Maintenance Of Renal Function Research Articles

Bladder neck closure and suprapubic catheter placement as definitive management of neurogenic bladder

ObjectiveSurgical management for neurogenic bladder may require abandonment of the native urethra due to intractable urinary incontinence, irreparable urethral erosion, severe scarring from previous transurethral procedures, or urethrocutaneous fistula. In these patients, bladder neck closure (BNC) excludes the native urethra and provides continence while preserving the antireflux mechanism of the native ureters. This procedure is commonly combined with ileovesicostomy or continent catheterizable stoma, with or without augmentation enterocystoplasty. Alternatively, BNC can be paired with suprapubic catheter diversion. This strategy does not require a bowel segment, resulting in shorter operative times and less opportunity for bowel-related morbidity. The study purpose is to examine preoperative characteristics, indications, complications, and long-term maintenance of renal function of BNC patients.MethodsA retrospective review of medical records of 35 patients who underwent BNC with suprapubic catheter placement from 1998 to 2007 by a single surgeon (LKL) was completed.ResultsNeurogenic bladder was attributable to spinal cord injury in 71%, 23% had multiple sclerosis, and 9% had cerebrovascular accident. Indications for BNC included severe urethral erosion in 80%, decubitus ulcer exacerbated by urinary incontinence in 34%, urethrocutaneous fistula in 11%, and other indications in 9%. The overall complication rate was 17%. All but two patients were continent at follow-up. Forty-nine per cent of patients had imaging available for review, none of which showed deterioration of the upper tracts.ConclusionsOur results suggest that BNC in conjunction with suprapubic catheter diversion provides an excellent chance at urethral continence with a reasonable complication rate.

Favorable outcomes with in situ techniques for surgical repair of complex renal artery aneurysms

The optimal method of operative management of complex branch renal artery aneurysms (RAAs) remains unclear, with recent reports predominantly espousing endovascular and ex vivo repair. We sought to determine the long-term outcome of RAA repair performed with autogenous in situ techniques. This was a cohort study of patients undergoing surgical repair of RAAs identified from our prospective vascular division registry (1984-2009). Twenty-six RAAs were repaired in 24 patients (17 women, 7 men; mean age, 52 ± 16 years). Mean size was 2.3 ± 0.7 cm (range, 0.7-4.0 cm). Twenty RAAs were repaired based on size and six for hypertension alone. Multiple RAAs were present in 13 patients (54%). Associated conditions included hypertension in 24 (100%), fibromuscular dysplasia in 6 (25%), coexistent renal artery stenosis in 6 (25%), and aortic aneurysm in 3 (12.5%). Reconstruction of first- or second-order branches was required in 25 RAAs (96%). In situ techniques were used in 22 repairs and included resection combined with autogenous vein bypass and interposition in 11, primary anastomosis to conjoined outflow vessels in 3, and aortic reimplantation in 2. Aneurysmorrhaphy was combined with vein patch angioplasty in 6, exclusion in 2, tailored primary closure in 1, and autogenous bypass in 1. Four patients underwent ex vivo reconstruction. Perioperative mortality was 0% and morbidity was 11.5%, including one nephrectomy during ex vivo repair for immediate thrombosis. Renal function was preserved (preoperative creatinine, 0.94 ± 0.3 vs postoperative creatinine 1.06 ± 0.4 mg/dL; P = .11). Systolic (SBP) and diastolic blood pressure (DBP) control improved after operation: preoperative SBP 142 ± 18 vs postoperative SBP 130 ± 15 mm Hg (P = .007) and preoperative DBP 86 ± 14 vs postoperative DBP 78 ± 10 mm Hg (P = .01). Long-term patency was evaluated in 18 reconstructions (69%) by duplex imaging or contrast radiography at an average long-term follow-up of 99 months (range, 1-300 months) and was 94%. Five-year freedom from rupture and survival by the Kaplan-Meier method was 100%. In situ techniques allow repair of complex RAAs involving branch vessels with minimal morbidity, improved blood pressure control, and maintenance of renal function. This operative approach further provides excellent long-term patency and survival in this relatively young patient population.

