Prostaglandin E1: a new agent for the prevention of renal dysfunction in high risk patients caused by radiocontrast media? PGE1 Study Group.

BACKGROUND: Acute renal failure following the administration of radiocontrast media (RCM) is a complication found especially in patients with impaired renal function. Within the limits of a pilot study, the objective was to (a) show the effectiveness and compatibility of prostaglandin E(1) (PGE(1)=Alprostadil) in preventing acute renal failure in patients with elevated levels of serum creatinine and (b) to identify the most appropriate PGE(1)-dose. METHODS: 130 patients with renal impairment (serum creatinine >/=1.5 mg/dl) were included in the study prior to intravascular RCM injection. The patients received one of three different doses of PGE(1) (10, 20, or 40 ng/kg bodyweight/min) or placebo (physiologic sodium chloride solution) intravenously over a time period of 6 h (beginning 1 h prior to RCM application). Serum creatinine was measured 12, 24, and 48 h post RCM-application and creatinine clearance was determined with two 12 h collection periods, as well as one 24 h collection within 48 h post RCM administration. Adverse events during PGE(1) administration were recorded. RESULTS: In the placebo group, the mean elevation of serum creatinine was markedly higher (0.72 mg/dl) 48 h after RCM administration compared with the three PGE(1) groups (0.3 mg/dl in the 10 ng/kg/min group, 0. 12 mg in the 20 ng/kg/min group, and 0.29 mg/dl in the 40 ng/kg/min group). No clinically relevant changes were seen regarding the creatinine clearance in the four groups examined. CONCLUSIONS: Results from this pilot-study suggest that intravenous PGE(1) may be used efficaciously and safely to prevent RCM-induced renal dysfunction in patients with pre-existing impaired renal function.     

Nephrotoxicity with cyclooxygenase 2 inhibitor use in children

The nephrotoxic potential of anti-inflammatory drugs alone and in compound preparations has been known for over fifty years. Nephrotoxicity associated with selective cyclooxygenase 2 (COX-2) inhibitor use is reported in adult patients but not in children. We present here the first report of reversible acute renal failure associated with the COX-2 inhibitor rofecoxib (Vioxx) in three children. Patient 1, an 18 month old girl with neonatal Bartter syndrome, developed acute renal failure with a peak creatinine of 1.9 mg/dl (164 μmol/l) and severe hyperkalemic metabolic acidosis. Patient 2, a 14 year old boy with a history of rheumatic fever, developed acute renal failure with a peak creatinine of 2.7 mg/dl (240 μmol/l). While patient 3, a healthy 14 year old girl, developed acute renal failure and tubulointerstitial nephritis confirmed on renal biopsy with a peak creatinine of 3.3 mg/dl (287 μmol/L). All children had been taking non-selective non-steroidal anti-inflammatory drugs (NSAID’s) immediately prior to rofecoxib use. Renal function returned to normal within one week in all three patients and has remained normal at follow-up. This paper highlights the nephrotoxic risk of COX-2 inhibitor use in the pediatric population.     

Risk factors in idiopathic renal vasculitis and glomerulonephritis

In this retrospective study, we analyzed clinical laboratory, and pathologic variables to determine their value in predicting survival and survival free of renal failure for 170 consecutive patients with idiopathic renal vasculitis and glomerulonephritis evaluated during a 15 year period. Of the 170 patients, 108 had focal segmental necrotizing glomerulonephritis alone (FSNGN), 33 had FSNGN and small-artery vasculitis, and 29 had FSNGN and medium-sized artery vasculitis. Considerable overlap of clinical, laboratory, and pathologic findings existed among the three groups. Overall patient survival was 81% at one year, 61% at five years, and 44% at ten years, significantly less than expected survival. Overall survival free of renal failure, by definition, was lower than patient survival. There were no differences among these three groups in patient survival or survival free of renal failure. Multivariate analysis identified leukocytosis and serum creatinine level as independent predictors of patient survival and survival free of renal failure. In addition, univariate analysis identified age and hypertension as significant risk factors but did not add independent predictive value for these two end points. In patients with serum creatinine levels less than 4 mg/dl, the effect of increasing levels of leukocyte count was significantly associated with poorer outcomes for both patient survival (P = 0.006) and survival free of renal failure (P = 0.024). Outcomes for these two end points were worse for patients with lower serum creatinine levels (less than 4.0 mg/dl) and high leukocyte counts (greater than 16,000/mm3) than for those with serum creatinine levels greater than or equal to 4.0 mg/dl.     

