Why should we focus on high-volume hemodiafiltration?

Though noticeable technological advances related to hemodialysis (HD) have been made, unfortunately, the survival rate of dialysis patients has yet to improve significantly. However, recent research findings reveal that online hemodiafiltration (HDF) significantly improves patient survival in comparison to conventional HD. Accordingly, the number of patients receiving online HDF is increasing. Although the mechanism driving the benefit has not yet been fully elucidated, survival advantages are mainly related to the lowering of cardiovascular mortality. High cardiovascular mortality among HD patients is seemingly attributable to the cardiovascular changes that occur in response to renal dysfunction and the HD-induced myocardial stress and injury, and online HDF appears to improve such secondary cardiovascular changes. Interestingly, patient survival improves only if the convection volume is supplied sufficiently over a certain level during online HDF treatment. In other words, survival improvement from online HDF is related to convection volume. Therefore, there is a growing interest in high-volume HDF in terms of improving the survival rate. The survival improvement will require a minimum convection volume of 23 L or more per 4-hour session for postdilution HDF. To obtain an optimal high convection volume in online HDF, several factors, such as the treatment time, blood flow rate, filtration fraction, and dialyzer, need to be considered. High-volume HDF can be performed easily and safely in routine clinical practice. Therefore, when the required equipment is available, performing high-volume HDF will help to improve the survival rate of dialysis patients.

Clinical usefulness of bioimpedance analysis for assessing volume status in patients receiving maintenance dialysis

Chronic volume overload is associated with left ventricular hypertrophy and high cardiovascular mortality in patients undergoing dialysis. Therefore, estimating body fluid status is important in these patients. However, most dry-weight assessments are still performed clinically, while attempts have been made to measure the volume status and dry weight of patients undergoing dialysis using bioimpedance analysis (BIA). BIA uses the electrical properties of the human body to alternate current flow and measures resistance values to estimate body water content and composition. BIA is divided into single-frequency BIA, multi-frequency BIA, and bioimpedance spectroscopy (BIS) according to the number of frequencies used, and into whole-body and segmental BIA according to whether or not the whole body is divided into segments. Extracellular water (ECW), intracellular water, and total body water (TBW) contents can be measured with BIA. Dry weight can be estimated by measuring the volume overload of the patient through the ECW/TBW and ECW-to-body weight ratios. Other estimation methods include the normovolemia/hypervolemia slope method, a resistance-reactance (RXc) graph, overhydration measurements using a body composition monitor, and calf BIS. In this review, we will examine the principles of BIA, introduce various volume status measurement methods, and identify the optimal method for patients undergoing dialysis.

Intracellular Remodeling and Accumulation of Aberrant Lysosomes in Differentiation of Tonsil-Derived Mesenchymal Stem Cells into Parathyroid-Like Cells

Differentiation of mesenchymal stem cells (MSC) into a variety of cell lineages such as adipocytes, osteocytes, and chondrocytes is often accompanied up-regulation of autophagy. In our study, we demonstrated that the expression of autophagy-associated proteins (p-Beclin 1, LC3A, LC3B, p-AMPK, p-mTOR and ATG3, ATG7, and ATG12-5) over a period of time was hardly distinguishable from control tonsil-derived MSC (TMSC). Despite the unnoticeable difference in autophagy activation between differentiated TMSC (dTMSC) and the control (cTMSC), we reported significant changes in intracellular compositions in differentiated TMSC into functional parathyroid-like cells secreting parathyroid hormone (PTH). By using transmission electron microscopy (TEM), we observed accumulation of multivesicular bodies (MVB) comprising small, degraded compartments densely accumulated as dark granular or amorphous clumps, multilamellar bodies and lipid droplets in dTMSC. However, no such structures were found in cTMSC. These results suggest that differentiation of TMSC into parathyroid-like cells producing PTH hormone is hardly dependent on autophagy activation in the beginning of our conditions. Furthermore, our results of intracellular remodeling and accumulated endo-lysosomal storage bodies in the later stages of TMSC differentiation present a possible role of the structures in PTH secretion.

