Jin Kuk Kim

Mesenchymal stem cell therapy for chronic renal failure

Importance of the field: Chronic kidney disease (CKD) has become a worldwide public health problem. Renal transplantation is the treatment of choice for end-stage renal disease, but is limited by a small number of organ donors and the immune barrier. To overcome these problems, new therapeutic strategies for tissue repair have recently emerged. Areas covered in this review: We discuss the therapeutic potential of mesenchymal stem cells (MSCs) in kidney injury and examine the latest reports providing evidence supporting MSC efficacy in the treatment of chronic renal failure (CRF). What the reader will gain: MSCs improve histological and functional outcomes in various CRF model systems. Paracrine effects rather than transdifferentiation might result in the prevention of progressive renal failure. In addition, MSCs can reprogram kidney cell differentiation, and modulate neo-kidney transplantation in CRF. Take home message: Although many practical problems remain to be addressed, treatment with MSCs will enter the mainstream of CRF treatment.

Changes in body fat mass in patients after starting peritoneal dialysis.

♦ Background: Peritoneal dialysis (PD) is characterized by gain in fat mass. Visceral fat mass is associated with metabolic syndrome and atherosclerosis rather than subcutaneous fat mass. In addition, the change in visceral fat mass is a more reliable predictor of survival in PD patients. In this study, we prospectively examined serial changes in fat composition and nutritional status and analyzed factors associated with gain in fat mass in patients undergoing PD. ♦ Methods: Body composition was assessed by bioelectric impedance analysis (BIA) and computed tomogram (CT). Nutrition status was assessed by Subjective Global Assessment (SGA), protein equivalent of nitrogen appearance (nPNA), serum albumin, C-reactive protein (CRP), and lipid profile. All measurements except BIA were performed on the seventh day and at 6 and 12 months after the start of PD. ♦ Results: 60 patients (30 men; mean age 55.0 ± 12.5 years) were enrolled. Increase in body weight continued during the 12 months but visceral and subcutaneous fat mass increased during the first 6 months and decreased during the second 6 months. While hematocrit and serum albumin decreased during the first 6 months, they did not change during the second 6 months. Serum creatinine, total cholesterol, and triglyceride increased similarly to the weight pattern. While nPNA decreased during the 12 months, Kt/V, SGA, and CRP did not change. Patients that had more visceral fat mass at the start of PD had less gain of visceral fat mass during the first 6 months (r = –0.821, p = 0.002). Patients that had more subcutaneous fat mass at the start of PD had less gain of subcutaneous fat mass (r = –0.709, p = 0.015). The change in weight was not associated with the change in visceral or subcutaneous fat during the first 6 months. ♦ Conclusion: Patients starting PD experience weight gain, including visceral and subcutaneous fat, during the first 6 months of PD. Patients with high baseline fat mass had less increase in fat mass than those with low baseline fat mass, regardless of visceral or subcutaneous fat mass.

Could mean platelet volume be a promising biomarker of progression of chronic kidney disease

Abstract The mean platelet volume (MPV), a readily available indicator of platelet activation and function, is a useful predictive and prognostic biomarker of cardiovascular and cerebrovascular disease (CVD). It is associated with a variety of prothrombotic and proinflammatory diseases. Larger platelets are more likely to aggregate and release greater quantities of adhesive molecules. MPV has seldom been investigated in patients with chronic kidney disease (CKD). This study aimed to investigate the relationship between MPV levels and the glomerular filtration rate (GFR) in patients with CKD. We reviewed the medical records of patients with CKD who visited the nephrology outpatient clinics of Soonchunhyang University Bucheon Hospital between January 2010 and May 2013. A total of 553 patients were included in the present retrospective study. According to the estimated GFR (eGFR) calculated by the abbreviated the Modification of Diet in Renal Disease (MDRD) equation, the patients were allocated to Group 1 (GFR, 60–89 ml/minute/1.73 m2; n = 64), Group 2 (GFR, 30–59 ml/minute/1.73 m2; n = 268), Group 3 (GFR, 15–29 ml/minute/1.73 m2; n = 147), or Group 4 (GFR, <15 ml/minute/1.73 m2 and non-dialysis; n = 74). Data were analyzed by Student’s t-test, the chi-squared test, Pearson’s correlation coefficient (r), Tukey’s honestly significant difference (HSD) test, and one-way analysis of covariance. The MPV values had a negative correlation with eGFR in patients with CKD (Pearson’s correlation coefficient = −0.553, p < 0.001). The mean MPV values in Groups 1–4 were 9.81 ± 0.13 fl, 10.34 ± 0.08 fl, 10.86 ± 0.09 fl, and 11.19 ± 0.11 fl, respectively (p < 0.001). Multiple comparisons of MPV values in the four groups by Tukey’s HSD test showed statistically significant intergroup differences, with all p values <0.001. Platelet counts and PDW decreased along with eGFR, and there were no significant differences with respect to plateletcrit. Patients with prevalent coronary artery disease (CAD) or CVD had higher MPVs than did those without CAD or CVD. MPV was significantly increased with progression of CKD. MPV may be a useful indicator of increased risks of CAD or CVD in patients with CKD.

