Renal effects of long-term treatment with 5-aminosalicylic acid

BACKGROUND:

A number of case reports link the use of 5-aminosalicylic acid (5-ASA) to interstitial nephritis in patients with inflammatory bowel disease (IBD).

OBJECTIVE:

To investigate whether the long-term use of 5-ASA has harmful effects on renal function in patients with IBD.

METHODS:

A retrospective analysis of 171 consecutive outpatients with Crohn’s disease or ulcerative colitis was conducted. Serum creati-nine levels and body weight were measured before and after treatment to calculate the creatinine clearance (CrCl) rate.

RESULTS:

In 171 patients (93 women, 78 men), the mean (± SD) dose of 5-ASA was 3.65±0.85 g/day with a cumulative dose of 11±7.7 kg over an interval of 8.4±5.9 years. Serum creatinine concentrations increased from 76.8 μmol/L to 88.7 μmol/L (n=171; P<0.0001) and the CrCl rate fell significantly from 104.6 mL/min to 93.1 mL/min (n=81; P<0.0001). There was one case of interstitial nephritis reported. Treatment groups included mesalamine (74.3%), sulfasalazine (15.2%) and combination (sulfalsalazine/mesalamine [10.5%]) with treatment durations of 7.2±4.5, 12.3±8.7 and 11.2±6.7 years, respectively. The duration of treatment was the most important covariate for change in CrCl and when analyzed by treatment group, those treated with sulfasazine had a strong correlation (r=−0.54, P=0.0145), while nonsignificant in the mesalamine group (r=0.06, P=0.7017). The decline in CrCl was negatively correlated with the pretreatment CrCl rate (r=−0.34; P=0.0024) and positively correlated with the mean daily dose of 5-ASA (r=0.32; P=0.0034).

CONCLUSION:

The present study is the first to demonstrate a significant dose- and treatment duration-dependant decline in CrCl. The risks need to be further evaluated because 5-ASA is widely used for long-term maintenance therapy in patients with IBD.     

5-Aminosalicylates and renal function in inflammatory bowel disease: a systematic review

Nephrotoxicity has been described in some patients with inflammatory bowel disease (IBD) treated with 5-aminosalicylic acid (5-ASA). Studies with 5-ASA treatment in which serum creatinine or creatinine clearance was measured regularly show that nephrotoxicity is exceptional (mean rate of only 0.26% per patient-year). There have been several case reports, including 46 patients, of renal disease associated with 5-ASA treatment in patients with IBD. 5-ASA treatment-related nephrotoxicity is reported most often within the first 12 months, but also delayed presentation after several years has been shown. The absence of a clear relationship between 5-ASA dose and the risk of nephrotoxicity suggests that this complication is idiosyncratic rather than dose-related. Most of the patients with renal disease associated with 5-ASA treatment suffered interstitial nephritis, with symptoms and signs being nonspecific, which may delay detection for many months. The nephrotoxicity potential of mesalazine and sulfasalazine seems to be similar. The risk with different oral preparations of 5-ASA is probably too small to influence the choice of agent. Mesalazine should be withdrawn when renal impairment manifests in a patient with IBD; if this does not result in a fall in serum creatinine, then renal biopsy should be considered. A trial of high-dose steroid may be recommended in patients whose renal function does not respond to drug withdrawal. The optimal monitoring schedule of serum creatinine in patients receiving 5-ASA treatment remains to be established, as there is no evidence to date that either the test, or the frequency of testing, improves patient outcomes.     

Chronic interstitial nephritis induced by 5-aminosalicylic acid: a new case report

5-aminosalicylic acid (5-ASA) used for the treatment of inflammatory bowel disease is known to induce chronic interstitial nephritis (CIN). However, the frequency of occurrence and the spectrum of severity of 5-ASA-induced CIN are not known. In this paper, we report a new case of CIN induced by 5-ASA in a patient treated for about 7 years for a Crohn disease. After that 5-ASA was discontinued and prednisone therapy started, renal function improved partially. About 30 observations of CIN induced by the use of 5-ASA in patients treated for inflammatory bowel disease have already been published. None were published in patients treated for other diseases such as arthritis rheumatism. The review of the literature suggests that the prognosis is poor and correlates with the duration of treatment, the cumulative dose and the level of renal impairment at diagnostic. We believe that the control of the renal function in patients treated by 5-ASA must be regular and prolonged.     

