Renal excretion and cyst accumulation of beta 2microglobulin in polycystic kidney disease

To determine the extent to which proximal tubule function is altered beta 2microglobulin (beta 2m), creatinine and Na were measured in serum, urine and cyst fluid of patients with autosomal dominant polycystic kidney disease and various degrees of renal insufficiency. Fractional excretion (FE beta 2m) was 0.11 +/- 0.03% in six normal subjects and 0.13 +/- 0.05% in nine patients with serum creatinine levels less than 1.6 mg/dl. In five patients with serum creatinine levels above 3.0 mg/dl, FE beta 2m was elevated (range 3.5 to 196%) and serum levels were higher than normal (30,600 +/- 6,910 micrograms/liter vs. 1,268 +/- 111). In seven patients beta 2m levels in 33 proximal cysts (cyst/serum Na greater than 0.8) equalled those in serum (cyst/serum beta 2m 0.98 +/- 0.20), whereas in 21 distal cysts (cyst/serum Na less than 0.4) beta 2m was less than in serum (cyst/serum beta 2m 0.17 +/- 0.07). Analysis of fluid in two patients with polycystic kidney nephrectomy several weeks posttransplant indicated that proximal cyst epithelium is permeable to beta 2m, but less so than to creatinine or urea. These studies show that proximal cysts cannot develop or maintain gradients for beta 2m, whereas distal cysts maintain low levels of the protein despite end-stage renal failure. The normal FE beta 2m values in nonazotemic autosomal dominant polycystic kidney disease patients and the low distal cyst levels of beta 2m in end-stage kidneys indicate that the cystic proximal nephrons do not contribute appreciably to the final urine.(ABSTRACT TRUNCATED AT 250 WORDS)     

Urinary excretion of monocyte chemoattractant protein-1 in autosomal dominant polycystic kidney disease

Autosomal dominant polycystic kidney disease (ADPKD) progresses to renal insufficiency in >50% of patients and is characterized by interstitial inflammation and fibrosis in the end stage. In a rat model of ADPKD, monocytes accumulate within the renal interstitium in association with increased levels of monocyte chemoattractant protein-1 (MCP-1) in cyst mural cells and increased excretion of this chemokine into the urine. For determining the extent to which this chemokine is abnormally expressed in patients with ADPKD, a cross-section study was performed of MCP-1 in urine, serum, and cyst fluid and MCP-1 production by mural epithelial cells cultured from the cysts of human patients with ADPKD. Upper boundaries for urinary MCP-1 excretion (>263 pg/mg creatinine) and serum creatinine concentration (>1.5 mg/dl) determined in 19 normal individuals were used to sort 55 ADPKD patients into three groups. In group 1 (n = 13), urine MCP-1 excretion (136 +/- 14 pg/mg creatinine) was not different from normal volunteers (152 +/- 16 pg/mg); serum creatinine levels and urine total protein excretion were normal as well. In group 2 (n = 27), urine MCP-1 excretion was increased (525 +/- 39 pg/mg creatinine), but serum creatinine levels and urine protein excretion were not different from normal. In group 3 (n = 15), urine MCP-1 excretion increased further (1221 +/- 171 pg/mg), serum creatinine levels increased to 4.3 +/- 0.8 mg/dl, and urine protein excretion rose to 0.64 +/- 0.28 mg/mg creatinine. Serum MCP-1 levels of ADPKD patients (84 +/- 9.9 pg/ml; n = 15) did not differ from normal. Levels of MCP-1 much higher than in serum or urine were found in cyst fluids obtained from nephrectomy specimens (range, 767 to 40,860 pg/ml; mean, 6434 +/- 841 pg/ml; n = 73). Polarized, confluent cultures of ADPKD cyst epithelial cells secreted MCP-1 into the apical fluid to levels eightfold greater than in the basolateral medium. Similar results were obtained with tubule epithelial cells cultured from normal human renal cortex. On the basis of these results, it is concluded that urinary excretion of MCP-1 is increased in the majority of adult patients with ADPKD and that the source of some of this chemokine may be the mural epithelium of cysts. Furthermore, it seemed that urinary MCP-1 excretion may have increased in these ADPKD patients before appreciable increases in serum creatinine concentration or urine protein excretion were detected. It is reasonable to include urine MCP-1 excretion among candidate surrogate markers in controlled, longitudinal studies of ADPKD.     

