Prediction of equilibrated postdialysis BUN by an artificial neural network in high-efficiency hemodialysis.

In urea kinetic modeling, postdialysis blood urea nitrogen (BUN) is usually underestimated with an overestimation of the Kt/V especially in high-efficiency hemodialysis (HD). Thus, an artificial neural network (ANN) was used to predict the equilibrated BUN (Ceq) and equilibrated Kt/V (eKt/V60) by using both predialysis, postdialysis, and low-flow postdialysis BUN. The results were compared to a Smye formula to predict Ceq and a Daugirdas' formula (eKt/V30) to predict eKt/V60. Seventy-four patients on high-efficiency or high-flux HD were recruited. Their mean urea rebound was 28.6+/-2%. Patients were divided into a "training" set (n = 40) and a validation set (n = 34) for the ANN. Their status was exchanged later, and the two results were pooled. In the prediction of Ceq, both Smye formula and low-flow ANN were equally highly accurate. In patients with a high urea rebound (>30%), although Smye formula lost its accuracy, low-flow ANN remained accurate. In the prediction of eKt/V60, both Daugirdas' formula and low-flow ANN were equally accurate, although the Smye formula was not so accurate. In patients with a high urea rebound, although both Smye and Daugirdas' formulas lost their accuracy, low-flow ANN remained accurate. We concluded that low-flow ANN can accurately predict both Ceq and eKt/V60 regardless of the degree of urea rebound.

Advanced glycation end product-induced proliferation in NRK-49F cells is dependent on the JAK2/STAT5 pathway and cyclin D1.

Advanced glycation end products (AGEs) are important in the pathogenesis of diabetic nephropathy, which leads to renal fibrosis. Previously, we found that the janus kinase (JAK)/signal transducers and activators of transcription (STAT) signaling pathway is necessary for AGE-induced cellular proliferation in normal rat kidney interstitial fibroblast (NRK-49F) cells. However, a direct link between JAK/STAT and cell-cycle progression has not been well established. In this regard, STAT5 has been found to induce cyclin D1 and proliferation in hematopoietic cells. Therefore, we examined effects of AGE on STAT5 and cell-cycle-dependent mitogenesis in NRK-49F cells. We found that AGE increased cyclin D1 expression and cyclin-dependent kinase (cdk)4 activity while decreasing p21(WAF1/CIP1) expression. We also found that AGE (100 microg/mL) induced STAT5 tyrosine phosphorylation. Meanwhile, AGE induced STAT5 protein-DNA binding activity, which was reversed by AG-490 (a specific JAK2 inhibitor) and STAT5 decoy oligodeoxynucleotide (ODN). In addition, STAT5 decoy ODN reversed AGE-induced cell-cycle-dependent cellular proliferation and cyclin D1 protein expression. We concluded that AGE induced cell-cycle-dependent cellular proliferation by inducing the JAK2-STAT5-cyclin D1 and cdk4 pathways in NRK-49F cells.

Fatal outcome after ingestion of star fruit (Averrhoa carambola) in uremic patients.

Clinical outcome of dialysis patients after eating star fruit (Averrhoa carambola) varies, but it may be fatal. In the past 10 years, 20 such patients were treated in our hospital when they developed clinical symptoms after eating the fruit or drinking star fruit juice. Their initial presentations included sudden-onset limb numbness, muscle weakness, intractable hiccups, consciousness disturbance of various degrees, and seizure. No other major events that might be responsible for these symptoms could be identified. Eight patients died, including one patient with a serum creatinine level of 6.4 mg/dL who had not yet begun dialysis. The clinical manifestations of the survivors were similar to those who died except for consciousness disturbance and seizure. Death occurred within 5 days despite emergent hemodialysis and intensive medical care. The survivors' symptoms usually became less severe after supportive treatment, and these patients subsequently recovered without obvious sequelae. The purpose of this article is to report that patients with renal failure who ingest star fruit may develop neurological symptoms and also run the risk for death in severe cases. Mortality may also occur in patients with chronic renal failure not yet undergoing dialysis.

Insulin and heparin suppress superoxide production in diabetic rat glomeruli stimulated with low-density lipoprotein.

