Significant Impairment Of Renal Function Research Articles

Associations Between Retinal Microvascular Abnormalities and Declining Renal Function in the Elderly Population: The Cardiovascular Health Study

Microvascular abnormalities in the kidney are common histopathologic findings in individuals with chronic kidney disease or renal failure. These abnormalities may represent one manifestation of ongoing systemic microvascular damage. We hypothesized that retinal microvascular abnormalities, when present, would be associated with progressive renal dysfunction in elderly individuals. The Cardiovascular Health Study (CHS) is a prospective, multicenter, cohort study initiated in 1989 designed to examine cardiovascular risk factors, morbidity, and mortality in elderly Americans. As part of an ancillary study, CHS participants underwent retinal photography in 1997 and 1998. Retinal microvascular abnormalities were assessed and graded by using standardized measures. Retinal microvascular abnormalities were defined as retinopathy (hard and soft exudates, hemorrhages, or microaneurysms) and/or retinal arteriolar abnormalities (arteriovenous nicking, focal arteriolar narrowing, or lowest quartile arteriole-venule ratio). Associations between these abnormalities and observed 4-year changes in serum creatinine levels and estimated glomerular filtration rates (eGFRs) from study years 5 to 9 (encompassing years 1994 to 2001) were examined by using regression modeling. A total of 1,394 CHS participants had retinal and serum creatinine data. After adjustments for age, race, sex, weight, diabetes, hypertension, angiotensin-converting enzyme inhibitor use, and proteinuria, participants with retinopathy showed a significant increase in serum creatinine level and decline in eGFR compared with those without retinopathy during the 4-year study period (+0.24 mg/dL [+21 micromol/L] versus -0.21 mg/dL [-19 micromol/L] and -0.48 mL/min/1.73 m2 [-0.01 mL/s/1.73 m2] versus +1.74 mL/min/1.73 m2 [+0.03 mL/s/1.73 m2], respectively). Participants with retinopathy also were significantly more likely to have an observed significant deterioration in renal function, defined as a 0.3-mg/dL (27-micromol/L) increase in serum creatinine level or 20% or greater decline in eGFR (odds ratio, 3.20; 95% confidence interval, 1.58 to 6.50; and odds ratio, 2.84; 95% confidence interval, 1.56 to 5.16, respectively). These associations remained in separate stratified analyses of patients with and without diabetes. The presence of retinal arteriolar abnormalities was not associated with deteriorating renal function. Retinal microvascular abnormalities defined as retinopathy were significantly associated with renal function deterioration. The observed findings were independent of effects of any associated diabetes or hypertension. These findings suggest that systemic microvascular disease may be associated with progressive renal dysfunction in the elderly population.

Different Effect of Cyclosporine A and Mycophenolate Mofetil on Passive Heymann Nephritis in the Rat

Background: While cyclosporine A (CsA) is an effective therapy for nephrotic syndrome, it has nephrotoxic side effects. We compared the anti-proteinuric effects and nephrotoxicity in rats with passive Heymann nephritis (PHN) of CsA and mycophenolate mofetil (MMF). Methods: PHN was induced in female Wistar rats. Two treatment groups consisting of 8 rats each received either 25 mg of CsA or 25 mg of MMF/kg body weight/day and were compared with untreated controls. Kidney function and proteinuria were monitored over 4 weeks. Western blots were used for densitometric analysis of renal cyclooxygenase-2 (COX-2) protein expression. Thromboxane B₂ (TxB₂) and 6-keto-PGF_1α were determined by radioimmunoassays (RIAs) in renal tissue and urine. Results: Rats with PHN exhibited a marked proteinuria of 12.76 ± 4.42 vs. 0.73 ± 0.28 mg/24 h (p < 0.01) and showed increased glomerular concentrations of TxB₂ and 6-keto-PGF_1α (992.6 ± 216.9 and 1,187.0 ± 54.2 pg/mg protein, respectively) compared with healthy controls (595 ± 196.17 and 729 ± 297.84, respectively) and a strongly induced COX-2 protein expression. CsA and MMF treatment reduced PHN-related proteinuria to 2.10 ± 1.47 and 1.47 ± 7.2 mg/24 h, respectively. In rats with PHN, CsA induced a significant deterioration of renal function and enhanced urine excretion of thromboxane A₂, paralleled by a significant, twofold increase in COX-2 protein expression and renal prostaglandins. By contrast, MMF treatment in rats with PHN was not nephrotoxic and had no effect on prostaglandin production. COX-2 protein expression under MMF was suppressed. Conclusion: While the antiproteinuric efficacy of MMF and CsA in PHN was comparable, the absence of nephrotoxicity might favor MMF in the treatment of nephrotic syndrome. The CsA-induced increase in COX-2 expression and COX-2-dependent prostacyclin may indicate a mechanism that compensates nephrotoxicity in the diseased and CsA-exposed kidney.