Are small changes in serum creatinine an important risk factor?

PURPOSE OF REVIEW: Serum creatinine levels are strongly associated with longitudinal risk for cardiovascular disease and mortality. Recent studies addressed whether worsening renal function - defined by small increases in creatinine - is independently associated with adverse outcomes. This review evaluates the recent literature on worsened renal function as an independent risk factor. RECENT FINDINGS: Studies have evaluated worsening renal function as a predictor of cardiovascular outcomes and mortality in three settings: cardiac surgery patients, hospitalized heart failure patients, and ambulatory coronary artery disease patients. Small creatinine changes following cardiac surgery were strongly associated with mortality risk. One study found a J-shaped association between 48 h post surgery creatinine change and 30-day mortality risk. Compared with patients with creatinine decreases of 0-0.3 mg/dl, patients with creatinine increases less than 0.5 mg/dl had a twofold adjusted mortality risk and those with creatinine increases of at least 0.5 mg/dl had a nearly sixfold mortality risk; surprisingly those with decreases over 0.3 mg/dl had a twofold adjusted risk. Worsening renal function was also a strong predictor of mortality for hospitalized heart failure patients independent of baseline creatinine; the magnitude of creatinine rise appeared to be linearly associated with mortality risk. However, one study found no independent association between worsening renal function and cardiovascular or mortality risk over longer follow-up. SUMMARY: Acute elevations in serum creatinine had a linear association with increased risk for adverse outcomes among patients hospitalized for cardiac surgery or heart failure. Future studies should determine interventions to prevent and treat in-hospital worsening renal function to reduce the risk for adverse outcomes.     

Abdominal aortic aneurysm repair in patients with preoperative renal failure

The purpose of this study was to determine the effect of preoperative renal failure on the outcome of patients undergoing infrarenal abdominal aortic aneurysm (AAA) repair. Of 251 patients undergoing AAA repair from 1977 to 1984, 10% had evidence of preoperative chronic renal failure. These patients were classified according to their preoperative serum creatinine values; group I had preoperative creatinine levels of 2 to 4 mg/dl, group II had creatinine levels greater than 4 mg/dl but no history of hemodialysis, and group III consisted of patients on chronic hemodialysis before operation. One of 16 patients in group I developed transient high-output renal failure postoperatively. Four of the six patients in group II (67%) developed significant postoperative deterioration of renal function and required acute hemodialysis. Of the four patients in group III maintained on chronic hemodialysis preoperatively, one died of sepsis from an ischemic colon. This experience suggests that patients with mild renal dysfunction (serum creatine value less than 4 mg/dl) can undergo elective AAA repair without additional morbidity. Patients on hemodialysis before operation can also safely undergo surgical repair of their AAAs electively if dialyzed the day before operation. Patients with severe renal dysfunction (serum creatinine greater than 4 mg/dl) who are not on hemodialysis should be considered for dialysis preoperatively in an attempt to reduce the high incidence of serious postoperative renal functional deterioration and subsequent morbidity.     

How valuable for prognosis is the perioperative assessment of serum creatinine values with reference to postoperative renal complications in risk patients?

