Diverse patterns of acid-base abnormalities associated with a modified sigmoid neobladder

In this study, we analyzed the pattern of metabolic acidosis in patients following the construction of a sigmoid neobladder and then search for the risk factors which affecting this. In 23 men aged 43-73 years and nine women aged 49-74 years who underwent sigmoid neobladder surgery, we performed physical examinations and blood tests every 3 months for 13-75 months (38.7+/-16.6: mean+/-SD). We monitored acid-base balance, serum electrolytes, creatinine, lipid and liver function in patients for up to 6 years postoperatively. Creatinine clearance over 24 h was determined preoperatively. According to pH and base excess measured during follow-up, patients were classified into three groups (normal, 17 patients; temporary acidosis, eight patients; persistent acidosis, seven patients). Patients with temporary acidosis could compensate spontaneously by 1 year without being given sodium bicarbonate; those with persistent acidosis could not compensate spontaneously and five of them required medication with sodium bicarbonate after 1 year. Serum creatinine in patients with persistent acidosis was consistently higher during follow-up than in the other two groups. Preoperative creatinine clearances in the normal, temporary, and persistent groups were 94.25+/-27.47, 95.19+/-18.63, and 69.18+/-16.18 ml/min/1.73 m(2), respectively, being significantly lower in the persistent group ( P<0.05). In this group, patients with creatinine clearances less than 70 ml/min/1.73 m(2) could not compensate for metabolic acidosis. Normal and temporary groups showed different changes of serum chloride and bicarbonate during follow-up (respectively higher and lower) although the renal functions of the two groups were similar. Chloride and bicarbonate varied reciprocally with pH and base excess. Temporal hyperchloremic metabolic acidosis was observed until a year after surgery. In conclusion, temporary acidosis can be caused in some patients in spite of normal renal function, although it is difficult to predict it. In addition, careful follow-up is required, especially in patients with a creatinine clearance <70 ml/min/1.73 m(2) who can encounter persistent acidosis.     

Blood pressure reduction associated with preservation of renal function in hypertensive patients with IgA nephropathy: a 3-year follow-up

BACKGROUND: The relative importance of hypertension in the progression of renal failure is well understood. Recently, several studies have provided evidence that antihypertensive therapy enhances renal survival. However, the specific antihypertensive drug regimens that are most effective in generating such long-term effects remain controversial. PATIENTS AND METHODS: Forty-nine hypertensive IgA nephropathy (IgAN) patients (39 +/- 7 years old, serum creatinine 1.1 +/- 0.2 mg/dl) with proteinuria received antihypertensive therapy with angiotensin-converting enzyme inhibitors (ACEi: 2.5-10 mg of benazapril daily) and calcium channel blockers (CCBs: 2.5-10 mg amlodipine daily) for 3 years. The patients' blood pressures in group one were controlled below 140/85 mmHg by increases in their first drug dose or by addition of the second drug in group 1. Blood pressures for patients in group 2 were controlled using the same two options, except to levels below 130/70 mmHg. Patients within the two groups were selected and controlled with regard to sex, age, and serum creatinine. The renal protective effects of each protocol were evaluated in terms of reductions in creatinine clearance. After 3 years of the above outlined blood pressure control regimens, the reductions in creatinine clearance were compared. RESULTS: Creatinine clearances decreased in group 1 patients (from 85.7 +/- 2.4 ml/min to 72.9 +/- 2.4 ml/min, p < 0.05). On the other hand, creatinine clearance remained essentially unchanged for patients in group 2 (from 87.2 +/-4.7 ml/min to 85.9 +/- 5.9 ml/min). Although creatinine clearance in both groups was almost the same at the start of study, there was a significant difference between them by the conclusion of the study (p < 0.05). Proteinuria and hematuria did not change significantly throughout the study and there were no significant differences in these respects between these two corresponding groups. There were no significant differences between the groups with reference to side-effects or complications. CONCLUSION: These data provide evidence that reducing blood pressure has protective renal effects in cases of mild renal insufficiency with hypertension in IgA nephropathy.     

Factors affecting renal allograft function in long-term recipients.