Management of hyperlipidaemia associated with heart transplantation.

The past 20 years have seen considerable advances in the field of organ transplantation that have together led to a notable increase in survival rates and a reduction in postoperative morbidity of transplant recipients. However, these advances have been accompanied by the appearance of other complications of transplantation, such as post-transplant hyperlipidaemia, hypertension and graft coronary vasculopathy (GCV). GCV is an accelerated form of atherosclerosis in transplanted hearts that has proven to be one of the most important late complications of heart transplantation and is the single most limiting factor for long-term survival. The most important factors favouring the development of hyperlipidaemia after heart transplantation are inappropriate diet in combination with reduced physical activity, adverse effects of immunosuppressive therapy (ciclosporin [cyclosporin], corticosteroids) and polygenic hypercholesterolaemia in combination with ischaemic cardiomyopathy. The treatment of hyperlipidaemia in heart transplant recipients results in a variety of complications and side effects. In particular, interactions between lipid-lowering drugs and immunosuppressive therapy have been observed. Early attempts at treatment with bile acid binding agents and nicotinic acid derivatives often proved insufficiently effective, and led to unacceptable adverse effects and significant disturbances of ciclosporin metabolism. Fibric acid derivatives provided moderate reductions in triglyceride and total cholesterol levels that were mostly--with the exception of gemfibrozil--accompanied by significant impairment of renal function. Probucol achieved only an unsatisfactory reduction in low-density lipoprotein (LDL) cholesterol. Omega-3 fatty acids lower cholesterol levels and improve endothelial function in heart transplant recipients; however, the significance of these effects is still under discussion. As in the general patient population, use of HMG-CoA reductase inhibitors (statins) achieved significant reductions in cholesterol levels. Use of these substances has resulted in significantly extended long-term survival times, significantly less GCV and fewer severe graft rejections. Selective cholesterol absorption inhibitors, administered with or without statins, could provide another treatment option for heart transplant patients with hypercholesterolaemia. In severe familial hypercholesterolaemia, which is rarely observed in heart transplant recipients, treatment with statins can be combined with extracorporeal cholesterol elimination procedures such as heparin induced extracorporeal LDL cholesterol precipitation (HELP). HELP enables total cholesterol levels to be kept within any desired target range, and has been used successfully and without adverse effects in heart transplant recipients.

Approach to the Patient With Recurrent Nephrolithiasis

Although recurring nephrolithiasis may not be as common as single-episode disease, it poses greater problems to the patient's daily lifestyle and general future health status. The general need for an adequate history, examination, and radiological assessment is acknowledged, but a more intensive investigative and management approach is required. Investigations for secondary causes are paramount and may lead to identification of unusual metabolic abnormalities and specific therapies. Such medical approaches entail consideration of dietary adjustments to lower the urinary excretion of components of the renal stones, pharmacological therapies to modulate urinary constituents and limit renal stone risk, and monitoring efficacy of the therapy over time. This approach will prevent significant deterioration of renal function and other serious metabolic consequences.