Methylprednisolone pulse therapy combined with mizoribine following tonsillectomy for immunoglobulin A nephropathy: clinical remission rate, steroid sparing effect, and maintenance of renal function

BackgroundThe long-term prognosis of immunoglobulin A nephropathy (IgAN) is reportedly poor. In Japan, tonsillectomy-steroid pulse therapy has frequently been used for treatment of early IgAN, with favorable outcomes. However, steroid usage is sometimes limited due to adverse reactions. To reduce the total dose of steroids, we have been using mizoribine (MZR) in combination with tonsillectomy-steroid pulse therapy since 2004. Here we report a retrospective evaluation of our protocol outcome.MethodsForty-two patients aged <70 years with histopathologically confirmed IgAN and an estimated glomerular filtration rate (eGFR) of 30 ml/min/1.73 m2 or higher were enrolled. After giving informed consent, all the patients underwent bilateral tonsillectomy. One week later, intravenous methylprednisolone pulse therapy (500 mg/day) was administered for 3 days, followed by oral prednisolone (30 mg/day and tapered to 0 over 7 months) and MZR (150 mg/day for 11 months). The complete remission (CR) rate and renoprotective effect were assessed.ResultsThe CR rate at 6, 12, and 24 months was 33.3, 69.1, and 76.2%, respectively. Despite a relatively low total steroid dose, renal function was satisfactorily maintained for 24 months or longer with no relapse. The eGFR in patients with stage 3 chronic kidney disease was significantly improved at 6 months after start of treatment. Three patients (7.1%) had mild and transient adverse events.ConclusionThis protocol appears to be highly effective and safe for IgAN patients with renal dysfunction.

Efficacy of Laparoscopic Renal Cryoablation as an Alternative Treatment for Small Renal Mass in Patients with Poor Operability: Experience from the Korean Single Center

The aim of this work was to evaluate the efficacy and safety of laparoscopic renal cryoablation (LRC) for the treatment of incidentally found small renal masses in patients with poor operability, from our initial experience in Korea. From June 2005 to April 2009, surgical and oncologic outcomes were evaluated from a database of 45 renal tumors in 39 patients who underwent LRC due to a high American Society of Anesthesiology (ASA) physical status score (i.e., over 3) or old age (i.e., over 70 years old). Mean (range) age was 63.3 years (range, 43-81), and mean tumor size was 2.5 cm (range 0.7-3.9). Mean of ASA physical status score of whole patients was 2.8 (range, 1-4), and 79.4% (31/39) of patients had an ASA physical status score over 3. Eleven patients (28.2%) were over 70 years old. Among 45 treated lesions, 23 (51.1%) were exophytic tumors, 17 (37.8%) were endophytic tumors, and the other 5 (11.1%) were mesophytic tumors. Mean operating time was 173.7 minutes (range, 110-220), and mean blood loss was 106.3 mL (range, 40-150). None of the patients developed major complications, including adjacent organ injury, collecting system injury, open surgical conversion, or conversion to nephrectomy. Pathologic examination revealed that 60% (27/45) of lesions were renal-cell carcinoma (RCC). During a mean follow-up duration of 23.5 months (range, 6-53), radiologic evidence of tumor recurrence was found in 1 patient (3.7% for RCC). With the exception of this patient, all other patients have remained free of recurrence or metastasis, as determined by a periodic radiologic work-up. Serum creatinine remains stable, with no statistical difference, compared to preoperative levels, in both whole patients and patients with solitary kidney. In this series, LRC for small renal tumors showed favorable oncologic and surgical outcomes, including maintenance of renal function, without adverse effects in selected patients with poor operability.

