Effect of Valsalva Maneuver on QT Dispersion in Hemodialysis Patients

Increased QT dispersion seems to be related to an increased risk of arrhythmia and sudden death, a common cause of mortality in hemodialysis (HD) patients. Increase in sympathetic tone has been documented in HD patients. In this study, we aimed to investigate the effect of changes in the autonomic tone on QT dispersion (QTd) in HD patients. Twenty HD patients (M/F 13/7; age, mean ±SD, 28 ± 10 years) and 22 age‐ and sex‐matched healthy controls (M/F 12/10; age, 30 ± 10 years) were included. The patients were dialyzed three‐times weekly; time on dialysis was 17 ± 8 months. The QT durations were measured from 12 lead surface EKGs and were corrected for RR intervals. Corrected maximum (QT_c max) and minimum (QT_cmin) QT intervals and their difference (QT _c d) were recorded. The effect of the Valsalva maneuver in the release phase on QT _c intervals and dispersion was assessed. The HD patients had prolonged values compared to controls: QT _c d, 59 ± 17 ms versus 35 ± 7 ms, p < 0.001; QT _c max, 458 ± 41 ms versus 397 ± 21 ms, p < 0.001; and QT _c min, 398 ± 36 ms versus 362 ± 25 ms, p < 0.001. After the Valsalva maneuver no changes were observed in controls: QT _c max, 397 ± 21 ms versus 396 ± 22 ms, p = 0.9; QT _c min, 362 ± 24 ms versus 358 ± 19 ms, p = 0.5; and QT _c d, 35 ± 7 ms versus 38 ± 10 ms, p = 0.15. Whereas, in HD patients all values were significantly shortened: QT_cmax, 458 ± 41 ms versus 427 ± 35 ms, p = 0.003; QT_c min, 398 ± 36 ms versus 379 ± 34 ms, p = 0.04; and QT_c d, 59 ± 17 ms versus 48 ± 15 ms, p = 0.01. The decrease in QTmax was more prominent than the decrease in QTmin, hence QT dispersion was significantly decreased after the Valsalva maneuver, but differences from controls were still significant. In conclusion, increased sympathetic activity may have a role in the prolonged QT duration and increased QT dispersion in HD patients.     

Volume Control in Hemodialysis Patients

Cardiovascular disease is the main cause of the high mortality of dialysis patients and is largely due to poor control of blood pressure. Establishing and maintaining normal extracellular volume (ECV) is required to achieve normotension. The dry weight concept links ECV and blood pressure by a simple clinical relationship. Dry weight is the ideal postdialysis weight that allows a constantly normal blood pressure to be maintained without using antihypertensive medications. Maintenance of normal ECV requires control of salt intake to reduce interdialytic weight gain ( i.e., saline overload) combined with the diffusive and convective removal of salt and water from the body during dialysis sessions. Several problems are to be faced when using the dry weight method. Clinical evaluation must take into account the following confounding factors: weight varies with nutrition, clinical symptoms are unspecific and sometimes discordant, and there is a lag time between ECV and blood pressure changes. On the other hand, achievement of dry weight is hampered by dialysis times that are too short (and weight gains that are too high), by antihypertensive medications, and by poor heart conditions. A longer session time allows for a slower, easier, and more comfortable ultrafiltration.     

The Effect of Frequent and Occasional Dialysis-Associated Hypotension on Survival of Patients on Hemodialysis