Effect of low-dose valsartan on proteinuria in normotensive immunoglobulin A nephropathy with minimal proteinuria: a randomized trial

BACKGROUND/AIMS: Immunoglobulin A nephropathy (IgAN) is a generally progressive disease, even in patients with favorable prognostic features. In this study, we aimed to investigate the antiproteinuric effect and tolerability of low-dose valsartan (an angiotensin II receptor blocker) therapy in normotensive IgAN patients with minimal proteinuria of less than 0.5 to 1.0 g/day. METHODS: Normotensive IgAN patients, who had persistent proteinuria with a spot urine protein-to-creatinine ratio of 0.3 to 1.0 mg/mg creatinine, were recruited from five hospitals and randomly assigned to either 40 mg of valsartan as the low-dose group or 80 mg of valsartan as the regular-dose group. Clinical and laboratory data were collected at baseline, and at 4, 8, 12, and 24 weeks after valsartan therapy. RESULTS: Forty-three patients (low-dose group, n = 23; regular-dose group, n = 20) were enrolled in the study. Proteinuria decreased significantly not only in the regular-dose group but also in the low-dose group. The change in urine protein-to-creatinine ratio at week 24 was -41.3% +/- 26.1% (p < 0.001) in the regular-dose group and -21.1% +/- 45.1% (p = 0.005) in the low-dose group. In the low-dose group, blood pressure was constant throughout the study period, and there was no symptomatic hypotension. In the regular-dose group, blood pressure decreased at weeks 8 and 12. No significant change in glomerular filtration rate, serum creatinine level, or serum potassium level was observed during the study period. CONCLUSIONS: Our results suggest that low-dose valsartan can significantly reduce proteinuria without causing any intolerability in normotensive IgAN patients with minimal proteinuria.

Hyperphosphatemia is associated with patency loss of arteriovenous fistula after 1 year of hemodialysis

BACKGROUND: The patency of arteriovenous access is important for stable and effective hemodialysis, and long-term technical survival is best achieved with a native arteriovenous fistula (AVF). However, maintaining AVF patency remains a challenge. This study was designed to determine the independent prognostic factors for AVF patency according to hemodialysis duration. METHODS: The primary study end point was unassisted patency of the AVF, which was defined as the time from the first fistula surgery to the first AVF failure. AVF failure was defined as an event that required percutaneous intervention or surgery to revise or replace the fistula, which occurred at least 2 months after fistula formation. RESULTS: We enrolled 478 patients with a mean age of 55.5+/-14.0 years, and mean duration of dialysis was 2.5+/-2.1 years. There were 109 cases (22.8%) of AVF failure. The factors related to AVF patency differed according to hemodialysis duration. Using a Cox-adjusted model, we observed a significant correlation between the incidence of AVF failure and diabetes within the initial 12 months of hemodialysis. Uncontrolled hyperphosphatemia (mean serum phosphorus>5.5 mg/dL during hemodialysis) was associated with patency loss of AVF after 1 year of hemodialysis. CONCLUSION: Various factors were associated with the development of patency loss of AVF as hemodialysis duration differed, and a preventive role of hyperphosphatemia control in AVF survival needs further clinical study.

Spontaneous abdominal intramuscular hematoma in a non-dialysis chronic kidney disease patient under cilostazol therapy / 영남의대학술지

Spontaneous intramuscular hematoma of the abdominal wall is a rare condition characterized by acute abdominal pain. It is often misdiagnosed as a surgical condition. It used to be associated with risk factors such as coughing, pregnancy, and anticoagulant therapy. Most cases of abdominal wall hematomas were rectus sheath hematomas caused by the rupture of either the superior or inferior epigastric artery, but spontaneous internal oblique hematoma was extremely rare. In this report, we present a case of spontaneous internal oblique hematoma in a 69-year-old man with non-dialysis chronic kidney disease who was taking cilostazol. The patient complained of abrupt abdominal pain with a painful palpable lateral abdominal mass while sleeping. The abdominal computed tomography showed an 8 cm-sized mass in the patient's left internal oblique muscle. The administration of cilostazol was immediately stopped, and the intramuscular hematoma of the lateral oblique muscle disappeared with conservative management.

