Conservative kidney management and kidney supportive care: core components of integrated care for people with kidney failure.

Integrated kidney care requires synergistic linkage between preventative care for people at risk for chronic kidney disease and health services providing care for people with kidney disease, ensuring holistic and coordinated care as people transition between acute and chronic kidney disease and the 3 modalities of kidney failure management: conservative kidney management, transplantation, and dialysis. People with kidney failure have many supportive care needs throughout their illness, regardless of treatment modality. Kidney supportive care is therefore a vital part of this integrated framework, but is nonexistent, poorly developed, and/or poorly integrated with kidney care in many settings, especially in low- and middle-income countries. To address this, the International Society of Nephrology has (i) coordinated the development of consensus definitions of conservative kidney management and kidney supportive care to promote international understanding and awareness of these active treatments; and (ii) identified key considerations for the development and expansion of conservative kidney management and kidney supportive care programs, especially in low resource settings, where access to kidney replacement therapy is restricted or not available. This article presents the definitions for conservative kidney management and kidney supportive care; describes their core components with some illustrative examples to highlight key points; and describes some of the additional considerations for delivering conservative kidney management and kidney supportive care in low resource settings.

[Comparison of benefits to non-dialysis CKD patients between darbepoetin alpha and epoetin beta pegol].

BACKGROUND: Erythropoiesis-stimulating agents (ESAs) are the mainstay of treatment for renal anemia in chronic kidney disease (CKD) patients. However, the difference in hematopoietic effect between darbepoetin alfa (DA) and continuous erythropoiesis receptor activator (CERA) has remained unclear in non-dialysis CKD patients. Another purpose of this study was to analyze the red blood cells indices under treatment with these two ESAs in ESA-naïve CKD patients. METHODS: This study was designed as a multicenter retrospective observational investigation, and included 61 patients receiving DA (group DA) and 36 patients receiving CERA (group CERA) for at least six months. Relative effect of these ESAs was determined by comparing means of the individual monthly average of the area under the curve above the initial level of hemoglobin (Hb), hematocrit (Hct), and red blood cell count (RBC) with the trapezoidal rule, which are maintenance ratios. Serial changes in mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC) were also evaluated. RESULTS: No differences were found in the mean ratios of Hb, Hct, and RBC, and maintenance ratios of these parameters. The ratio of MCH in group CERA was decreased compared with that in group DA. Subsequent decrease in MCV was also remarkable in group CERA. CONCLUSIONS: It is speculated that iron demand increased during the administration of CERA, which was suggested by changes in the red cell indices. Reticulocyte indices and iron-related parameters could provide a more detailed explanation and the significance of iron supplementation during administration of CERA should be clarified when compared with other types of ESA.

Low level of seroconversion after a novel influenza A/H1N1/2009 vaccination in Japanese patients with rheumatoid arthritis in the 2009 season.

We examined change in the antibody titre against pandemic influenza A/H1N1/2009 before and after vaccination in Japanese patients with rheumatoid arthritis. This observational study was conducted with the participation of five hospitals in Japan. A total of 89 patients with rheumatoid arthritis were included in this study. The seroprotection and seroresponse rates to vaccination with the pandemic influenza A/H1N1/2009 vaccine were analysed. The seroprotection rates prior to the vaccination were 5.6% in the Japanese patients with rheumatoid arthritis. The seroprotection rates after subcutaneous vaccination were 55.1%. The seroresponse rate after subcutaneous vaccination was 50.6% in the patients with rheumatoid arthritis. Both the seroprotection and seroresponse rates obtained after the vaccination with the pandemic influenza A/H1N1/2009 vaccine were low in Japanese patients with rheumatoid arthritis. We should realise that a vaccination against this newly emerged influenza virus may protect only half of the Japanese patients with rheumatoid arthritis in a real world.

A case of encapsulating peritoneal sclerosis at the clinical early stage with high concentration of matrix metalloproteinase-2 in peritoneal effluent.