Hyperphosphatemia and poor uremia control are established cardiovascular risk factors in patients with end-stage renal disease (ESRD) associated with impaired endothelial dependent and independent vasodilation (EDV and EIV). Nocturnal hemodialysis [6 × 8 h/week] augments dialysis dose and offers normal phosphate (Pi) balance. We hypothesized that NHD would restore EDV (endothelial function) and EIV (vascular smooth muscle cell function) by simultaneously improving uremia and Pi control. 2 groups of ESRD patients (mean age 41 ± 2 years) stratified according to their baseline plasma Pi levels (normal Pi <1.8 mM, high Pi >1.8 mM) were studied. Dialysis dose (Kt/V per session), plasma Pi, blood pressure (BP) and brachial artery responses to reactive hyperemia (EDV), and sublingual nitroglycerin (EIV) were examined before, 1 and 2 months after conversion from conventional hemodialysis (CHD) [3 × 4 h/week] to NHD. After 2 months, NHD increased dialysis dose (from 1.24 ± 0.06 to 2.04 ± 0.08; p = 0.02) and lowered BP (from 140 ± 5/82 ± 3 to 119 ± 1/71 ± 3, p = 0.01) in all patients. In patients with adequate Pi control during CHD, EDV was normalized after 1 month of NHD. In contrast, in the high Pi group, 1 month of NHD was sufficient to reduce plasma phosphate levels, but 2 months of NHD was required for EDV to improve.  

     

Physiologic Inhibitors of Coagulation in Patients on Chronic Hemodialysis

Patients on hemodialysis are at increased risk for bleeding and thromboses. The intriguing balance between these risks is more complex than once thought, as endogenous clotting factors and their regulators come into contact with bioincompatible dialyzer membranes, in the setting of an extracorporeal circuit of blood flow, in the face of the uremic state. In this review, we summarize the current data on the interaction between the physiologic inhibitors of coagulation and hemodialysis. Data sources and study selection were obtained from research and review articles related to the endogenous anticoagulation pathway published in English on MEDLINE from 1972 to 2002. While protein C activity and protein S antigen concentrations are increased, there is no change in antithrombin III levels during hemodialysis in relation to predialysis levels. Plasma protein Z, which has only recently been studied in uremic subjects, is increased as well. In addition, hemodialysis leads to elevated tissue factor plasminogen inhibitor, thrombomodulin, tissue plasminogen activator, and plasminogen activator inhibitor-1 activities. The potential functional significance of these observations is discussed. Finally, as erythropoietin is commonly prescribed to uremic patients and is recognized to be prothrombotic, an appraisal of its interaction with the naturally occurring anticoagulants is presented. It is apparent that we are only beginning to realize the complexity of the interplay between this myriad of serum factors and hemodialysis. Further research is needed to shed light on this underexplored area of hemodialysis.     