Effect of chronic theophylline administration on amphotericin B nephrotoxicity in rats

The effect of chronic theophylline administration on amphotericin B nephrotoxicity was investigated in rats. A 7-day treatment of amphotericin B (5 mg/kg/day i.p.) significantly reduced the glomerular filtration rate (GFR) measured as inuline clearance and creatinine clearance (0.74 +/- 0.29 and 0.16 +/- 0.04 ml/min, respectively) in comparison to vehicle-treated rats (2.04 +/- 0.23 and 1.29 +/- 0.19 ml/min, respectively). The reduced GFR led to evaluations in serum creatinine and BUN concentrations (0.94 +/- 0.09 and 78 +/- 11 mg/dl) in comparison to their own values before treatment (0.45 +/- 0.11 and 19 +/- 3 mg/dl). In addition amphotericin B induced an increase in sodium and a decrease in potassium excretion, the fractional sodium excretion was elevated 50-fold. The methylxanthine, theophylline, had a beneficial effect on the outcome of amphotericin-B-induced renal failure. The inuline clearance was 1.17 +/- 0.04 ml/min, the creatinine clearance 0.43 +/- 0.03 ml/min, the serum creatinine concentration 0.76 +/- 0.05 mg/dl and the BUN concentration 40 +/- 6 mg/dl. Theophylline had no effect on total sodium excretion and potassium excretion. The fractional sodium excretion, however, improved significantly. Theophylline as well as sodium deoxycholate, the detergent of amphotericin B, given alone had no effect on renal hemodynamics measured after 7 days.     

Effects of famotidine, a new histamine H2-receptor antagonist, on renal function

The effects of famotidine on renal function were investigated. Eight healthy men (N) and 8 renal patients with varying degrees of renal failure (R.F.) participated in the trial. They were given either famotidine (40 mg) or cimetidine (800 mg) for 7 days. Cimetidine produced a significant decrease in creatinine clearance (from 131.6 +/- 12.9 to 107.7 +/- 3.4 ml/min (N), and 22.2 +/- 3.9 to 18.1 +/- 3.5 ml/min (R.F.], and increase in serum creatinine (from 0.96 +/- 0.05 to 1.09 +/- 0.04 mg/dl (N), and 3.46 +/- 0.62 to 3.86 +/- 0.51 mg/dl (R.F.], and a decrease in creatinine excretion (from 24.0 +/- 1.1 to 22.6 +/- 0.8 mg/kg/24 hr (N], respectively, although the reduction in creatinine excretion in the renal failure group was small. On the other hand, the famotidine treatment produced no significant changes in renal function in both subjects (creatinine clearance, 136.5 +/- 5.7 to 133.6 +/- 6.0 ml/min (N), and 21.9 +/- 3.6 to 20.9 +/- 4.1 ml/min (R.F.); serum creatinine, 0.98 +/- 0.02 to 0.99 +/- 0.02 mg/dl (N), and 3.24 +/- 0.43 to 3.46 +/- 0.55 mg/dl (R.F.); and urinary creatine, 25.1 +/- 1.0 to 25.3 +/- 1.0 mg/kg/24 hr (N), and 17.2 +/- 1.4 to 16.6 +/- 1.5 mg/kg/24 hr (R.F.]. There were no changes in the percent sodium excretion, or the serum and urinary beta 2-microglobulin in both groups.     

Renal allograft rejection with normal renal function in simultaneous kidney/pancreas recipients: does dissynchronous rejection really exist?