A randomized crossover study of single biweekly administration of epoetin-alpha compared with darbepoetin-alpha in chronic kidney disease patients not receiving dialysis

BACKGROUND: Recent evidence demonstrates that high doses of epoetin-alpha (EPO-alpha) can be administrated at extended intervals, despite its relatively short serum half-life. However, no prospective randomized trials on the effects of extended dosing intervals of EPO-alpha compared with darbepoetin-alpha (DA-alpha) have been performed. This study was designed to investigate whether a single biweekly (Q2W) administration of a high dose of EPO-alpha is as effective as DA-alpha for anemia in chronic kidney disease (CKD) patients not receiving dialysis. METHODS: Sixty non-dialysis CKD patients were equally randomized to either Q2W subcutaneous EPO-alpha (10,000 unit) or DA-alpha (50microg) therapy groups for the first 6 weeks. After a 6-week washout period, the participants of the EPO-alpha and DA-alpha treatment groups switched to the alternate regimen for 6 weeks. The mean hemoglobin (Hb) levels after erythropoiesis stimulating agent (ESA) therapy and percentage change in Hb levels from baseline to the end of the study were analyzed. RESULTS: The mean Hb levels of postESA therapy increased significantly compared with those of preESA therapy in both ESA regimens. The percentage increase in Hb levels and erythropoietin resistance index did not show a significant difference between the different ESA regimens. No difference was observed between the regimens regarding mean Hb levels after ESA therapy. Additionally, there were no serious adverse effects leading to withdrawal from treatment. CONCLUSION: Biweekly high doses of EPO-alpha therapy may be equally as effective as Q2W DA-alpha therapy in maintaining target Hb levels in non-dialysis CKD patients.

Association of acute tubular necrosis with gross hematuria in cirrhosis-related immunoglobulin A nephropathy

Immunoglobulin A (IgA) nephropathy associated with cirrhosis is the most common form of secondary IgA nephropathy (IgAN). Cirrhosis-related IgAN is usually clinically silent with a rare occurrence of gross hematuria, unlike in cases of idiopathic IgAN. Especially, acute tubular necrosis (ATN) associated with gross hematuria is very rare in cirrhosis-related IgAN, although acute renal failure is a frequently reported complication in advanced cirrhosis. Herein, we report an unusual case of ATN requiring renal replacement therapy, associated with gross hematuria in a patient with nonalcoholic, hepatitis B virus-associated cirrhosis. Results of a histopathological analysis revealed obstruction of the lumen of renal tubules by red blood cell casts, a marked tubular necrosis, and IgA deposition in the mesangium. The patient's renal function and gross hematuria were clearly improved after lamivudine treatment.

Association of acute tubular necrosis with gross hematuria in cirrhosis-related immunoglobulin A nephropathy

Immunoglobulin A (IgA) nephropathy associated with cirrhosis is the most common form of secondary IgA nephropathy (IgAN). Cirrhosis-related IgAN is usually clinically silent with a rare occurrence of gross hematuria, unlike in cases of idiopathic IgAN. Especially, acute tubular necrosis (ATN) associated with gross hematuria is very rare in cirrhosis-related IgAN, although acute renal failure is a frequently reported complication in advanced cirrhosis. Herein, we report an unusual case of ATN requiring renal replacement therapy, associated with gross hematuria in a patient with nonalcoholic, hepatitis B virus-associated cirrhosis. Results of a histopathological analysis revealed obstruction of the lumen of renal tubules by red blood cell casts, a marked tubular necrosis, and IgA deposition in the mesangium. The patient's renal function and gross hematuria were clearly improved after lamivudine treatment.