Cirrhosis Ameliorates Renal Osteodystrophy in Patients on Regular Hemodialysis

Cirrhosis (Cir) is often associated with chronic renal failure (CRF) in Egyptian patients on regular hemodialysis (RHD). This is largely attributed to hepatosplenic schistosomiasis and concomitant Hepatitis C viral infection. As the liver has a major role in vitamin D3 activation, we designed this study to envisage the impact of Cir on renal osteodystrophy (ROD). It included 130 consecutive age‐ and gender‐matched subjects in 4 categories. Group I: 39 patients (34 male and 5 female; mean age 48.8 years) with Cir normal renal function; group II: 37 patients (30 male and 7 female; mean age 49.0 years) with CRF and normal liver function, on RHD for a mean duration of 6 ± 3.9 years; group III: 41 patients (30 male and 11 female; mean age 50.7 years) with CRF and concomitant Cir, stable on RHD for a mean duration of 7.0 ± 4.0 years; and group IV: 16 normal volunteers (13 male and 3 female; mean age 46.3 years). The prevalence of diabetes as well as previous infection with schistosomiasis was similar in all patient groups and that of HCV infection was alike in groups I and III. In all subjects, conventional parameters of liver and renal function were tested; in addition to measurement of serum total protein, albumin, calcium, phosphate, total and bone‐specific alkaline phosphatase (B‐ALP), parathormone (PTH), 5‐hydroxycholecalciferol (5HD), 1,25‐dihydroxycholecalciferol (1,25HD), Cross Laps (CXL) as a marker of bone resorption, and aminoterminal propeptide of type I procollagen (PINP) as a measure of bone formation. Bone mineral density (BMD) was measured by either Dual Energy X‐ray Absorptiometry (DEXA) or Computerized Tomography (CT). Group II patients displayed the typical CRF profile comprising hypocalcemia, hyperphosphatemia, increased total and bone‐specific alkaline phosphatases, high PTH and 25HD, low 1,25HD, increased PINP as well as CXL, and generally decreased BMD. Cir (Group III) significantly (p value at least <0.5) modified this profile in several aspects: it checked hypocalcemia (mean 8.8 vs. 7.9 mg/dL in groups II and III, respectively), hyperphosphatemia (5.15 vs. 4.9 mg/dL), and the elevation of B‐ALP (62 vs. 30.5 μg/L) and PTH (89 vs. 78 pg/mL). It lowered the serum level of 25HD (18.7 vs. 13.7 ng/mL), augmented the deficiency of 1,25HD (13.4 vs. 8.0 pg/mL), did not appreciably affect the increase in bone formation (PINP 77.9 vs. 75.5 ng/mL), but ameliorated its excessive resorption (CXL 21 860 vs. 30 328 pmol/L) noticed in group II. This was associated with amelioration of the dialysis‐associated osteopenia (70 vs. 33.5%) and increased incidence of osteosclerosis (30 vs. 61%), as measured by bone mineral density. Conclusion: Our data indicate that Cir ameliorates ROD through decreased bone resorption. This is associated with better tolerance to 1,25HD deficiency, which initiates the cascade of hypocalcemia, hyperparathyroidism, and increased bone resorption in CRF. Such tolerance may reflect upregulation of vitamin D receptors as a consequence of the humoral perturbation supervening in Cir, involving IGF‐1, estrogens, or other vitamin D metabolites as 24,25 HD.     

The Effect of Lipid A Analog E5531 on Membrane Properties of Dipalmitoylphosphatidylcholine

The effect of the lipid A analog E5531 on the phospholipid membrane was determined and compared with that of the lipid A from Escherichia coli (EC). E5531 decreased the phase transition temperature of dipalmitoylphosphatidylcholine (DPPC) membrane and increased the fluidity and permeability. On the other hand, EC increased the phase transition temperature and decreased the membrane fluidity and permeability. These results suggest that the reason for the difference of biological effects of E5531 and lipid A from EC would be caused by the differences from the effect on the cell membranes.     

Factors Affecting Flow-Mediated Vasodilatation in Hemodialysis Patients

Clinical manifestation of overt vascular disease may be preceded for years by endothelial dysfunction. Objective: This study was undertaken to evaluate endothelial function in ESRD patients and correlation between endothelial function and clinical and biochemical parameters. Methods: 32 stable ESRD patients (male : female = 16 : 16, average age: 55.2 ± 13.0) on hemodialysis were included. A 10‐MHz ultrasound transducer was used to image the brachial artery. Brachial artery diameter was measured, and reactive hyperemia was induced by inflation to 250 mmHg for 5 min and then deflation of a pneumatic cuff. After release of the cuff, brachial artery diameter was measured. Results: In the entire study population and non‐diabetic group, the %FMD (% flow‐mediated dilatation, % change of brachial artery diameter between before and after cuff inflation) did not show any significant correlation with duration of dialysis, age, hypertension, albumin, CRP, total cholesterol, LDL and HDL cholesterol, and triglyceride. However, the %FMD of diabetic patients was lower than that of non‐diabetics. Among the patients with diabetes, the group of patients with FMD of <5.2% showed significant lower serum albumin and significantly higher ln(CRP) levels compared to the group of patients with FMD ≥5.2%. The %FMD showed significant positive correlation with serum albumin level and significant negative correlation with ln(CRP) in diabetic patients. Conclusion: These findings suggest that endothelial dysfunction, estimated by FMD, was significantly more prominent in diabetic ESRD, especially with low serum albumin and high CRP levels.     