Patients with diabetic nephropathy frequently show increased levels of circulating low-density lipoprotein (LDL) and oxidized LDL, which have been reported to be related to the generation of oxygen-free radicals. In the present study, we evaluated the effects of insulin and heparin on the superoxide production of glomeruli, which were isolated from rats with streptozotocin-induced diabetes for one week, one month, and three months, respectively, and the glomeruli were stimulated with native and oxidized LDL. LDL was isolated from normal subjects with normolipidemia, and the superoxide was measured by using a spectrophotometer. The results demonstrated that the poorly controlled diabetic rat glomeruli showed a significantly higher production of superoxide than normal glomeruli under basal status and after stimulation, and this production increased further with the progression of diabetes. Insulin suppressed both the basal and stimulated production of superoxide in diabetic glomeruli, but not in normal glomeruli. Heparin suppressed superoxide production of diabetic glomeruli stimulated by either native or oxidized LDL, and it also partly suppressed superoxide production of normal glomeruli stimulated by oxidized LDL. Our results suggest that glomerular injury in diabetics with hyperlipidemia may be mediated through enhanced generation of oxygen-free radicals, which can be partially attenuated by insulin and heparin.

Relationships between beta-cell function and diabetic duration and albuminuria in type 2 diabetes mellitus.

To clarify whether beta-cell function deteriorates with increasing albuminuria and duration of diabetes, we investigated the insulin and c-peptide response to oral glucose tolerance test in 47 healthy subjects and 75 normoalbuminuric (group 1), 30 microalbuminuric (group 2), and 35 macroalbuminuric (group 3) Type 2 diabetes mellitus patients. The total area under the insulin curve (AUCI) values of groups 1, 2, and 3 were 245 +/- 16, 193 +/- 17, and 88 +/- 8 pmol/L.h, respectively, significantly lower than that (624 +/- 34 pmol/L.h) of the healthy group. The mean total area under the c-peptide curve (AUCC-P) values of groups 1, 2, and 3, respectively, were 2.50 +/- 0.11, 2.05 +/- 0.15, and 1.73 +/- 0.07 nmol/L.h, respectively, significantly lower than that (5.47 +/- 0.19 nmol/L.h) of the healthy controls. The mean AUCI and AUCC-P values of group 3 were significantly reduced compared to those of group 1. The mean AUCI and AUCC-P values of patients with 0-5, 5-10, 10-15, and > 15 years' duration were significantly decreased compared to those of healthy subjects. The mean AUCI and AUCC-P values of patients with > 15 years' duration were significantly lower than those of patients with 0-5 years' duration. The mean hemoglobin Alc values of the three diabetic groups were not significantly different. These data suggest that beta-cell function deterioration was associated with increasing albuminuria and diabetic duration in Type 2 diabetic patients.

Altering expression of alpha3beta1 integrin on podocytes of human and rats with diabetes.

The adhesion molecule integrin alpha3beta1 is the major receptor of podocyte to the glomerular capillary basement membrane (GBM). Since progressive alteration of the glomerular extracellular matrix (ECM) compartment leading to GBM thickening is common in diabetic nephropathy, we investigated the cellular distribution of alpha3beta1 integrin in podocytes of patients with diabetic nephropathy and streptozotocin-induced diabetic rats, and we evaluated the effects of high glucose on the cultured rat podocytes. Both human and rat kidneys were stained using the immunoelectron microscopy and immunoperoxidase technique with mouse monoclonal antibodies to human integrin alpha3 subunit. The results showed that both the number of immunogold particles and the staining of integrin alpha3 subunit on podocytes were weaker in patients with diabetic nephropathy than those of control kidneys. The staining of alpha3 on podocytes in the poorly-controlled diabetic rats was also weaker after one and three months of hyperglycemia. However, the staining was identical to controls in rats with only one week of hyperglycemia. High glucose (25 mM) but not streptozotocin in vitro suppressed the alpha3 expression of cultured rat podocytes. Our results demonstrated that the expression of integrin alpha3beta1 on podocytes was suppressed in both human and rats with diabetes, possibly due to the effects of hyperglycemia, and the suppression became more severe with the duration of diabetes.

Effects of different sampling methods for measurement of post dialysis blood urea nitrogen on urea kinetic modeling derived parameters in patients undergoing long-term hemodialysis.