BACKGROUND: Between July 1, 1994 and December 1, 1998, 147 simultaneous kidney/pancreas transplantations were performed at our center. Of 95 patients who experienced at least one acute renal allograft rejection episode after transplantation, 7 (7.4%) developed rejection in the presence of stable and normal or near-normal renal function. METHODS: The indication for renal allograft biopsy was a rising serum lipase, i.e., suspected pancreatic rejection. All seven patients were treated with steroids and augmentation of the tacrolimus dose, with a fall in the serum lipase and no change in the serum creatinine. RESULTS: The serum creatinine levels just before, at the time of, 1 week after the biopsy, and at most recent follow-up were 1.4+/-0.4, 1.3+/-0.3, 1.2+/-0.2, and 1.2+/-0.2 mg/dl. The serum lipase levels just before, at the time of, 1 week after the biopsy, and at most recent follow-up were 1022+/-1157 mg/dl, 874+/-996 mg/dl, 243+/-260 mg/dl, and 94+/-75 mg/dl. The tacrolimus dosages and levels at the time of the biopsy and 1 week later were 14.9+/-5.0 mg/day and 15.0+/-4.0 ng/ml, and 16.4+/-6.3 mg/day and 15.1+/-6.8 ng/ml. CONCLUSIONS: These findings suggest that, in patients undergoing simultaneous kidney/pancreas transplantation, the entity of dissynchronous pancreatic allograft rejection without renal allograft rejection may not really exist. These data also make an additional fundamental point that acute rejection may occur in patients with normal and stable renal function.     

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.     

Improved renal function after renal artery revascularization

An experience with 20 patients with renovascular hypertension and renal insufficiency secondary to renal artery stenosis is presented. The mean follow-up was 29 months. Eighteen patients had atherosclerotic renal artery stenosis and two patients had transplant renal artery stenosis. The mean preoperative blood pressure of 162 +/- 5 mmHg decreased significantly to 105 +/- 2 mm Hg (p less than 0.001). The serum creatinine also decreased from a mean preoperative level of 4.7 +/- 0.7 mg/dl to a mean postoperative level of 2.3 +/- 0.3 mg/dl (p less than 0.001). Similarly, the creatinine clearance improved from a mean preoperative level of 28 +/- 2 ml /min to a mean postoperative level of 45 +/- 8 ml/min (p less than 0.03). Four patients (20%) with improved renal function died from 4 days to 15 months postoperatively. Two patients (10%) have progressed to end stage renal disease. These findings demonstrate that renal revascularization is clearly beneficial in the short-term and long-term improvement of renal function.     

Renal structure and hypertension in autosomal dominant polycystic kidney disease

Hypertension has been reported to occur in 50 to 75 percent of subjects with autosomal dominant polycystic kidney disease (ADPKD) prior to the onset of marked renal insufficiency but concurrent with cystic deformation of the renal parenchyma. The present study was undertaken to examine whether the renal structural abnormalities are greater in hypertensive (HBP) versus normotensive (NBP) male and female patients with ADPKD who were matched within gender groups for age, body surface area, serum creatinine concentration (males HBP 1.2 +/- 0.02 vs. NBP 1.1 +/- 0.03 mg/dl. NS: females HBP 0.9 +/- 0.03 vs. NBP 0.9 +/- 0.02 mg/dl, NS) and creatinine clearance (males HBP 100 +/- 3 vs. NBP 108 +/- 3 ml/min/1.73 m2, NS: females HBP 97 +/- 3 vs. NBP 96 +/- 2 ml/min/1.73 m2, NS). Renal volume was significantly greater in the HBP compared to the NBP group (males HBP 624 +/- 47 vs. NBP 390 +/- 43 cm3, P less than 0.0005; females HBP 446 +/- 32 vs. NBP 338 +/- 24 cm3, P less than 0.002). Since increased renal volume is due to increased cysts, the results indicate that the early high incidence of hypertension in ADPKD correlates with the renal structural abnormalities in this disorder.     

Peritonfal Dialysis in the Treatment of Severe Hypercalcemia

A 56-year-old man with multiple myeloma and compromised renal function underwent peritoneal dialysis for the treatment of severe hypercalcemia. During dialysis, peritoneal clearances, of total calcium, unbound calcium, urea, and creatinine were assessed. Clearances of total calcium (4.8 ± 0.4 ml/min) and unbound calcium (7.8 ± 0.5 ml/min) were shown to vary directly with the clearances of urea (15.5 ± 1.3 ml/min) and creatinine (8.5 ± 0.8 ml/min). Despite relatively low clearances of all these solutes, during the period of 42 hours, 1,638 mg of calcium was removed in the dialy-sate and total serum calcium decreased from 17.6 mg/dl to 10.2 mg/dl. Our data indicates that peritoneal dialysis is an effective adjunct in controlling severe hypercalcemia and should be considered when other forms of therapy are inadequate.     