Interstitial nephritis in patients with inflammatory bowel disease treated with mesalamine

Mesalamines are slow-release formulations of 5-aminosalicylic acid (5-ASA) and are effective as primary treatment and maintenance therapy in inflammatory bowel disease. Interstitial nephritis is a recognized side effect. We report two cases of biopsy-confirmed interstitial nephritis in patients being treated with 5-ASA. Both had a trial of steroid therapy. One patient had partial recovery of renal function but the other patient was in chronic renal failure and likely was approaching the need for dialysis. Interstitial nephritis is an under-recognized complication of 5-ASA therapy. Early identification and withdrawal of this drug can lead to a partial or complete reversal of renal dysfunction.     

Outcome and prognostic indicators of diffuse proliferative lupus glomerulonephritis treated with sequential oral cyclophosphamide and azathioprine

OBJECTIVE: To study the outcome and prognostic indicators of diffuse proliferative glomerulonephritis (DPGN) in patients with systemic lupus erythematosus (SLE) treated with sequential oral cyclophosphamide (CYC) and azathioprine (AZA). METHODS: SLE patients with biopsy-proven DPGN treated with sequential oral CYC and AZA were studied. Those who achieved renal remission at 12 months were identified, and the clinical predictors of complete remission were evaluated by regression analysis. All patients were followed up until a relapse of the nephritis or a doubling of the serum creatinine level occurred. The timing and risk factors for flares and creatinine doubling were evaluated by Kaplan-Meier analysis and with the Cox proportional hazards model. RESULTS: We studied 55 patients (47 women, 8 men; mean +/- SD age at renal biopsy 31.1 +/- 10.4 years); 25 (46%) had a serum creatinine level >106 micromoles/liter, and 29 (53%) had nephrotic syndrome. At 12 months posttreatment, 37 (67%) had complete remission and 12 (22%) had partial remission. The initial serum creatinine level was an independent predictor of complete remission. Excluding the 4 patients who were treatment- resistant or died, 21 patients (41%) had renal flares during a median followup of 4 years. The cumulative risk of renal flare was 6% at 1 year, 21% at 3 years, and 32% at 5 years. The median time to relapse was 43 months. The histologic activity score and the mean daily dose of CYC were multivariate predictors of renal flare, by Cox regression. At the last followup visit, 9 of 54 patients (17%) had a doubling of the creatinine level, 6 of whom (11%) underwent dialysis. The cumulative risk of creatinine doubling was 8.4% at 5 years and 18.2% at 10 years. An increasing chronicity index at the time of initial renal biopsy was an independent predictor of deterioration in renal function. CONCLUSION: Sequential therapy with oral CYC followed by AZA appears to be an effective treatment regimen for DPGN in patients with SLE, with 89% of patients achieving complete or partial remission at 12 months, 62.8% remaining in remission after 5 years, and 81.8% having stable renal function after 10 years. Predictors of treatment resistance and relapse include increasing serum creatinine level, higher histologic activity scores, and a lower dose of CYC. Increasing chronicity indices predict a deterioration of renal function.     

Mesalazine induced interstitial nephritis.

5-Aminosalicylic acid (5-ASA) has structural similarities to both phenacetin and aspirin, which are known to cause 'analgesic nephropathy'. Because of the increasing use of 5-ASA, this paper draws attention to two cases of severe interstitial nephritis resulting from 5-ASA and emphasises the importance of monitoring renal functions of patients with inflammatory bowel diseases who are receiving 5-ASA preparations.     

Renal function and blood pressure in patients receiving long-term, low-dose cyclosporine therapy for idiopathic autoimmune uveitis.