Successful Rechallenge with Darbepoetin Following Immunosuppressive Therapy in a Dialysis Patient with Erythropoietin-Induced Pure Red Cell Aplasia / 대한내과학회지

Patients with erythropoiesis-stimulating agent (ESA)-induced pure red cell aplasia (PRCA) should not routinely be switched to an alternative ESA or to darbepoetin-alpha because anti-erythropoietin (anti-EPO) antibodies cross-react with all kinds of recombinant ESAs. We present a case of ESA-induced PRCA in a 69-year-old man on hemodialysis whose anemia improved with reintroduction of darbepoetin-alpha following immunosuppressive therapy. The patient developed severe anemia after 15 months of subcutaneous administration of erythropoietin-alpha. After the diagnosis of PRCA, erythropoietin-alpha was discontinued and immunosuppressive therapy with a combination of prednisolone and oral cyclophosphamide was initiated. After 4 months of immunosuppressive therapy, the anti-EPO antibody titer was markedly decreased; however, esophageal candidiasis developed. Additional therapy with cyclosporine alone instead of prednisone and cyclophosphamide was performed, and anti-EPO antibody was subsequently not detected. Darbepoetin-alpha was then reintroduced, and the patient's anemia improved without red cell transfusion. In conclusion, ESA-induced PRCA was successfully treated with reintroduction of darbepoetin-alpha following immunosuppressive therapy.

Diagnosis of Primary Glomerular Diseases / 대한내과학회지

Glomerular diseases occurring in the absence of a known systemic process are called primary. This review focuses on the approach and diagnosis of primary glomerular disease. Inflammatory and/or noninflammatory insults to glomeruli results in a multiplicity of signs and symptoms of diseases, including hematuria, proteinuria, azotemia, edema, and hypertension. Patients with glomerular diseases generally present with one of the following clinical syndromes: asymptomatic urinary abnormalities, nephrotic syndrome, acute nephritic syndrome, rapidly progressive glomerulonephritis, or chronic glomerulonephritis. The urinalysis, the degree of proteinuria, the estimated glomerular filtration rate, and patient characteristics often allow the differential diagnosis of glomerular disease prior to renal biopsy. However, a renal biopsy is usually required to establish diagnosis and treatment of most glomerular disease.

A Case of P-ANCA-Positive Anti-Glomerular Basement Membrane Antibody Disease / 대한내과학회지

Up to 40% of patients with anti-glomerular basement membrane (GBM) disease, which is a rare autoimmune disorder usually manifesting as rapidly progressive glomerulonephritis (RPGN), are positive for circulating anti-neutrophil cytoplasmic antibody (ANCA). Many previous reports showed poor outcomes in these "double-positive" patients. We report a patient with perinuclear (p)-ANCA positive anti-GBM disease who presented with RPGN and required hemodialysis. Plasmapheresis and steroid and cyclophosphamide therapy were initiated following renal biopsy and resulted in normalization of anti-GBM antibody and p-ANCA titers, recovery of renal function, and discontinuation of hemodialysis. This case suggests that aggressive immunosuppression with plasmapheresis in patients who are p-ANCA positive with anti-GBM disease should be considered, even in those with severe renal dysfunction.

Cefepime-Induced Nonconvulsive Status Epileticus Presenting as Coma in a Patient with ESRD on Hemodialysis / 대한신장학회지

Cefepime-induced nonconvulsive status epilepticus (NCSE) in end-stage renal disease (ESRD) patients receiving hemodialysis has only rarely been reported. Here we report a case of cefepime-induced NCSE presenting as coma in a patient with ESRD on hemodialysis. A 73-year-old man, who had been receiving maintenance hemodialysis, developed aphasia and coma during cefepime therapy for epidural abscess. Emergent eletroencephalography (EEG) revealed evidence of NCSE. The abnormal EEG findings were resolved and comatose mentality was completely recovered after cessation of cefepime and administration of anticonvulsive drugs. Cefepime-induced NCSE should be considered if neurological symptoms including comatose mentality develops during cefepime therapy in a patient with renal failure.

