Higher survival rates of chronic hemodialysis patients on anti-hypertensive drugs.

BACKGROUND: The effects of anti-hypertensive drugs on survival have not been examined in a large cohort of hemodialysis (HD) patients. METHODS: We examined the relationship between blood pressure, anti-hypertensive drug therapy, and survival using the nationwide HD registry of the Japanese Society for Dialysis Therapy. Outcomes were confirmed using the coded ID numbers of the 2005 and 2006 registries. Logistic analyses were performed to determine the effect of anti-hypertensive drug therapy on survival. RESULTS: A total of 163,668 patients (50.6% men; 31.5% with diabetes mellitus; mean age 63.6 years) on HD 3 times a week in 2005 were studied. Mean (SD) levels of systolic and diastolic blood pressure were 153.4 (24.1) and 78.7 (13.7) mm Hg, respectively, before the HD session. Two-thirds of the HD patients were prescribed anti-hypertensive drugs and the numbers of anti-hypertensive medications were: 1 in 26.8%, 2 in 24.4%, and 3 or more in 14.5% of the total patients. The 1-year mortality rate was 6.6% overall: 8.5% in patients not prescribed anti-hypertensive drugs and 5.6% among those prescribed anti-hypertensive drugs. The odds ratio (95% confidence interval) for the 1-year mortality rate was 0.724 (0.681-0.770, p < 0.0001) for patients prescribed anti-hypertensive drugs, after adjusting for age, sex, diabetes mellitus, body mass index, HD duration, serum albumin, and systolic blood pressure. CONCLUSION: Survival was better in patients prescribed anti-hypertensive drugs, particularly renin-angiotensin system inhibitors, than in those not prescribed anti-hypertensive drugs. The causality on this association remained to be determined and prospective studies on blood pressure target levels and the effects of anti-hypertensive drug class in HD patients are warranted.

Adenosine A1 receptor antagonist improves intradialytic hypotension.

Intradialytic hypotension is a most frequent complication of hemodialysis and may contribute to cardiovascular events and high mortality. There is a hypothesis that an increase in adenosine generation during hemodialysis may cause vasodilation and a decrease in cardiac output, which results in systemic hypotension. We studied whether this can be blocked by an adenosine A1 receptor antagonist. We investigated the effects of an A1 antagonist, FK352, injection in 30 chronic hemodialysis patients with frequent intradialytic hypotension by a prospective, multicenter, double-blind placebo-controlled study for 4 weeks after 4 weeks of the observation period. Intradialytic hypotension was defined as systolic blood pressure (SBP) less than 110 mmHg, with SBP drop of more than 30 mmHg from the predialysis level. The efficacy of FK352 was primarily assessed by the reduction rate of dialysis hypotension between the FK352 and placebo groups. Incidence of emergency treatments caused by hypotension was evaluated. FK352 (50 mg, intravenous) or an equivalent placebo was injected into the dialysis circuit 1 h after starting dialysis. Blood pressure and heart rate were monitored every 30 min during dialysis. FK352 significantly improved intradialytic hypotension (P=0.046), in that the reduction rates of intradialytic hypotension in the FK352 and placebo groups were -12.8% (Q1 (first quantile), Q3 (third quantile): -27.5, -1.7), and +8.3% (Q1, Q3: -16.6, +16.7), respectively. The frequency of discontinuation of dialysis was significantly reduced by FK352. No apparent side effects were observed from treatment with FK352. In conclusion, the A1 antagonist FK352 may offer a novel therapeutic option for chronic dialysis patients associated with intradialytic hypotension.

Significantly rapid relief from steroid-resistant nephrotic syndrome by LDL apheresis compared with steroid monotherapy.

Rapid amelioration of hypercholesterolemia by LDL apheresis (LDL-A) was performed for long-standing nephrotic syndrome (NS) with hyperlipidemia due to focal segmental glomerulosclerosis (FGS) and the clinical data and prognosis were compared between LDL-A-treated and nontreated groups. Seventeen steroid-resistant NS patients treated with LDL-A (LDL-A group) and 10 NS patients treated with steroids only (steroid-monotherapy (SM) group) were compared. Serum cholesterol and phospholipid levels were significantly lowered only in the LDL-A group (p < 0.01, respectively). The LDL-A group showed a significant decrease of urinary protein (UP, p < 0.01) and increase of serum albumin (p < 0.05). Average time needed to achieve a decrease of UP to less than nephrotic range (< 3.5 g/day) was significantly shorter in the LDL-A group than in the SM group (p < 0.01). Although this is not a prospective study, it is highly expected that a rapid improvement of hypercholesterolemia by LDL-A in steroid-resistant NS will provide more rapid relief from NS than steroid therapy alone.