OBJECTIVE: To determine the renal side effects of long-term, low-dose cyclosporine therapy (initial dose, 5 mg/kg body weight per day) in patients with autoimmune idiopathic uvetis. DESIGN: Cohort study with at least 2 years of follow-up. SETTING: A teaching hospital in Paris, France (H?pital Pitié-Salpétrière). PATIENTS: Sixteen patients with idiopathic autoimmune uveitis who were normotensive and had normal renal function before treatment. Cyclosporine was administered orally for at least 2 years at an initial dosage of 5 mg/kg body weight per day. RESULTS: After 2 years of treatment, the serum creatinine level increased by 35 +/- 5 mumol/L (0.40 +/- 0.06 mg/dL) (95% CI, 25 to 46 mumol/L, [73 +/- 4 to 108 +/- 4 mumol/L]). Creatinine clearance decreased significantly from 120 +/- 5 mL/min to 75 +/- 4 mL/min. Glomerular filtration rate decreased from 116 +/- 8 mL/min to 75 +/- 3 mL/min, and effective renal plasma flow decreased from 455 +/- 24 mL/min to 338 +/- 30 mL/min (P less than 0.05). Cyclosporine induced a significant increase in serum uric acid, total cholesterol, and serum potassium levels. Blood pressure was normal in all patients before treatment; 81% (95% CI, 64% to 98%) of these patients developed hypertension after 24 months of treatment. Blood pressure was controlled with a single drug in all but two patients. CONCLUSIONS: In patients with healthy native kidneys, long-term cyclosporine therapy, even at a low dose (5 mg/kg per day), is nephrotoxic and is associated with a high incidence of hypertension.     

Chromium-51 ethylenediamine tetraacetic acid glomerular filtration rate: a better predictor than glomerular filtration rate calculated by the Cockcroft-Gault formula for renal involvement in systemic lupus erythematosus patients

OBJECTIVE: To investigate whether the ethylenediamine tetraacetic acid (EDTA) glomerular filtration rate (GFR) is a better indicator of the degree of renal involvement than serum creatinine concentration or creatinine clearance calculated by the Cockroft-Gault formula. METHODS: We studied prospectively all systemic lupus erythematosus (SLE) patients with normal or borderline serum creatinine concentration (<110 micromol/l) and urinary sediment abnormalities and/or proteinuria in the last 2 yr. EDTA-GFR, serum creatinine concentration, calculated creatinine clearance (Cockroft-Gault formula) and 24-h urine protein were determined at the same time. Renal biopsies were performed in patients with low values of EDTA-GFR or significant proteinuria. RESULTS: Twenty-three patients were identified, of whom 22 were females. The average age of the patients was 31.6+/-8.2 yr. Biopsies were assigned to WHO classes as follows: class II, 1 patient; class III, 6 patients; class IV, 10 patients; class V, 6 patients. The average serum creatinine concentration, EDTA-GFR and calculated creatinine clearance were 79.8+/-mol/l, 74.5 ml/min and 97 ml/min respectively. EDTA-GFR showed abnormal values (<80 ml/min) in 15 of the 23 patients (65.2%) while calculated creatinine clearance was abnormal (<80 ml/min) in three of the 23 patients (13%) (P<0.001). Using the Pearson correlation test, we did not find any correlation between EDTA-GFR or creatinine clearance values and the sum of activity and chronicity indices. CONCLUSION: GFR performed by EDTA-GFR correctly predicted renal involvement in SLE patients, whereas GFR calculated by the Cockcroft-Gault formula may have underestimated renal function. Significant numbers of patients with WHO class III, IV or V lupus nephritis may be missed if biochemical creatinine clearance or serum creatinine concentration alone is used to assess renal disease.     

Pretransplant renal function predicts survival in patients undergoing orthotopic liver transplantation