Mycobacterial infection in a series of 1261 renal transplant recipients

To describe the incidence and clinical characteristics of mycobacterial infection in renal transplant recipients. We retrospectively analyzed the cases of mycobacterial infection in a series of 1261 renal transplants carried out in our Unit of Renal Transplantation from 1980 to 2000. Demographic parameters and clinical antecedents such as age, cause of end-stage renal disease, time of follow-up of the graft, previous renal function and type of immunosuppression were considered. Moreover, the clinical onset, diagnostic tools, treatment policy and evolution were studied. The pathogenesis of the different types of mycobacteria isolated was also analyzed. Diagnosis was made with the Ziehl-Neelsen staining method. Culture was performed by the conventional Löwenstein-Jensen method and the Bactec-460 radiometric method. We found mycobacterial infection in 27 patients (2.1%), due to Mycobacterium tuberculosis in 20 cases, M. kansasii in five patients, and M. fortuitum in two patients. The mean elapsed time from the renal transplant was 20.5 months; the infection appeared in 18 patients during the first eight months after transplantation. The clinical onset was pulmonary infection in 17 cases (12 M. tuberculosis and five M. kansasii); five had urinary symptoms (three M. tuberculosis and two M. fortuitum); three cases of M. tuberculosis infection had abdominal symptoms; another one began with a perineal tuberculous abscess; the rest of the patients were asymptomatic. The types of specimen on which microbiological identification was carried out were, in decreasing order: sputum and/or bronchial washing/pleural aspiration, urine, feces, gastric and peritoneal fluids, bone marrow and blood. The first-line drug isoniazid had the highest resistance index in the susceptibility test. Clinical dissemination was observed in eight patients, four of whom died. Another three patients had a significant impairment in renal function, and in one of these patients an allograft nephrectomy was necessary due to a severe septic syndrome. Mycobacterial infection, mainly by M. tuberculosis, has an important impact on kidney transplant recipients, particularly during the first year after surgery. Diagnosis often presents some difficulties, and a delay in treatment represents a determinant factor for the evolution, with a risk of death or permanent damage in renal function. Therefore, early diagnosis is mandatory. When the Mantoux reaction is positive, antituberculous prophylaxis seems advisable.

Polyomavirus reactivation in native kidneys of pancreas alone allograft recipients.

Polyomavirus infection is common in childhood, with a seroprevalence of 60% to 100%. These viruses remain latent mostly in the kidney. Impairment in cellular immunity can allow reactivation of the virus. Reactivation can occur in 10% to 45% of renal allografts. A higher intensity of immunosuppression and the allogeneic microenvironment of the graft have been suggested to predispose to reactivation. There are limited data on the status of viral activity in the native kidneys of non-renal solid organ recipients. Thirty-eight recipients of pancreas transplant alone were evaluated for evidence of polyomavirus reactivation by urine cytology. All had received induction therapy and were maintained on tacrolimus, mycophenolate mofetil, and prednisone. The renal function and degree of exposure to immunosuppressive agents of patients shedding polyomavirus-infected renal tubular cells were compared with those of patients with negative urine cytology. Screening cytology was performed 16 months (mean) after transplantation. Four subjects (11%) had polyomaviruria. The renal function at baseline and time of screening was comparable between the two groups. The 12-hour trough levels of tacrolimus were significantly higher in patients with positive cytology compared with those without viruria. The doses of mycophenolate mofetil and prednisone were not different between the two groups. This study shows that polyomavirus reactivation in native kidneys and urinary tract of pancreas transplant alone patients is not uncommon. In these recipients, viral reactivation was not associated with significant renal functional impairment. The results also suggest that patients who are exposed to higher blood levels of tacrolimus are at higher risk of viral reactivation.

Partial nephrectomy using a microwave tissue coagulator

The conventional method of partial nephrectomy with renal vascular clamping has a risk of excessive blood loss and renal function deterioration. Recently, a microwave tissue coagulator is often used at partial nephrectomy. It is thought that the microwave tissue coagulator can easily control the bleeding from renal parenchyma, thus renal vascular clamping is dispensable and renal function is less deteriorated.We performed 13 cases of partial nephrectomy using the microwave tissue coagulator at Yokohama city university between 1994 and 2000. Although renal vessels were clamped in many cases for a few minutes, renal function had not been worsened in all cases.We performed partial nephrectomy with less blood loss and with no significant renal function deterioration by using the microwave tissue coagulator.