Renal function is not considered to be as important as cardiovascular or respiratory function during the perioperative period. Nevertheless, recent studies demonstrate a significant correlation between preoperative levels of creatinine and postoperative disturbances of kidney function. METHOD AND RESULTS: In a retrospective study 250 patients with the ASA physical status classification III and IV were investigated. All patients had a preoperative creatinine level greater than 1.0 mg/dl. For further investigations patients were divided into two groups; group I consisted of patients with preoperative creatinine level of 1.0-1.19 mg/dl; group II patients had preoperative creatinine levels greater than 1.2 mg/dl. Postoperatively these parameters were monitored on the 1st, 3rd and 5th days. A deterioration of renal function was seen postoperatively in all high risk patients (Tables 3, 4). Group II patients showed significant changes in kidney function on the 3rd and 5th postoperative days (p less than 0.005). During the study period the creatinine levels in this group did not return to normal values. In this group four patients suffered acute postoperative kidney failure, and two of these died. DISCUSSION AND CONCLUSION: In a recent study Hou et al. [5] could show that 5% of all patients suffer renal insufficiency during their hospital stay. Mortality for acquired renal failure is still 40-70%. The most important factor in the development of disturbances of kidney function is pre-existing kidney disease. The patients investigated in this study were high-risk patients. Cardiovascular complications during the perioperative phase are common, and hemodynamically mediated renal failure is the most frequent form of kidney failure.(ABSTRACT TRUNCATED AT 250 WORDS)     

Exacerbation of renal failure due to hypothyroidism in a patient with ischemic nephropathy

A case of acute-on-chronic renal failure in a 70-year-old woman with ischemic nephropathy and primary hypothyroidism is presented. Her renal function became progressively worse as the level of serum creatinine increased from 283 to 628 micromol/l (3.2-7.1 mg/dl) within 8 months. Her thyroid function had been normal before the exacerbation of renal failure, but it was markedly reduced with a marked elevation of serum thyroid-stimulating hormone. Thyroid hormone replacement therapy resulted in rapid improvement of the renal function to 159 micromol/l (1.8 mg/dl) of serum creatinine. The development of primary hypothyroidism seemed to worsen the already impaired renal function in this case. We suggest the assessment of thyroid function in patients with unexplained deterioration of renal failure.     

Acute renal failure secondary to oral ciprofloxacin therapy: a presentation of three cases and a review of the literature

The fluoroquinolones represent a new class of antimicrobial agents with a broad spectrum of activity. We report three cases of acute renal failure following ciprofloxacin in patients without a previous history of renal insufficiency. The average baseline creatinine was 1.1 mg/dl and rose to an average of 4.0 mg/dl during therapy. The length of antecedent ciprofloxacin therapy ranged from several days to several weeks. Other causes of acute renal failure and postobstructive uropathy were excluded. Kidney size was normal-to-increased. Gallium scans were positive in one of two patients studied. Peripheral eosinophilia developed in one case, suggesting an acute hypersensitivity reaction to the drug. The acute renal failure in all cases was non-oliguric and was completely reversed after discontinuation of ciprofloxacin. In two of the three reported cases there was an increased creatinine to BUN ratio, but increased production of creatinine (i.e., rhabdomyolysis) was unlikely with a normal serum creatinine phosphokinase (CPK). In addition, we performed in vitro studies which eliminated the possibility of methodological artifact. The nephrotoxicity of the quinolones has been linked to the development of crystalluria in experimental animals. However, in humans, crystalluria is unlikely and renal damage has not been noted. There have been only two previous case reports of acute renal failure due to oral ciprofloxacin therapy. In one, biopsy showed acute interstitial nephritis. We conclude that oral ciprofloxacin therapy may lead to acute renal failure secondary to tubulointerstitial nephritis characterized by an increased creatinine to BUN ratio. Patients placed on ciprofloxacin therapy need to be followed closely.     