Survival of End-Stage Renal Disease Diabetic Patients on Hemodialysis

Purpose: To analyze survival and causes of mortality in end‐stage renal disease (ESRD) diabetic patients treated by hemodialysis. Methods: Data of 1203 ESRD hemodialyzed patients between 1975 and 2002 were analyzed, 116 patients were excluded and 1087 patients included in the study. We studied the prevalence of the diabetic nephropathy, the rate of survival and causes of death by comparing diabetic patients with a control group of patients without diabetes. Results: Among the 1087 patients requiring dialysis, 272 (25%) were diabetic and 815 non‐diabetic whose causal nephropathy was nephroangiosclerosis 32%, glomerulonephritis 15%, chronic interstitial nephropathy 14%, and others 14%. The diabetics were older at the beginning of dialysis than non‐diabetic patients: 60.33 ± 11.39 years vs. 52.23 ± 17.20 years, p < 0.001. Average time on dialysis is more important in non‐diabetic than diabetic group [5.90 ± 5.73 years vs. 2.71. ± 2.48 years, p < 0.001]. The rate of death was higher in diabetics than in control group [71.7% vs. 55.8%, respectively, p < 0.003]. The difference in survival between the two groups remains significant for the same age. Death caused by cardiovascular disorders is higher in diabetics (68.8%) than non‐diabetics (31.2%) (p < 0.05). Among death causes, stroke is the most frequent cause in diabetics (18.4% vs. 11.6%) in non‐diabetics, p < 0.05. Death by heart failure and infections is higher in diabetics but the difference is not statistically significant (12.3% in diabetics vs. 9.4% in non‐diabetics for heart failure and 13.8% vs. 11.4% for infections). Death due to neoplasms is higher in non‐diabetics (4.39% vs. 1.02% in diabetics, p < 0.05). Conclusion: In our cohort, mortality in diabetic patients is higher than in non‐diabetic patients. Cardio‐vascular disorders are the most cause of death in diabetics and above all stroke, whereas mortality due to neoplasms is higher in non‐diabetic patients. Diabetes is an important risk factor of mortality in hemodialysis patients.     

The Effect of the Membrane Fluidity on Pharmacokinetics for Lipid A Analog E5531

The effect of the dispersing procedure on the aggregate size, membrane fluidity and the pharmacokinetics were evaluated for the lipid A analog E5531. The size of the aggregates prepared by the pH-jump method (pH 11.0 → 7.3) was decreased, reaching 20 nm with increasing dispersing time in 0.003 N NaOH (pH 11.0). The membrane fluidity of the aggregates increased with increasing dispersing time. When prepared by the normal dilution method (pH 7.3 → 7.3), the size of the aggregates remained constant at 150 nm and the membrane fluidity was smaller compared to samples prepared by the pH-jump method. Using samples with different degrees of hydration and different membrane fluidities prepared by the pH-jump method, the pharmacokinetics after intravenous administration into rats were evaluated, and the data obtained confirmed that the membrane fluidity was correlated with the pharmacokinetics in rat. In addition, E5531 vials were stable for 24 months at room temperature when used within 24 hr after reconstitution.     

血液透析膜的制备改性及组件设计

血液透析是治疗肾功能衰竭的一种最重要方法,而血液透析器是血液透析净化临床医学的重要器械之一.透析膜是血液透析器的关键核心元件,对治疗效果起着决定性作用.本文较全面的介绍了血液透析膜材料发展历程及趋势;并详细阐述了透析膜材料的血液相容性及改性方法的研究,包括抗凝血性、氧化应激、补体激活等方面;此外,也对透析膜组件的发展历程进行了较为详细的介绍.     