Effects of H2-receptor antagonists on renal function in cyclosporine-treated renal transplant patients

H2-receptor antagonists have been frequently avoided in cyclosporine-treated transplant patients because of concern regarding possible exacerbation of nephrotoxicity. To determine whether the reported increase of serum creatinine levels in cyclosporine-treated transplant patients receiving H2-receptor antagonists was due to a true decrease in glomerular filtration rate or was secondary to altered renal tubular handling of creatinine, simultaneous inulin and creatinine clearances were analyzed in 11 cyclosporine-treated renal transplant recipients before and after H2-receptor antagonist administration. Seven patients received one week of cimetidine 300 mg p.o. four times daily and eight received one week of ranitidine 150 mg p.o. two times daily. Prior to study, all patients had stable renal function and were maintained on prednisone (mean dose 0.2 +/- 0.01 mg/kg/day) and cyclosporine (mean dose 5 +/- 0.6 mg/kg/day). Four patients were also receiving azathioprine (2 mg/kg/day). Cimetidine administration resulted in a significant increase (P less than 0.05) in mean serum creatinine concentration from 2.0 +/- 0.3 mg/dl to 2.4 +/- 0.3 mg/dl and a significant reduction (P less than 0.05) in mean creatinine clearance remained unchanged during this same period. Serum creatinine levels returned to baseline values for all patients following discontinuation of the drug. Ranitidine administration had no consistent effect on serum creatinine concentration, creatinine clearance or inulin clearance. Cyclosporine trough levels and BUN were unchanged by either drug. These results confirm previous observations demonstrating an increase in serum creatinine and a reduction in creatinine clearance following administration of H2 receptor antagonists, especially cimetidine. Failure to document a simultaneous reduction in inulin clearance is consistent with the hypothesis that H2-receptor antagonists do not exacerbate cyclosporine nephrotoxicity and lower GFR, but rather compete with creatinine for tubular secretion.     

What is the best hydration regimen to prevent contrast media-induced nephrotoxicity?

BACKGROUND: Hydration is a commonly used method to prevent the decline in GFR after contrast media (CM) application. So far, there have been no controlled, randomized trials investigating the most effective route of fluid administration. METHODS: Thirty-nine patients with normal renal function (65 +/- 9 years, serum creatinine 0.9 +/- 0.2 mg/dl, GFR = 110 +/- 31 ml/min/1.73 m2) receiving at least 80 ml of low-osmolality CM during an angiographic procedure were randomized to one of the following hydration regimens: Group 1: volume expansion with 300 ml saline during CM administration (n = 20, serum creatinine 0.8 +/- 0.1 mg/dl, GFR 119 +/- 27 ml/min/1.73 m2); Group 2: intravenous administration of at least 2,000 ml saline within 12 h before and after CM application (n = 19, serum creatinine 0.9 +/- 0.2 mg/dl, GFR 101 +/- 32 ml/min/1.73 m2). GFR was measured by CM clearance (Renalyzer) at baseline and 48 hours after CM administration. The primary end point was the mean change in the GFR after 48 hours, the secondary one was the incidence of CM-induced nephropathy (CMIN), defined as a decrease in GFR of more than 50% from the baseline GFR within 48 hours. RESULTS: Patients of group 1 showed a significantly (p < 0.05) higher decline in GFR (delta GFR 34.6 +/- 25.7 ml/min/1.73 m2) compared to patients receiving the intravenous prehydration regimen (delta GFR 18.3 +/- 25.0 ml/min/1.73 m2). The incidence of CMIN was lower in prehydrated patients (5.3%) compared to the other group (15%). CONCLUSION: In patients with normal renal function, intravenous prehydration seems to be a very effective and feasible method to prevent the decline in GFR after contrast media exposure. Volume expansion given only during the CM exposure appears not to be sufficient enough to prevent renal damage.     