A simple and reliable sampling method for measuring post-dialysis blood urea nitrogen (C2) has not been well established. Therefore, the effects of different methods of sampling C2 on calculating urea kinetic modeling (UKM) derived parameters were studied in patients on hemodialysis. At first, C2 values were sampled at the end of hemodialysis at a blood flow rate of 300 ml per min (blood flow rate (Qb) 300 ml per min). They were then divided into two groups. In group 1 (n = 11), C2 samples were taken after slowing down Qb to 100 ml per min for 3 min (C2-100); the blood pump was then stopped for 1 min, and C2 was again sampled (C2-100-stop). Finally, C2 was sampled with Qb restored to 100 ml per min and the venous line clamped for another 12 sec (C2-100-clamp). In group 2 (n = 11), C2 samples were collected after Qb was slowed down to 50 ml per min for 3 min (C2-50), and C2-50-stop was then measured. Finally, C2-50-clamp was measured. Using C2-clamp as a reference standard, UKM parameters were calculated using a variable volume, single pool UKM. The authors found that Kt/V calculated by C2-300, C2-100, and C2-50 overestimated the reference Kt/V by 8.4-9.1%, 5.1%, and 3%, respectively. In contrast, protein catabolic rate and time-averaged BUN were affected only minimally. Therefore, a low flow technique with a Qb of 50 ml per min for 3 min can be used for the routine estimation of C2 and UKM-derived parameters with reasonable accuracy.

Treatment of PermCath-related sepsis in uremic patients.

Patients who use PermCath as the vascular access for long-term hemodialysis are occasionally confronted with catheter-related infections. Recently, we have treated 17 patients suffering from PermCath-related sepsis. The clinical presenting features were leukocytosis in 14/17, high fever and shaking chill during dialysis in 12/17, and signs of exit site infection in 3/17. No shock was found. All patients received clinical evaluation to exclude infection sources other than from blood and inside the catheter, such as pulmonary, genitourinary, hepatobiliary and cutaneous systems. Blood drawn from both PermCath and peripheral vein was sent for bacterial culture. Bacterial culture of the blood samples from PermCath revealed Staphylococcus sp. in 7/17, Pseudomonas sp. in 5/17, Enterobacter sp. in 4/17, Streptococcus sp. in 1/17. Fourteen blood samples from peripheral vein showed positive culture results identical to those from PermCath, but negative study were noted in three other patients. The patients were divided into two treatment groups: Group I: systemic antibiotics without PermCath removal in 7, Group II: "locked-in" retention in addition to systemic anti-biotics in 10. Antibiotics were empirically chosen according to bacteriological studies. In the "locked-in" retention treatment, antibiotics were retained into both the inflow and outflow PermCath lumens in the exact volume of each lumen for 24 hours. The antibiotics solutions were replaced on a daily basis. The same antibiotics were also given intravenously. Duration of treatment depended on clinical progression and follow-up blood culture results and ranged between 13 and 24 days. The schedule of dialysis was not changed through the period of PermCath-related sepsis. The sepsis was cured in all group II cases but not in 2 of group I and resulted in mortality in these 2 patients. The PermCaths were preserved in 5/7 in group I with two mortality cases and all except one preserved in group II patients without mortality. We suggested that "locked-in" retention in addition to systemic antibiotics is the treatment of choice for the patients with PermCath-related sepsis. This method also preserves the functional integrity of PermCath, which is the lifeline vascular access of the patients with exhausted native vessels.

Intravenous repletion of phosphorus deficiency in the chronic renal failure patients with severe hypophosphatemia.

Severe hypophosphatemia is a potentially life-threatening medical condition and might lead to a fatal outcome in critically ill patients. The situation is further complicated by the co-morbid renal failure. We evaluated the efficacy and safety of the intravenous phosphate repletion in 15 renal failure patients with severe hypophosphatemia. Six patients with advanced renal failure and nine patients under maintenance hemodialysis, 7 males and 8 females, aged between 42 and 83 years old, were found to have serum phosphate level < 1.2 mg/dL from various medical conditions and were treated with intravenous phosphate infusion. The phosphate solution prepared from sodium dihydrogen phosphate (NaH2PO4), containing 13 mg/ml phosphate and 0.5 meq/ml sodium, in the dosage 2.5-3.0 mg phosphate/Kg body weight, was administered through the central venous lins every 6-8 hours. The infusion was discontinued once serum phosphate level reached 5.0-5.5 mg/dL. Serum ionized calcium, phosphate and intact parathyroid hormone levels were serially followed at different intervals, respectively. The hemodialyzed uremic patients received their dialysis treatment as scheduled. All patients survived the hypophosphatemic period and regained normal phosphate levels after repletion. The amount of phosphate administered to reach the target level ranged between 3438 and 9150 mg and the duration of treatment varied between six and seventeen days. Hypocalcemia (< 4.2 mg/dL) was noted at eight occasions during the whole treatment period but none was symptomatic. Eleven patients recovered from the offending illness. However, four patients expired due to reasons not directly consequent to and temporally remote from hypophosphatemia. We conclude that prompt repletion of severe hypophosphatemia and phosphate deficiency with relatively slower rate of NaH2PO4 solution intravenous infusion is a safe and effective mode of treatment for renal failure and uremic patients. The longer treatment period allowed the administered minerals full equilibration. The risk of hyperkalemia is avoided and the sodium/volume load can be eliminated by dialysis.