Clinical Characteristics of Upper Gastrointestinal Bleeding in Hemodialysis Patients

Upper gastrointestinal bleeding (UGIB) frequently occurs in hemodialysis (HD) patients. But, clinical characteristics of UGIB in HD patients are not well reported yet.
Objective:  This study was designed to compare the clinical characteristics of UGIB between HD patients and normal population with intact renal function.
Methods:  This study enrolled 24 HD patients with UGIB. Age- and sex-matched 26 patients with UGIB and normal renal function were selected as control group during the same period. Of the cases with UGIB, esophageal variceal bleedings due to liver cirrhosis were excluded in this study. We investigated the results of treatment and UGIB-associated mortality for 3 months after the event and then compared previous gastrointestinal (GI) symptoms (Sx), endoscopic findings, treatment results, and mortality between HD patients and control.
Results:  The results are summarized in the table.  

     

Changes of Plasma Amino Acid Profile in Hemodialysis Patients

Background:  The aim of this study was to investigate the influence of HCV on two markers of systemic inflammation, serum CRP, and interleukin-6 (IL-6) in HD patients.
Methods:  The study included 118 HD patients (47% males, age 47 ± 13 years, 9% diabetics) who were treated by on standard HD for at least 6 months. The patients were divided in two groups, depending on the presence (HCV+) or absence (HCV–) of serum antibodies against HCV. Serum albumin (S-Alb), plasma high sensitivity CRP (hsCRP), IL-6, and alanine aminotransferase (ALT) were measured, and the values were compared with 22 healthy controls.
Results:  The median of hsCRP, IL-6, and the hsCRP/IL-6 ratio were: 3.5 vs. 2.1 mg/L, p < 0.05; 4.3 vs. 0.9 pg/mL, p < 0.0001; and 0.8 vs. 2.7 pg/mL, p < 0.0001 for patients and controls, respectively. Age, gender, S-Alb, IL-6, and hsCRP did not differ between the HCV+ and HCV– patients. However, HCV+ patients had higher ALT (29 ± 21 vs. 21 ± 25 UI/L) and had been a longer time on HD (6.1 ± 3.0 vs. 4.0 ± 2.0 years) (p < 0.0001), respectively. Moreover, HCV+ patients had a significantly lower median hsCRP/IL-6 ratio (0.7 vs. 0.9; p < 0.05) as compared to the HCV group.
Conclusion:  The finding that the hsCRP/IL-6 ratio was lower in HCV+ patients than in HCV– patients suggests that hsCRP may be a less useful marker of inflammation in HCV+ patients and that a different cut-off value for hsCRP may be required to define inflammation in HD patients.     

Effect of Divalent Cations on the Membrane Properties of the Lipid A Analog E5531

To obtain information on the effects of Mg²⁺on the membrane properties of the lipid A analog E5531, we determined the size, structure, zeta potential, membrane fluidity, and micropolarity of the aggregates and the permeability of the E5531 membrane after the addition of Mg²⁺. E5531 forms a vesicle structure and within the molar ratio of [E5531]:[Mg²⁺] = 1:3, Mg²⁺ increased the zeta potential of the E5531 membrane, but did not change the size of the aggregates (approximately 20 nm). Within that molar ratio, Mg²⁺ decreased the membrane fluidity and micropolarity of E5531 and increased the phase transition temperature. Above the molar ratio of [E5531]:[Mg²⁺] = 1:5, the size of the aggregates was increased, but at [E5531]:[Mg²⁺] = 1:3, the size of the aggregates was similar to that in the absence of Mg²⁺ (approximately 20 nm), and we could stabilize the aggregates in rat plasma.     

