD (n = 126; 11.8 [7.5-17.6]ng/ml; p < 0.001). In multivariate logistic regression analysis, the plasma S100A12 level (odds ratio [OR] 5.71; 95% confidence interval [CI] 1.29-25.3; p = 0.022) was identified as an independent factor associated with PAD prevalence. Another factor associated with PAD prevalence was the ankle-brachial index (OR 0.54; 95% CI 0.40-0.74; p < 0.001). CONCLUSION: These results suggest that plasma S100A12 levels are strongly associated with PAD prevalence in ESRD patients undergoing HD.