Uninephrectomy does not potentiate contrast media nephrotoxicity in the streptozotocin-induced diabetic rat

We studied the effect of radiographic contrast media on renal function in both streptozotocin-induced diabetic rats and normoglycemic rats with reduced renal functional mass. Male Sprague-Dawley induced-diabetic rats and weight-matched controls were divided into unilaterally nephrectomized and intact groups prior to an intravenous challenge with sodium diatrizoate (Urografin) at two dose levels, 1,300 and 2,600 mg iodine/kg. Serum creatinine concentration did not change on the 1st and 3rd day after a dose of 1,300 mg/kg of iodine in normal or induced-diabetic rats. Consequent to a dose of 2,600 mg/kg of iodine, induced-diabetic rats had a significant increase in serum creatinine levels to 0.9 +/- 0.45 mg/dl (control 0.68 +/- 0.11 mg/dl). The observed increase in serum creatinine concentration after treatment with sodium diatrizoate was significantly correlated with the degree of hyperglycemia, but not with prior unilateral nephrectomy. Unilateral nephrectomy, prior to administration of sodium diatrizoate did not potentiate the risk of radiocontrast agent injury in induced-diabetic rats. From these findings, we infer that: (1) streptozotocin-induced diabetes in the rat confers a risk for the development of radiocontrast-induced acute renal failure and (2) as judged by the rise in serum creatinine concentration after exposure, there is an increased risk of acute renal failure associated with a higher dose of radiocontrast material.     

Renal function in burns

The present study evaluates the evolution of renal function parameters and serum electrolytes in 34 severely burned patients. The population was arbitrarily subdivided in a group with normal renal function (n = 24) and a group with acute renal failure (n = 10), defined by the fact that serum creatinine rose above 2.5 mg/dl at least once. The patient group with normal renal function was characterized by a normal to high creatinine clearance, reaching a consistent peak at day 2 of follow-up. Serum sodium and fractional sodium excretion were low. Further disturbances were a low serum protein, an early hypocalcemia and hypophosphatemia, and a discrete metabolic alkalosis. The patients developing acute renal failure maintained a low fractional sodium excretion. They were in general of older age and had more severe burns than the patients with normal renal function. The survival rate in the patients with acute renal failure was 30%, compared to 75% in the patients, who maintained normal renal function.     

Parturition in Six Renal Allograft Recipients

Between 1983 and 1994, we studied renal function and neonatal conditions for eight pregnancies and births to six women who had received renal transplants in order to assess the effect of an allograft on pregnancy and its outcome. The gestation period was 34 to 39 weeks (mean 36 weeks and 4 days), and four pregnancies ended before term. All eight babies were delivered by cesarean section. Intrauterine growth retardation (IUGR) was found in both babies of one woman who had been treated with conventional (without cyclosporin) immunosuppression. The serum creatinine level did not change during gestation in any of the women but was elevated after delivery in four. Four mothers suffered from proteinuria (25–364 mg/dl) during gestation, but the proteinuria disappeared after delivery in all but one case. The one exception, persistent proteinuria of 100–200 mg/dl, was assumed to result from the recurrence of the original renal disease (IgA nephropathy). The reduction of creatinine clearance and hydronephrosis of one graft noted during gestation were later reversed. None of the eight babies (four females and four males) was congenitally malformed, and their Apgar scores were 6 to 9 (median 8). They are now 3 months to 11 years old, and seven of them are healthy and show good growth. One of the two IUGR babies has not grown well; her weight and height are more than 1 SD below the mean for her age, and she is mentally retarded and suffers from muscle weakness. Compared with dialysis patients, female renal allograft recipients have a better quality of life because they can safely deliver a child if they observe the criteria for pregnancy established for renal allograft recipients.     

Successful pregnancy in a patient with medullary cystic disease and severe renal impairment