Posterior retroperitoneoscopic partial nephrectomy using microwave tissue coagulator for small renal tumors.

Laparoscopic partial nephrectomy remains surgically challenging because of the potential for excessive blood loss, infection, and the development of urinary fistulas. In addition, posterior retroperitoneoscopic partial nephrectomy is not popular because of the limited space for surgical manipulation. We evaluated the usefulness of a microwave tissue coagulator in posterior retroperitoneoscopic partial nephrectomy for small posterior renal tumor. Posterior retroperitoneoscopic partial nephrectomy was performed without renal pedicle clamping using a microwave tissue coagulator in six patients with small posterior renal tumors. The mean operative time was 136 minutes (range 78-180 minutes), and the blood loss was <20 mL. No serious operative complications occurred, and there was no significant deterioration of renal function. Posterior retroperitoneoscopic partial nephrectomy using a microwave tissue coagulator can be a safe and less invasive method for the treatment of small posterior renal tumors.

Effects of fluid and dobutamine treatment on renal function during partial superior mesenteric artery occlusion and reperfusion.

We compared the effects of dobutamine, fluid resuscitation and their combination on renal function during experimental intestinal ischaemia and reperfusion. Superior mesenteric artery (SMA) blood flow was reduced to 30% from the baseline for 120 minutes in 24 anaesthetized pigs (ischaemic group); 24 pigs (sham group) served as non-ischaemic controls. The animals were further assigned into four treatment arms. In the control arms, the animals were given only basic fluid therapy. In the fluid therapy arms, pulmonary capillary wedge pressure (PCWP) was maintained at 10 mmHg with intravenous fluids. In the dobutamine treatment arm, dobutamine hydrochloride was infused at a dose of 10 microg/min/kg. In the combined dobutamine-fluid therapy arms, dobutamine at 10 microg/min/kg was given and PCWP was maintained at 10 mmHg with fluids. At 120 minutes, the occluder was released in all study groups and the animals were followed for an additional 60 minutes. Renal function was evaluated by means of serum and urine creatinine. urine volume and creatinine clearance. Systemic and regional haemodynamics as well as intramucosal pH, intramucosal-arterial pCO2 gradient, and portal venous-arterial lactate gradient were measured. In the ischaemic groups, diuresis increased and serum and urine creatinine decreased significantly in fluid (p < 0.01, p < 0.01 and p < 0.05, respectively) and dobutamine-fluid (p < 0.01, p < 0.001 and p < 0.001, respectively) treated groups during SMA ischaemia. After SMA reperfusion, diuresis decreased in control group (p < 0.05) and in animals treated with dobutamine alone (p < 0.01). In addition, urine creatinine increased in dobutamine treated group (p < 0.05), and creatinine clearance decreased in control group (p < 0.01). Renal function and diuresis during the SMA occlusion and reperfusion did not differ between ischaemic and sham groups. All fluid treated groups had lower serum creatinine during SMA occlusion than control groups (p < 0.001). Intestinal ischaemia caused by partial SMA occlusion did not influence renal function. On the contrary, SMA reperfusion resulted in a significant impairment of renal function both in ischaemic and sham operated animals. The impairment was most obvious in control groups and in animals treated with dobutamine alone.

LAPAROSCOPIC PARTIAL NEPHRECTOMY WITH A MICROWAVE TISSUE COAGULATOR FOR SMALL RENAL TUMOR

LAPAROSCOPIC PARTIAL NEPHRECTOMY WITH A MICROWAVE TISSUE COAGULATOR FOR SMALL RENAL TUMOR

Incidence and outcome of a 10-fold indomethacin overdose in premature infants

We reviewed the incidence and morbidity of a 10-fold medication error among all premature infants treated with indomethacin. We detected 4 incidents among 1059 indomethacin doses given to infants weighing less than 1000 g. None of the infants had intracranial hemorrhage, necrotizing enterocolitis, or significant deterioration of renal function. (J Pediatr 1999;135:105-7)

Evaluation of renal function in elderly heart failure patients on ACE inhibitors

A total of 187 heart failure patients aged 65–92 years, with pretreatment serum creatinine levels below 200 μmol/l, were monitored for more than 12 months on angiotensin-converting enzyme (ACE) inhibitor...