The natural history of renal allograft function in long-term recipients is not known. To characterize renal allograft function and the factors that affect it, we reviewed the records of all patients who received a renal allograft at the University of Wisconsin between 1965 and 1981 and selected those who had annual data on renal function for at least 10 years. We identified 155 patients--78 with living-related donors and 77 with cadaveric donors. All patients were adults receiving azathioprine and prednisone. Renal function was estimated by calculated creatinine clearances (Ccr), which correlated well with measured 24-hour creatinine clearances. The creatinine clearance data for each patient were plotted versus time. In 73% of patients, the creatinine clearance increased for several years before reaching a peak value. After the peak, the creatinine clearance declined in a linear manner. Stepwise regression analyses indicated that allografts from cadaveric donors had a greater increase in creatinine clearance from the value at year 1 to the peak than allografts from living-related donors (0.35 +/- 0.25 v 0.21 +/- 0.23 mL/s [21.4 +/- 15.0 v 12.7 +/- 13.8 mL/min]; P less than 0.001). The average time to reach the peak value of creatinine clearance was longer in cadaveric allografts (6.8 +/- 3.5 v 4.6 +/- 4.0 years; P less than 0.001). Postpeak, the rate of decline in creatinine clearance was faster in cadaveric allografts than in living-related ones (0.06 +/- 0.05 v 0.04 +/- 0.04 mL/s/yr [3.50 +/- 2.99 v 2.55 +/- 2.16 mL/min/yr]; P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Beneficial effects of fluvastatin on progressive renal allograft dysfunction

To assess the time-dependent changes in renal function in relation to antioxidant and lipid-lowering effects of fluvastatin in hyperlipidemic renal transplant recipients, 20 patients were treated with fluvastatin 40 mg/d for 12 months, after failure of a dietary program. Plasma malondialdehyde (MDA) levels and lipid profiles were evaluated in relation to serum creatinine and calculated creatinine clearances 18 months before and during the fluvastatin treatment. Mean baseline lipid values were: total cholesterol 318 mg/dL, triglycerides 212 mg/dL, LDL cholesterol 219 mg/dL, HDL cholesterol 58 mg/dL, apolipoprotein A 176 mg/dL, and apolipoprotein B 145 mg/dL. During 12 months of treatment, fluvastatin produced consistent and significant reductions in total and LDL cholesterol (-18.4% and -24.1%), triglycerides (-17.7%), and apolipoprotein B (-22.7%) as well as an increase in HDL cholesterol (12.3%) and apolipoprotein A (9.2%). Plasma MDA levels decreased by 41.8% (from 3.5 +/- 0.3 to 1.8 +/- 0.1 nmol/mL, P =.00002). Creatinine clearance, which had been declining at a rate of 0.32 mL/min/month during the previous 18 months before treatment, progressively improved during treatment, giving a positive slope of the creatinine clearance, which increased by 0.35 mL/min/month, (P =.016; 53.3 +/- 4.2 mL/min vs 49.8 +/- 4.1 mL/min pretreatment). Multiple linear regression analysis revealed that MDA was the parameter most closely associated with the variability in creatinine clearance. In conclusion, renal transplant patients with lipid abnormalities display renoprotective activity of fluvastatin, possibly due to its lipid-lowering and antioxidant effects.     

Renal handling of enalaprilat.