Urine levels of CD46 (membrane cofactor protein) are increased in patients with glomerular diseases.

Soluble membrane cofactor protein (MCP, CD46) has not been detected by conventional ELISA in human urine. Here, we established a highly sensitive assay method for determination of urinary MCP (uMCP) using monoclonal antibody-coated paramagnetic beads. This method enabled us to detect less than 0.05 ng/ml of purified membrane and recombinant soluble MCP, a sensitivity 10-fold higher than that of conventional ELISA. In normal subjects, the levels of uMCP were <0. 05 ng/ml. The levels of uMCP were elevated in patients with IgA nephropathy and more prominently in patients with rapidly progressive glomerulonephritis. The levels of uMCP were correlated significantly with those of serum MCP (sMCP) and N-acetyl-beta-glucosaminidase and nonsignificantly with those of beta(2)-microglobulin, total urine protein, or serum creatinine. The properties of uMCP were inconsistent with those of the reported sMCP, since uMCP showed three bands on SDS-PAGE/immunoblotting with molecular mass profiles different from those of sMCP. uMCP exhibited factor I cofactor activity for cleavage of C3b comparable to that of sMCP. The origin of uMCP, however, remains to be determined. These results, taken together with the parameter correlation profiles, suggested that uMCP is secreted or produced secondary to tubular or glomerular damage. The physiological role and clinical significance of uMCP are now within the scope of our investigation by establishment of this assay.

Early treatment with corticosteroids ameliorates proteinuria, proliferative lesions, and mesangial phenotypic modulation in adult diffuse proliferative IgA nephropathy.

Diffuse proliferative immunoglobulin A (IgA) nephropathy has the potential risk for end-stage renal disease. However, treatment of IgA nephropathy has not been well established. To determine whether early treatment with corticosteroids ameliorates the proliferative lesions of diffuse proliferative IgA nephropathy, we conducted a prospective, randomized, controlled trial. Inclusion criteria were as follows: duration of abnormal urinalysis results less than 36 months, proteinuria less than 1.5 g/d of protein, serum creatinine level less than 1.5 mg/dL, and mesangial cell proliferation or matrix accumulation involving more than 50% of glomeruli. Twenty-one patients were randomly assigned to two groups: the corticosteroid group and the antiplatelet group. After 1 year of treatment, repeated renal biopsy was performed in 19 patients. We evaluated glomerular filtration rate, blood pressure, proteinuria, and histological parameters, including light microscopic findings and staining of alpha-smooth muscle actin (alphaSMA), as a marker of myofibroblast-like cells and fibronectin EDA (EDA-FN) as an indicator of renal fibrosis. After 1 year of treatment, proteinuria significantly decreased in the corticosteroid group. Histological findings, such as mesangial cell proliferation, mesangial matrix accumulation, and cellular crescents, showed significant improvement in the corticosteroid group but not in the antiplatelet group. Expression of alphaSMA in glomeruli significantly decreased in the corticosteroid group but not in the antiplatelet group. EDA-FN did not change in either group. We conclude that early treatment with corticosteroids for adult diffuse proliferative IgA nephropathy is effective in reducing renal injury.

Cardiovascular effect of normalizing the hematocrit level during erythropoietin therapy in predialysis patients with chronic renal failure.

