The pharmacokinetic properties of sarpogrelate hydrochloride (sarpogrelate), a selective serotonin type 2 receptor antagonist, were investigated in twelve patients on maintenance hemodialysis (HD). A single dose (100mg) of sarpogrelate was administered orally, and plasma levels of sarpogrelate and M-1, a major metabolite of sarpogrelate that has more potent antiserotonergic effects, were measured on a HD day and a non-HD day. The hemodialytic clearances of sarpogrelate and M-1 were investigated on the HD day.
On the non-HD day the maximum concentration (Cmax) and the half-life (T_1/2) of sarpogrelate ware 437.1±381.3ng/ml and 0.9±0.3h, respectively. The Cmax and T_1/2 of M-1 were 28.3±4.5ng/ml and 1.5±0.4h, respectively. These data were similar to those in healthy volunteers. The time to maximum concentration (Tmax) of sarpogrelate and M-1 was 2.2±1.3h and 2.5±2.2h, respectively. There were no significant differences between the pharmacokinetic parameters on the HD day and on the non-HD day. The hemodialytic clearance of sarpogrelate and M-1 was 0.84ml/min and -2.54ml/min, respectively. These data suggest that little drug was removed by HD.
A simulation calculated on the basis of the above pharmacokinetic parameters indicated that there was no cumulative action when 100mg of sarpogrelate was consecutive days given to hemodialytic patients three times a day.
We measured plasma concentrations of serotonin in hemodialysis patients on a HD day and a non-HD day. Plasma serotonin concentrations did not rise in the hemodialysis patients. There were no significant changes in the plasma serotonin concentration of the hemodialytic patients after a single dose of sarpogrelate.

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Atrial natriuretic peptide (ANP) levels reflect circulating blood volume and atrial pressure. To assess the correlation between plasma ANP levels and systolic pulmonary arterial pressure (PAP) in maintenance hemodialysis (HD) patients, we examined 23 patients immediately before and after HD. Plasma ANP concentrations were measured by a specific and sensitive radioimmunoassay. Tricuspid reguritation was recorded by contrast Doppler echocardiography. PAP was computed by a modification of the Bernoulli formula as the sum of the transtricuspid gradient and right atrial pressure (PAP=4V²+10mmHg, where V is the maximal velocity of the tricuspid regurgitant jet, and 10mmHg is average right atrial pressure).
The mean plasma ANP level after HD was markedly lower than before HD (before: 265±185pg/ml, after: 64±85pg/ml, p<0.0001). The mean PAP level was also reduced by HD (before: 35.3±10.1mmHg, after: 25.7±7.1mmHg). There was a significant correlation between plasma ANP and PAP levels (before HD: r=0.67, p<0.001, after HD: r=0.43, p<0.05). There was also a significant correlation between the change in plasma ANP level and the change in PAP by HD (r=0.67, p<0.001). The two of the 23 patients who had a history of pulmonary edema within the previous 6 months showed PAP values over 40mmHg after HD.
In conclusion, plasma ANP concentrations reflect PAP, and measurement of PAP by contrast echocardiography seems to be a safe and useful method of estimating the ideal weight of HD patients.

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The efficacy and pharmacodynamics of a proton-pump inhibitor, omeprazole, were studied in 5 patients on maintenance hemodialysis with peptic ulcer, hemorrhagic ulcer or hemorrhagic gastric polyp as complications. An oral dose of 20mg of omeprazole was given every morning before breakfast for 7 days, All patients were found to have endoscopic and/or symptomatic improvement. Plasma concentrations of omeprazole were measured in 4 of the 5 patients, until 24 hours after administration on days 1 and 7, and pharmacodynamic parameters were calculated. Cmax was slightly higher than in the healthy controls on day 1 but the values were similar on day 7. Tmax and AUC values were comparable on days 1 and 7 and were similar to those in the healthy controls. The t_1/2 values on day 1 and 7 were the same and slightly lower than in the healthy controls. In conclusion, omeprazole is a potent agent for the treatment of digestive ulcers and upper gastrointestinal bleeding in dialysis patients. The results of this pharmacodynamic study have shown that the same dose of omeprazole can be administered to dialysis patients as to patients with normal renal function.

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A 43-year-old male who had been maintained on chronic hemodialysis for fourteen years came to our hospital complaining of urethral bleeding. Bladder fiberscopy showed widespread mucosal mossy change, and biopsy revealed nephrogenic adenoma with chronic inflammation. Sixteen cases of nephrogenic adenoma of the bladder previousely reported in the Japanese literature, and our own case, are reviewed and the pathogenesis of this abnormality is discussed.