Most converting enzyme inhibitors share a predominantly renal dual elimination pathway consisting of glomerular filtration and tubular secretion. Since enalaprilat has two functional acidic groups, it is likely that it may be secreted via the proximal tubule organic acid system and, thus, its clearances would exceed that of glomerular filtration rate markers. We therefore examined the renal clearance of enalaprilat in normal volunteers and compared it with simultaneously measured inulin and creatinine clearances to explore the contribution of tubular secretion to the renal elimination of the drug. Twelve healthy male subjects with an age range of 24 to 58 years (mean +/- SE, 33.1 +/- 2.8) were studied. They had representative height (178.6 +/- 1.99 cm) and weight (73.3 +/- 2.1 kg) and had normal renal function as judged by blood urea nitrogen (BUN) (6 +/- 0.3 mmol/L [17 +/- 0.8 mg/dL]), plasma creatinine (88 +/- 3 mumol/L [1.0 +/- 0.03 mg/dL]), and creatinine clearance determined by a prestudy 24-hour urine collection (123.2 +/- 6.2 mL/min). Results are as follows: mean creatinine clearance, 2.12 mL/s (127 mL/min); mean inulin clearance, 119.1 ml/min mean creatinine clearance/inulin clearance, 1.07 mean enalaprilat protein binding, 37.9% unbound enalaprilat clearance, 222.4 ml/min; and the mean fractional enalaprilat clearances were: enalaprilat clearance/creatinine clearance, 1.72 (P less than 0.05, difference from 1.0); enalaprilat clearance/inulin clearance, 1.85, (P less than 0.05, difference from 1.0). Our results demonstrate that the clearance of free enalaprilat exceeds that of inulin and creatinine, suggesting that elimination of the drug proceeds through two complementary pathways, namely glomerular filtration and tubular secretion.     

Incidence of acquired renal cysts in biopsy specimens

AIMS: This study investigated whether or not acquired renal cysts develop in patients with mild chronic renal failure. METHODS: A retrospective study was carried out using renal biopsy specimens from 720 patients. A renal cyst was defined as a tubule dilated >200 microm. RESULTS: Renal cysts were found in 21 of 720 renal biopsy specimens. Serum creatinine of 21 patients with renal cysts was significantly higher than that of 699 patients without cysts (2.59 +/- 2.64 vs. 1.09 +/- 0.79 mg/dl) (p < 0.0001). Poor renal function (serum creatinine >1.6 mg/dl) reveals more cyst formation on biopsy specimens than good renal function (serum creatinine <1.5 mg/dl). Cysts were observed in 11 of 607 (1.8%) patients less than 50 years of age and in 10 of 113 (8.8%) patients over 51 years. To exclude simple cysts which are commonly observed in older subjects, 11 patients under 50 years of age were extensively examined. Mean serum creatinine was 2.98 +/- 3.06 mg/dl (0.7-10.4 mg/dl). These 11 patients revealed low creatinine clearance of 47.5 +/- 25.6 ml/min (5-71 ml/min). Creatinine clearances in 7 patients were 52-71 ml/min (serum creatinine 0.7-2.0 mg/ dl). One of 11 biopsy specimens with cysts was examined by immunohistochemistry on lectin. This specimen was positive for tetragonolobus lectin and negative for peanut lectin, suggesting that the epithelial cells lining the cyst were derived from proximal tubules, unlike those of simple cysts. CONCLUSION: These results suggest that low normal renal function such as creatinine clearances 52-71 ml/min due to nephron loss is sufficient to induce acquired cyst development in various renal diseases.     

Lercanidipine in patients with chronic renal failure: the ZAFRA study

OBJECTIVE: The objective was primary to evaluate the safe use of a new calcium channel blocker, lercanidipine, in patients with chronic renal failure (CRF). The secondary objective was to study the protective effect of calcium channel blocker on renal function in CRF patients previously treated with ACE inhibitors or angiotensin receptor blockers. DESIGN AND METHODS: The study recruited 203 CRF patients (creatinine >1.4 mg/dL for males, creatinine > 1.2 mg/dL for females, or creatinine clearance <70 mL/min). All patients were receiving ACE inhibitors (63.4%) or angiotensin II antagonist (36.6%) therapy, but they had higher blood pressure than recommended for CRF (130/85 mmHg). No patients were under diuretic treatment. Patients were clinically evaluated 1, 3, and 6 months after starting treatment with lercanidipine. Samples for urine and blood examination were taken during the examination. When needed, a third drug was added to the treatment, excluding diuretics. Creatinine clearance was measured using 24 h urine collection. RESULTS: 175 patients rendered valuable for the study (age 63.9+/-11.9 years, 52.9% males and 47.1% females). Blood pressure (BP) significantly decreased from 162+/-17/93+/-8.3 mmHg to 132+/-12/78+/-6 mmHg. 89.2% of patients showed a significant BP reduction, and 58.1% achieved optimal BP control (<130/85 mmHg). Seven patients (3.4%) showed untoward effects. Not one case of edema was detected, and the prevalence of adverse effects related to vasodilatation was extremely low (three patients, 1.48%). Plasmatic creatinine did not change (1.9+/-0.5 baseline versus 1.9+/-0.6 mg/dL), but creatinine clearance increased at the end visit (41.8+/-16.0 baseline versus 45.8+/-18.0 mL/min, p=0.019). Plasmatic cholesterol also decreased from 221+/-46 to 211+/-35 mg/dL (p=0.001). CONCLUSIONS: Lercanidipine showed a high antihypertensive effect in CRF patients. It has a good tolerability profile and showed an interesting effect on plasmatic lipids. An improvement in renal function, measured through creatine clearance, was detected.     