Phosphoinositide 3-kinase is required for high glucose-induced hypertrophy and p21WAF1 expression in LLC-PK1 cells.

Transforming growth factor-beta (TGF-beta), Smads, and the cyclin-dependent kinase (cdk) inhibitor p21(WAF1) are important in the pathogenesis of diabetic tubular hypertrophy. Phosphoinositide 3 kinase (PI3K)/Akt kinase activity is increased in diabetic glomerular hypertrophy. Thus, we studied the role of PI3K in high glucose (30 mM)-induced p21(WAF1), Smad2/3, and cell cycle-dependent hypertrophy in LLC-PK1 cells. We found that high glucose time-dependently (1-48 h) increased PI3K/Akt kinase activity. LY294002 (a PI3K inhibitor) attenuated high glucose-induced cell cycle-dependent (G(0)/G(1) phase) hypertrophy at 72 h while attenuating high glucose-induced p21(WAF1) gene transcription and protein expression at 36-48 h. LY294002 also attenuated high glucose-induced binding of p21(WAF1) to the cyclin E/cdk2 complex, whereas attenuating high glucose-induced TGF-beta bioactivity, Smad2/3 phosphorylation, and Smad2/3 DNA-binding activity at 36-48 h. We concluded that PI3K is required for high glucose-induced cell cycle-dependent hypertrophy, p21(WAF1) transcription and expression, p21(WAF1) binding to the cyclin E/cdk2 complex, TGF-beta bioactivity, and Smad2/3 activity in LLC-PK1 cells.

Increased glomerular and extracellular malondialdehyde levels in patients and rats with focal segmental glomerulosclerosis.

BACKGROUND: Evidence suggests an increase in oxidative stress in patients with chronic kidney disease, as glomerulosclerosis is the prerequisite for chronic kidney disease; whether the oxidative stress already exists early on is not known. MATERIALS AND METHODS: In this study we measured the plasma and urinary levels of malondialdehyde (MDA), the end product of lipid peroxidation, and assessed the immunoreactivity of MDA and superoxide dismutase (SOD) in glomeruli of patients and rats with primary focal segmental glomerulosclerosis (FSGS), and compared our findings with those of minimal change disease (MCD) and normal controls (NC). RESULTS: Our results showed that plasma MDA level was significantly increased in patients with FSGS compared with both patients with MCD and normal controls. The urinary MDA level was also significantly increased and was significantly correlated with plasma MDA level in patients with FSGS. The immunostaining for glomerular MDA and SOD was significantly higher in the patients with FSGS than in either the patients with MCD or NC, and was also significantly higher in rats with puromycin aminonucleoside (PAN)-induced FSGS than in rats with MCD. Glomerular MDA level was significantly correlated with the degree of glomerulosclerosis in the patients with FSGS. CONCLUSIONS: Our data suggest that oxidative stress occurs early on before the onset of renal failure, and may play an important role in the pathogenesis of glomerulosclerosis.

Alterations of glomerular and extracellular glutathione peroxidase levels in patients and rats with focal segmental glomerulosclerosis.

Glutathione peroxidase (GPX) is an important antioxidant that effectively scavenges hydrogen peroxide. Recent studies have revealed that plasma GPX activity is decreased in patients with chronic kidney failure. However, there have been no reports on renal and urinary GPX levels in patients with kidney disorders. Therefore in this study we have measured the plasma and urinary GPX levels and glomerular GPX immunostaining in patients with focal segmental glomerulosclerosis (FSGS) and normal kidney function as compared with those in patients with minimal change disease (MCD) and those in normal control subjects. Rats with puromycin aminonucleoside-induced FSGS were also studied. The results showed that the plasma GPX level was significantly lower in FSGS patients than in either MCD patients or normal control subjects (both P <.01). The urinary GPX level was also significantly lower in FSGS patients than in either MCD patients (P <.05) or normal control subjects (P <.01). The immunostaining score of glomerular GPX was significantly lower in FSGS patients than in normal control subjects (both P <.05). Serial examinations of glomerular GPX immunostaining in FSGS rats also demonstrate a decrease in the score with the progression of disease. Our results indicate that all the plasma, urinary, and glomerular GPX levels are decreased in FSGS patients, indicating a decreased antioxidant defense in the early stages of chronic glomerular diseases.