In encapsulating peritoneal sclerosis (EPS), matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases are involved in the remodeling of peritoneal tissue. We measured the MMP-2 concentration in the peritoneal effluents of a patient with EPS who discontinued continuous ambulatory peritoneal dialysis (CAPD) therapy because of ultrafiltration failure and/or underdialysis. First, we report a 58-year-old female patient who discontinued CAPD therapy because of underdialysis. Several months after cessation of CAPD, she complained of slightly blood-colored ascites and had an elevated level of C-reactive protein (CRP) in plasma. She was diagnosed as having clinical early-stage EPS. Peritoneal effluents drained from this case, and from 11 patients who discontinued CAPD therapy because of ultrafiltration failure and/or underdialysis, and who underwent peritoneal lavage with 1.5% dextrose peritoneal dialysis fluid for several months, were analyzed by gelatin zymography. MMP-2 concentration was also measured by enzyme-linked immunosorbent assay (ELISA). MMP-2 concentration in peritoneal effluent of this patient was highest compared with that of the other patients. There was some tendency of a positive correlation between MMP-2 concentration per 1 g protein and D/Pcr, and was negative correlation between MMP-2 concentration per 1 g of protein and D/D0 glucose. We concluded that MMP-2 is involved in the peritoneal remodeling of long-term CAPD therapy and the progression of EPS.

Multimeric vitronectin in ascites is involved in fibroblast spreading of EPS in patients on CAPD therapy.

BACKGROUND: Although encapsulating peritoneal sclerosis (EPS) is a serious complication of continuous ambulatory peritoneal dialysis (CAPD) therapy, the mechanism of the fibroneogenesis in EPS remains unknown. Because fibroblast adhesion and spreading to the extracellular matrix is the first step in peritoneal fibrosis, we investigated fibroblast spreading factor in ascites obtained from patients with EPS (EPS ascites). METHODS: To analyze fibroblast spreading activity, various concentrations of EPS ascites obtained from two EPS patients were coated on culture plates, and then the number of human fibroblasts (TIG-3) that had spread was counted. Each fraction of gel-filtered EPS ascites was also analyzed by this activity. Next, we examined the effect of the addition of Arg-Gly-Asp (RGD) peptides, several antibodies against adhesion molecules, and heparin on the fibroblast spreading activity in the EPS ascites. RESULTS: The fibroblast spreading activity of EPS ascites was about four times greater than that in ascites from a patient with nephrotic syndrome. Two major peaks (peak I and II) of spread cells were obtained when ascites were gel-filtered. The fibroblast spreading activities of the two peaks were abolished by the addition of RGD peptides and polyclonal antibody against vitronectin (VN). Immunoblotting analysis revealed that the two peaks contained VN and that peak I contained multimeric VN. Heparin, at 10 microg/ml, augmented the fibroblast spreading activity of peak I to about three times greater than the control. CONCLUSIONS: The results indicate that multimeric VN in EPS ascites plays a potential role in peritoneal fibrogenesis in EPS and that heparin may participate in peritoneal fibrosis in EPS.

[Effect of oral intake of an enteric capsule preparation containing Bifidobacterium longum on the progression of chronic renal failure].

Since the accumulation of intestinal putrefactive products, such as indole and phenol, is known to play a role in the exacerbation of chronic renal failure, reduction of these intestinal putrefactive products can be expected to retard the progression of renal failure. In the present study, an enteric capsule preparation containing Bifidobacterium longum(Bifidus HD) was administered orally to 27 patients with chronic renal failure(CRF) for 6 months. Though no significant effect was found in the whole group, a significant retardation of the progression of renal failure was found in patients with an initial serum creatinine level > or = 4.0 mg/dl or those with an initial serum inorganic phosphate level > or = 4.0 mg/dl. There was no adverse effect observed in any case. Bifidus HD is considered a useful tool for suppressing the progression of chronic renal failure(CRF) in the conservative period.

Ascites from patients with encapsulating peritoneal sclerosis augments NIH/3T3 fibroblast proliferation.