The objective of this study was to determine the impact of pretransplant renal function on graft and patient survival rates after orthotopic liver transplantation (OLT) using the United Network for Organ Sharing (UNOS) database for adults who underwent OLT between 1988 and 1996. Based on calculated creatinine clearance (CCr) at the time of OLT, patients were classified arbitrarily into those with normal renal function (>70 mL/min) and mild (40-69.9 mL/min), moderate (20-39.9 mL/min), and severe (<20 mL/min) renal insufficiency. Of the 20,281 patients who underwent transplantation, complete data were available for 19,261 patients. Of these, 12,778 (67%) had normal CCr (mean, 118 +/- 50 mL/min) and 4,419 (22%) had mild (56 +/- 8.5 mL/min), 1,560 (8%) had moderate (30 +/- 5.7 mL/min), and 504 (3%) had severe (14 +/- 3.6 mL/min) renal failure. UNOS status 1 was more common in patients with moderate and severe renal failure. Primary graft nonfunction and 30-day mortality rates were higher and 1-, 2-, and 5-year graft and patient survival rates were lower in patients with moderate or severe renal failure. Multiple regression analysis showed that renal failure was an independent predictor of 30-day and 2-year mortality after adjusting for the recipient's age, sex, etiology of liver disease, diabetes status, body mass index, cold ischemic time, and UNOS status. CCr less than 40 mL/min was associated with significantly lower short-term and long-term graft and patient survival rates. In conclusion, our findings suggest that when Mayo End-Stage Liver Disease (MELD) score is used to prioritize organ allocation, lower-than-expected graft and patient survival rates may be seen.     

Monitoring of tinzaparin in a ten day treatment dose in elderly patients

PURPOSE: Renal impairment, which is frequently observed in elderly patients, raises the question of low molecular weight heparins treatment dose adjustment in this population. Thus, we conducted a prospective study to determine whether tinzaparin, administered subcutaneously at treatment dose (175 anti-Xa IU/kg) once daily for 10 days, does accumulate in patients older than 70 years of age. METHODS: Accumulation criteria were an increase of plasma anti-Xa and anti-IIa levels determined prior to the first injection and on days 2, 5, 7 and 10. The characteristics of the 30 consecutive included patients receiving tinzaparin at treatment dose (six men, 24 women) were: age 87.0 +/- 5.9 years (range: 71-96 years), body weight: 62.7 +/- 14.6 kg (range: 38-90 kg) and creatinine clearance 40.6 +/- 15.3 mL/min (range: 20-72 mL/min). RESULTS: None of the patients required a dose adjustment of tinzaparin over the 10-day treatment period. Anti-Xa and anti-IIa activity levels on day 2 were 0.66 +/- 0.20 IU/mL (range: 0.26-1.04 IU/mL) and 0.33 +/- 0.10 IU/mL (range: 0.18-0.55 IU/mL), respectively. These levels did not significantly change over the 10 days. These results favor the absence of the accumulation effect of tinzaparin. There was no correlation between anti-Xa and anti-IIa activities and age, weight, or creatinine clearance. Concerning the side-effects, only one minor hematoma at the injection site was reported. CONCLUSION: Tinzaparin may thus be administered in older patients with renal impairment, at a treatment dose (175 anti-Xa IU/kg/d) for a 10-day treatment period, without accumulation effect nor hemorrhagic side-effect in patients with creatinine clearance greater than 20 mL/min.     

Allopurinol-induced chronic granulomatous interstitial nephritis

Although drug induced interstitial nephritis is a relatively common cause of renal failure,granulomatous forms remain a rare condition. The development of a chronic granulomatous interstitial nephritis due to allopurinol is exceptional, only three cases have been described previously. We report on a patient who presented a granulomatous interstitial nephritis after 10 years of allopurinol administration (300 mg/day). At diagnosis, he had end stage renal disease and dialysis treatment was needed. Two months after drug withdrawal and on corticoid treatment a slow recovery of renal function was observed, allowing the interruption of dialysis. Two years after, the creatinine clearance is 23 ml/min,being dialysis free. We discuss the differential diagnosis of granulomatous interstitial nephritis and its rare association with allopurinol treatment.     

Serum cystatin C concentration compared with other markers of glomerular filtration rate in the old old