Renal changes in heterozygous Fabry's disease--a family study.

Two sisters, one with a long history of proteinuria and the other of hematuria, came for examination. Physical examination and routine laboratory workups did not show any significant abnormalities. The renal ultrastructural changes in case 1 showed marked enlargement and foamy vacuolation of all the glomerular capillary visceral epithelial cells, which was not found in other glomerular cells. The renal changes in case 2 showed similar lesions but with fewer cells involved and also with less severity, but the involved cells showed marked lamellation within the vacuoles. The serum alpha-galactosidase activity was 4.9 and 3.0 nmol/h/mL serum, respectively (normal values, 12.1 +/- 1.6 nmol/h/mL serum, mean +/- SD, n = 11), thus confirming the heterozygous variety of Fabry's disease. Our findings in these two cases reveal that patients with heterozygous Fabry's disease may present with renal symptoms only, which may be either proteinuria or hematuria.

Differential effects of circulating IgA isolated from patients with IgA nephropathy on superoxide and fibronectin production of mesangial cells.

BACKGROUND: IgA nephropathy (IgAN) is characterized by predominant deposition of IgA in the glomerular mesangium. Serum IgA is often elevated in patients with IgAN, and it has been postulated that it is responsible for the mesangial lesions. However, the direct effect of circulating IgA on mesangial cells is not clear. METHODS: We investigated the effects of sera and IgA which were isolated from patients with IgAN on thymidine uptake, superoxide and fibronectin production and fibronectin mRNA expression of cultured rat mesangial cells, and we compared the findings to the effects of IgA isolated from patients with non-IgA mesangial proliferative glomerulonephritis (MsPGN) and normal controls. IgA was isolated with affinity chromatography using cyanogen bromide activated Sepharose 4B coupled to sheep antihuman IgA antiserum. RESULTS: Our results demonstrated that both sera and IgA from patients with IgAN dose-dependently increased mitogenesis of mesangial cells as measured by (3)H-labeled thymidine uptake. The thymidine uptake by sera and IgA isolated from patients with IgAN was significantly higher than that of sera and IgA isolated from patients with MsPGN and normal controls. Sera and IgA from patients with IgAN significantly enhanced superoxide and fibronectin production and fibronectin mRNA expression of mesangial cells. The superoxide and fibronectin production was also significantly higher as compared with patients with MsPGN and normal controls. CONCLUSIONS: Our results indicate that circulating IgA isolated from patients with IgAN is different from that of patients with MsPGN and normal controls and may potentially induce oxidative injury and production of extracellular matrix of glomerular mesangial cells in IgAN.

Differential effects of FMLP-activated neutrophils from patients with IgA nephropathy enhanced endothelin 1 production of glomerular mesangial cells.

BACKGROUND: Neutrophil infiltration in the glomeruli is common in patients with IgA nephropathy (IgAN). The pathogenetic roles of the infiltrated neutrophils and their relationship with glomerular mesangial cells, however, are not clear. METHODS: We examined the effects of coculture with N-formyl-methionyl-leucyl-phenylalanine (FMLP) activated neutrophils on the viability, endothelin 1 (ET-1) production, and ET-1 mRNA expression of rat glomerular mesangial cells. Neutrophils were isolated from 15 IgAN patients, from 13 patients with non-IgA mesangial proliferative glomerulonephritis (MsPGN), and from 10 normal controls. RESULTS: The ET-1 production by mesangial cells was significantly higher after stimulation with FMLP-activated neutrophils from IgAN patients than that of MsPGN patients and normal controls, and this effect was significantly abolished by pretreating mesangial cells with superoxide dismutase and partly abolished by catalase. The ET-I mRNA expression of mesangial cells showed a parallel increase with ET-1 protein. The trypan blue exclusion test showed significant mesangial cell death after stimulation with FMLP-activated neutrophils as compared with quiescent neutrophils, and the cell death was also prevented by superoxide dismutase but not catalase. The FMLP-activated neutrophils from IgAN patients produced more superoxide than those of MsPGN patients and normal controls. CONCLUSION: The FMLP-activated neutrophils from patients with IgAN have differential effects in enhancing the cell death and the ET-1 production of glomerular mesangial cells through the release of superoxide.