Bone histology in patients with nephrotic syndrome and normal renal function

BACKGROUND: The prevalence of metabolic bone disease in patients with nephrotic syndrome (NS) at normal level of renal function remains uncertain. METHODS: To address this issue, we studied 30 patients (20 men and 10 women, mean age 27.3 +/- 11.7 years) with NS who had normal renal function (mean creatinine clearance 103 +/- 4 ml/min). We evaluated their serum calcium, phosphorus, alkaline phosphatase, immunoreactive parathyroid hormone (iPTH), vitamin D metabolites, urinary calcium, and skeletal survey. The extent of bone mineralization was analyzed by histomorphometric analysis of iliac crest bone biopsy specimens in all patients. The findings on bone histology were correlated with biochemical parameters. RESULTS: The mean duration of NS was 35.5 +/- 26.9 months, with a protein excretion of 7.3 +/- 3.2 g/24 hr and a serum albumin of 2.2 +/- 0.8 g/dl. Total serum calcium was 7.8 +/- 0.8 mg/dl, whereas ionized calcium was 5.7 +/- 0.7 mg/dl, phosphorus 3.2 +/- 1.2 mg/dl, and alkaline phosphatase 149 +/- 48.6 U/liter. Serum iPTH levels were normal in all except two patients. The mean serum 25-hydroxyvitamin D [25(OH)D] level was 3.9 +/- 1.2 ng/ml (normal 15 to 30 ng/ml), whereas 1,25-dihydroxyvitamin D was 24 +/- 4.7 pg/ml (normal 16 to 65). There was an inverse correlation between serum levels of 25(OH)D and the magnitude of proteinuria (r = -0.42, P < 0.05). The mean 24-hour urinary calcium excretion was 82 +/- 21 mg/day. The skeletal survey was normal in all patients. Bone histology was normal in 33.3% of the patients, whereas 56.7% had isolated osteomalacia (OSM), and 10% had an increased bone resorption in association with defective mineralization. The severity of OSM measured by mineralization lag time correlated linearly with the duration (r = 0.94, P < 0.0001) and the amount (r = 0.97, P < 0.0001) of proteinuria. All patients with NS for more than three years had histological changes. Patients with OSM had lower 25(OH)D and serum albumin as compared with those with normal histology (P < 0.005). Bone mineralization had no significant correlation with serum iPTH, divalent ions, or vitamin D levels. CONCLUSIONS: OSM is a frequent finding in adult patients with NS, even at a normal level of renal function. Its severity correlates with the amount and duration of proteinuria.     

Analysis of risk factor for patients and renal survival in anti-myeloperoxidase antibody (MPO-ANCA) associated glomerulonephritis

We investigated the clinical and histological features and the outcome of 15 patients with antimyeloperoxidase antibody(MPO-ANCA) associated glomerulonephritis. The patients were divided into two groups on the basis of renal functional outcome: Group 1 consisted of 7 patients where an initial deterioration in renal function was improved at the final observation. Group 2 included 8 patients who had a progressive deterioration in renal function leading to end stage renal disease or chronic dialysis, or who died. We compared the clinical and histological features at renal biopsy and the outcome following steroid therapy between the two groups. Group 1 patients had significantly lower levels of serum creatinine and UN, and higher values for creatinine clearance (Ccr) than Group 2 patients(1.9 +/- 0.6 vs. 6.7 +/- 4.7 mg/dl, 29 +/- 7 vs. 73 +/- 39 mg/dl, 30 +/- 9 vs. 10 +/- 5 ml/min, p < 0.05, respectively). Histologically, Group 1 patients had a significantly lower percentage of crescent formation than Group 2 patients(41 +/- 6 vs. 74 +/- 4%, p < 0.05), whereas there was no significant difference in tubulo interstitial damage between the 2 groups. Moreover, in 4 patients of Group 1 where a second renal biopsy was performed two months after steroid therapy, marked attenuation in acute tubulo-interstitial changes was observed in association with a rapid improvement of renal function. These results suggest that diffuse tubulo-interstitial inflammatory changes despite a relatively low frequency of cellular crescent formation may be a prognostically important histological feature showing a good response to steroid therapy.     

