Better correction of metabolic acidosis, blood pressure control, and phagocytosis with bicarbonate compared to lactate solution in acute peritoneal dialysis.

Lactate solution has been the standard dialysate fluid for a long time. However, it tends to convert back into lactic acid in poor tissue-perfusion states. The aim of this study was to evaluate the efficacy of magnesium (Mg)- and calcium (Ca)-free bicarbonate solution compared with lactate solution in acute peritoneal dialysis (PD). Renal failure patients who were indicated for dialysis and needed acute PD were classified as shock and nonshock groups, and then were randomized to receive either bicarbonate or lactate solution. Twenty patients were enrolled in this study (5 in each subgroup). In the shock group, there were more rapid improvements and significantly higher levels of blood pH (7.40 +/- 0.04 versus 7.28 +/- 0.05, p < 0.05), serum bicarbonate (23.30 +/- 1.46 versus 18.37 +/- 1.25 mmol/L, p < 0.05), systolic pressure (106.80 +/- 3.68 versus 97.44 +/- 3.94 mm Hg, p < 0.05), mean arterial pressure (80.72 +/- 2.01 versus 73.28 +/- 2.41 mm Hg, p < 0.05), percentages of phagocytosis of circulating leukocytes (65.85% +/- 2.22 versus 52.12% +/- 2.71, p < 0.05), and percentages of positive nitroblue tetrazolium (NBT) reduction test without and with stimulation (14.43 +/- 1.93 versus 9.43 +/- 2.12, p < 0.05 and 65.08 +/- 6.80 versus 50.23 +/- 4.21, p < 0.05, respectively) in the bicarbonate subgroup compared with the lactate subgroup. In the nonshock group, blood pH, serum bicarbonate, and phagocytosis assays in both subgroups were comparable. Lactic acidosis was more rapidly recovered and was significantly lower with bicarbonate solution for both shock and nonshock groups (3.63 +/- 0.37 versus 5.21 +/- 0.30 mmol/L, p < 0.05 and 2.92 +/- 0.40 versus 3.44 +/- 0.34 mmol/L, p < 0.05, respectively). Peritoneal urea and creatinine clearances in both subgroups were comparable for both shock and nonshock groups. There was no peritonitis observed during the study. Serum Mg and Ca levels in the bicarbonate subgroup were significantly lower, but no clinical and electrocardiographic abnormality were observed. We concluded that Mg- and Ca-free bicarbonate solution could be safely used and had better outcomes in correction of metabolic acidosis, blood pressure control, and nonspecific systemic host defense with comparable efficacy when compared to lactate solution. It should be the dialysate of choice for acute PD especially in the poor tissue-perfusion states such as shock, lactic acidosis, and multiple organ failure.

Multiple bilateral giant fibroadenomas associated with cyclosporine A therapy in a renal transplant recipient.

A 31-year-old woman developed a right breast mass following cyclosporine A therapy after a renal transplant. Several large breast masses continued to grow bilaterally. Mammography and ultrasonography showed features of giant fibroadenomas. The diagnosis was confirmed by biopsy of one of the masses. Awareness of the association between cyclosporine A therapy and fibroadenoma development in renal transplant recipients is highlighted.

Angiotensin converting enzyme inhibitor and chronic renal failure.

To evaluate the renal protection of enalapril a study was made in 37 patients with chronic renal failure and hypertension. Sixteen patients had diabetic nephropathy with the serum creatinine ranging from 2.0 to 4.0 mg/dl. Twenty-one patients had non-diabetic chronic renal failure with serum creatinine from 2.2 to 6.3 mg/dl. Of 16 patients with diabetic nephropathy, 6 served as control and 10 received enalapril. Nine patients in the non-diabetic chronic renal failure group served as controls, while 12 were given enalapril. The control patients received alpha methyldopa (500 mg/day) for blood pressure control. In the studied patients enalapril was given at the dose of 5-10 mg/day. Over a period of 2 yrs, enalapril attenuated progression of renal failure in patients with diabetic nephropathy at the serum creatinine level from 2 to 2.9 mg/dl (creatinine clearance 21.5-38.4 ml/min) when compared with control patients. At the serum creatinine of 3 to 4 mg/dl progression of renal failure did not differ from control patients. In non-diabetic renal failure progression of renal failure was delayed in patients with serum creatinine level ranging from 2.2 to 5 mg/dl (creatinine clearance 18-42 ml/min); patients with serum creatinine level ranging from 5.5 to 6.3 mg/dl had deterioration of renal function as control patients. Proteinuria was decreased in all patients on enalapril. Thus, for preventing progression of renal failure, enalapril should be given in chronic renal failure with milder degree of renal function impairment; in diabetic nephropathy it should be started earlier at the lower serum creatinine level than in non-diabetic chronic renal failure, yet with comparable creatinine clearance.

