Superior patient survival for continuous ambulatory peritoneal dialysis patients treated with a peritoneal dialysis fluid with neutral pH and low glucose degradation product concentration (balance)

BACKGROUND: In recent years, laboratory and clinical research has suggested the need for peritoneal dialysis fluids (PDFs) that are more biocompatible than the conventional PDFs commonly used today. Bioincompatibility of PDF has been attributed to low pH, lactate, glucose, glucose degradation products (GDPs), and osmolality. PDFs with neutral pH and low GDPs are now available commercially. In vitro and early clinical studies suggest that these solutions are indeed more biocompatible but, as of now, there is no evidence that their use improves patient outcome. METHODS: Using a dedicated database of over 2000 patients treated with PD in Korea, we were able to conduct a retrospective observational study comparing outcomes for incident continuous ambulatory PD patients treated with a standard, conventional, heat-sterilized PDF to the outcomes for patients treated with a novel, low GDP, neutral-pH PDF prepared in a dual-compartment, double-bag PD system (Balance; Fresenius Medical Care, St. Wendel, Germany). In an intention-to-treat analysis, patient and technique survival, peritonitis-free survival, and peritonitis rates were compared in 611 patients treated with Balance for up to 30 months and 551 patients with a standard PDF (stay . safe; Fresenius Medical Care) treated in the same era and with equivalent follow-up. RESULTS: The patients were well matched for most relevant characteristics except older age distribution for the patients treated with the standard PDF. Patients treated with Balance had significantly superior survival compared to those treated with the standard PDF (74% vs 62% at 28 months, p = 0.0032). In a multivariate Cox regression model including age, diabetes, and gender, the survival advantage persisted (relative risk of death for Balance 0.75, 95% confidence interval 0.56 - 0.99, p = 0.0465). Modality technique survival was similarin Kaplan-Meieranalysis for both PDFs. No differences were detected in peritonitis-free survival or in peritonitis rates between the two solutions. CONCLUSION: This study, for the first time, suggests that treatment with a novel biocompatible PDF with low GDP concentration and neutral pH confers a significant survival advantage. The exact mechanisms for such a survival advantage cannot be determined from this study. The usual criticisms of observational studies apply and the results reported here strongly warrant the undertaking of appropriately designed, randomized, controlled clinical trials.ope

A case of severe Lactic acidosis induced by metformin overdose

Metformin is an oral hypoglycemic agent belonging to the biguanide class that has been used to treat type II diabetes mellitus worldwide. Lactic acidosis is a rare, but serious, adverse effect in metformin-treated patients with renal and hepatic disease, cardiac or respiratory insufficiency, severe infection, and any hypoxic condition. Large overdoses of metformin can also lead to lactic acidosis. Attempted suicide with metformin is rare. Treatment with bicarbonate is generally accepted, although there is no clear evidence that it improves the outcome of lactic acidosis. Bicarbonate hemodialysis and continuous veno-venous hemodiafiltration (CVVHDF) are probably both beneficial in correcting the acidosis, and by actively removing metformin and lactate from the circulation. We report the case of a patient with severe lactic acidosis induced by metformin intoxication who recovered fully after treatment with a combination of bicarbonate hemodialysis and CVVHDFope

Development of objective indicators for quantitative analysis of sodium intake: the sodium to potassium ratio of second-void urine is correlated with 24-hour urinary sodium excretion