Pyuria in patients treated with indinavir is associated with renal dysfunction

BACKGROUND: Indinavir therapy is associated with a continuum of crystal-related syndromes, including nephrolithiasis, renal colic, flank pain without recognizable stone formation, dysuria and asymptomatic crystalluria. A frank nephropathy has been recognized recently as part of the spectrum. METHODS: A retrospective analysis of 72 HIV-infected individuals receiving indinavir was performed to identify the frequency and risk factors for indinavir-associated nephropathy and urinary complications. Individuals treated with nucleoside analogues alone served as controls. RESULTS: Mean serum creatinine levels rose from 1.03 +/- 0.16 mg/dl to 1.11 +/- 0.22 mg/dl at week 12 and 1.15 +/- 0.27 mg/dl at week 24 (both, p < 0.01). Thirteen individuals developed serum creatinine levels > or =1.4 mg/dl. Increased serum creatinine levels were found more frequently in women (p < 0.01) and were associated with pyuria and microhematuria (p < 0.01). Frank renal colic and/or nephrolithiasis (seven patients) and urinary pH were not associated with serum creatinine levels > or =1.4 mg/dl. The mean duration of indinavir treatment, until sterile pyuria occurred, were 22 weeks and 32 weeks until the first rise of serum creatinine levels to > or =1.4 mg/dl. Ten patients showed both findings, pyuria preceded the first rise in serum creatinine levels to > or = 1.4 mg/dl (18 vs. 27 weeks, p = 0.02). Renal biopsy, done in three patients, revealed tubulointerstitial disease with crystals in collecting ducts. In 21 patients, among them 11 with pyuria, indinavir was replaced for various reasons and pyuria disappeared in nine. In these patients mean serum creatinine levels decreased from 1.43 mg/dl at withdrawal of indinavir to 1.04 mg/dl three months later (p < 0.01). CONCLUSION: Indinavir therapy is associated with a decrease in renal function which is reversible after withdrawal. In addition, indinavir-associated tubulointerstitial disease does no in patients taking indinavir may help to identify patients being at risk for nephrotoxicity.     

The product of duration and amount of proteinuria (proteinuria index) is a possible marker for glomerular and tubulointerstitial damage in IgA nephropathy

BACKGROUND/AIMS: IgA nephropathy (IgAN) is one of the major causes for chronic renal failure (CRF). Presence of massive proteinuria, hypertension, increased serum creatinine level and sclerotic histopathological changes of the glomerulus are known to be determinants for the progression of CRF. However, the relationships between duration of proteinuria/hematuria and histopathological changes, which may be correlated with the renal prognosis, have not been clarified. METHODS: A cross-sectional, univariate analysis of clinical parameters on the four glomerular and three tubulointerstitial histopathological grades in 57 untreated biopsy-proven IgAN patients (M/F = 32/25) was performed. RESULTS: The age at the time of renal biopsy (35.2 +/- 13.0 years; mean +/- SD), average duration of proteinuria (5.3 +/- 5.8 years), mean urinary protein excretion (0.99 +/- 1.22 g/day), serum creatinine (Cr 0.97 +/- 0.28 mg/dl), Cr clearance (Ccr 75.5 +/- 29.4 ml/min), and blood urea nitrogen (BUN 15.4 +/- 3.9 mg/dl) were well correlated with both histopathological grades. The product of duration (years) and urinary protein excretion (g/day) at the time of renal biopsy was more significantly correlated with glomerular and tubulointerstitial histopathological grades and serum Cr. CONCLUSION: The natural course of IgAN is steadily progressive depending on the duration and amount of proteinuria. The product of these two factors (proteinuria index) may be a useful predictor for glomerular and interstitial histopathological changes and the fate of renal function in IgAN.     

Ezetimibe treatment in hypercholesterolemic kidney transplant patients is safe and effective and reduces the decline of renal allograft function: a pilot study.

BACKGROUND: Ezetimibe has shown efficacy in the therapy of hypercholesterolemia in renal transplant patients. This is the first study investigating the effect of ezetimibe on renal function in kidney transplant recipients. METHODS: Fifty-six patients with statin-resistant hypercholesterolemia (total cholesterol >200 mg/dl) after renal transplantation received additional ezetimibe therapy (10 mg/day) for 12 months. A group receiving statin therapy (n=28) served as controls in this prospective study. RESULTS: Total cholesterol and LDL cholesterol concentrations decreased significantly in the ezetimibe-treated patients but remained stable in the control group (delta total cholesterol: -24+/-49 mg/dl vs 19+/-49 mg/dl, P<0.01; delta LDL: -30+/-39 mg/dl vs -3+/-31 mg/dl, P<0.01). Mean creatinine clearance remained stable in ezetimibe-treated patients but decreased significantly in control group (delta Cockcroft-Gault: 0.9+/-7.3 ml/min vs - 4.8+/-12.8 ml/min, P=0.025; delta Modification of Diet in Renal Disease: -0.4+/-6.2 ml/min/1.73 m(2) vs 4.7+/-8.8 ml/min/1.73 m(2), P=0.033). CONCLUSIONS: The data of our prospective case-control study suggest that ezetimibe appears to ameliorate the decline of renal function after renal transplantation.     