Heat stroke-induced multiple organ failure.

The effect of excessive heat accumulated in the body is life threatening. It could damage not only body fluid electrolyte haemostasis, but kidney, liver, and hematologic function. The example reported herein was a Thai laborer, previously healthy, 32 years of age. He joined the tricycle race from Chiang Mai to Lumpoon, which is about 30 km. The tournament was held on a late morning of high humidity and a temperature of 35 degrees C. After biking 25 km, he began having heavy perspiration and suffered from severe myalgia and high fever. He suddenly lapsed into unconsciousness and fell down. He was admitted to the Lumpoon Hospital because of convulsions, and 2 days afterward, anuria, anemia, thrombocytopenia, coagulopathy, and liver impairment were detected. He was later transferred to the Faculty of Medicine for further intensive treatment. Lab analyses showed marked azotemia (BUN 96 mg%, Cr 10.6 mg%), elevation of muscle enzyme (CPK greater than 1000 U/L, SGOT greater than 650 U/L), liver failure (SGPT greater than 650 U/L, DB/TB = 23.0/30.0 mg%) and disseminated coagulopathy; platelet 17,000/mm3, PT 51.1 sec (control 12.5), and PTT 73.5 sec (control 37.7). He was treated with bicarbonated hemodialysis trice weekly. Blood-exchange transfusion was performed 3 times during the first 2 weeks with 10 units of fresh whole blood in each exchange. His ventilation required support by a ventilator. After a month, his consciousness, the liver function, and hematologic conditions became to recuperate. By 6 weeks postadmission, renal function eventually improved. This report is intended to warn the unprepared athlete entering an extreme, long-lasting exercise in an inappropriate climate.

The jaundiced heart: evidence of blunted response to positive inotropic stimulation.

Obstructive jaundice has been known to cause severe hemodynamic disturbance. The present study was therefore designed to assess the cardiac involvement in jaundiced patients. The multiple-gated blood pool cardioscintigraphic studies were done in 9 jaundiced patients who had either cholestatic or obstructive jaundice (mean total bilirubin 29.30 +/- 3.30 mg/dL), and in 8 normal volunteers (total bilirubin less than 1 mg%). None of the patients had evidences of obvious cirrhosis, intrinisic heart disease, or septicemia. Following intravenous dobutamine there was comparable change of blood pressure and heart rate in both groups. However the response of left ventricular ejection fraction (LVEF) to dobutamine (10 micrograms/kg/min x 5 min) was strikingly blunted in the jaundiced patients as compared to that seen in the normal controls (3.56 +/- 0.9 vs. 12.7 +/- 2.2%, p less than 0.005). Our present data thus show that there is blunted myocardial contractile response to the inotropic stimulation in jaundiced patients. Such myocardial refractoriness to beta-1 stimulation may contribute to the susceptibility of jaundiced patients to postoperative shock and acute renal failure.

Intrarenal infusion of gallopamil in acute renal failure. A preliminary report.

In order to ascertain the protective role of a potent calcium entry blocking agent in human acute renal failure, 10 patients were randomised to treatment with either intrarenal gallopamil plus intravenous furosemide (frusemide) 0.5 mg/kg/h for 24 hours, or furosemide alone. Gallopamil was infused into each kidney at the rate of 40 to 80 micrograms/min for 4 hours. During 7 days of post-treatment follow-up, the gallopamil treatment group exhibited a significantly higher urine output [257 ml/h vs 81 ml/h (p less than 0.001) after 2 days, and 199 ml/h vs 120 ml/h (p less than 0.005) after 7 days] and creatinine clearance [20 vs 4 ml/min (p less than 0.005) after 2 days, and 38 vs 14 ml/min (p less than 0.001) after 7 days] than the furosemide-only control group. Furthermore, gallopamil treatment accelerated the decline of serum creatinine after renal failure and reduced the requirement for dialysis. Although patient numbers were small, these results indicate that the addition of intrarenal gallopamil to intravenous furosemide treatment enhances the recovery of renal function after acute renal failure.