The optimal target hematocrit (Ht) level in recombinant human erythropoietin (rHuEPO) therapy remains controversial and has hardly been investigated in predialysis patients. We prospectively studied the regression of left ventricular hypertrophy (LVH) on echocardiography in nine predialysis patients with chronic renal failure after a partial correction (target Ht, 30%) and normalization (target Ht, 40%) of the Ht with rHuEPO treatment. Twenty-four-hour ambulatory blood pressure monitoring was also performed. The administration of rHuEPO significantly increased Ht to the target values. The rate of renal failure progression did not change during rHuEPO treatment for 12 months (Cr, from 6.2 +/- 2.0 to 5.5 +/- 2.1 mg/dL). The left ventricular mass index (LVMI) tended to decrease after a partial correction of anemia (Ht, 32.1% +/- 1.8%) at 4 months, whereas it tended to significantly decrease after normalization of Ht (Ht, 39.1% +/- 2.4%) at 12 months (baseline, 140.6 +/- 12.1 g/m2; partial correction, 126.9 +/- 10.0 g/m2; normalization, 111.2 +/- 8.3 g/m2). All patients had received antihypertensive medication before rHuEPO administration, and additional drugs were also required in four cases during the study. As a result, a good overall blood pressure control was obtained without any adverse effects on the circadian blood pressure rhythm. In conclusion, from the perspective of LVH regression, the normalization of Ht was found to be more effective than that associated with a partial correction of anemia during rHuEPO therapy.

Low density lipoprotein apheresis therapy for steroid-resistant nephrotic syndrome. Kansai-FGS-Apheresis Treatment (K-FLAT) Study Group.

BACKGROUND: The pathogenic role of hyperlipidemia in long-standing nephrotic syndrome (NS) is known to be responsible for both the progression of glomerulosclerosis and tubulointerstitial injury, especially in focal segmental glomerulosclerosis (FGS). METHODS: Aggressive lipid lowering treatment by low density lipoprotein (LDL) apheresis (LDL-A) using a dextran sulfate cellulose column to treat patients with steroid-resistant or frequently recurrent severe NS was performed first without fixing the protocol in eight patients with FGS and one with minimal change nephrotic syndrome (MCNS). The period of NS before LDL-A, number and average intervals of LDL-A until the end of the therapy, and the prognosis were investigated. Next, a multicenter study with a fixed protocol of LDL-A treatment was designed in combination with steroid therapy for treatment twice a week for three weeks and weekly for six weeks, and was performed in 17 patients with FGS. The effects on the state of NS in addition to the change of urinary eicosanoid metabolites and remission rates were evaluated. RESULTS: In the preliminary study, along with a rapid improvement of hyperlipidemia, a high incidence of remission was achieved by LDL-A performed at relatively short intervals. In the multicenter study with a fixed protocol, there was a significant decrease of urinary protein (P < 0.001) and increase of serum albumin (P < 0.02) as well as a decrease of thromboxane B2 (TXB2) excretion (P < 0.05) after the treatment. Urinary excretion of TXB2 was significantly reduced after LDL-A (P < 0.05). The rate of entering into complete or incomplete remission was 71% with a relatively short duration of nephrotic-range proteinuria using the LDL-A therapy in comparison with steroid therapy alone. CONCLUSION: The rapid improvement of hypercholesterolemia with LDL-A treatment may provide a new approach for a high rate of improvement in the degree of NS in steroid-resistant NS of FGS and MCNS.

Cyclosporin A mono-therapy in nephrotic syndrome with contra-indication of steroid therapy.

We describe three cases of nephrotic syndrome with a contra-indication for steroid therapy successfully treated with cyclosporin A (CsA). A 21-year-old man with focal segmental glomerulosclerosis (FSGS) complicated by necrosis of the femoral head, and a 34-year-old woman and a 48-year-old man with minimal change disease (MCD) complicated by psychogenic reaction and diabetes mellitus, respectively, were given CsA at initial dosages of 3.8-5.0 mg/kg/day and immediately remitted completely. However, two of these patients suffered relapses when CsA was tapered. They are currently maintained in complete or partial remission on CsA at dosages of 3.2-4.7 mg/kg/day. These findings suggest that CsA mono-therapy may be useful in nephrotic syndrome patients contra-indicated for steroid therapy.

Dihydropyridine type calcium channel blocker-induced turbid dialysate in patients undergoing peritoneal dialysis.