Cyst decompression surgery for autosomal dominant polycystic kidney disease.

A prospective study was undertaken to evaluate the efficacy of surgical cyst decompression for retarding the progression of renal failure and for the management of chronic pain associated with autosomal dominant polycystic kidney disease (ADPKD). Thirty patients with ADPKD and pain (14 patients), renal insufficiency (4 patients), or both (12 patients) underwent unilateral (19 patients) or bilateral (11 patients) cyst reduction surgery. The patients were monitored for 21 +/- 2 months postoperatively. The probability of being painfree was 80% at 1 yr and 62% at 2 yr. Preoperative and 1-to 3-month postoperative serum creatinine levels and GFR (clearance of insulin or (125I) iothalamate) were not significantly different (2.2 +/- 0.3 versus 2.2 +/- 0.3 mg/dL and 49 +/- 8 versus 54 +/- 9 mL/min/1.73 m2, respectively). One-year serum creatinine levels remained unchanged in patients with normal preoperative renal function (1.0 +/- 0.07 versus 1.0 +/- 0.05 mg/dL), whereas those with preoperative progressive renal insufficiency had no difference in the mean slope of reciprocal serum creatinine plots preceding and after surgery (-0.008 +/- 0.001 versus -0.009 +/- 0.002 dL/mg/month). In patients who underwent unilateral surgery, split function isotope scans showed no change in function of the operated kidney when compared with the nonoperated kidney. Surgical cyst decompression provides effective relief of chronic pain without compromising renal function. However, the data in this article do not support the use of this procedure to slow progression of renal insufficiency in ADPKD.     

Low risk of contrast nephropathy in high-risk patients undergoing spiral computed tomography angiography with the contrast medium iopromide and prophylactic oral hydratation

BACKGROUND: Spiral computed tomography angiography (CTA) is a sensitive and specific technique for visualizing renal arteries and diagnosing renal artery stenosis (RAS). Whether spiral CTA is associated with increased risk of contrast nephropathy (CN) in patients with impaired renal function is unknown. METHODS: We prospectively studied 50 patients with chronic renal insufficiency (serum creatinine concentration greater than 1.58 mg/dl) who underwent spiral CTA with iopromide, a nonionic, low-osmolar contrast agent. Fourteen patients had diabetes mellitus. Patients were encouraged to drink 1 l of water 12 hours before and 2 l over 24 hours after the procedure. The presence of CN was defined by an increase of 20% or more in the baseline serum creatinine level within or 72 hours after administration of the radio-contrast agent. RESULTS: In the entire group, mean serum creatinine levels increased significantly from 2.92 +/- 1.39 to 3.06 +/- 1.55 mg/dl (p = 0.02) and mean creatinine clearance decreased from 29.8 +/- 12.9 to 28.9 +/- 12.8 ml/min (p = 0.009) 72 h after administration of the contrast medium. Two patients experienced an increase in serum creatinine level of 20%. Renal function returned to baseline within seven days in the 2 patients. Absolute changes in creatinine clearance after the administration of radiocontrast medium were similar in nondiabetic and diabetic patients and in the subgroup of patients, with a baseline serum creatinine of < 3 mg/dl and > or = 3 mg/dl. CONCLUSIONS: In patients with chronic renal insufficiency, spiral CTA performed with iopromide, a nonionic, low-osmolar contrast medium and a prophylactic oral hydratation, is a minimally invasive technique with low risk of contrast nephropathy.     

Marked increase of asymmetric dimethylarginine in patients with incipient primary chronic renal disease.