Relationship of Hypoalbuminemia to Multiple Clinical Factors in Hemodialysis Patients

Research shows that low albumin is correlated with higher morbidity and mortality in the dialysis population. The reasons for this are multi‐factorial and may be related to inadequate protein intake, infection and sepsis, inadequate dialysis, or catabolism of uremia. USRDS data show that ESRD Network 16 tends to have lower albumins compared to other ESRD Networks. Objective: To evaluate albumin status of HD patients at Puget Sound Kidney Centers, Everett, WA (ESRD Network 16) and identify potential factors that may put patients at risk of hypoalbuminemia. Methods: Clinical and biochemical data were collected for 3 months on 221 HD patients. Data included serum albumin (bromcresol purple), calcium, phosphorus, CO₂, Hct, % saturation, ferritin, PTH, BUN, Kt/V, URR, nPCR, hours of HD treatment, interdialytic fluid weight gains, DW changes, incidence of infection and hospitalization, catheter use for dialysis access, presence of diabetes and other co‐morbidities, dialyzer reuse, social/psychological status, and use of nutrition supplements. All biochemical data were collected after the longest interdialytic period and analyzed at the same reference laboratory. Data were averaged for each patient for the 3 months and correlations between parameters were determined using Chi‐square analysis. Results: 25% of all patients had albumins <3.2 g/dL (reference range for normal population 3.5–5.0 g/dL). Patients with lower albumins were significantly more likely to have DM (p < 0.02), use catheters for HD access (p < 0.001), had infections during the previous month (p < 0.001), been hospitalized during the previous month (p < 0.002), have co‐morbid issues (p < 0.001), and use nutrition supplements (p < 0.002). No other factors were significantly correlated with lower albumin. Conclusion: Factors other than nutrition seem to be related to hypoalbuminemia. This study has prompted improved protocols for catheter care and use, infection control, and early intervention for nutrition supplement use. Increased screening and monitoring at‐risk patients (those with diabetes and other co‐morbid conditions) has resulted in improved patient care.     

PEM燃料电池膜电极边框对膜应力的影响研究

利用有限元法分析了不同膜电极边框材料以及组装方式在装夹状态下对燃料电池质子交换膜(PEM)造成的应力影响,结果表明在边框两端与PEM交界处均会存在应力集中现象,并且随着边框模量的减小而减弱.相比于边框与PEM直接接触装配,相同边框材料与PEM粘贴装配对PEM损伤更小.根据模拟结果提出了优化方案,以期给研究设计人员提供参考.     

Impact of Ischemic Heart Disease on Early Access Failure in Nondiabetic Hemodialysis Patients

Lynchburg Nephrology Dialysis Inc. started its nightly home hemodialysis (NHHD) program in September 1997.
Purpose of study:  To evaluate episodes of exit site infections, catheter sepsis, safety, and longevity of accesses for patients doing NHHD.
Methods:  If IJ catheter was chosen, patient was started on Coumadin 2 mg/day when catheter was placed. If catheter malfunctioned, it was locked with a thrombolytic agent and Coumadin was adjusted to meet a goal INR of 1.5–2.25. If the problem persisted, the catheter was exchanged. For catheters, the B-D InterLink device was used to prevent air emboli and infection, and a locking device was used to prevent disconnects. If AV fistula was used, 4 buttonholes were established using 16 gauge needles. If AV graft was used, patients were taught the ladder cannulation technique using 16 gauge needles.
Results:  As of September 1, 2003, 45 patients have completed training and have performed 27,063 treatments at home. Total catheter time at home was 930 months. Total AV fistula and AV graft time at home was 190 and 20 months, respectively. Upon completion of training, 34 patients were using tunneled IJ catheters, 10 using AV fistulas, and 1 using an AV graft. The IJ catheter exit site and sepsis infection rate was 0.35 and 0.49 episodes/1000 patient days, respectively. Average catheter life was 8.5 months with the longest 66.7 months and the shortest 0.2 months. The AV fistula and graft exit site and sepsis infection rates were 0.16 and 0 episodes/1000 patient days, respectively. Catheter complications included 1 episode of disconnect due to patient's failure to use locking device, 1 episode of central stenosis, and 1 episode of intracranial hemorrhage, due to prolonged INR, with resolution of symptoms.
Conclusion:  Data support that tunneled IJ catheters, AV fistulas, and AV grafts were effective and safe permanent accesses for patients on NHHD.     