Fetal urology

Although it becomes vitally important only after birth, renal function already plays significant role in maintaining fetal metabolic equilibrium. The kidneys significantly contribute to production of amniotic fluid. Adequate amount of amniotic fluid is needed to stimulate the intrauterine fetal respiratory activity. Intrauterine breathing is essential for lung development. As a result, oligohydramnion is conducive to pulmonary hypoplasia. The latter may lead to neonatal demise soon after birth. In extrauterine life kidneys eliminate nitrogen containing metabolic byproducts. Inadequate renal function results therefore lethal uremia. Integrity of ureters and the urethra is essential for the maintenance of renal function. Retention of urine causes degeneration of the functional units of the kidneys and ensuing deterioration of renal function. Intrauterine kidney puncture or shunt procedure may delay this process in some cases. On the other hand, once renal function has been damaged, no therapy can restart it. Certain anomalies of renal excretory pathways may also be associated with other congenital abnormalities, making the therapeutic efforts pointless. Presence of these associated intrauterine defects makes early pregnancy termination a management alternative, as well as it affects favorably perinatal mortality rates.

β1-Integrin is required for kidney collecting duct morphogenesis and maintenance of renal function

Deletion of integrin-beta1 (Itgb1) in the kidney collecting system led to progressive renal dysfunction and polyuria. The defect in the concentrating ability of the kidney was concomitant with decreased medullary collecting duct expression of aquaporin-2 and arginine vasopressin receptor 2, while histological examination revealed hypoplastic renal medullary collecting ducts characterized by increased apoptosis, ectasia and cyst formation. In addition, a range of defects from small kidneys with cysts and dilated tubules to bilateral renal agenesis was observed. This was likely due to altered growth and branching morphogenesis of the ureteric bud (the progenitor tissue of the renal collecting system), despite the apparent ability of the ureteric bud-derived cells to induce differentiation of the metanephric mesenchyme. These data not only support a role for Itgb1 in the development of the renal collecting system but also raise the possibility that Itgb1 links morphogenesis to terminal differentiation and ultimately collecting duct function and/or maintenance.

Nephrectomy Elicits Impact of Age and BMI on Renal Hemodynamics: Lower Postdonation Reserve Capacity in Older or Overweight Kidney Donors

Renal functional reserve could be relevant for the maintenance of renal function after kidney donation. Low-dose dopamine induces renal vasodilation with a rise in glomerular filtration rate (GFR) in healthy subjects and is thought to be a reflection of reserve capacity (RC). Older age and higher body mass index (BMI) may be associated with reduced RC. We therefore investigated RC in 178 consecutive living kidney donors (39% males, age 48 +/- 11 years, BMI 25.5 +/- 4.1). RC was determined as the rise in GFR ((125)I-iothalamate), 4 months before and 2 months after donor nephrectomy. Before donor nephrectomy, GFR was 114 +/- 20 mL/min, with a reduction to 72 +/- 12 mL/min after donor nephrectomy. The dopamine-induced rise in GFR of 11 +/- 10% was reduced to 5 +/- 7% after donor nephrectomy (p < 0.001). Before donor nephrectomy, older age and higher BMI did not affect reserve capacity. After donor nephrectomy, the response of GFR to dopamine independently and negatively correlated with older age and higher BMI. Moreover, postdonation reserve capacity was absent in obese donors. The presence of overweight had more impact on loss of RC in younger donors. In conclusion, donor nephrectomy unmasked an age- and overweight-induced loss of reserve capacity. Younger donors with obesity should be carefully monitored.