Intraglomerular metastasis: a necropsy study.

Intraglomerular metastasis is a rare phenomenon. Four cases are reported here. The primary malignancies in these four cases were squamous cell carcinoma of the lung, adenocarcinoma of pancreas, haematological malignancy...

Lupus Nephritis

Effective treatment of lupus nephritis requires an understanding of disease pathogenesis, risk stratification by World Health Organization (WHO) classification and therapeutic options. Mesangial lupus nephropathy is generally associated with an excellent prognosis, whereas proliferative lupus nephropathy, especially the diffuse variant, is often characterised by hypertension, red blood cell casts and significant deterioration of renal function. Nephrotic syndrome in the absence of hypertension, active urinary sediment or significant hypocomplementaemia suggests the membranous variant of lupus nephropathy. Membranous nephropathy generally confers a good prognosis. However, persistent nephrotic range proteinuria may be accompanied by loss of renal function and end stage renal disease. Glucocorticoids, usually prednisone or methylprednisolone, remain the most effective, rapidly acting immunomodulatory therapy for both the initial episode or recurrence of active renal disease. A role for cyclophosphamide in the treatment of lupus nephritis has been established in prospective, randomised trials. The benefits of intravenous cyclophosphamide were seen in groups of patients failing prednisone, establishing cyclophosphamide as salvage or rescue therapy for patients unresponsive to glucocorticoids. Additional therapeutic strategies include azathioprine, cyclosporin, and plasmapheresis. Ancillary management can consist of hypertension control, use of angiotensin-converting enzyme inhibitors, dietary restriction of salt and protein, and lipid lowering drugs. Current treatment of lupus nephritis is associated with preservation of renal function in the vast majority of patients; however, novel agents that are more effective and less toxic are required.

Haemolytic-uraemic syndrome outbreak caused by Escherichia coli O111:H-: clinical outcomes.

In South Australia in 1995, we treated 20 children with haemolytic-uraemic syndrome associated with Escherichia coli O111:H-. The source of the outbreak was contaminated locally produced semi-dry fermented sausage (mettwurst). One child died of multiple haemorrhagic cerebral infarcts. Eighteen children required renal dialysis (for a median of 14 days); 12 months after discharge five still had significant impairment of renal function. Other major complications included colonic necrosis (3), cerebral haemorrhage/infarction (3), convulsions (4), and glucose intolerance (2). Although E. coli O111:H- has been associated with sporadic cases of haemolytic-uraemic syndrome, this was the first large outbreak reported in Australia.

Association of anticardiolipin antibodies with intraglomerular thrombi and renal dysfunction in lupus nephritis.

We studied positivity for anti-cardiolipin antibody, intraglomerular capillary thrombi on renal biopsy, and the progression of renal disease in 51 patients (10 male and 41 female), mean age 37 years (range 17-65 years), with a diagnosis of systemic lupus erythematosis and clinically evident nephritis confirmed by renal biopsy. Serum creatinine, serum indicators of disease activity and biopsies were analysed in subgroups according to thrombi and anticardiolipin status. End-points were death or chronic dialysis requirement and survival. Degree of sclerosis, crescent formation and necrosed glomeruli were all greater in those specimens positive for thrombi and in those specimens of patients who were serum ACA-positive, suggesting a relationship to disease activity/severity at presentation. The increase in serum anti-DNA antibodies and ANA and the reduction in C3 and C4 were significant in ACA-positive patients, with a strong relationship to disease activity when compared with changes in the ACA-negative patients (p < 0.05 in all cases). There was no significant difference when patients were separated according to the presence or absence of thrombi. Renal function at presentation was worse in patients with intracapillary thrombi and ACA positivity (p = 0.085 and p = 0.042, respectively). All patients progressed, but only those with intracapillary thrombi or anti-cardiolipin antibody positivity had a significant deterioration in renal function. Twenty-one thrombotic episodes occurred in 14 patients, of whom 13 were ACA-positive. Anticardiolipin antibody is a strong predictor of the presence of intraglomerular thrombi in SLE patients with renal involvement. The presence of thrombi and/or anticardiolipin antibodies indicate a worse long-term renal outcome. Anti-cardiolipin antibody positivity is a strong predictor of systemic vascular thrombotic complications.