In patients with uremia, increased blood concentrations of the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA) have been linked to the severity of atherosclerosis and to excess cardiovascular mortality. The ADMA levels and several traditional cardiovascular risk factors were assessed in 44 untreated nonsmoking patients with confirmed primary chronic renal disease at different stages of renal disease. True GFR was assessed by means of the inulin-clearance technique. For comparison, nonsmoking subjects matched with respect to age, gender, and body-mass index were examined. Mean plasma ADMA concentration was markedly higher (P < 0.0001) in all patients combined (4.2 +/- 0.9 micromol/L) than in control subjects (n = 16; age 45 +/- 10 yr; serum creatinine 1.0 +/- 0.1 mg/dl; ADMA 1.4 +/- 0.7 micromol/L). However, mean ADMA levels were similar in patients with normal renal function (n = 16; age 41 +/- 9 yr; serum creatinine 1.1 +/- 0.1 mg/dl; GFR 120 +/- 14 ml x min(-1) x 1.73 m2; ADMA 4.0 +/- 0.7 micromol/L), in patients with moderate renal failure (n = 15; 47 +/- 7 yr; 1.8 +/- 0.3 mg/dl; 65 +/- 10 ml x min(-1) x 1.73 m2; 3.8 +/- 0.6 micromol/L) and in patients with advanced renal failure (n = 13; 46 +/- 9 yr; 4.2 +/- 0.9 mg/dl; 25 +/- 4 ml x min(-1) x 1.73 m2; 4.7 +/- 1.2 micromol/L). Furthermore, ADMA levels were increased to the same extent in normotensive (n = 17; 4.0 +/- 0.8 micromol/L) and in hypertensive (n = 27; 4.2 +/- 0.9 micromol/L) patients. In contrast to ADMA, mean total plasma homocysteine concentration were similar in control subjects (10.6 +/- 2.9 micromol/L) and in patients with normal GFR (11.0 +/- 2.9 micromol/L), but were significantly higher in patients with moderate renal failure (17.7 +/- 4.1 micromol/L) and particularly in patients with advanced renal failure (28.2 +/- 10.6 micromol/L). Finally, mean total serum cholesterol concentrations were comparable in the control group and in the three groups of patients with renal disease. In contrast to several traditional cardiovascular risk factors, markedly increased blood concentrations of ADMA, a putative biochemical marker of atherosclerosis, are present even in nonsmoking patients without diabetes with incipient primary renal disease. Thus, the early increase of ADMA levels may be of relevance for the excess cardiovascular morbidity and mortality due to arterio- and atherosclerotic complications in patients with renal disease.     

Effective long-term immunosuppression maintained by low cyclosporine levels in primary cadaveric renal transplant recipients

Nephrotoxicity and cost are the major problems in the use of cyclosporine (CsA) in renal transplantation. Thus, maintenance of CsA levels at the lower limits of the therapeutic range is desirable. The lowest CsA level effective in preventing rejection while avoiding nephrotoxicity has not been defined. We report on 44 primary cadaveric renal transplant recipients treated with a protocol that involved a progressive reduction in the trough CsA levels. CsA was initiated at an oral dose of 15 mg/kg, and this dose was adjusted to achieve serum trough levels, as measured by radioimmunoassay, of 150-200 ng/ml during the first month, 100-150 ng/ml during the second month, 75-100 ng/ml during the third month, and 50-75 ng/ml thereafter. Patient and graft survival at 18 months were 94% and 83.6%, respectively. The mean daily CsA doses were 6.7 +/- 3.1 mg/kg at 6 months, 5.5 +/- 3.2 mg/kg at 12 months, and 4.7 +/- 2.4 mg/kg at 18 months. Corresponding trough serum CsA levels were 94 +/- 59 ng/ml, 64 +/- 22 ng/ml, and 44 +/- 21 ng/ml at 6, 12, and 18 months, respectively. Mean serum creatinine concentrations were 1.8 +/- 0.6 mg/dl at 6 months, 1.7 +/- 0.5 mg/dl at 12 months, and 1.6 +/- 0.5 mg/dl at 18 months. The mean serum creatinine concentration at 18 months was not significantly different from that of 18 conventionally treated primary cadaveric renal transplant recipients (1.6 +/- 0.5 vs. 1.4 +/- 0.4 mg/dl, P = .31). A total of 67% of patients did not have any rejection episodes under this protocol, while 71% of patients never developed CsA nephrotoxicity. No patient was taken off CsA for progressive nephrotoxicity. We conclude that trough serum CsA levels of 50-75 ng/ml, as measured by radioimmunoassay, are sufficient to maintain effective immunosuppression in the long-term management of primary cadaveric renal transplant recipients. These values are much lower than previously recommended, and this approach ameliorates chronic CsA nephrotoxicity.