The effect of renal revascularization on kidney function

A study of the changes in excretory renal function after renal revascularization for hypertension is performed in kidneys monitored with both preoperative and postoperative split renal function studies. Although the changes in creatinine clearances and effective renal plasma flows were not statistically significant for the total group, those kidneys with severe reductions in function were significantly benefitted. Seven of the eight kidneys with creatinine clearances less than 30 ml/min preoperatively had significant increases in creatinine clearances postoperatively (P < 0.02). Likewise, all seven kidneys with effective renal plasma flows less than 100 ml/min before operation had statistically significant improvements (P < 0.005). The fact that all patients in this study had a favorable blood pressure response to revascularization points to the independence of the pressure-regulating mechanisms and excretory functions of the kidney.     

Serial changes in renal function in cardiac surgical patients

Cardiopulmonary bypass is widely believed to be injurious to renal function. The low incidence of renal dysfunction with modern techniques of bypass led us to reexamine this concept by monitoring urine output and creatinine clearance in 18 adult patients undergoing nonpulsatile, hemodilution cardiopulmonary bypass for coronary artery bypass grafting (12 patients) or valve procedures (6 patients). Samples were taken before, during (mean duration of bypass, 105 +/- 26 minutes [+/- standard deviation]), and every two hours after bypass for 24 hours. Urine output (42 +/- 37.7 mL/h) and creatinine clearance (57 +/- 40.4 mL/min) were surprisingly low in the period before cardiopulmonary bypass (all values normalized to a body surface area of 1.73 m2). Urine volumes rose to 305 +/- 149.6 mL/h and creatinine clearance to 252 +/- 176.9 mL/min during bypass and decreased to stable values after eight hours in the postoperative unit (urine output, approximately 60 mL/h, and creatinine clearance, approximately 75 mL/min). Renal dysfunction did not develop in any patient. Nine patients who required loop diuretics for low urine output 18 hours postoperatively had a sustained increase in both urine output and creatinine clearance lasting up to six hours. We conclude the following: modern techniques of cardiopulmonary bypass are not injurious to renal function; urine output and creatinine clearance are decreased before cardiopulmonary bypass, probably because of preoperative dehydration; and loop diuretics in the postoperative period increase both urine output and creatinine clearance for as long as six hours after administration.     

Effects of halothane and isoflurane on transient renal dysfunction associated with infrarenal aortic cross-clamping.