Does renal function improve after diagnosis of malignant phase hypertension?

The nature of the relationship between high blood pressure and kidney damage is controversial. There is a view that essential non-malignant hypertension does not cause renal damage in patients with normal renal function and no proteinuria at first presentation. In contrast, patients with malignant hypertension (MHT) not due to underlying renal disease often exhibit progressive renal impairment, although there can be a dissociation between short-term changes in renal function and the long-term renal outcome. It has been established that the association of MHT and renal impairment is associated with a grave prognosis. To investigate further the changes in renal function after diagnosis of MHT. We studied the clinical features, renal function and survival of patients on the West Birmingham MHT Register. Patients presenting with no or only mild-to-moderate renal impairment (defined as an initial serum creatinine level < 300 micromol/L) were categorized as group 1 patients. Patients with severely impaired renal function, defined as a serum creatinine level > or = 300 micromol/l at presentation, were categorized as group 2 patients. Patients who subsequently suffered a deterioration in renal function were defined as those whose serum creatinine level had risen at follow-up (group A). Patients with an invariant or improving renal function at follow-up were those whose serum creatinine level neither rose nor fell (group B). Clinical characteristics and survival of patients in group 1 were therefore compared with those of patients in group 2; features of patients in group A were compared with those of patients in group B. We studied a total of 169 patients with MHT [107 men, aged 49.4 +/- 13.3 years (mean +/- SD)]. Of these, 136 (80.5%) patients had an initial serum creatinine level < 300 micromol/l (group 1). After a median follow-up of 53 months (interquartile range 15-103), the serum creatinine level of 56.8% (96 of 169) patients had risen (group A). Patients with MHT with only mild-to-moderate renal impairment at presentation (creatinine level < 300 micromol/l, group 1) had lower serum urea, creatinine and blood pressure levels at follow-up compared with those of patients with initially impaired renal function. Although there was no significant change in follow-up serum urea and creatinine levels compared with initial levels in patients in group 2 (paired Wilcoxon test, NS), there was a significant deterioration in renal function in patients in group 1 (P = 0.001). Group 2 patients had a shorter median survival time than did group 1 patients (15 versus 59 months, Lee-Desu statistic 15.4, P = 0.0001). Patients whose serum creatinine level had risen (group A) had significantly higher initial serum urea and creatinine levels and follow-up blood pressures than did those whose renal function had remained invariant or improved (group B). However, there was no significant difference between the median survival times of patients in groups A and B (51 versus 58 months, Lee-Desu statistic 0.377, P = 0.54). We suggest that renal function continues to deteriorate in some patients with MHT, despite a good degree of control of their blood pressures having been achieved at follow-up. However, the renal function of 16 of the 33 patients with severe renal impairment at presentation either remained invariant or was found to have improved at follow-up. There was no evidence that those cases whose renal function remained invariant were confined to those who had presented with less renal impairment. The severity of MHT at presentation and the amount of renal impairment did not predict the outcome. In contrast the quality of control of the blood pressure that had been obtained at follow-up did predict the outcome. Careful monitoring of renal functioning and effective treatment of the blood pressure is mandatory in patients with MHT.