Beneficial effect of intrarenal verapamil in human acute renal failure.

Cellular Ca2+ influx during the reperfusion period after an ischemic insult has been proposed to be a crucial pathogenetic factor in the development of experimental acute renal failure (ARF). The present study, therefore, examined the potential beneficial effect of intrarenal verapamil, a calcium entry blocking agent, on ARF in patients. Twelve patients were enrolled in the study. Six ARF patients (experimental group)--ARF caused by malaria (4 patients) and leptospirosis (2 patients)--had a catheter placed in their renal artery; verapamil was infused at 100 micrograms/min for 3 h and intravenous furosemide, 0.8 mg/kg/h x 24 h was also administered. Another six ARF patients (control group)--ARF caused by malaria (5 patients) and leptospirosis (1 patient)--were treated with intravenous furosemide alone. Baseline renal function was comparable in both groups; GFR (3.16 +/- 3.24 vs 0.7 +/- 1.5 mL/min, NS), serum creatinine (Scr), (9.1 +/- 2.1 vs 11.3 +/- 2.2 mg/dL, NS), and urine volume (V) (41.79 +/- 4.77 vs 34.54 +/- 13.52 mL/h, NS), were comparable in the experimental and control groups. Twenty-four hours posttreatment, the increment of GFR (9.66 +/- 4.25 vs 1.32 +/- 0.50 mL/min, P less than .02) and V (181.8 +/- 61.7 vs 79 +/- 18 mL/h, P less than .04), were significantly greater in the experimental group as compared to the control group. The course of ARF was also shorter in the experimental group (6.5 +/- 2.1 vs 13 +/- 1.1 days, P less than .05), who also required less dialysis. Thus, combination of a renal arterial infusion of verapamil and intravenous furosemide significantly improves the renal function in tropical ARF as compared to intravenous furosemide alone.

Furosemide and dopamine in malarial acute renal failure.

The effects of furosemide and furosemide with dopamine on renal function were studied in 23 patients with acute renal failure due to falciparum malaria whose serum creatinine ranged from 230 to 947 mumol/l. Furosemide given intravenously at the dosage of 200 mg 6 hourly for a period of 4 days did not alter the clinical course of renal failure. Intravenous administration of furosemide (200 mg 6 hourly) with dopamine (1 microgram/kg/min) for 4 days increased creatinine clearance and arrested the progress of renal failure when the serum creatinine was less than 400 mumol/l, but failed to alter the course of renal failure when the serum creatinine exceeded 600 mumol/l.

Phosphate depletion arrests progression of chronic renal failure independent of protein intake.

Following 5/6 nephrectomy, 18 rats were fed a normal diet. After 30 days, serum creatinine (SCr), urine protein excretion and urine volume were increased compared to pre-nephrectomy (0.27 +/- 0.1 vs. 1.62 +/- 0.6 mg/deciliter, 17.0 +/- 10.3 vs. 257.6 +/- 13.4 mg/24 hr, and 16.6 +/- 4.4 vs. 39.2 +/- 11.7 ml/24 hr, respectively, all P less than 0.001). At this time, when serum phosphorus (SPi) and serum calcium (SCa2+) were normal, the rats were separated into two groups, matched and paired by body weight and SCr, and housed separately in metabolic cages. Animals of one group ingested a normal diet supplemented with dihydroxyaluminum aminoacetate (DHAAA), 15 g%, to induce phosphate depletion (PD). The second group ingested the same diet supplemented with 7.5% glycine and was the phosphate replete (PR) group. All rats were pair fed throughout the study to maintain similar caloric, protein, carbohydrate, vitamin, and mineral intakes. At six weeks after separation, SPi was decreased in PD vs. PR group (2.85 +/- 0.8 vs. 6.71 +/- 1.2 mg/deciliter, P less than 0.001) and SCa2+ was increased in the PD group (11.98 +/- 0.7 vs. 10.03 +/- 0.7 mg/deciliter, P less than 0.001). Urine urea nitrogen, body weight, and sodium, potassium and solute excretion were similar between the groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenine nucleotide metabolism and mitochondrial Ca2+ transport following renal ischemia.