Aortic cross-clamping for reconstructive aortic surgery is associated with impairment of renal function. Halothane or isoflurane was used to assess the influence of volatile anesthesia on renal hemodynamics during aortic surgery. Nineteen patients with normal preoperative creatinine clearances who were scheduled for reconstructive aortic surgery were randomly divided into two groups: halothane group (n = 9) and isoflurane group (n = 10). Induction of anesthesia consisted of midazolam, fentanyl, and pancuronium. Anesthesia was maintained with fentanyl and halothane or isoflurane in nitrous oxide and oxygen (50/50). Systemic hemodynamics were similar in both groups throughout surgery. Before aortic cross-clamping, effective renal plasma flow (ERPF) (131I-hippuran clearance) and glomerular filtration rate (GFR) (99Tc-DTPA clearance) were significantly lower in the halothane group (118.4 +/- 25.6 and 19.7 +/- 5.2 mL/min, respectively) than in the isoflurane group (253.4 +/- 51.5 and 44.9 +/- 8.4 mL/min) (P less than 0.05 for both). During cross-clamping, the renal variables were not markedly affected in either group and remained higher in the isoflurane-anesthetized patients (232.9 +/- 47.1 and 49.5 +/- 1.2 mL/min for ERPF and GFR, respectively) than in the halothane-anesthetized patients (132.4 +/- 31.6 and 14.8 +/- 3.7 mL/min, respectively) (P less than 0.05). After aortic unclamping, ERPF increased markedly in both groups (467.8 +/- 122 and 362.5 +/- 57.7 mL/min in the halothane and isoflurane groups, respectively), as did GFR (74.8 +/- 22 and 71.8 +/- 13.1 mL/min, respectively). These results suggest that anesthesia with halothane is associated with transient renal vasoconstriction during abdominal surgery. In contrast, aortic cross-clamping during isoflurane anesthesia was not associated with renal hemodynamic impairment.     

The renal safety profile of fluvastatin: results of a pooled analysis

A pooled analysis was designed to evaluate the effects of fluvastatin on the kidney, in terms of renal adverse events, laboratory abnormalities, and renal function over time. An analysis of adverse events was performed on data from 30 completed clinical trials of fluvastatin in 11,815 patients. An analysis of renal function was also performed on data from patients who participated in long-term studies >6 months in treatment duration. Creatinine clearance was calculated using the Cockcroft-Gault formula. Mean creatinine clearance values were in the normal to near-normal range at baseline. Changes in creatinine clearance and serum creatinine from baseline were similar in fluvastatin-treated patients and placebo-treated patients. In the all-fluvastatin group, mean creatinine clearance (+/-standard deviation) increased from 87.8 (+/-42.8) mL/min at baseline to 89.4 (+/-41.2) mL/min at endpoint. In the placebo group, mean creatinine clearance (+/- standard deviation) increased from 87.7 (+/- 43.9) mL/min at baseline to 88.7 (+/-41.4) mL/min at endpoint. In the all-fluvastatin group, mean serum creatinine (+/- standard deviation) decreased from 1.14 (+/-0.20) mg/dL at baseline to 1.11 (+/-0.20) mg/dL at endpoint. In the placebo group, mean serum creatinine (+/-standard deviation) decreased from 1.15 (+/-0.22) mg/dL at baseline to 1.12 (+/-0.22) mg/dL at endpoint. The incidence of renal adverse events was low and comparable between the fluvastatin and placebo treatment groups. This pooled analysis demonstrates that fluvastatin treatment across the approved daily dose range of 20 mg to 80 mg does not adversely affect creatinine or creatinine clearance over time in dyslipidemic patients.     

Evaluation of kidney function in renal transplant patients receiving long-term cyclosporine

We prospectively assessed renal function in a group of 29 renal transplant patients receiving cyclosporine (CsA) in order to determine the course of their renal function over time and the relationship between different markers of glomerular function. We measured serum creatinine, DPTA, and creatinine clearances, and urinary albumin excretion. The clinical course of 24 patients (83%) permitted repeat studies over a period of 32 +/- 1 (SEM) months, and in these patients DTPA clearance, creatinine clearance, and the serum creatinine concentration did not vary with time. Five of the patients (17%) lost their grafts and returned to dialysis. On initial evaluation patients who lost their grafts had a lower DPTA clearance than those whose function was maintained (29 +/- 3 v 46 +/- 2 mL/min/1.73 m2 body surface area [BSA], respectively, P less than 0.005) and all of them had a DTPA clearance of less than 40 mL/min/1.73 m2 BSA. There was an inverse correlation between the log of the urinary albumin excretion and the DTPA clearance (n = 33, r = -0.59, P less than 0.001), a direct correlation with the serum creatinine concentration (N = 33, r = 0.89, P less than 0.0001), but no correlation with time after transplantation. Thus, despite the continued use of CsA, renal function over time was stable in patients who underwent repeated studies, as was the relationship between the DTPA clearance and the clinically used markers of transplant function, the serum creatinine concentration, and the creatinine clearance.     