OBJECTIVES: To assess serum cystatin C, compared with other markers of renal function, as a marker of renal function in the old old (aged 85 and older). DESIGN: A cross-sectional analysis of data obtained in medically stable people aged 70 and older in a geriatric ward at a university hospital. SETTING: University hospital in Belgium. PARTICIPANTS: Forty-eight patients (17 men, 31 women) mean age +/- standard deviation 84.4 +/- 6.3 without acute illness or overt malignancy 7 days after admission were included. Twenty-five patients were aged 85 and older. MEASUREMENTS: Blood samples and 24-hour urine collections were obtained from each patient to determine serum creatinine, serum cystatin C levels, serum albumin, and creatinine clearance. Glomerular filtration rate (GFR) was estimated using the Cockcroft-Gault formula and the Modification of Diet in Renal Study Group (MDRD) formula. On the same day, clearance of 51chromium ethylenediamine tetraacetic acid was performed in all patients as the criterion standard of GFR. RESULTS: Serum creatinine (r=0.68), serum cystatin C (r=0.62), urinary creatinine clearance (r=0.57), the Cockcroft-Gault formula (r=0.82), and the MDRD-formula (r=0.65) correlated significantly with GFR (P <.0001). Regression analysis showed that serum cystatin C and serum creatinine were comparable markers of renal function (Y=0.442 +/- 0.007 x GFR and Y=0.494 +/- 0.01 x GFR respectively). Receiver operating characteristic analysis showed a similar area under the curve for serum cystatin C and serum creatinine (P=.5) in detecting renal impairment (GFR <80 mL/min). The Cockcroft-Gault formula provides a good estimation of GFR when the GFR is less than 60 mL/min (Y=1.11 +/- 1.04 x GFR). When the GFR is greater than 60 mL/min, the Cockcroft-Gault formula underestimates GFR (Y=11.01 +/- 0.66 x GFR). In patients aged 85 and older, a slight decrease in GFR (51.8 +/- 21.3 mL/min vs 65.2 +/- 34.3 mL/min in patients aged 70-84; P=.10) is observed. This is reflected by a nonsignificant increase in serum cystatin C (P=.06), whereas serum creatinine is identical in both groups (P=.88). CONCLUSION: Serum cystatin C, serum creatinine, the Cockcroft-Gault formula, the MDRD formula, and urinary creatinine clearance are comparable markers of renal function in the overall older population. The Cockcroft-Gault formula underestimates renal function in older people with GFR greater than 60 mL/min. In our study, serum cystatin C was not superior to serum creatinine in the detection of renal impairment.     

Amylase-creatinine clearance ratio. A simple test to predict gentamicin nephrotoxicity

The initial target of aminoglycoside nephrotoxicity is the proximal tubule. Yet, no simple test is available to predict such toxicity. Taking advantage of the fact that amylase is filtered in the glomerulus and reabsorbed by the proximal tubules, we prospectively examined in 23 patients if changes in renal amylase creatinine clearance ratio (ACCR) can predict gentamicin nephrotoxicity. Eighteen of these patients had an initial creatinine clearance (rCcr) above 30 mL/min. Eleven of them (group A) had an ACCR above 3.5% (control 3% +/- 1.03%) and all exhibited an average reduction of 32.2% +/- 11.6% in rCcr following one week of gentamicin therapy. In contrast, only one of seven patients (group B) with an initial ACCR below 3.5% had a reduction, albeit transient, in rCcr. During gentamicin therapy, group A patients had a further increase in ACCR which was proportional to the reduction observed in rCcr (r = -.54). Our preliminary data suggest that ACCR may prove a simple and possibly a reliable predictor of kidney function deterioration during gentamicin therapy in patients with rCcr above 30 mL/min: patients with pretherapy ACCR above 3.5% may exhibit a deterioration in the creatinine clearance during the first week of therapy. For patients with pretherapy renal failure (rCcr less than 30 mL/min) the creatinine levels (but not the ACCR) seem to retain their significance in predicting and monitoring further renal function deterioration during aminoglycoside therapy.     

Utility of cystatin-C in hospitalized patients. Comparing with different methods of assessing renal function