Induction of heat shock protein 70 protects mesangial cells against oxidative injury.

The heat shock response is an immediate cellular response to elevated temperatures and other types of injury that consists of the synthesis of so-called heat shock protein (hsp). This study was designed to investigate the production and the protective role of the 70 kDa hsp (hsp70) in cultured rat mesangial cells. When mesangial cells undergo thermal (45 degrees C, 15 min) stimulation, they express hsp70 mRNA expression and increased hsp70 protein production. Following this, Northern blots show an enhanced gene expression of hsp70 at one hour that reached a maximum by 12 hours after heat shock. The hsp70 protein production, estimated by Western blots, was detectable 12 hours after heat shock and reached a maximum by 36 hours. Oxidative injury generated by xanthine and xanthine oxidase inhibited cell survival and cellular proliferation, as measured by trypan blue exclusion and [3H]-labeled thymidine uptake. It did not affect hsp70 mRNA expression. Furthermore, when mesangial cells were preconditioned by heat shock, subsequent oxidative injury caused less inhibition of cell survival and cellular proliferation. Pretreatment of cells with quercetin, a transcription inhibitor, abolished the protective effect of heat shock on subsequent oxidative injury. We conclude that heat shock, not oxidative injury, induces hsp70 in mesangial cells, and this induction of hsp70 protects mesangial cells against subsequent oxidative injury.

Epidermal growth factor in renal hypertrophy in streptozotocin-diabetic rats.

Epidermal growth factor (EGF) concentrations in the plasma, kidneys and urine of 31 streptozotocin-diabetic rats and 21 insulin-treated diabetic rats were measured to study the role of EGF in initiating renal hypertrophy in the diabetic rats. Renal hypertrophy occurred from day 7 in the diabetic rats, but not in the insulin-treated rats. Renal EGF was not different between the diabetic and control rats, while that in the insulin-treated rats was significantly less than in the diabetic rats. There were no significant changes in plasma EGF in any of the rats. Urine EGF was 119 +/- 7.9 ng/day at day 7 in the control rats but it was significantly increased from day 2 in the diabetic rats (320 +/- 52.9 ng/day at day 2 and 298 +/- 18.4 ng/day at day 7), while in the insulin-treated rats it was significantly less than that in the diabetic rats (134 +/- 8.34 ng/day at day 2 and 220 +/- 15.2 ng/day at day 7). Since the kidney is the main source of urine EGF and EGF has been shown to induce renal growth both in vitro and in vivo, we conclude that EGF may have initiated renal hypertrophy in diabetic rats.

Effects of manidipine hydrochloride on blood pressure in hypertensive patients--a comparison with nifedipine retard.

Manidipine hydrochloride (MH) is a new calcium channel antagonist which is not yet available in Taiwan. Thus, a clinical trial was performed. The clinical effects and adverse effects of MH were compared with those of nifedipine hydrochloride retard monotherapies. Sixty-three out-patients with mild to moderate hypertension and no advanced systemic diseases were randomly divided into 2 groups. Twenty patients remained in each group after some patients withdrew from the study. Blood pressure decreased significantly after treatment in both groups (p < 0.01). In the manidipine group, systolic blood pressure (SBP) decreased from 164 +/- 14 to 140 +/- 18 mmHg and diastolic BP (DBP) decreased from 99 +/- 6 to 87 +/- 7 mmHg by the 8th week. In the nifedipine group, SBP decreased from 163 +/- 11 to 134 +/- 17 mmHg and DBP decreased from 101 +/- 10 to 88 +/- 9 mmHg by the 8th week. Pulse rates did not change significantly. Antihypertensive efficacy was 18/20 (90%) and 19/22 (86.4%) in the manidipine and nifedipine groups, respectively. There were a few adverse effects in both groups, the reaction was severe as to lead to the discontinuation of medication in two patients in the nifedipine group. No significant changes in laboratory tests were identified in either group, except for minimal decreases of lactate dehydrogenase and creatine kinase in the nifedipine group. We conclude that MH was equally safe and effective as nifedipine and it may have less severe side effects compared to nifedipine.