We previously reported that manidipine, a new dihydropyridine type calcium channel blocker, produced chylous peritoneal dialysate being visually indistinguishable from infective peritonitis in 5 patients undergoing continuous ambulatory peritoneal dialysis (CAPD) [Yoshimoto et al. 1993]. To study whether such an adverse drug reaction would also be elicited by other commonly prescribed calcium channel blockers in CAPD patients, we have conducted postal inquiry to 15 collaborating hospitals and an institutional survey in International Medical Center of Japan as to the possible occurrence of calcium channel blocker-associated non-infective, turbid peritoneal dialysate in CAPD patients. Our diagnostic criteria for drug-induced turbidity of dialysate as a) it developed within 48 h after the administration of a newly introduced calcium channel blocker to the therapeutic regimen, b) absence of clinical symptoms of peritoneal inflammation (i.e., pyrexia, abdominal pain, nausea or vomiting), c) the fluid containing normal leukocyte counts and being negative for bacterial and fungal culture of the fluid, and d) it disappeared shortly after the withdrawal of the assumed causative agent. Results showed that 19 out of 251 CAPD patients given one of the calcium channel blockers developed non-infective turbid peritoneal dialysis that fulfilled all the above criteria. Four calcium channel blockers were suspected to be associated with the events: benidipine [2 out of 2 (100%) patients given the drug], manidipine [15 out of 36 (42%) patients], nisoldipine [1 out of 11 (9%) patients] and nifedipine [1 out of 159 (0.6%)] in descending order of frequency. None of the patients who received nicardipine, nilvadipine, nitrendipine, barnidipine and diltiazem (25, 7, 2, 1 and 8 patients, respectively) exhibited turbid dialysate. In conclusion, we consider that certain dihydropyridine type calcium channel blockers would cause turbid peritoneal dialysate being similar to that observed in patients developing infective peritonitis. To avoid unnecessary antibiotic therapy the possibility of this adverse reaction should be ruled out whenever a CAPD patient receiving a dihydropyridine type calcium channel blocker develops turbid dialysate.

Effects of low-dose simvastatin therapy on serum lipid levels in patients with moderate hypercholesterolemia: a 12-month study. The Simvastatin Study Group.

The aim of this study was to investigate the safety and long-term effects on serum lipid levels of low-dose simvastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, in Japanese patients with moderate primary hypercholesterolemia. We assigned 201 patients (68 men and 133 women; mean +/- SD age, 61.3 +/- 10.2 years) with serum total cholesterol levels > or = 220 mg/dL to receive simvastatin 5 mg each evening; the treatment period was 1 year. Serum total cholesterol, triglycerides, and low-density lipoprotein (LDL) cholesterol levels decreased significantly in response to simvastatin therapy, and the changes were maintained throughout the treatment period. Mean total cholesterol decreased from 269.9 +/- 35.4 mg/dL to 215.2 +/- 34.5 mg/dL (20.3%), triglycerides decreased from 183.0 +/- 110.2 mg/dL to 155.5 +/- 88.5 mg/dL (15.0%), and LDL cholesterol decreased from 180.0 +/- 33.1 mg/dL to 130.1 +/- 35.1 mg/dL (27.7%). Total cholesterol, triglycerides, and LDL cholesterol tended to decline when the pretreatment values were higher; the critical values and the bidirectional changes of the serum lipid levels were 188.1, 109.5, and 91.6 mg/dL, respectively. Although the serum level of high-density lipoprotein cholesterol did not change significantly, it tended to increase more when the pretreatment values were lower; the "critical value" was 70 mg/dL. Nine patients experienced mild adverse events, but none discontinued simvastatin during the 12-month treatment period. We found that low-dose simvastatin therapy is effective in achieving long-term decreases in serum lipid levels and is well tolerated by patients with moderate hypercholesterolemia. Simvastatin therapy may result in normalization of serum lipid levels.

Indoxyl sulfate and progression of renal failure: effects of a low-protein diet and oral sorbent on indoxyl sulfate production in uremic rats and undialyzed uremic patients.

We have previously demonstrated that indoxyl sulfate is a stimulating factor for the progression of glomerular sclerosis in uremic rats. In this study we determined if a low-protein diet or oral sorbent (AST-120) could reduce the serum and urine levels of indoxyl sulfate in 5/6-nephrectomized uremic rats and undialyzed uremic patients. The uremic rats were treated by fasting or AST-120 for 2 days. The serum and urine levels of indoxyl sulfate dramatically decreased 1-2 days after fasting or AST-120 treatment. We then measured the serum and urine levels of indoxyl sulfate and calculated protein intake from urinary amounts of urea nitrogen using Maroni's equation in 80 undialyzed uremic patients with creatinine clearance less than 30 ml/min. The serum and urine levels of indoxyl sulfate were significantly lower in the patients on a low-protein diet than in those in the normal-protein diet group. Administration of AST-120 significantly decreased serum and urine levels of indoxyl sulfate in 22 undialyzed uremic patients. In conclusion, a low-protein diet or AST-120 reduced the serum and urine levels of indoxyl sulfate, a stimulating factor for glomerular sclerosis, in both uremic rats and undialyzed uremic patients.