BACKGROUND/OBJECTIVES: To date, sodium intake has been evaluated based on spot urine instead of 24-hour (hr) urine collection. Nevertheless, the optimal method for assessing daily sodium intake remains unclear. SUBJECTS/METHODS: Fifteen male (age 32.7 +/- 6.5 years) participants were offered 3 meals with a total of 9-10 g salt over 24 hours, and 24-hr urine was collected from the second-void urine of the first day to the first-void urine of the second day. Twenty-four-hr urinary sodium (24UNa) was estimated using Tanaka's equation and the Korean formula, and spot urine Na, potassium (K), chloride (Cl), urea nitrogen (UN), creatinine (Cr), specific gravity (SG) and osmolality (Osm) were measured. The ratios of urinary Na to other parameters were calculated, and correlations with total measured 24UNa were identified. RESULTS: Average 24-hr urine volume was 1,403 +/- 475 mL, and measured 24UNa was 143.9 +/- 42.1 mEq (range, 87.1-239.4 mEq). Measured 24UNa was significantly correlated with urinary Na/UN (r = 0.560, P < 0.01), urinary Na/Osm (r = 0.510, P < 0.01), urinary Na/Cr (r = 0.392, P < 0.01), urinary Na/K (r = 0.290, P < 0.01), 24UNa estimated using Tanaka's equation (r = 0.452, P < 0.01) and the Korean formula (r = 0.414, P < 0.01), age (r = 0.548, P < 0.01), weight (r = 0.497, P < 0.01), and height (r = 0.393, P < 0.01) in all spot urine samples. Estimated 24UNa based on the second-void spot urine of the first day tended to be more closely correlated with measured 24UNa than were estimates from the other spot urine samples. The significant parameters correlated with the second-void urine of the first day were urinary Na/K (r = 0.647, P < 0.01), urinary Na/Cr (r = 0.558, P < 0.05), and estimated 24UNa using Tanaka's equation (r = 0.616, P < 0.05) and the Korean formula (r = 0.588, P < 0.05). CONCLUSIONS: Second-void urine is more reliable than first-void urine for estimating 24UNa. Urinary Na/K in the second-void urine on the first day is significantly correlated with 24UNa. Further studies are needed to establish the most reliable index and the optimal time of urine sampling for predicting 24UNa.ope

Severe Symptomatic Hyponatremia Caused by Low Dose Oral Cyclophosphamide: A Case Report

Cyclophosphamide (CY), an alkylating agent, is frequently used in the treatment of various autoimmune disorders and malignancies. Acute hyponatremia is a well-known side effect of moderate to high dose intravenous CY treatment, but is rare in patients treated with low dose intravenous CY. We report the case of a severe symptomatic hyponatremia in a 68-year-old woman with renal impairment who was treated with oral CY (100 mg/day) for anti-neutrophil cytoplasmic antibody (ANCA) associated glomerulonephritis (GN). This case demonstrates that even oral CY could be associated with life threatening acute hyponatremia and should be used with caution.ope

Severe cutaneous hypersensitivity to icodextrin in a continuous ambulatory peritoneal dialysis patient

Icodextrin, a glucose polymer, is widely used as an alternative to glucose as the osmotic agent in peritoneal dialysis (PD). We describe a case of a continuous ambulatory peritoneal dialysis patient who developed severe cutaneous hypersensitivity after initiation of icodextrin PD solution. Erythematous skin lesions gradually disappeared after discontinuation of icodextrin PD solution. Although the safety and efficacy of icodextrin PD solution is well documented, clinicians should be mindful of the possibility of severe adverse cutaneous reactions to icodextrin PD solution.ope

Kidney-derived mesenchymal stem cells contribute to vasculogenesis, angiogenesis and endothelial repair

We isolated a clonal cell line (4E) from kidneys of mice expressing green fluorescent protein controlled by the endothelial-specific Tie2 promoter. When grown in a three-dimensional matrigel matrix they formed a fluorescent capillary network. In vivo angiogenesis assays using growth factor-depleted matrigel implanted plugs promoted a moderate angiogenesis of host endothelial cells. Using vascular endothelial growth factor (VEGF)-A and fibroblast growth factor-2 in the plugs containing 4E-cells resulted in a robust vasculogenesis. Transplantation of 4E cells into mice with acute renal ischemia showed selective engraftment in the ischemic kidney which promoted tubular regeneration by increasing epithelial proliferation and inhibiting apoptosis. This resulted in an accelerated functional recovery 3 days after ischemia. These mice showed a 5-fold increase in tissue VEGF expression compared to controls, but no difference in plasma VEGF level corresponding with better preservation of peritubular capillaries, perhaps due to a local paracrine effect following systemic 4E infusion. One month after ischemia, 9% of engrafted 4E cells expressed green fluorescent protein in the peritubular region while half of them expressed alpha-smooth muscle actin. Our study shows that kidney mesenchymal stem cells are capable of differentiation toward endothelial and smooth muscle cell lineages in vitro and in vivo, support new blood vessel formation in favorable conditions and promote functional recovery of an ischemic kidneyope