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We report a case of hydrocele of the scrotum and penis after placement of a peritoneal catheter. The patient was a 36-year-old male who did not have any clinical evidence of inguinal hernia at the time of initial presentation. ^99mTechnetium intraperitoneal scanning was used to identify a peritoneoscrotal communication. The communication was confirmed, and surgically closed. A repeat peritoneoscrotography verified the success of the operation and CAPD could be continued. Peritoneoscrotography may be an effective technique for identifying anatomical communications resulting in dialysate leakage.

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We encountered a patient with Alport syndrome who manifested end-stage renal failure. The patient was 20-year-old man with a history of hematuria since 6 years of age who developed bilateral deafness at 11 years of age. He was referred to our hospital because of pulmonary edema, hyperkalemia and azotemia. On admission his BUN level was 136.8mg/dl and his serum creatinine was 19.5mg/dl. Peritoneal dialysis was performed immediately to treat uremia. Since he had not received a regular medical examination and the size of both kidneys was within normal limits, a percutaneous renal biopsy was performed to investigate the etiology of the disease. Light microscopy showed approximately 80% sclerosis of the glomeruli and an excess of foam cells in the interstitium, while electron microscopy revealed irregular thickening and splitting of the glomerular basement membrane. A diagnosis of end-stage renal failure due to Alport syndrome was made. Since the gene responsible for Alport syndrome is known to be a type IV collagen α5 chain gene (COL4A5), we investigated abnormalities in exons 47-51 by the polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP)-silver staining method, but no abnormalities were detected. Because of the lack of an accurate family history, we are considering this a case of juvenile-type Alport syndrome involving a unidentified mutation. This case illustrates that renal blopsy is a useful diagnostic tool in patients with azotemia of unknown etiology.

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Acyclovir is commonly used in the treatment of herpes virus infections. However, there have been sporadic reports of acyclovir encephalopathy with diverse neurological symptoms that have been especially severe in patients with renal impairment.
We recently encountered two dialysis patients with suspected acyclovir encephalopathy, who developed diverse neurological symptoms after starting oral therapy with this drug and who improved following blood purification.
Case 1 involved a 43-year-old man who was diagnosed as having herpes zoster and was treated with 4, 000mg/day of acyclovir orally. He had been on CAPD for chronic renal failure caused by IgA nephropathy since the age of 35 years. Diverse central nervous system symptoms began to appear the next day. The symptoms were improved by direct hemadsorption therapy. Case 2 involved a 48-year-old man who had been on hemodialysis for chronic renal failure since 38 years of age. He received 4, 000mg/day of acyclovir after herpes zoster was diagnosed. Diverse central nervous system symptoms began to appear 2 days later, and these symptoms were improved by hemofiltration dialysis. Since both patients had high blood acyclovir concentrations (46.8μmol/l and 41.1μmol/l, respectively), adiagnosis of acyclovir encephalopathy was made. Vidarabine was used to treat the herpes infection in case 2, and the symptoms improved without serious toxicity.
When a hemodialysis patient is treated with acyclovir, the patient should be closely monitored for the potential development of acyclovir encephalopathy. If acyclovir encephalopathy occurs, appropriate blood purification should be performed immediately, as this measure appears to be effective. Herpes infection in a hemodialysis patient was safely treated with vidarabine in combination with hemofiltration dialysis without any accumulation of the drug or overt toxicity when half the standard dose (about 6mg/kg) was infused over 4 hours.

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We report a rare case of acute renal failure (ARE) due to the thrombosis-dominant type of disseminated intravascular coagulation syndrome (DIC) in a female patient. The patient was found to have high plasma levels of plasminogen activator inhibitor-1 (PAI-1) caused by severe urinary tract infection associated with hypoglycemic coma. The diagnosis of DIC was delayed because the initial examination showed a normal level of plasma fibrin degradation products (FDP). Further coagulation studies revealed that the FDP level was indirectly by the elevated PAI-1 level in this patient. Proinflammatory cytokines, such as tumor necrosis factor-alpha (TNFα) and interleukin-1 beta (IL-1β) have been shown to upregulate plasma PAI-1 level which was often associated with severe infection. Since high levels of PAI-1 suppress fibrinolytic activity and FDP production, it may be beneficial for patients with thrombocytopenia to receive mild anti-coagulant therapy early in the course of treatment.

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