Role of Genetic Factors in Vascular Access Thrombosis in Hemodialysis Patients

Vascular access thrombosis is a frequent complication in hemodialysis (HD) patients. Genetic mutations, inflammation, and changes in the vascular wall are some factors that are thought to increase thrombosis risk. In this study, we tested for possible relationships between vascular thrombosis and some known thrombophilic mutation/polymorphisms in coagulation factors [factor V Leiden (FVL), prothrombin (Pt) G20210A, methylene tetrahydrofolate reductase (MTHFR C677T), factor XIII (F-XIII) Val34Leu, alpha-fibrinogen (AF) Thr312Ala, factor VII (F-VII) R353Q] and angiotensin I converting enzyme (ACE) gene in our HD patients. Patients who had experienced at least 3 episodes of AVF thrombosis composed of the study group, and patients who had never encountered this complication composed of the control group. None of the patients in either group had a history of diabetes mellitus, atherosclerosis, dialysis-related amyloidosis, or vasculitis. In order to find the frequency of F-XIII Val34Leu, AF Thr312Ala, and F-VII R353Q polymorphisms in our population, we also searched persons without renal disease or history of thrombosis (normal group). Results are summarized in Table. There was a tendency toward thrombotic mutation/polymorphisms in the study group for FVL, Pt G20210A, ACE I/D, and AF Thr312Ala. We suggest that patients who develop recurrent AVF thrombosis should be screened for the above-mentioned factors and investigated for other possible risk factors. This screening would allow more effective focus on prophylaxis.  

     

膜过滤技术在维生素B12生产中的应用

采用聚偏氟乙烯(PVDF)中空纤维微滤膜对维生素B12发酵液进行了除菌研究.发酵液经过微滤膜过滤后,菌体完全去除(去除率100%),远高于离心机除茵效果(去除率70%),滤液的澄清度及质量得到提高.另外,对污染膜的清洗研究表明,一般情况下0.1%的NaOH溶液清洗效果理想,当污染严重时,超声波振荡清洗效果最有效.     

A Report on 4 New Cases of Nephrogenic Fibrosing Dermopathy in Chronic Hemodialysis Patients

Nephrogenic fibrosing dermopathy (NFD) is a rare entity affecting patients with renal failure, often on chronic dialysis or after transplantation (TXP). The patient profile at risk for this debilitating condition is yet undefined as is the role of renal failure in its etiology. We diagnosed 4 chronic hemodialysis (HD) patients with NFD. A 55-year-old Caucasian male on HD for 5 years, secondary to diabetic nephropathy, developed woody, indurated skin of the extremities, decreased mobility, and wheelchair dependence. He died within 1 year. A 66-year-old African-American male with diabetes, hypertension, and pancreatic cancer developed thick indurated skin on his extremities after being on HD for approximately 20 months. He died 3 months later from sepsis. A 26-year-old Caucasian female on HD for approximately 10 years, secondary to hyperoxaluria-induced renal failure, had undergone combined liver and kidney TXP with primary nonfunction of the renal TXP. She succumbed to cholangitis approximately 1 year after progressive skin thickening and joint contractures were noted. A 75-year-old Caucasian female with renal failure secondary to recurrent hemolytic uremic syndrome and TXP failure was dialysis dependent for 6 years. Over a 3-month period, she developed skin changes consistent with NFD and entered hospice care secondary to marked deterioration in her quality of life. In all of these cases, skin changes were restricted to the extremities, sparing the trunk, face, and internal organs. Skin biopsy findings included thickened dermis with particularly thickened collagen bundles, mucin deposition, and fibroblast proliferation and were distinct from scleromyxedema and scleroderma. Autoimmune disease workup was negative. Indeed, NFD is a novel cutaneous fibrosing disorder of progressively debilitating nature in patients with renal failure that needs further clinical and pathological characterization.