We present a successful pregnancy in a 37-year-old women with severe renal impairment due to medullary cystic disease. She presented five years earlier with hypertension and chronic renal failure with creatinine was 2.1 mg/dl (Ccr 35 ml/min). She had had two successful pregnancies in the past, nine and seven years earlier. Diagnosis of medullary cystic disease (MCD) was made based on typical ultrasound appearance, sodium wasting and acidosis out of the proportion to the degree of renal failure. Over the next 5 years, a slow progression of chronic renal failure was observed with creatinine reaching 5.1 mg/dl (Ccr 15,4 ml/min), shortly before she became pregnant in December 2001. Her hypertension remained well-controlled and serum creatinine decreased at the beginning of the second trimester to 3.7 mg/dl with subsequent increase toward the end of the pregnancy. She required increasing doses of erythropoietin and intravenous iron supplementation to maintain hemoglobin levels. The polyhydramnios developed necessitating five procedures of amnio reduction. She was not treated by dialysis. A boy weighing 1,600 g was delivered by cesarean section in the 35th week of gestation. The mother's creatinine rose to 5.2 mg/dl (Ccr 15 ml/min) post partum and her renal function declined only slightly over the next 20 months. Our report illustrates that successful fetal and maternal outcome can be achieved even in cases of advanced renal failure preceding gestation. It appears that the type of renal disease influences the pregnancy course and outcome and thus should be considered in patient counseling and therapeutic decisions.     

Acute phosphate nephropathy following oral sodium phosphate bowel purgative: an underrecognized cause of chronic renal failure

The findings of diffuse tubular injury with abundant tubular calcium phosphate deposits on renal biopsy are referred to as nephrocalcinosis, a condition typically associated with hypercalcemia. During the period from 2000 to 2004, 31 cases of nephrocalcinosis were identified among the 7349 native renal biopsies processed at Columbia University. Among the 31 patients, 21 presented with acute renal failure (ARF), were normocalcemic, and had a history of recent colonoscopy preceded by bowel cleansing with oral sodium phosphate solution (OSPS) or Visicol. Because the precipitant was OSPS rather than hypercalcemia, these cases are best termed acute phosphate nephropathy. The cohort of 21 patients with APhN was predominantly female (81.0%) and white (81.0%), with a mean age of 64.0 yr. Sixteen of the 21 patients had a history of hypertension, 14 (87.5%) of whom were receiving an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker. The mean baseline serum creatinine was 1.0 mg/dl, available within 4 mo of colonoscopy in 19 (90.5%) patients. Patients presented with ARF and a mean creatinine of 3.9 mg/dl at a median of 1 mo after colonoscopy. In a few patients, ARF was discovered within 3 d of colonoscopy, at which time hyperphosphatemia was documented. Patients had minimal proteinuria, normocalcemia, and bland urinary sediment. At follow-up (mean 16.7 mo), four patients had gone on to require permanent hemodialysis. The remaining 17 patients all have developed chronic renal insufficiency (mean serum creatinine, 2.4 mg/dl). Acute phosphate nephropathy is an underrecognized cause of acute and chronic renal failure. Potential etiologic factors include inadequate hydration (while receiving OSPS), increased patient age, a history of hypertension, and concurrent use of an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker.     

A randomized trial on the effect of mannitol on postoperative renal function in patients with obstructive jaundice

A randomized trial was undertaken to reassess the effectiveness of mannitol in preventing postoperative renal impairment in patients with obstructive jaundice. The study included 31 patients with obstructive jaundice (bilirubin, 3 mg/dl or higher) randomly allocated in two groups to receive (n = 17) or not receive (n = 14) preoperative mannitol. Sixty-five percent of patients had a creatinine clearance below 70 ml/min before surgery. Serum bilirubin and bacteribilia had no relation with preoperative renal function. No relation was found between serum bilirubin value and the percentage fall in postoperative creatinine clearance. Compared with the preoperative values, the postoperative creatinine clearance was significantly impaired in the mannitol group (p = 0.03) and remained almost unaltered in the no-mannitol group. Three patients (9.7%) died of acute renal failure; two were in the mannitol group and one was in the no-mannitol group. Serum fibrin degradation products were not sensitive markers for impending renal failure. There was no significant difference in postoperative serum sodium concentration or in the urinary sodium excretion. Administration of mannitol did not improve the postoperative renal function of jaundiced patients, nor did it prove beneficial in preventing renal failure. Our results suggest that severe disturbances of body-fluid compartments may be the basic mechanism underlying kidney dysfunction in obstructive jaundice and that further water depletion induced by mannitol may indeed prove detrimental.     