Mitochondrial Ca2+ accumulation and mitochondrial respiratory dysfunction have been observed after renal ischemia. The present study examined the effects of ischemia and reperfusion on cellular energy production and mitochondrial Ca2+ transport after 50 min of bilateral renal artery and vein clamping in the anesthetized rat. Prior to reflow, tissue ATP and total adenine nucleotide levels were severely reduced. These nucleotide levels recovered towards normal but remained lower than control values throughout 24 h of reperfusion. Energy-linked mitochondrial Ca2+ uptake was unmeasurable, mitochondrial Ca2+ efflux was increased and the mitochondria were unable to maintain a steady-state free Ca2+ concentration prior to reflow. Three hours of reperfusion was associated with a normalization of mitochondrial Ca2+ uptake, release, and steady-state buffering. However, progressive deterioration subsequently occurred in these processes. Thus the mitochondrial Ca2+ accumulation previously observed during the later stages of postischemic reperfusion (3-24 h) is due neither to an increase in the rate of active Ca2+ uptake nor to a decrease in the rate of Ca2+ release. The present results therefore suggest that passive mitochondrial Ca2+ accumulation may occur during the later stages of reperfusion, probably due to a progressive increase in the cytosolic Ca2+ concentration.

Detrimental effect of hypophosphatemia on the severity and progression of ischemic acute renal failure.

Phosphate depletion may prevent progression of experimental chronic renal failure. The present study was designed to examine the effect of phosphate depletion on the severity and progression of ischemic acute renal failure. Two groups of rats, phosphate-depleted (PD) and phosphate-repleted (PR), were pair-fed a regular diet for 10 days; the diet of the PD rats also contained 15 g% dihydroxyaluminum aminoacetate. After 10 days, serum phosphate in PD rats averaged 3.9 +/- 0.7 mg%, compared to 6.1 +/- 0.6 mg% in the PR rats (p less than 0.001). The weight gain during the equilibration period was comparable in both groups (24.2 +/- 9.3 vs. 25.7 +/- 10.4 g; NS). Creatinine clearance, hematocrit, renal cortical adenine nucleotides, tissue calcium, mitochondrial calcium and mitochondrial respiration were similar in both groups after 10 days of the diet. A 50-min bilateral clamping of both renal arteries and veins was then undertaken in both groups. The PD rats demonstrated more severe acute renal failure at 24 h after the ischemic insult. Serum creatinine and creatinine clearance for the PD and PR rats were 4.0 +/- 0.6 versus 3.1 +/- 0.9 mg% (p less than 0.005) and 7.8 +/- 8.1 versus 85.3 +/- 70.7 microliter/min (p less than 0.001), respectively. Tissue calcium (131.3 +/- 103.0 vs. 63.5 +/- 36.0 mmol/kg dry weight; p less than 0.02) and mitochondrial calcium (49.4 +/- 24.0 vs. 29.5 +/- 14.6 nmol/mg prot.; p less than 0.02) were significantly higher in the PD rats.(ABSTRACT TRUNCATED AT 250 WORDS)

In vitro versus in vivo mitochondrial calcium loading in ischemic acute renal failure.

Progressive mitochondrial Ca2+ accumulation and respiratory dysfunction have been observed during reperfusion after renal ischemia. The present study demonstrated that normal mitochondria, isolated in the presence of high Ca2+ concentrations, are capable of accumulating large amounts of Ca2+ in vitro and exhibit depressed respiratory rates. Since mitochondria isolated from reperfused ischemic tissue may be exposed to high concentrations of Ca2+ during the isolation procedure, the present study examined the effect of in vitro versus in vivo mitochondrial Ca2+ loading on mitochondrial function during ischemic acute renal failure (ARF) in anesthetized rats. When ruthenium red was added during isolation to prevent mitochondrial Ca2+ exchange with the medium, mitochondrial Ca2+ increased from 10.8 +/- 0.3 to 65.6 +/- 11.6 nmol/mg (P less than 0.001) after 24 h of postischemic reperfusion; this resulted in a 47% reduction in the acceptor-control ratio (ACR) from 4.19 +/- 0.09 to 2.70 +/- 0.13 (P less than 0.001). These data were compared with an increase in mitochondrial Ca2+ from 52.5 +/- 2.9 to 167.6 +/- 25.4 nmol/mg (P less than 0.001) and a 95% fall in ACR (3.84 +/- 0.40 to 1.15 +/- 0.08, P less than 0.001) at 24 h of reperfusion when no ruthenium red was added. However, at each time point examined, in vivo mitochondrial Ca2+ accumulation was shown to account for 50% or more of the mitochondrial respiratory dysfunction observed during ischemic ARF.