Fabry Disease With Aortic Regurgitation

Aortic regurgitation is not so rare in patients with Fabry disease. Enzyme replacement therapy has become the standard medical care for Fabry disease in recent years. A 31-year-old man with Fabry disease, treated with recombinant alpha-galactosidase enzyme replacement for 19 months was admitted for evaluation of exertional dyspnea. Cardiac workup revealed left ventricular hypertrophy, increased left ventricular size, and moderate to severe aortic regurgitation. He underwent mechanical valvular replacement and heart biopsy. Histology of his aortic valve showed myxoid degeneration of valve leaflets. His heart muscle revealed extensive hypertrophy with vacuolization and the absence of lamellar bodies. We report a case of Fabry disease with aortic regurgitation in a man who underwent valvular replacement operation during enzyme replacement therapy.

Ischemic monomelic neuropathy: a rare complication after vascular access formation

To the Editor, Patients with end-stage renal disease require an arteriovenous fistula (AVF). Although an AVF has numerous advantages, it can result in neurological or ischemic problems with hemodynamic disturbance. In 1983, Wilbourn et al. [1] described ischemic monomelic neuropathy (IMN), defined as a type of multiple axonal-loss mononeuropathy distally in a limb, resulting from an impaired blood supply after graft insertion. IMN is a very rare complication, but requires an early diagnosis and treatment. We report a case of IMN after an AVF operation and the results of a literature review. A 44-year-old woman visited a vascular surgeon for hemodialysis access. She had been diagnosed with type 2 diabetes 15 years previously. She had a 3-year history of hypertension and chronic kidney disease and was a hepatitis B virus carrier. Laboratory studies showed a white blood cell count of 5,600/mL, hemoglobin of 9.1 g/dL, blood urea nitrogen (BUN) of 49.3 mg/dL, and serum creatinine of 7.6 mg/dL. The patient had outpatient surgery with a brachiocephalic graft on the left elbow. The patient was admitted 7 days af ter the operation for weight gain, dyspnea, and general weakness. At that time, the hemoglobin was 8.2 g/dL, BUN 93.3 mg/dL, and serum creatinine 17.6 mg/dL. Metabolic acidosis was noted and a chest X-ray showed mild pulmonary congestion. The patient underwent emergency hemodialysis via a jugular vein catheter. After her uremia improved, she complained of swelling and numbness of the left hand and reduced grip strength. On examination, the fistula was patent and her radial pulse was palpable. The movement of the thumb was weak and she could not move her other fingers. She had no sensation in any modality. Nerve conduction studies performed 3 weeks postoperatively showed a decreased nerve conduction velocity and amplitude for the motor and sensory parts of the left hand (Table 1). Both lower legs had markedly decreased motor and sensory function, compatible with a diabetic patient. We diagnosed IMN of the left hand and peripheral polyneuropathy of both legs. Table 1 Nerve conduction study of upper extremities: initially Although she required fistula ligation, we and the surgeon decided to observe her because 1 month had already passed since the first operation and an extra ligation would require another operation for access. Her diabetic polyneuropathy was treated with pregabalin. After 2 months, she could grip a pencil. A follow-up nerve conduction test revealed improvement in the ulnar nerve, although defects remained in the median nerve (Table 2). She did not want to undergo more surgery. So we continued to observe her as an outpatient. Table 2 Nerve conduction study of upper extremities: after 2 months IMN is a sensory/motor impairment without tissue necrosis, but with a transient reduction in blood flow. IMN is a form of steal phenomenon as the access surgery steals blood flow from distal nerve tissue [2], causing multiple axonal-loss mononeuropathy distally in the limb. IMN is often under-recognized and misdiagnosed, but its known incidence is 0.5% to 3.0% [3]. If a patient on hemodialysis complains of hand pain, physicians need to consider many diseases, including soft tissue swelling, wound hematoma, carpal tunnel syndrome, vascular steal syndrome, and IMN [4]. The most important factor in diagnosing IMN is that of the clinical manifestations. Acute pain, weakness, and muscle paralysis immediately after an operation are common symptoms. Since these symptoms are nonspecific, after AVF formation, the motor or sensory function of the operated hand should be checked and nerve conduction studies should be done. Low amplitudes and reduced or even undetectable motor or sensory nerve conduction velocities are compatible with IMN. Axonal loss of the median, radial, and ulnar nerves can also be observed [3]. Electromyograms show denervation, including fibrillation potentials and motor unit loss. Since past neuropathy can be assumed to lower the ischemic injury threshold, diabetes, atherosclerotic disease, and women have an increased risk of IMN [2,4,5]. Nevertheless, IMN has been reported for a patient with no risk factors. In addition, a brachiocephalic fistula is commonly associated with this complication because the brachial artery is the only blood supply to the distal arm. The most important treatment for IMN is immediate closure of the access; this increases the probability of recovery [3,4]. Early closure of the fistula leads to partial or full restoration of the sensory and motor function [5]. Some clinicians reported treatment using a banding operation [3]. Redfern and Zimmerman [5] reported an improvement in two patients under observation, like our case. However, it is not clear whether those patients had IMN [5]. Anticonvulsants, antidepressants, and narcotics have been used for pain control [2]. Better education and awareness on the part of the surgeon and nephrologist should lead to an early diagnosis and the proper management of IMN [4]. Therefore, we report this case of IMN after an AVF operation with a literature review.