Clinicopathological features of diabetic and nondiabetic renal diseases in type 2 diabetic patients with nephrotic-range proteinuria

Heavy proteinuria with or without features of nephrotic syndrome is associated with many primary and systemic diseases. For diabetic patients, distinguishing nondiabetic renal disease (NDRD) from diabetic nephropathy (DN) is important in choosing treatment modalities and determining renal prognosis. However, clinical relevance of heavy proteinuria is inconsistent with clinical DN assessments. This study investigated the clinicopathological features and renal outcomes of DN and NDRD in type 2 diabetic patients with nephrotic-range proteinuria.We enrolled 220 cases of type 2 diabetic patients who underwent renal biopsy. They were grouped according to the presence of nephritic-range proteinuria and pathological features. Baseline characteristics, laboratory findings, types of pathological diagnosis, and renal outcomes were analyzed in patients with heavy proteinuria.Upon kidney biopsy, 129 patients (58.6%) showed nephritic-range proteinuria. Patients with heavy proteinuria (an average urine protein-to-creatinine ratio of 10,008 ± 7307 mg/gCr) showed lower serum albumin levels and higher total cholesterol levels, but did not show any difference in age, duration of diabetes, renal function, or the presence of retinopathy compared with those with mild-to-moderate proteinuria (an average urine protein-to-creatinine ratio of 1581 ± 979 mg/gCr). Renal biopsy revealed that the prevalence of NDRD was 37.2% in patients with heavy proteinuria, which was significantly lower than that in patients with mild-to-moderate proteinuria (63.7%). The most common pathological types of NDRD were membranous nephropathy (41.7%), IgA nephropathy (14.6%), and minimal change disease (10.4%). NDRD patients showed lower prevalence of diabetic retinopathy and better kidney function irrespective of proteinuria. Immunosuppressive treatment was administered more frequently in patients with heavy proteinuria (56.3%) compared with patients with mild-to-moderate proteinuria (20%) because of the pathological differences according to the amount of proteinuria. Renal outcomes were significantly worse in patients with DN than in patients with NDRD.DN patients with heavy proteinuria exhibited different prevalence of NDRD and worse prognosis. Renal biopsy in type 2 diabetic patients should be more extensively considered to accurately diagnose NDRD, guide further management, and predict renal outcomes, especially in patients with nephrotic-range proteinuria.ope

Removal of large middle molecules via haemodialysis with medium cut-off membranes at lower blood flow rates: an observational prospective study

BACKGROUND: Online haemodiafiltration (OL-HDF) may improve middle molecular clearance in contrast to conventional haemodialysis (HD). However, OL-HDF requires higher convective flows and cannot sufficiently remove large middle molecules. This study evaluated the efficacy of a medium cut-off (MCO) dialyser in removing large middle molecular uraemic toxins and compared it with that of conventional high-flux (HF) dialysers in HD and predilution OL-HDF. METHODS: Six clinically stable HD patients without residual renal function were investigated. Dialyser and treatment efficacies were examined during a single midweek treatment in three consecutive periods: 1) conventional HD using an HF dialyser, 2) OL-HDF using the same HF dialyser, and 3) conventional HD using an MCO dialyser. Treatment efficacy was assessed by calculating the reduction ratio (RR) for β2-microglobulin (β2M), myoglobin, κ and λ free light chains (FLCs), and fibroblast growth factor (FGF)-23 and measuring clearance for FLCs. RESULTS: All three treatments showed comparable RRs for urea, phosphate, creatinine, and uric acid. MCO HD showed greater RRs for myoglobin and λFLC than did HF HD and predilution OL-HDF (myoglobin: 63.1 ± 5.3% vs. 43.5 ± 8.9% and 49.8 ± 7.3%; λFLC: 43.2 ± 5.6% vs. 26.8 ± 4.4% and 33.0 ± 9.2%, respectively; P <  0.001). Conversely, predilution OL-HDF showed the greatest RR for β2M, whereas MCO HD and HF HD showed comparable RRs for β2M (predilution OL-HDF vs. MCO HD: 80.1 ± 4.9% vs. 72.6 ± 3.8%, P = 0.01). There was no significant difference among MCO HD, HF HD, and predilution OL-HDF in the RRs for κFLC (63.2 ± 6.0%, 53.6 ± 15.5%, and 61.5 ± 7.0%, respectively; P = 0.37), and FGF-23 (55.5 ± 20.3%, 34.6 ± 13.1%, and 35.8 ± 23.2%, respectively; P = 0.13). Notably, MCO HD showed improved clearances for FLCs when compared to HF HD or OL-HDF. CONCLUSIONS: MCO HD showed significantly greater RR of large middle molecules and achieved improved clearance for FLCs than conventional HD and OL-HDF, without the need for large convection volumes or high blood flow rates. This would pose as an advantage for elderly HD patients with poor vascular access and HD patients without access to OL-HDF. TRIAL REGISTRATION: Clinical Research Information Service (CRIS): KCT 0003009. The trial was prospectively registered on the 21 Jul 2018.ope