The phosphoinositide-3 kinase γ–Akt pathway mediates renal tubular injury in cisplatin nephrotoxicity

Nephrotoxicity is a frequent complication of cisplatin-based chemotherapy often limiting its use. In this study, we attempted to the role of the phosphoinositide-3 kinase (PI3K)-gamma-Akt pathway in this form of acute kidney injury. Using PI3K-gamma knockout mice, we found that a conventional dose of cisplatin was more lethal in the knockout mice where the blood urea nitrogen and serum creatinine were significantly higher in them than in wild-type mice. Phosphorylation of Akt in the renal tubules was abrogated in the knockout mice with the severity of renal dysfunction and numbers of TUNEL (terminal deoxynucleotidyl transferase (TdT) mediated nick-end labeling)-positive renal tubule cells being higher in the knockout than in wild-type mice. Cisplatin treatment significantly increased. Caspase-3 activity, histone-associated DNA fragments, and number of annexin V-positive cells was significantly higher in cisplatin-treated primary cultured renal tubular epithelial cells of knockout mice. Transfection of dominant-active forms of Akt and PI3K-gamma ameliorated apoptosis of the tubule epithelial cells derived from the knockout mice. Our results suggest that the PI3K-gamma-Akt pathway lessens apoptosis and plays a critical role in the maintenance of renal function in cisplatin-induced acute kidney injury.

Role of Oxidative Stress in Celecoxib-Induced Renal Damage in Wistar Rats

Celecoxib, a selective cyclo-oxygenase-2 (Cox-2) inhibitor, prevents the formation of prostaglandins, responsible for maintenance of renal function. Celecoxib administration may lead to renal damage. Since free radicals and antioxidant mechanisms play a significant role in renal injury; this study was designed to evaluate the role of oxidative stress in celecoxib-induced renal damage. The administration of celecoxib resulted in moderate and mild tubulointerstitial nephritis in chronic and acute group. The renal function tests were significantly altered only in the chronic group. The results in both the acute and the chronic group showed (1) a significant increase in the lipid peroxidation and in the activities of superoxide dismutase, catalase and glutathione-S-transferase and (2) a decrease in nitrite, reactive thiols and glutathione. In conclusion, our study suggests that chronic administration of celecoxib may have a damaging effect on kidney, as evident through altered histopathology and renal functions. This damage may be mediated by oxidative stress.

An Innovative Option for Venous Reconstruction After Pancreaticoduodenectomy: the Left Renal Vein

IntroductionPancreatic ductal adenocarcinoma has a high mortality rate with limited treatment options. One option is pancreaticoduodenectomy, although complete resection may require venous resection. Pancreaticoduodenectomy with venous resection and reconstruction is becoming a more common practice with many choices for venous reconstruction. We describe the technique of using the left renal vein as a conduit for venous reconstruction during pancreaticoduodenectomy. MethodsThe technique for use of the left renal vein as an interposition graft for venous reconstruction during pancreaticoduodenectomy is described as well as outcomes for nine patients that have undergone the procedure. ResultsNine patients, seven men, with a mean age of 57 years, have undergone the operation. There were eight interposition grafts and one patch graft. Mean operating time was 7.8 hours, and mean tumor size was 3.4 cm. Eight patients had node-positive disease, and six had involvement of the vein. Mean hospital stay was 14 days and perioperative morbidity included a superficial wound infection, delayed gastric emptying, ascites, and gastrointestinal bleeding in one patient each. Creatinine ranged from 0.8–1.1 mg/dl preoperatively and from 0.7–1.3 mg/dl at discharge. Mean follow-up was 6.8 months with normal creatinine values noted through the follow-up period. Two patients had died during follow-up from recurrent disease at 8.3 and 18.2 months after the operation. ConclusionsThe left renal vein provides an additional choice for an autologous graft during pancreaticoduodenectomy with venous resection. The ease of harvesting the graft and maintenance of renal function distinguish its use.