Are glomerular lesions alternatives to microalbuminuria in predicting later progression of diabetic nephropathy?

We inquired whether the type of diabetic glomerulosclerosis, diffuse or nodular, is of value as an alternative to microalbuminuria in predicting later progression of renal disease. To answer this question, we conducted a retrospective cohort study in eleven Japanese non-insulin-dependent diabetes mellitus patients with normo- to microalbuminuria. Nodular diabetic glomerulosclerosis was found in six patients, and diffuse diabetic glomerulosclerosis in five patients. The mean follow-up period was 41.5 months (range 12-65). Three patients developed persistent proteinuria and one developed chronic renal failure. Mean level of serum creatinine in all patients was elevated from 0.97 +/- 0.23 mg/dl (SD) to 1.10 +/- 0.37 mg/dl (P = 0.098). The rate of increase in serum creatinine was 0.068 +/- 0.115 mg/dl/year in nodular diabetic glomerulosclerosis, and 0.023 +/- 0.069 mg/dl/year in a diffuse one. No difference was found between these two types of diabetic glomerulosclerosis (P = 0.445). We conclude that in normo- to microalbuminuria diabetic nephropathy the type of diabetic glomerulosclerosis, diffuse or nodular, is not necessarily an alternative to microalbuminuria in predicting its later progression in Japanese non-insulin-dependent diabetes mellitus patients.

Accumulation of indoxyl-beta-D-glucuronide in uremic serum: suppression of its production by oral sorbent and efficient removal by hemodialysis.

We identified and quantified indoxyl-beta-D-glucuronide in uremic serum and urine to determine the metabolism of indoles including indoxyl sulfate in uremic patients. Serum levels of indoxyl-beta-D-glucuronide were markedly increased in undialyzed uremic patients, in patients on hemodialysis, and in patients on continuous ambulatory peritoneal dialysis. Urinary excretion of indoxyl-beta-D-glucuronide was also increased in undialyzed uremic patients. Urinary indoxyl-beta-D-glucuronide was significantly correlated with serum indoxyl sulfate, indicating that a high serum level of indoxyl sulfate leads to the enhanced synthesis of indoxyl-beta-D-glucuronide. Oral sorbent (AST-120) administration markedly decreased the serum and urine levels of indoxyl-beta-D-glucuronide as well as indoxyl sulfate in the undialyzed uremic patients. Serum indoxyl-beta-D-glucuronide could be efficiently removed by hemodialysis despite its high protein-binding ratio of about 50%. In conclusion, the serum level of indoxyl-beta-D-glucuronide increases in uremic patients due to renal insufficiency and its increased production. The production of indoxyl-beta-D-glucuronide can be suppressed by oral sorbent treatment, and serum indoxyl-beta-D-glucuronide can be efficiently removed by hemodialysis.

Interleukin-1 and its naturally occurring antagonist in peritoneal dialysis patients.

We have assessed the levels of interleukin-1b (IL-1b) and interleukin-1 receptor antagonist (IL-1RA) in both serum and peritoneal dialysate effluents (PDE) from nineteen continuous ambulatory peritoneal dialysis patients (CAPD) without peritonitis and three CAPD patients with peritonitis. IL-1 beta and IL-1RA were tested using a specific ELISA immuno-assay. Fifteen normal healthy volunteers severed as control. The serum levels of IL-1RA in CAPD patients were significantly increased comparatively to their levels in healthy volunteers (p < 0.001). CAPD patients without peritonitis (stable patients) showed relatively low levels of IL-1RA in peritoneal dialysate effluents (114.4 +/- 85.1 pg/ml). Patients with peritonitis showed very high serum levels of IL-1RA at the onset of acute infection (4710 +/- 50 pg/ml). The levels of IL-1RA in PDE were very high during the onset of bacterial peritonitis (5744 +/- 254 pg/ml). The clinical recovery from peritonitis was characterized by a fall in IL-1RA in both serum and dialysate. Serum levels IL-1 beta showed a different pattern, it was not detectable in stable CAPD patients as well as in normal healthy volunteers. It was detectable only in serum of patients with peritonitis (10 +/- 0.8 pg/ml). Likewise, in most stable patients, IL-1 beta-PDE levels were not detectable, but substantial amounts can be detected in PDE during bacterial infection (80 +/- 15 pg/ml). The increase in serum and PDE levels of IL-1 beta during bacterial infection was very rapid, this cytokine disappeared in serum and PDE, 2 or 3 days before the clinical recovery.(ABSTRACT TRUNCATED AT 250 WORDS)

Identification and characterization of membrane cofactor protein (CD46) in the human kidneys.