Use of the serum creatinine to estimate glomerular filtration rate in health and early diabetic nephropathy. Collaborative Study Group of Angiotensin Converting Enzyme Inhibition in Diabetic Nephropathy

We evaluated 100/serum creatinine, 24-hour creatinine clearance, and simultaneously measured creatinine clearance or creatinine clearance estimated by the formula devised by Cockcroft and Gault in comparison with measurements of glomerular filtration rate (GFR) using iothalamate among 136 patients with diabetic nephropathy. We also evaluated 100/serum creatinine, simultaneously measured creatinine clearance or creatinine clearance estimated by the Cockcroft and Gault formula in comparison with measurements of GFR using inulin among 88 healthy adults, 21 hypercalciuric kidney stone formers and their hypercalciuric relatives, and one man with chronic nephritis. Creatinine clearances measured simultaneously were closely correlated to GFR (r = 0.93) as were creatinine clearances, estimated by the Cockcroft and Gault formula (r = 0.84) when GFR ranged from 16 to 175 mL/min (0.27 to 2.92 mL/s). These observations confirm the clinical use of either creatinine clearances during water diuresis or estimates of creatinine clearance by the Cockcroft and Gault formula in the assessment of kidney function.     

Renal function and cardiopulmonary bypass in pediatric cardiac surgical patients

We studied prospectively the perioperative changes of renal function in nine children undergoing cardiac surgery with cardiopulmonary bypass (CPB). Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured with inulin and ¹³¹I-hippuran clearances before CPB, during hypo and normothermic CPB, following sternal closure and 1 h postoperatively. Urinary alpha glutathione S-transferase (alpha GS-T) was measured pre- and postoperatively as a marker for tubular cellular damage. Plasma and urine creatinine and electrolytes were measured. Free water, osmolal and creatinine clearances, as well as fractional excretion of sodium (FeNa) and potassium transtubular gradient (TTKG) were calculated. GFR was normal before and after surgery. ERPF was low before and after surgery; it increased significantly immediately after CPB. Filtration fraction (FF) was abnormally elevated before and after surgery; however, a significant decrease during normothermic CPB and sternal closure was found. Alpha GS-T presented a moderate, but nonsignificant increase postoperatively. FeNa also increased in this period, but not significantly. Creatinine, osmolal, free water clearances, as well as TTKG, were normal in all patients pre- and postoperatively. We conclude that there is no evidence of clinically significant deterioration of renal function in children undergoing repair of cardiac lesions under CPB. Minor increases of alpha GS-T in urine postoperatively did not confirm cellular tubular damage. There was no tubular dysfunction at that time.Supported by grant 1030645 from FONDECYT.     

Preservation of renal function following partial or radical nephrectomy using 24-hour creatinine clearance

OBJECTIVE: To compare the effect on renal function of partial and radical nephrectomy using creatinine clearance measurements from 24-hr urine collection. METHODS: All patients with a solid enhancing renal mass suspicious for renal cell carcinoma, a normal contralateral kidney, and not dialysis dependent were enrolled in this prospective cohort study. Patients were treated with partial or radical nephrectomy by one urologist. Creatinine clearance (CrCl) measurements were prospectively obtained by 24-hr urine collection preoperatively, and at 3, 6, and 12 mo postoperatively. Mean change in creatinine clearance from baseline was compared at 3, 6, and 12 mo. Serum creatinine and Cockcroft-Gault calculations were also performed for comparison. Mixed model analysis incorporating patient and tumor characteristics and the procedure type was performed in SAS Version 9.1. RESULTS: Sixty-three consecutive patients were enrolled in this study. The partial nephrectomy (n=26) and radical nephrectomy (n=37) groups were similar with respect to age, sex, presence of hypertension, vascular disease, diabetes mellitus, and angiotensin converting enzyme inhibitor or receptor blocker use. The postoperative change in creatinine clearance was significantly less (p-value < 0.0001) in the partial nephrectomy group (-0.09mL/s, -6.1%) compared to the radical nephrectomy group (-0.56mL/s, -31.6%). Linear regression analysis showed intervention type (partial vs. radical nephrectomy) was the most significant predictor of change in creatinine clearance (p-value < 0.0001). CONCLUSIONS: There is significantly less deterioration in the overall renal function of patients who are treated with partial nephrectomy compared to radical nephrectomy. This highlights the importance of performing nephron-sparing surgery on appropriate patients.     