Renal Response After High-Dose Melphalan and Stem Cell Transplantation Is a Favorable Marker in Patients With Primary Systemic Amyloidosis

Primary systemic (AL) amyloidosis is a rare plasma cell disorder characterized by soft-tissue deposition of monoclonal light chain fragments. High-dose melphalan followed by autologous stem cell transplantation currently has become the treatment of choice. Favorable outcome is ensured with achievement of hematologic response, but little is known about organ response. This study was undertaken to determine the prognostic importance of renal response after high-dose melphalan and stem cell transplantation. All patients with AL amyloidosis who underwent autologous stem cell transplantation between 1996 and December 2002 were selected for study. Renal response is defined as a 50% or greater reduction in proteinuria with less than 25% decline in renal function. Exclusion criteria included pretransplantation dialysis therapy or dialysis dependence posttransplantation, treatment mortality, lack of proteinuria assessment posttransplantation, and baseline proteinuria with protein less than 1 g/d. Of 105 patients, 47 were excluded for stated reasons. Renal response was achieved in 60.3% of evaluated patients. Proteinuria was reduced by greater than 90% in 37.9% and returned to normal in 15.5%. Median response time was 12 months. Renal response was associated with a greater increase in serum albumin level (P = 0.001), maintenance of renal function (P < 0.001), and better survival (P = 0.0003). Renal responders had better survival regardless of hematologic response (P = 0.01 to 0.05). Currently, high-dose melphalan followed by stem cell transplantation is the most effective treatment for AL amyloidosis for those who are eligible. Our data show that renal response after high-dose melphalan followed by stem cell transplantation is associated with improved survival. Renal response is an independent marker of treatment success and can be used in cases in which determination of hematologic response is difficult.

Plasma and urine nitric oxide levels in healthy Turkish children

Nitric oxide (NO) is an important messenger molecule with a wide range of actions in virtually all cell systems and organs. In kidneys it participates in glomerular and medullary hemodynamics, tubuloglomerular feed-back, renin secretion, and extracellular fluid balance. Although the role of NO in regulating renal function in adults is well-established, it has recently been suggested that NO has a more critical role in maintaining basal renal blood flow and glomerular filtration rate (GFR) in the developing kidney. NO is rapidly metabolized to the stable end products nitrite and nitrate, which are more slowly excreted into the urine. Thus these metabolites can be recommended as useful markers of endogenous NO synthase activity, despite limited data about age-related changes in in-vivo NO production. The aims of this study were to determine age-related normal reference values of serum and urinary NO metabolites and to assess the probable relationship between these metabolites and the GFR. Normal levels of NO end products in blood and urine of 296 healthy children (117 female, 179 male) between the ages of 0 and 16 were investigated, as was whether these values change with age. Serum and urinary nitrate levels did not differ according to sex. Serum nitrate levels are higher in younger children, especially in the newborn period, and decrease with age. Nitrate levels in urine are higher in younger children with a peak in infancy (1 month to 1 year) and decrease with age. It was demonstrated that this decrease in serum and urinary nitrate levels with age parallels the increase in GFR. In conclusion, urinary NO products may be an indirect marker of serum NO levels and NO might have an important regulatory function both in the maintenance of renal function and in the maturation of the developing kidneys.

Preventing renal complications in diabetic patients: the Diabetics Exposed to Telmisartan And enalaprIL (DETAIL) study*