Does Body Fat Mass Define Survival in Patients Starting Peritoneal Dialysis

♦ Background and Aims: Peritoneal dialysis (PD) is characterized by a gain in fat mass. Unlike subcutaneous fat, visceral fat is associated with metabolic syndrome and survival. We prospectively examined whether visceral or subcutaneous fat could predict outcome in patients undergoing PD. ♦ Methods: We studied 117 new patients (57 men) undergoing PD between February 2006 and November 2011. Baseline body composition was measured on computed tomograms. Visceral obesity was defined as a visceral fat area exceeding 100 cm2, and subcutaneous obesity, as a subcutaneous fat area exceeding 130 cm2. ♦ Results: Among the 117 patients, 37 and 29 were diagnosed with visceral and subcutaneous obesity respectively. Visceral and subcutaneous obesity were both present in 21 patients. In the study population, the 1-year and 5-year survival rates were 94% and 59%. The rates of peritonitis and exit-infection were 0.31 and 0.14 episodes per patient-year. Mortality was greater in patients with visceral obesity than in those without visceral obesity (p = 0.005). Visceral obesity had no influence on peritonitis and exit-infection rates. Subcutaneous obesity was associated neither with survival nor with peritonitis or exit-site infection. In a multivariate Cox regression analysis, visceral obesity was not a risk factor for poor outcome. ♦ Conclusions: Increased visceral fat at PD initiation is not an independent predictor of poor survival. Any impact of visceral or subcutaneous fat mass on outcomes in patients undergoing PD would be better defined by larger, long-term studies.

Use of multidetector computed tomography for evaluating coronary artery disease in patients undergoing dialysis

Aim:  Cardiovascular disease is the most common cause of death in patients undergoing dialysis. The accuracy of multidetector computed tomography (MDCT) for detecting coronary disease has not been determined, and little information is available regarding the performance of MDCT in patients undergoing dialysis.