Serum creatinine is the most widely use parameter to assessing renal function, even though limitations, some time is necessary measure 24 h creatinine clearance (CLcr), or estimate Cockroft-Gault (C-G) or MDRD formulas. Different methods can offer different results, and cause confusion in clinicians. Using Cystatin-C as new parameter of renal function could suppose an important improvement. The objective of our study was to compare the different methods from renal evaluation and establish the utility of cistatina-C in the hospital area. In the study were included 70 patients (44 men) selected of random way, predominate patients with kidney disease and diabetics, which was made CLcr and calculated C-G and MDRD formulas. The mean age of the patients was 66+/-14 years, mean weight 73+/-17 Kg, creatinine 2,14+/-1,77 mg/dL, cystatin-c 1,77+/-1,18 mg/L, CLcr 54,39+/-36,2 mL/min. The correlation of 1/Crea with the Clcr, C-G and MDRD formulas was respectively: 0,7735, 0.8269 and 0.9613, (p< 0.0001). The correlation of 1/Cist with the Clcr, C-G and MDRD was respectively: 0,836, 0.8142 and 0.832, (p<0,0001). By Bland-Altman graphs the average of the difference between CLcr with CG and MDRD was 2,8 mL/min and -1,5 mL/min respectively. Comparing CG with MDRD was 1,7 mL/min. The average of the observed absolute differences between CLcr with CG and MDRD was 13.5 mL/min and 17.1 mL/min respectively. Between this formulas the average was 12.5 mL/min. Statistically significant differences between the different methods from renal evaluation do not exist (p>0,05). In conclusion, most of the urine collections could be avoided with the use of the formulas. Cystatin-c is far beyond the creatinine, mainly to detect slight renal alteration (sensitivity 80,4% U.S. 44,7% in men) becoming a promising alternative, that could reduce considerably hidden renal insufficiency (non detected by creatinine), although more studies are needed to confirm.     

Creatinine clearance and contrast nephropathy in patients with normal creatinine levels

The main risk factor for contrast nephropathy is the presence of poor renal function. Plasma creatinine level is not a reliable measure of renal function as its value could lie within the normal range despite the presence of significant nephropathy. The purpose of this study was to evaluate the creatinine clearance rate as a predictor of contrast nephropathy in patients with a normal plasma creatinine level. The study included 273 consecutive patients with non-ST elevation acute coronary syndrome (NSTEACS) and a normal plasma creatinine level at admission who underwent coronary angiography. Patients who developed contrast nephropathy had a lower creatinine clearance rate at admission (66.3 mL/min vs. 83.4 mL/min; P<.001). A creatinine clearance rate < 80 mL/min had a sensitivity of 81% for predicting contrast nephropathy. Creatinine clearance should be measured routinely in patients with NSTEACS who are scheduled for coronary angiography.     

Management of corticosteroid-dependent eosinophilic interstitial nephritis: A case report

Introduction:Drug-induced acute interstitial nephritis (DI-AIN) is an important cause of acute kidney injury. In renal biopsy specimens, tubulitis with eosinophilic infiltration is suggestive of DI-AIN. Although corticosteroid therapy and discontinuation of the offending drug can improve renal dysfunction in most cases of DI-AIN, some patients experience AIN recurrence, leading to corticosteroid dependency. Corticosteroid-dependent eosinophilic interstitial nephritis presents a difficult dilemma in diagnosis and information regarding optimum management is limited.Patient concerns:A 25-year-old man, who received treatment with carbamazepine, zonisamide, valproate, and lacosamide for temporal lobe epilepsy, showed an increase in serum creatinine level from 0.98 to 1.29 mg/dL over a period of 6 months. Although he exhibited no symptoms, his serum creatinine level continued to increase to 1.74 mg/dL.Diagnosis:Renal biopsy revealed tubulitis and interstitial inflammatory infiltrates with eosinophils. Immunological and ophthalmological examinations showed no abnormal findings, and thus, his renal dysfunction was presumed to be caused by DI-AIN. Although oral prednisolone (PSL) administration (40 mg/d) and discontinuation of zonisamide immediately improved his renal function, AIN recurred 10 months later. The increase in PSL dose along with discontinuation of valproate and lacosamide improved renal function. However, 10 months later, recurrent AIN with eosinophilic infiltration was confirmed by further biopsy. The patient was therefore diagnosed with corticosteroid-dependent eosinophilic interstitial nephritis.Interventions:To prevent life-threatening epilepsy, carbamazepine could not be discontinued; hence, he was treated with an increased dose of PSL (60 mg/d) and 1500 mg/d of mycophenolate mofetil (MMF).Outcomes:MMF was well tolerated and PSL was successfully tapered to 5 mg/d; renal function stabilized over a 20-month period.Lessons:The presence of underdetermined autoimmune processes and difficulties in discontinuing the putative offending drug discontinuation are contributing factors to corticosteroid dependency in patients with eosinophilic interstitial nephritis. MMF may be beneficial in the management of corticosteroid-dependent eosinophilic interstitial nephritis by reducing the adverse effects related to high-dose and long-term corticosteroid use.     