Diabetic nephropathy is characterised by hypertension and persistent proteinuria. If ineffectively controlled, a progressive decline in renal function can result in end-stage renal disease. Patients with diabetic nephropathy are also at greatly increased risk of cardiovascular disease. Angiotensin-converting enzyme (ACE) inhibitors display additional renoprotective effects beyond systemic blood pressure lowering, perhaps due to reduction in intraglomerular pressure by inhibition of angiotensin II activity. In type 2 diabetics, ACE inhibitors have variable effects, with some studies showing a reduction in microalbuminuria, prevention of the progression to macroalbuminuria and maintenance of renal function. Randomised studies have demonstrated that angiotensin II receptor blockers (ARBs), as well as controlling systemic blood pressure, delay progression of proteinuria in patients with diabetic nephropathy. Telmisartan has a number of features that may make it particularly suitable for the treatment of diabetic nephropathy. In addition to its long duration of action and almost exclusive faecal excretion, its high lipophilicity should assist in tissue penetration. The Diabetics Exposed to Telmisartan And enalaprIL (DETAIL) study was designed to compare the long-term renal outcome of treatment with telmisartan 40.80 mg versus enalapril 10.20 mg (with titration to the higher dose after 4 weeks) in patients with type 2 diabetes, mild-to-moderate hypertension and albuminuria. The primary endpoint is the change in glomerular filtration rate after 5 years' randomised treatment. Secondary endpoints are annual changes in glomerular filtration rate, serum creatinine and urinary albumin excretion, as well as incidences of end-stage renal disease, cardiovascular events, all-cause mortality and adverse events. The groundbreaking DETAIL study revealed that telmisartan conferred comparable renoprotection to enalapril and was associated with a low incidence of mortality.

Why inhibitors of mammalian target of rapamycin will be important in organ transplantation

Purpose of review Current immunosuppressive protocols usually include a calcineurin inhibitor, an antiproliferative agent, and steroids; antibody induction is also given in many units. Because 1-year patient and graft survival rates are now excellent, the target of novel immunosuppressive development has moved to the prevention of chronic graft nephropathy in patients who have undergone renal transplantation or the maintenance of renal function in recipients of other organs. Many clinical trials are now based on the avoidance or sparing of calcineurin inhibitor. Inhibitors of mammalian target of rapamycin cause no nephrotoxicity. It is therefore believed by many that this class of drugs may play an important role in the immunosuppressive protocols of the future. Recent findings Histologic and outcome data are now available from calcineurin inhibitor avoidance/sparing trials. Other studies indicate that inhibitors of mammalian target of rapamycin may be beneficial in preventing allograft vasculopathy by the specific inhibition of atherogenesis. There are also antitumor and antifungal properties of these drugs that may be of value. However, the risk of delayed graft function after transplantation seems to be increased, presumably because of the inhibition of regeneration of damaged tubular epithelial cells. The combination of an inhibitor of mammalian target of rapamycin with a calcineurin inhibitor may lead to extensive tubular cell injury and death and a unique form of cast nephropathy. Summary Drugs using inhibitors of mammalian target of rapamycin provide a real opportunity to treat patients with much lower exposure to calcineurin inhibitors. Long-term studies remain to be completed that show whether this might lead to important reductions in drug-related kidney damage. Evidence is starting to accumulate that the use of a mammalian target of rapamycin inhibitor early after transplantation might be contraindicated because of impairment in tubular regeneration.

MYCOPHENOLATE MOFETYL (MMF) THERAPY USED IN A PRIMARY IMMUNOSUPPRESSIVE REGIMEN FOLLOWING ORTHOTOPIC LIVER TRANSPLANTATION (OLT)