Intravenous iron and erythropoiesis-stimulating agents in haemodialysis: A systematic review and meta-analysis

AIM: Higher dosages of erythropoiesis-stimulating agents (ESAs) have been associated with adverse effects. Intravenous iron is used to optimize ESA response and reduces ESA doses in haemodialysis patients; this meta-analysis evaluates the magnitude of this effect. METHODS: A literature search was performed using MEDLINE, Embase and the Cochrane Collaboration Central Register of Clinical Trials from inception until December 2014, to identify randomized controlled trials of intravenous iron and ESA, in patients undergoing haemodialysis for end-stage kidney disease. Dosing of IV iron in concordance with the Kidney Disease Improving Global Outcomes guidelines was considered optimal iron therapy. RESULTS: Of the 28 randomized controlled trials identified, seven met the criteria for inclusion in the meta-analysis. Results of random-effects meta-analysis show a statistically significant weighted mean (95% CI) difference of -1733 [-3073, -392] units/week in ESA dose for optimal iron versus suboptimal iron. The weighted average change in ESA dose was a reduction of 23% (range -7% to -55%) attributable to appropriate dosing of intravenous iron. A comparison of intravenous iron versus oral iron/no iron (five trials) showed a greater reduction in ESA dose, although this did not reach statistical significance (weighted mean difference, 95% CI: -2,433 [-5183, 318] units/week). The weighted average change in ESA dose across the five trials was a reduction of 31% (range -8% to -55%). CONCLUSION: Significant reductions in ESA dosing may be achieved with optimal intravenous iron usage in the haemodialysis population, and suboptimal iron use may require higher ESA dosing to manage anaemia.ope

2018 Kidney Disease: Improving Global Outcomes (KDIGO) Hepatitis C in Chronic Kidney Disease Guideline Implementation: Asia Summit Conference Report

In 2018, Kidney Disease: Improving Global Outcomes (KDIGO) published a clinical practice guideline on the prevention, diagnosis, evaluation, and treatment of hepatitis C virus (HCV) infection in chronic kidney disease (CKD). The guideline synthesized recent advances, especially in HCV therapeutics and diagnostics, and provided clinical recommendations and suggestions to aid healthcare providers and improve care for CKD patients with HCV. To gain insight into the extent that the 2018 guideline has been adopted in Asia, KDIGO convened an HCV Implementation Summit in Hong Kong. Participants included nephrologists, hepatologists, and nurse consultants from 8 Southeast Asian countries or regions with comparable high-to-middle economic ranking by the World Bank: mainland China, Hong Kong, Japan, Malaysia, Singapore, South Korea, Taiwan, and Thailand. Through presentations and discussions, meeting participants described regional practice patterns related to the KDIGO HCV in CKD guideline, identified barriers to implementing the guideline, and developed strategies for overcoming the barriers in Asia and around the world.ope