Drug dosage in patients with renal failure optimized by immediate concurrent feedback

OBJECTIVE: To examine the impact of immediate concurrent feedback on dose adjustment in patients with renal failure. DESIGN: Prospective 12-month study in patients with various degrees of renal failure, with comparison to a retrospective control group. SETTING: A 39-bed unit of a university hospital providing primary and tertiary care. PATIENTS: Patients with renal failure (estimated creatinine clearance < or = 50 mL/min) receiving at least 1 pharmacologically active drug. INTERVENTIONS: Education of physicians and immediate concurrent feedback on the ward giving estimated creatinine clearance and dose recommendations for renally eliminated drugs adjusted to individual renal function. MEASUREMENTS AND MAIN RESULTS: The percentage of dosage regimens adjusted to renal function and cost assessment of drug therapy were calculated. Overall, 17% of the patients had at least 1 estimated creatinine clearance < or = 50 mL/min. In the intervention group, the dose of 81% of renally eliminated drugs was adjusted to renal function, compared with 33% in the control group ( P <.001). The mean difference in cost between standard and adjusted dose of renally eliminated drugs in the intervention and control groups was 5.3 +/- 12.3 and 0.75 +/- 2.8 Swiss francs (approximately US$3.5 and US$0.5), respectively ( P <.001), accounting for 16.5% and 2.8%, respectively, of daily medication costs of all drugs. CONCLUSIONS: The proportion of doses of renally eliminated drugs adjusted to renal function can be substantially increased by immediate concurrent feedback. This saves drug costs and has the potential to prevent adverse drug reactions.     

Estimating renal function in lupus nephritis: comparison of the Modification of Diet in Renal Disease and Cockcroft Gault equations

Estimates of renal function are widely used in clinical practice and research. We assessed the performance of the Cockcroft-Gault (CG) and the Modification of Diet in Renal Disease (MDRD) equations in lupus nephritis patients. Data from ninety-seven lupus nephritis patients in the Hopkins Lupus Cohort were reviewed. Two renal function estimates, the CG and the MDRD, were compared with the 24 h creatinine clearance (CrCl). In the entire group of patients, the CG and MDRD equations had good global agreement with CrCl (R-square = 0.91 and 0.69, respectively). On average the CG equation overestimated CrCl by 2.36 mL/min/1.73 m(2), whereas the MDRD equation underestimated CrCl by 5.85 mL/min/1.73 m(2), P = 0.0004. The CG equation had greater accuracy (mean squared error) than the MDRD equation (14.93 versus 28.47 mL/min/1.73 m(2), P = 0.002) when predicting CrCl. Although both equations lacked precision (standard deviation of the difference scores) in patients with CrCl > or = 60 mL/min/1.73 m(2), the CG equation was more precise than the MDRD equation in this group, (15.68 versus 29.58 mL/min/1.73 m(2), P = 0.003). In lupus nephritis patients, the CG equation was superior to the MDRD equation as an estimate of CrCl. However, both equations lacked precision in patients with CrCl > or = 60 mL/min/1.73 m(2).     

Acute interstitial nephritis due to methicillin

Fourteen patients are described with a syndrome of methicillin-induced interstitial nephritis. In all patients severe renal dysfunction developed with an average peak serum creatinine of 8 mg/100 ml. An increased total peripheral eosinophil count was found in all patients. All patients had sterile pyuria and each of nine patients studied by Wright's stain of urine sediment had marked eosinophiluria. These findings are suggestive of methicillin-induced interstitial nephritis, although proteinuria was a variable finding in our patients. Eight of 14 patients in our study received prednisone therapy for their interstitial nephritis, and the time lapse between maximal and final base line serum creatinine levels was statistically less in the prednisone-treated compared to the nontreated groups. Clinical manifestations of this syndrome are discussed, and the light and electron microscopic and immunofluorescent findings on renal biopsy are described.