A191 Aims: MMF is a new immunosuppressive (IS) drug for use following OLT which may decrease acute rejection and lead to a reduction in calcineurin inhibitors (CNI) in case of nephrotoxicity. Few studies have evaluated its early use in a primary IS regimen on a large cohort of liver transplant recipients. The aims of this study were: a) to evaluate the impact of MMF on patient survival, frequency of acute and chronic allograft rejection, rate of post-transplant infectious events; and b) to quantify CNI reduction in case of nephrotoxicity. Methods: Patients with MMF in a primary IS regimen (group A) were compared to those without initial MMF (group B). Prognostic analysis used χ2, Kruskal-Wallis, T test and log-rank tests, and the Kaplan Meier method. Results: From 1995 to 2003, 169 adult recipients (173 OLT) were followed for 34 months (109 males, 60 females; age: 48 years). An IS regimen with MMF-CNI-corticosteroids was prescribed in group A (95 consecutive patients, mean follow-up 30.5±10 months), and an azathioprine-CNI-corticosteroid regimen was used in group B (74 patients, mean follow-up 44.4±16 months). Within group B, MMF was never used in 48 patients and secondarily introduced in 26 patients in order to reduce CNI (nephrotoxicity in 20% of cases). Post-transplant survival was significantly higher in group A than in group B at 1 year (90.1±3,1% vs 78.4±4.8%, p=0.02) and 2 years (87±3.8% vs 77±4.9%, p=0..05). Acute and chronic rejection rates were significantly lower in group A than in group B (18.9% vs 43.2%, p= 0.0005 and 0% vs 3.9%, p=0.05). The retransplantation rate did not differ in the two groups (1.1% vs 4.1%). The global rate of early bacterial and CMV-induced events did not differ in the two groups (group A: 34% and 35% versus group B: 31% et 29%). In group A, a decrease in the dose of MMF dose was required in 35% of cases and total arrest in 23% of cases. Frequencies of renal dysfunction and severe renal dysfunction (clearance of creatinine <80 ml/min or <30 ml/min) did not differ in the 2 groups at one year (51.7% vs 48.3% and 0% vs 0%), 2 years (37.7% vs 62.3% and 0% vs 1.9%) or 3 years (72.7% vs 83.7%, and 9.1% vs 6.4%). In group B, secondary use of MMF (mean 36 months post-OLT) in 20 transplant recipients with renal dysfunction led to a reduction in CNI (cyclosporine 0.6 mgkg-1d-1 vs 2.6 mgkg-1d-1, p=0.002, tacrolimus 0.02 mgkg-1d-1 vs 0.08, p=0.009) and a stabilization of renal function with an increase in creatinine clearance of 8 ml/min in 1 year compared to patients from group B without MMF. Conclusions: MMF is an efficient and safe immunosuppressant following OLT which reduces rejection and improves 1- and 2-year survival without significantly increased infectious hazard. Moreover, it enables reduction of CNI and maintenance of renal function in cases of nephrotoxicity.

Management of patients with renal artery stenosis. Reappraisal of operative treatment

Arterial hypertension is most often the first symptom of renal artery stenosis (RAS). Appropriate screening methods for the diagnostic workup of hypertension are colour-coded duplex ultrasound and captopril scintigraphy. Angiography (intraarterial digital subtraction angiography) represents the diagnostic "gold standard", which is the prerequisite for the selection of the most suitable therapeutic method. Atherosclerosis is the most common disease in elderly patients presenting with RAS. In younger patients, fibromuscular dysplasia is more frequent. Five main types with different prognosis and therapeutic indications can be classified. Rare causes of RAS are dissection, renal artery aneurysm with combined stenosis, and especially in children and adolescents middle aortic syndrome with hypoplasia of the visceral arteries. Every patient with RAS of hemodynamic relevance in the presence of hypertension should be treated, whereas therapeutic risk and benefit must be weighed up individually. Aims are the improvement of hypertension and the maintenance of renal function. Surgical techniques, which are described subsequently, are indicated in all patients who need further simultaneous treatment of the abdominal vessels (abdominal aortic aneurysm, aortoiliac or visceral artery stenosis or aneurysm, respectively). In atherosclerotic ostial stenoses, angioplasty (PTA) and open surgery (normally transaortic endarterectomy) are concurrent methods. In our experience, the long-term results of surgical reconstruction seem to be superior. Both procedures are subject to an ongoing randomized study in our department. The outcome of surgical treatment for RAS is satisfying, the operative risk especially in isolated renal artery lesions is negligible.