Plasma morphine and glucuronide (M3G and M6G) concentrations in hospice inpatients

Plasma morphine, morphine-3-glucuronide (M3G), and morphine-6-glucuronide (M6G) concentrations were quantified by high performance liquid chromatography (HPLC) in 36 hospice inpatients receiving morphine orally or subcutaneously. The data were analyzed in relation to dose, serum creatinine, serum gamma glutamyl transferase, and presence or absence of opioid-induced adverse effects. There were significant associations (P < 0.05) between plasma morphine, M3G (subcutaneous route only), and M6G concentrations and dose for both routes of administration. The mean dose-corrected plasma morphine concentration for the subcutaneous group was three times that of the oral group, confirming present oral to subcutaneous dose conversion practices. Nineteen patients experienced symptoms attributed to morphine: nausea and vomiting in ten and acute delirium in nine. Serum creatinine was elevated in patients with adverse effects (P = 0.031), as were the dose-corrected plasma M3G (P = 0.029) and M6G (P = 0.043) concentrations. All seven patients with serum creatinine concentrations above the normal range had symptoms attributed to opioid-induced adverse effects. Plasma M3G, M6G, and dose-corrected plasma M3G and M6G concentrations were significantly (P < 0.001) higher in these patients than in those with normal serum creatinine concentrations. The data indicate that accumulation of M3G and M6G may be a causal or aggravating factor in the nausea and vomiting and cognitive function profile of palliative and terminal care patients with significant renal function impairment.

Effects of Misoprostol on Nonsteroidal Anti-Inflammatory Drug-Induced Renal Insufficiency in Patients with Stable Chronic Renal Failure: A Double-Blind, Crossover Study.

Nonsteroidal anti-inflammatory drugs (NSAIDs) have the ability to induce acute deterioration in renal function by inhibiting the production of vasodilatory prostaglandins, thereby disrupting intrarenal hemodynamic balance in patients with stable, mild, chronic renal failure. Misoprostol is a synthetic prostaglandin E-1 analog suitable for oral administration and is widely used in conjunction with NSAIDs to prevent another NSAID-induced complication, gastric ulcers. This investigation utilized a prospective double-blind, randomized, placebo-controlled crossover study designed to evaluate the possible renal protective effects of misoprostol on the renal function of patients with mild, stable, chronic renal failure, who intercurrently ingested ibuprofen 800 mg 8H or indomethacin 25 mg 8H. The mean baseline glomerular filtration rate of the patients who participated in the study was 53 ml/min (misoprostol)/55 ml/min (placebo), and 57 ml/min (misoprostol)/57 ml/min (placebo) in Study I (ibuprofen) and Study II (indomethacin), respectively. At this level of renal functional impairment, the use of the selected NSAIDs did not produce further significant impairment of renal function; hence, a renal protective role for misoprostol could not be demonstrated. To solve the question posed in our study, it will be necessary to conduct future investigations utilizing a recruitment GFR and serum creatinine values in the range of 35 ml/min and less and 2.0 mg/dl and greater, respectively.

Etoposide-Platin Combination Therapy for Chemorefractory Gestational Trophoblastic Disease

The purpose of this study was to determine activity of etoposide-platin combination chemotherapy for chemorefractory gestational trophoblastic disease. A retrospective review of patients treated with etoposide-platin chemotherapy for chemorefractory trophoblastic disease was conducted. Patients received etoposide 100 mg/m 2 and cisplatin 20 mg/m 2 on Days 1 through 5 of 14- to 21-day cycles. Patient characteristics, responses, and toxicity were recorded. Seven women received etoposide-platin for chemorefractory disease. The median WHO prognostic index score upon initiation of therapy was 16 (range, 10-20) and patients had received a median 6 cycles of prior combination chemotherapy. Five patients developed grade IV neutropenia, four developed neutropenic sepsis, and two required platelet transfusions. Two patients developed significant deterioration of renal function. Six (86%) patients had complete responses, with normalization of hCG values, but only three (43%) patients with low pretherapy hCG levels have had sustained remissions. Etoposide-platin chemotherapy is an active regimen for the treatment of women with chemorefractory gestational trophoblastic disease but has significant hematologic and renal toxicity when used as salvage therapy. Future studies should investigate the incorporation of etoposide-platin into initial therapy of women with high-risk disease.