Features of atherosclerosis in hemodialysis patients

Background Cardiovascular disease is the main cause of mortality in dialysis patients. Carotid intima–media thickness (CIMT) is used as a surrogate marker of early atherosclerosis. Atherosclerosis can cause vascular access failure. The purpose of this study was to define the clinical features of atherosclerosis in hemodialysis patients based on CIMT and to define the relationship between CIMT and access failure. Methods In this cross-sectional study, the CIMT of 60 patients on hemodialysis was examined using B-mode Doppler ultrasonography between May 2012 and November 2012. Carotid atherosclerosis was defined as a CIMT≥0.9 mm or the incidence of atherosclerotic plaques. Results The patients’ mean age was 54.5±10.6 years, and 60% of the patients were male. The CIMT was 0.81±0.47 mm (range, 0.35–2.50 mm). The group with atherosclerosis was characterized by older age compared with those without atherosclerosis. Patients with atherosclerosis showed much shorter durations of access patency than their counterparts in the nonatherosclerosis group (hazard ratio, 2.822; 95% confidence interval, 1.113–7.156; P=0.029). Moreover, being overweight was associated with a 2.47-fold (95% confidence interval, 1.101–5.548) increased primary access failure. Conclusion This study shows that atherosclerosis is associated with older age. Patients who are overweight and have atherosclerosis may have shortened access patency.

Clinical utility of far-infrared therapy for improvement of vascular access blood flow and pain control in hemodialysis patients

Background Maintenance of a well-functioning vascular access and minimal needling pain are important goals for achieving adequate dialysis and improving the quality of life in hemodialysis (HD) patients. Far-infrared (FIR) therapy may improve endothelial function and increase access blood flow (Qa) and patency in HD patients. The aim of this study was to evaluate effects of FIR therapy on Qa and patency, and needling pain in HD patients. Methods This prospective clinical trial enrolled 25 outpatients who maintained HD with arteriovenous fistula. The other 25 patients were matched as control with age, sex, and diabetes. FIR therapy was administered for 40 minutes during HD 3 times/wk and continued for 12 months. The Qa was measured by the ultrasound dilution method, whereas pain was measured by a numeric rating scale at baseline, then once per month. Results One patient was transferred to another facility, and 7 patients stopped FIR therapy because of an increased body temperature and discomfort. FIR therapy improved the needling pain score from 4 to 2 after 1 year. FIR therapy increased the Qa by 3 months and maintained this change until 1 year, whereas control patients showed the decrease in Qa. The 1-year unassisted patency with FIR therapy was not significantly different from control. Conclusion FIR therapy improved needling pain. Although FIR therapy improved Qa, the unassisted patency was not different compared with the control. A larger and multicenter study is needed to evaluate the effect of FIR therapy.

Ferritin as a predictor of decline in residual renal function in peritoneal dialysis patients

Background/Aims Aims: Inflammation is an important factor in renal injury. Ferritin, an inflammatory marker, is considered an independent predictor of rapid renal progression in patients with chronic kidney disease. However, the relationship between ferritin and residual renal function (RRF) in patients undergoing peritoneal dialysis (PD) remains unclear. Methods We reviewed the medical records of patients who started PD between June 2001 and March 2012 at Soonchunhyang University Bucheon Hospital, Korea. A total of 123 patients were enrolled in the study. At 1 month after the initiation of PD, RRF was determined by a 24-hour urine collection and measured every 6 months thereafter. Clinical and biochemical data at the time of the initial 24-hour urine collection were considered as baseline. Results The RRF reduction rate was significantly greater in patients with high ferritin (ferritin ≥ 250 ng/mL) compared with those with low ferritin (ferritin < 250 ng/mL; -1.71 ± 1.36 mL/min/yr/1.73 m2 vs. -0.84 ± 1.63 mL/min/yr/1.73 m2, respectively; p = 0.007). Pearson correlation analysis revealed a significant negative correlation between the baseline serum ferritin level and the RRF reduction rate (r = -0.219, p = 0.015). Using multiple linear regression analysis and adjusting for other risk factors, baseline serum ferritin was an independent factor for the RRF reduction rate (β = -0.002, p = 0.002). Conclusions In this study we showed that a higher ferritin level was significantly associated with a more rapid RRF decline in patients undergoing PD.