Membrane cofactor protein (MCP, CD46) is an integral protein that serves as a cofactor for factor I in inactivating C3b/C4b deposited on the same cell membrane as C3bi/C4c+C4d. This C3b/C4b inactivation is closely associated with self-protection of host cells from autologous complement attack. We have studied the distribution and properties of MCP in the normal human kidney by immunohistochemical and immunoblotting methods using monoclonal antibodies against MCP. MCP was predominantly expressed on the juxtaglomerular apparatus. Glomerular capillary walls, mesangial areas, and tubulus were also MCP positive. Glomerulus MCP was composed of two major bands of 45-65 kDa, which were similar to those of lymphocyte MCP. The proportion of the high and low molecular weight components in glomerulus MCP, however, was considerably different from that of lymphocyte MCP among the individual samples tested. Glomerular epithelial cells and mesangial cells from an individual having equal amounts of high and low molecular weight components in the lymphocytes were cultured separately and the properties of their MCP investigated. MCP in the mesangial cells and glomerular epithelial cells showed profiles in which the upper band was predominant. The results may explain the unique distribution of the high and low molecular weight forms in the glomerulus. These forms of MCP together with factor I were all capable of inactivating C3b to C3bi. Message analysis suggested that glomerular epithelial cells and mesangial cells synthesized a single species of mRNA of 4.2 kb from which the polymorphic MCP species were generated. Flow cytometric analysis suggested that MCP was minimal in mesangial cells. These results, taken together with the previous reports on the distribution of other complement regulatory proteins, infer that the distribution profile of MCP is rather similar to that of DAF but differs from those of CD59 and CR1 in the normal human kidney; this may reflect the differences between their roles or functional properties in renal tissue.

[Pharmacokinetic study of ofloxacin using saliva concentration in chronic renal failure].

We evaluated saliva concentration as a parameter of therapeutic drug monitoring (TDM) of Ofloxacin (OFLX) in patients with severe renal failure (CRF). Saliva OFLX concentration correlated closely with serum OFLX concentration as shown in healthy subjects, although it was significantly lower (about three-quarters), indicating that OFLX had less penetration into saliva in patients with renal failure. Saliva concentration was almost equal to serum concentration during hemodialysis, which might have been due to the constant dialysis of OFLX. In conclusion, saliva concentration was useful for TDM of OFLX in patients with CRF, as it is in healthy subjects.

Treatment of dialysis-induced hypotension with L-threo-3,4-dihydroxyphenylserine.

L-threo-3,4-dihydroxyphenylserine (L-DOPS), a precursor of noradrenaline (norepinephrine), which is converted into noradrenaline when orally administered, was given orally to haemodialysed patients exhibiting dialysis-induced hypotension. In five patients given 300 mg L-DOPS plasma concentrations reached a peak of 1.43 +/- 0.59 micrograms/ml 6 h after administration and decreased slowly to disappear after 36 h. Plasma noradrenaline concentrations showed a significant increase (P < 0.05), reaching a peak of 1.28 +/- 0.64 ng/ml after 24 h and declined to 0.75 +/- 0.47 ng/ml by 48 h. Administration of L-DOPS to six patients during dialysis for 6 consecutive weeks showed no accumulation in the blood. Oral administration of 200-400 mg L-DOPS to 34 patients 1 h before dialysis prevented dialysis-induced hypotension and decreased the number of concurrent treatments required for hypotension. The signs and symptoms of hypotension were improved in 73.5% of the patients and persisted after dialysis in 64.7%. The preventive effect of L-DOPS was significantly more prominent in patients with predialysis systolic blood pressure less than 100 mmHg and in patients with non-diabetic nephropathy. L-DOPS appeared to be an effective and well-tolerated treatment for the prevention of dialysis-induced hypotension.