Will the addition of pentoxifylline reduce proteinuria in patients with diabetic glomerulosclerosis refractory to maximal doses of both an angiotensin-converting enzyme inhibitor and an angiotensin receptor blocker?

BACKGROUND: While interruption of angiotensin synthesis and angiotensin blockade are well know to reduce proteinuria and preserve renal function in patients with diabetic glomerulosclerosis, many patients still have significant proteinuria after having reached maximal doses of those medications. We chose to examine the effect of the addition of pentoxifylline to the therapeutic regimen of patients with significant proteinuria and chronic renal insufficiency who had reached maximal does of an angiotensin-converting enzyme inhibitor (ACEI) and an angiotensin receptor blocker (ARB), on the reduction of proteinuria and the preservation of renal function. METHODS: Seven male patients with diabetic glomerulosclerosis with proteinuria of at least 1.5 g/24 hours and a creatinine clearance of at least 15 ml/min despite maximal doses of an ACEI and an ARB for over 12 months were treated with pentoxifylline adjusted for creatinine clearance. They were then compared with 7 similar patients matched for age, duration of medications, proteinuria, creatinine clearance and mean arterial pressure. The groups were compared for any significant differences on at baseline and at 12 months. RESULTS: Although proteinuria decreased in the pentoxifylline group (5.657 +/- 3.5227 to 3.799 +/- 3.647 g/24 hours) there was no significant difference from the control group (4.743 +/- 2.320 to 4.986 +/- 2.941 g/24 hours). Similarly both groups lost creatinine clearance (41.0 +/- 27.44 to 29.33 +/- 22.21 ml/min with pentoxifylline and 45.57 +/- 21.854 to 27.33 +/- 27.105 ml/min in controls), but there was no significant difference in either clearance or mean arterial pressure. CONCLUSION: Although there was a trend toward the reduction of proteinuria, we found no statistical benefit in proteinuria reduction or preservation of renal function by the addition of pentoxifylline to maximal doses of ACEIs and ARBs.     

Long-term effects of enalapril and nicardipine on urinary albumin excretion in patients with chronic renal insufficiency: a 1-year follow-up

The long-term effects of converting enzyme inhibitors and calcium channel blockers on proteinuria and the progression of renal disease in patients with hypertension and chronic renal insufficiency are not well established. We have studied the long-term effects of treating hypertension with an angiotensin-converting enzyme inhibitor, enalapril, and a calcium channel blocker, nicardipine, on urinary albumin excretion (UAE) and on renal function in 16 patients with hypertension and chronic renal insufficiency (creatinine clearance ranging between 17 and 62 ml/min). After 1 year of treatment, these agents caused a similar decrease in blood pressure. Only enalapril, however, caused a significant decrease in UAE (from 641 +/- 98 to 292 +/- 47 mg/24 h, p less than 0.01), whereas UAE did not change in the group treated with nicardipine (675 +/- 78 vs. 601 +/- 75 mg/24 h). Creatinine clearance at the beginning of the study was similar in the group treated with enalapril and in the group treated with nicardipine (35 +/- 3.6 vs. 40 +/- 4.1 ml/min). After 1 year of follow-up, creatinine clearance remained unchanged in both groups of patients. These studies demonstrate that both enalapril and nicardipine can effectively reduce blood pressure in patients with hypertension and chronic renal insufficiency. Enalapril but not nicardipine, however, appears to reduce urinary albumin excretion in these patients. Whether the reduction in UAE has any significant impact on the progression of renal disease remains to be established.     