Multiple Metastatic Infection Related to Arteriovenous Graft Infection in an ESRD Patient on Hemodialysis / 대한신장학회지

Arteriovenous vascular access infection associated with S. aureus bacteremia may cause metastatic complications, which relate to a poor outcome especially if proper diagnosis and treatment are delayed. We report a case of a 61-year-old male patient on maintenance hemodialysis who developed multiple metastatic infections associated with arteriovenous graft infection caused by methicillin-resistant Staphylococcus aureus (MRSA). At 7th hospital day, multiple metastatic infections, including osteomyelitis of clavicle, vertebral osteomyelitis, and tendinitis of the 5th finger proximal interphalangeal joint, were diagnosed by CT of chest, ultrasonography of hands, and whole body bone scan. Infected arteriovenous graft was removed and antibiotics was administrated for 18 weeks. Thereafter, MRSA bacteremia and clinical symptoms and signs related to metastatic infections were improved.

Delayed Recovery of Sedation by Continuous Midazolam Infusion in an ESRD Patient on Peritoneal Dialysis: A Case Report / 대한신장학회지

Midazolam, a benzodiazepine derivatives, is widely used in intensive care unit for sedation of patients who require mechanical ventilation. Although midazolam has a short acting time, it might cause a prolonged sedation, especially in patients with renal failure. We report the case of a 76-year-old man who received peritoneal dialysis and showed prolonged sedation after stopping continuous infusion of midazolam. The patient who has received maintenance hemodialysis for five months admitted in intensive care unit to manage pneumonia and severe congestive heart failure. In ICU, hemodialysis was transferred to peritoneal dialysis due to severe cardiac dysfunction. He was treated with mechanical ventilation under sedation with midazolam. However, even though stopping midazolam, deep sedation by midazolam was not restored. The patient completely recovered from sedation after 280 hours.

Comparison of Once-Biweekly Administration of Epoetin-alpha with Darbepoetin-alpha in Chronic Kidney Disease Patients Not Receiving Dialysis / 대한신장학회지

PURPOSE: It is very important to correct renal anemia by erythropoiesis stimulating agents (ESA) because anemia is associated with poor outcomes in chronic kidney disease (CKD) patients. We investigated whether once-biweekly (Q2W) treatment with epoetin-alpha (EPO-alpha) is as effective as Q2W darbepoetin-alpha (DA-alpha) in CKD patients who are not on dialysis. METHODS: Fifteen CKD patients not receiving dialysis with renal anemia (M:F 6:9, age 60.1+/-7.2 years, eGFR-MDRD 15.7+/-6.4 mL/min/1.73m2, DM 46.7%) were enrolled. All patients received Q2W subcutaneous DA-alpha (40 microgram) for 10 weeks. After 6 weeks of wash-out period, patients were switched to Q2W subcutaneous EPO-alpha (10,000 IU) for 10 weeks. RESULTS: There were no significant differences in baseline parameters, such as hemoglobin (Hb), serum ferritin, and transferrin saturation, between before DA-alpha therapy and before EPO-alpha therapy. Hb levels significantly increased after completion of ESA therapy (DA-alpha, 9.8+/-0.4 vs. 10.4+/-0.6 g/dL, p=0.001; EPO-alpha, 9.6+/-0.7 vs. 10.2+/-0.4 g/dL, p=0.003). After completion of ESA therapy, Hb levels did not reveal significant differences between two groups (p=0.123). Erythropoietin resistance index (8.2+/-1.6 vs. 8.4+/- 1.5 IU/kg weight/g hemoglobin/week, p=0.136) and % increase of Hb (106.7+/-5.5 vs. 106.8+/-6.4%, p=0.776) were not significantly different between DA-alpha therapy and EPO-alpha therapy. There were no significant adverse effects observed during study periods. CONCLUSION: These findings indicate that Q2W high dose (10,000 IU) of EPO-alpha therapy in CKD patients who are not on dialysis may be effective in maintaining Hb levels as Q2W DA-alpha therapy.