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.     

Fulminant meningococcemia and acute renal failure in a 3-year-old boy

Acute renal failure is a common occurrence in sepsis, but is rarely reported in meningococcemia. We present a young child diagnosed with fulminant meningococcemia who had several poor prognostic factors, including hypotension, thrombocytopenia, purpura fulminans, seizures, the absence of meningitis with meningococcemia, and acute renal failure, which was successfully treated with peritoneal dialysis. Peritoneal dialysis was started on the 5th day because the patient had been anuric for 48 h. At that time, analysis showed that the child was both hypokalemic and hypophosphatemic. His serum blood urea nitrogen was 61 mg/dl, creatinine 2.75 mg/dl, potassium 2.8 mEq/l, and phosphorus 0.7 mg/dl. Urine output began on the 12th day post admission and normalization of serum creatinine was achieved on the 26th day. In conclusion, renal failure is an important complication of meningococcemia and, to be effective, sometimes long-term peritoneal dialysis is required. Profound metabolic abnormalities, such as hypokalemia and hypophosphatemia, may occur paradoxically in the presence of oliguria.     

Renal sarcoidosis with normal serum vitamin D and refractory hypercalcemia

Introduction

Sarcoidosis is a multi-system disorder characterized by non-caseating epithelioid granulomas in multiple organs. Renal involvement may usually occur as granulomatous interstitial nephritis, but renal failure is uncommon. We report a case of renal-limited sarcoidosis diagnosed by renal biopsy, associated with abnormal calcium metabolism.

Case presentation

A 30-year-old Caucasian male presented with unexplained renal function impairment and hypercalcemia. The patient did not have any history of kidney disease, cough, skin rash, dysuria, hematuria or any other symptoms. Physical examination was unremarkable. Serum creatinine was 2.2 mg/dl and serum calcium was 11.5 mg/dl. Serum intact parathyroid hormone level (12 pg/mL) was decreased. Serum angiotensin-converting enzyme (ACE), 1,25-dihydroxyvitamin D (1,alpha-25 vit D) and pre-proparathyroid hormone (PTHrP) levels and urinary calcium excretion were all in normal range. The renal biopsy showed severe interstitial nephritis with non-caseating granuloma. The patient was treated with prednisone with starting dose of 1 mg/kg. After 2 months of prednisone therapy, serum creatinine decreased. However, because of continued of hypercalcemia unresponsive to low calcium diet and prednisone, chloroquine was prescribed. Six months after the onset, the patient's serum creatinine is stable at 1.30 mg/dl, serum calcium is 10.8 mg/dl, and serum ACE and 1,alpha-25 vit D levels are in normal range. He does not have any signs of extra-renal relapse.

Conclusion

The mechanisms of abnormal calcium metabolism in this patient with renal-limited sarcoidosis are unclear.     

Calcemic response to parathyroid hormone in renal failure: role of phosphorus and its effect on calcitriol.

The calcemic response to parathyroid hormone (PTH) is decreased in renal failure. The reduction of hyperphosphatemia improves the calcemic response to PTH in animals with advanced renal failure. However, since low calcitriol levels in renal failure may also contribute to the decreased calcemic response to PTH, the improved calcemic response observed during the reduction of serum phosphorus may be partially mediated by an increase in serum calcitriol levels. The present study evaluated the calcemic response to PTH in rats with moderate and advanced renal failure and how this response was modified by a high and a low phosphorus diet. In addition, the effect of a change in dietary phosphorus on calcitriol levels was also evaluated. A 48-hour continuous infusion of 1-34 rat PTH increased the serum calcium level to 18.2 +/- 0.4 mg/dl in normal rats, versus 13.7 +/- 0.9 and 12.1 +/- 0.2 mg/dl in rats with moderate and advanced renal failure, respectively. During the PTH infusion, a high phosphorus diet increased the serum phosphorus and resulted in a reduced calcemic response to PTH at each level of renal function; respective serum calcium levels were 13.8 +/- 0.6 mg/dl in normals, 11.2 +/- 0.2 mg/dl in moderate renal failure and 9.6 +/- 0.5 mg/dl in advanced renal failure. In normal rats and in rats with moderate renal failure, dietary phosphorus restriction during the PTH infusion increased serum calcitriol levels. In rats with advanced renal failure, serum calcitriol levels were lower than in the other two groups and were not affected by changes in dietary phosphorus.(ABSTRACT TRUNCATED AT 250 WORDS)     