Cardiorespiratory responses to hypertonic saline solution in cardiac operations

Infusion of small volumes of hypertonic saline solution (HS) seems to be of benefit in patients with impaired perfusion. The cardiorespiratory response to a 7.2% NaCl solution prepared in hydroxyethylstarch (HES) solution was investigated prospectively in patients undergoing prolonged cardiopulmonary bypass (CPB) (HS-HES group; n = 15); 6% HES 200/0.5 solution was infused in a control group (HES group; n = 15). Volume was given preoperatively to double low pulmonary artery occlusion pressure (less than 4 mm Hg) within 20 minutes. Hemodynamics, oxygen transport variables, and pulmonary gas exchange were studied before and after infusion as well as before and after CPB. Significantly less HS-HES solution (3.06 +/- 0.2 mL/kg) than 6% HES 200/0.5 solution (10.3 +/- 0.9 mL/kg) was necessary to double baseline pulmonary artery occlusion pressure. Fluid balance during CPB was negative in the HS-HES patients (-0.05 mL/kg.min CPB) and was lowest in this group even 5 hours after CPB. Mean arterial pressure, pulmonary arterial pressure, and heart rate were without differences between the groups. Changes in cardiac index (+40%) and total systemic resistance (-25%) were significantly most pronounced in the HS-HES patients, continuing even until the end of operation. Pulmonary gas exchange (arterial oxygen tension, intrapulmonary right-to-left shunting) was least compromised in these patients, particularly after bypass. Oxygen consumption was without difference between the groups; oxygen delivery increased significantly more in the HS-HES patients due to the larger increase in cardiac output.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of sirolimus in the development of chronic allograft nephropathy

PURPOSE: The effect of sirolimus (SRL) in renal function was studied in renal transplant recipients. PATIENTS AND METHODS: We studied 20 patients who underwent live related kidney transplantation 1 to 2 years prior under cyclosporine (CsA) treatment and displayed serum creatinine values between 2 and 3 mg/dL. The patients were randomized into 2 groups prospectively. The calcineurin inhibitors (CNI) group continued taking CsA; the SRL group underwent a switch from CsA to SRL. Biopsies were performed to assess chronic allograft nephropathy (CAN) findings and TGFbeta1 in the transplanted kidneys at the beginning and the end of the study. Creatinine clearance, serum creatinine, and proteinuria values were detected in the beginning as well as at 1, 3, 6, and 12 months later. RESULTS: At the beginning of the study, the creatinine clearance and serum creatinine levels were 52.21 mL/min and 2.05 mg/dL in the CNI group and 47.76 mL/min and 2.13 mg/dL in the SRL group, respectively. At 12 months, these values were 48.11 mL/min and 2.57 mg/dL in the CNI group and 50.45 mL/min and 2.12 mg/dL in the SRL group, respectively. Creatinine clearance values between the 2 groups at 12 months were statistically different. Although it was not significant, there was a tendency toward decreases inflammatory infiltration and TGFbeta1 levels in the SRL group compared with the CNI group on the second biopsies. CONCLUSION: Pathologic findings of CAN development, serum creatinine, and creatinine clearance values were ameliorated in the SRL group. We concluded that SRL positively affected long-term graft survival.     

Volume supplementation with iso-sodium solution prevents hypernatremia after head injury

OBJECTIVE: To evaluate our developed volume supplement protocol in preventing hypernatremia after head injury. METHODS: Iso-sodium solution was infused to keep the 8-hour water balance positive in 20 head-injured patients with hypotonic urine. RESULTS: Serum sodium concentrations moved to within a normal range in 6 patients and were temporarily increased in 12 patients. Seven of the 12 showed a negative cumulative water balance and slightly low creatinine clearance. Mean arterial pressure in the other five patients was lower after supplementation and was positively related to sodium excretion. Hypernatremia could not be prevented in the other two patients and they did not survive. Creatinine clearance was below 40 mL/min/m2 in these two patients before supplementation. CONCLUSION: Our protocol worked effectively in patients in whom renal function was preserved. Decreased creatinine clearance because of preexisting dehydration and lower arterial pressure disturbed increase in urinary sodium excretion and temporarily aggravated the hypernatremia.