Low Dose Megestrol Acetate for Maintenance Hemodialysis Patients / 대한신장학회지

PURPOSE: Maintenance hemodialysis (HD) patients have a high prevalence of malnutrition and inflammation. Megestrol acetate (MA) has been shown to increase appetite in cancer patients but the usual dose of MA (400-800 mg/day) was associated with serious side effects in HD patients. We evaluated the changes in nutritional and inflammatory parameters after low dose of MA treatment in malnourished HD patients METHODS: Inclusion criteria were maintenance HD patients who showed serum albumin <3.5 g/dL or <4.0 g/dL with anorexia. Serum chemical parameters, cytokines, Subjective Global Assessment, dry weight, Kt/V, nPCR, SF36 quality of life, fat free mass (FFM), and body fat mass (BFM) were measured. Patients were instructed to take 5 mL (200 mg) of MA solution once a day. RESULTS: Fourteen patients (seven male, age 52+/-10 years, mean HD duration 48+/-59 months) were included. One patient died of pneumonia. Seven patients dropped out because they refused to take the drug after one to three months of treatment; two of them complained of thirst, three of them ate too much, and two had both. Six patients (four male and two female) have completed six months of study. Serum albumin (3.1+/-0.5 to 3.6+/-0.4 g/dL), TIBC (184.2+/-27.9 to 205.0+/-25.8 microgram/ dL), BFM (11.9+/-5.7 to 16.6+/-7.4 kg), protein intake (57.0+/-32.5 to 68.7+/-39.2 g/day), and energy intake (1,521+/-690 to 1,724+/-879) were increased. Serum CRP and IL-6 decreased without statistical significance. No significant adverse effects were observed in all patients who had completed study. CONCLUSION: Low dose MA can improve the nutritional status, inflammation, and anorexia in maintenance HD patients.

Gluteal and Thigh Compartment Syndrome due to Rhabdomyolysis Following Prolonged Immobilization: A Case Report / 대한신장학회지

Compartment syndrome is rarely associated with non-traumatic rhabdomyolysis. We report the case of a 23-year-old man who developed compartment syndrome associated with rhabdomyolysis caused by prolonged immobilization after antidepressive drug overdose. Elevation of serum creatine phosphokinase and myoglobinuria indicated rhabdomyolysis. Painful swelling of the right buttock and thigh and right lower limb paralysis with sensory and motor deficit were suggestive of gluteal and thigh compartment syndrome with the complication of sciatic nerve injury. The patient received an immediate fasciotomy, medical treatment and rehabilitation. At five months after initial treatment, the patient could walk independently with nearly full recovery of his right lower limb function.

A Case of Encapsulating Peritoneal Sclerosis, Presenting as Hemoperitoneum, Successfully Treated by Enterolysis / 대한신장학회지

Encapsulating peritoneal sclerosis (EPS) is an uncommon but fatal complication of peritoneal dialysis (PD). Recently, there were some reports of advanced EPS cases that were successfully treated by enterolysis although an intestinal perforation or leakage from intestinal anastomosis were associated with a high mortality. We experienced a case of EPS in a 53-year-old man on PD for 3.5 years without a previous history of episode of peritonitis who presented with hemoperitoneum during treatment of peritonitis. EPS was diagnosed radiologically according to typical CT findings; The series of CT scans revealed how to develop in sequence from a very subtle findings to full-blown findings of EPS. Enterolysis was performed because the patient did not respond to conservative management such as cessation of PD with transfer to hemodialysis, nutritional support and steroid therapy. In spite of intestinal perforation during surgery, he was successfully treated with enterolysis. Therefore, we report this case with review of the literature.

Inguinal Hernia Presenting as Scrotal Edema in Patients on Continuous Ambulatory Peritoneal Dialysis / 대한신장학회지

Scrotal edema may develop during continuous ambulatory peritoneal dialysis (CAPD). The two etiologic mechanisms are peritoneo-scrotal communication through a patent processus vaginalis or extravasation of dialysate through a defect of abdominal wall. We report two cases of scrotal edema due to inguinal hernia by peritoneo-scrotal communication during CAPD. The etiology of scrotal edema was confirmed by peritoneal scintigraphy and/or computed tomography. Scrotal edema due to inguinal hernia was completely resolved by a surgical repair of hernia and did not recur despite of resumption of peritoneal dialysis.