Renal tubule function in beta-thalassemia after hematopoietic stem cell transplantation

Advances in hematopoietic stem cell transplantation (HSCT) for beta-thalassemia major make the long-term outcome of these patients very important. Few data on long-term renal function of thalassemia patients are available. We evaluated the renal function in children after successful allogeneic HSCT for beta-thalassemia. Twenty-nine patients were included; the mean age at HSCT was 4.9 years. Mean follow-up time was 7.6 years. After HSCT, two patients developed acute renal failure and two had graft versus host disease. At last follow up, height standard deviation score (SDS) remained the same, but weight SDS had improved. Mean hemoglobin was 12.5 g/dl, and serum ferritin level was 545 ng/ml. All children had normal estimated glomerular filtration rate (GFR). One patient had hypertension and proteinuria, 10 years after HSCT. When comparing 39 children of the same age with beta-thalassemia of similar disease severity but who had not experienced HSCT, we found that the parameters of renal tubule function were better in patients that had undergone HSCT, as demonstrated by urine protein level (0.36 mg/mg creatinine vs 3.03 mg/mg creatinine, P < 0.001), osmolality (712 mosmol/kg vs 573 mosmol/kg, P = 0.006), N-acetyl-beta-D: -glucosaminidase (17.7 U/g creatinine vs 42.9 U/g creatinine, P = 0.045), and beta 2 microglobulin (0.09 microg/mg creatinine vs 0.13 microg/mg creatinine, P = 0.029). This study showed a low incidence of long-term renal impairment after HSCT and indicated that renal tubule function may be better in beta-thalassemia patients after HSCT.     

Deterioration in renal function associated with fibrate therapy

BACKGROUND: Fibric acid derivatives (fibrates) are commonly used for the treatment of hyperlipidemia. A side-effect of these medications that is not well recognized is deterioration in renal function during therapy. This study reviewed a series of patients who showed such a deterioration. METHODS: The design was a retrospective chart review. Data extracted included creatinine, urea, cyclosporine levels, medical history, and medications. Charts were examined for other potential reasons for a change in creatinine. RESULTS: There were a total of 10 patients. All were males between the ages of 37 and 71. All had a history of renal insufficiency. Six had received a renal transplant and, of these, 5 were on cyclosporine. Reasons for underlying renal impairment included diabetes, hypertension, nephrosclerosis, and renal disease of unknown etiology. Most patients had risk factors for or the presence of vascular disease. The mean pre-treatment creatinine was 182 +/- 14 micromol/l (2.1 +/- 0.2 mg/dl) (mean +/- SE), compared to a peak creatinine on the medication of 247 +/- 16 micromol/l (2.8 +/- 0.2 mg/dl) (p < 0.001). The post-medication mean was 183 +/- 13 (2.1 +/- 0.1 mg/dl) (p < 0.001 vs maximum creatinine). Urea values also increased with therapy and decreased following discontinuation of the fibrate. Cyclosporine levels did not change with treatment. All recorded creatine kinase values were within the normal range. CONCLUSIONS: A group of 10 men showed a reversible deterioration in renal function while being treated with a fibrate for hyperlipidemia. The mechanism involved in the deterioration in renal function is not clear. The most plausible mechanism is one based on renal hemodynamics, given the rapid and complete reversibility that was noted and the finding that most patients had risk factors for vascular disease. If patients with pre-existing renal dysfunction are to receive a trial of fibrate therapy, this should be done with caution and