Encapsulating peritoneal sclerosis (EPS) remains one of the major causes of dropout in continuous ambulatory peritoneal dialysis by reducing ultrafiltration capacity. To demonstrate whether ascites from patients with EPS (EPS ascites) has fibroblast proliferation activity, we used NIH/3T3 fibroblasts to examine the effects of EPS ascites on fibroblast proliferation activity by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Encapsulating peritoneal sclerosis ascites dose-dependently augmented NIH/3T3 fibroblast proliferation. The protein kinase C inhibitors and the tyrosine kinase inhibitors partially inhibited the stimulatory effects of EPS ascites on fibroblast proliferation activity. In EPS ascites, levels of interleukin (IL)-1beta, IL-6, IL-8, transforming growth factor (TGF)-beta1, hepatocyte growth factor (HGF), and platelet-derived growth factor (PDGF)-AB were elevated. The treatment with IL-1beta, HGF, TGF-beta1, and PDGF-AB alone or in combination at similar concentrations to those in EPS ascites exhibited small but significant fibroblast proliferation activities. We conclude that EPS ascites stimulate NIH/3T3 fibroblast proliferation via protein kinase C and tyrosine kinase. The elevated cytokine and growth factors partly contribute to the EPS ascites-induced fibroblast proliferation.

Impaired urinary concentrating ability in genetically polyuric mice.

Newly recognized strain of mice with hereditary polyuria (PUS mice) was characterized. Polyuria was inherited as a single autosomal-recessive trait. At 15 weeks, PUS mice excreted hypotonic (urine osmolality: PUS;270.8 +/- 15.5 vs. cont.; 3,228.6 +/- 163.6 mosm/kg) polyuria (urine volume: PUS; 25.0 +/- 1.5 vs. cont.; 1.1 +/- 0.1 ml/day). In PUS mice, plasma osmolality was slightly elevated as well as urinary excretion of vasopressin (AVP). Although PUS mice could concentrate urine after 24 h water deprivation, urine osmolality remained low. Blunted response to continuous infusion of dDAVP, a synthetic V2 agonist, was also observed. These in vivo studies indicated renal resistance to AVP contributed to the polyuria in this strain of mice. Microanalysis of isolated tubular segments revealed that AVP-induced cAMP accumulation in cortical collecting ducts (CCD) of PUS mice was significantly lower (60%) with or without a phosphodiesterase inhibitor, IBMX. Vasopressin induced similar cAMP accumulation in medullary ascending limbs of Henle (MAL), and medullary collecting ducts (MCD) between PUS and control mice. In CCDs, PUS mice had low basal adenylate cyclase (AdC) activity and responded less to AVP and forskolin stimulation than control mice. No difference in cyclic AMP phosphodiesterase activity was detected between control and PUS mice. These results indicate that impaired cAMP accumulation due to low AdC activity may be related to the impaired renal concentrating ability observed in this new strain of mice.

Changes in peritoneal coagulation and fibrinolysis after discontinuation of chronic peritoneal dialysis.

OBJECTIVES: To study changes in peritoneal function after transfer from chronic peritoneal dialysis (CPD) to hemodialysis (HD), especially the effects on peritoneal coagulation, fibrinolytic markers, and mesothelium. DESIGN: Prospective observational study. SETTING: A tertiary-care university hospital. PATIENTS: Nine patients who transferred from CPD to HD were enrolled in the study after giving fully informed consent. METHODS: After transfer to HD, the peritoneal cavity was lavaged with low glucose PD solution once per day through PD catheters left in place. Thrombin-antithrombin III complex (TAT) was measured serially as a marker of peritoneal coagulation. As fibrinolytic markers, fibrinogen/fibrin degradation products (FDP) and plasmin-alpha2-antiplasmin complex (PIC) were assessed. Cancer antigen 125 (CA125) was measured as a marker of mesothelial cell mass. RESULTS: Levels of peritoneal TAT and FDP were much higher than plasma levels, indicating high local fibrin turnover. Transfer to HD induced a significant fall in mean peritoneal TAT, from 115.8 +/- 52.1 to 60.7 +/- 21.8 ng/mL, p < 0.05. Except for 1 patient with a 20-fold increase, mean peritoneal FDP decreased significantly, from 43.6 +/- 11.1 to 19.6 +/- 3.5 microg/mL, p < 0.05. Mean peritoneal PIC increased significantly, from 1.9 +/- 0.4 to 3.9 +/- 0.6 microg/mL, p < 0.05. Peritoneal CA125 increased from 156.4 +/- 57.3 to 1426.2 +/- 389.4 U/mL, p < 0.05. CONCLUSIONS: Peritoneal fibrin turnover was accelerated on CPD and stabilized after transfer to HD. Transfer to HD also induced mesothelial regeneration.