Coxibs—Beyond the GI Tract: Renal and Cardiovascular Issues

Although the coxibs have demonstrated superior gastrointestinal safety compared to traditional non-selective NSAIDs, questions remain regarding their effects on the renal and cardiovascular systems. In terms of renal function, both Type 1 and Type 2 cyclooxygenase (COX-1 and COX-2) are expressed constitutively in the kidney. Prostaglandins do not play a major role in the maintenance of renal function in healthy individuals but they become profoundly important in certain clinical situations such as renal stress, or volume depletion. In such situations the effects of the coxibs and non-selective NSAIDs are likely to be similar. The incidence of renal side effects is low (1–5%) and the patients at risk of renal complications are well defined and can usually be identified prospectively and followed up as appropriate. From the cardiovascular point of view, questions have been raised as to whether the coxibs have a prothrombotic effect. Here we review the available evidence and consider various hypotheses for an apparent increase in cardiovascular events reported in one coxib study (the VIGOR trial). Because of a lack of anti-platelet activity, coxibs are not suited for the provision of cardiovascular prophylaxis, and in patients at risk of myocardial infarction the prophylactic use of aspirin should always be considered. Although evidence suggests that use of coxibs with low-dose aspirin is safer than the combination of traditional NSAIDs with aspirin, further studies are required to confirm that this is the case.

Cyclooxygenase-1 derived prostaglandins are involved in the maintenance of renal function in rats with cirrhosis and ascites.

1. The maintenance of renal function in decompensated cirrhosis is highly dependent on prostaglandins (PGs). Since PG synthesis is mediated by cyclooxygenase-1 and -2 (COX-1 and COX-2), the present study was designed to examine which COX isoform is involved in this phenomenon. 2. Renal COX-1 and COX-2 protein expression and distribution were analysed by Western blot and immunohistochemistry in nine rats with carbon tetrachloride-induced cirrhosis and ascites and 10 control animals. The effects of placebo and selective COX-1 (SC-560) and COX-2 (celecoxib) inhibitors on urine flow (V), urinary excretion of sodium (U(Na)V) and PGE(2) (U(PGE2)V), glomerular filtration rate (GFR), renal plasma flow (RPF), the diuretic and natriuretic responses to furosemide and renal water metabolism were assessed in 88 rats with cirrhosis and ascites. 3. COX-1 protein levels were found to be unchanged in kidneys from cirrhotic rats. In contrast, these animals showed enhanced renal COX-2 protein expression which was focally increased in the corticomedullary region. Although U(PGE2)V was equally reduced by SC-560 and celecoxib, only SC-560 produced a significant decrease in U(Na)V, GFR and RPF and a pronounced impairment in the diuretic and natriuretic responses to furosemide in rats with cirrhosis and ascites. Neither SC-560 nor celecoxib affected renal water metabolism in cirrhotic rats. 4. These results indicate that despite abundant renal COX-2 protein expression, the maintenance of renal function in cirrhotic rats is mainly dependent on COX-1-derived prostaglandins.

Cyclo-oxygenase-2 inhibitors and the kidney: a case for caution.

Cyclo-oxygenase (COX) is one of the key enzymes in the biosynthesis of prostaglandins. Two isoforms of this enzyme COX-1 and COX-2 are known to exist. Among other functions, prostaglandins play an important role in the protection of the gastric mucosa and maintenance of renal function in pathophysiological conditions which would otherwise threaten it. Conventional nonsteroidal anti-inflammatory drugs (NSAIDs) block prostaglandin synthesis, resulting in gastric mucosal injury and renal dysfunction in susceptible individuals. The recent introduction of selective COX-2 inhibitors, celecoxib and rofecoxib, appear to induce less gastrointestinal morbidity. Although conclusive data are still lacking, there is evidence to suggest that COX-2 antagonists may be capable of causing some of the same renal syndromes seen in association with the older, less selective NSAIDs.

Primary focal segmental glomerulosclerosis in children: prognostic factors.

To study the clinical course and the predictors of outcome in children and adolescents, 39 patients with nephrotic syndrome and primary focal segmental glomerulosclerosis (FSGS) were followed for a mean of 84.6 months. Thirty-six patients were treated with prednisone, either alone or in conjunction with cyclophosphamide. The clinical course was one of sustained remission in 4 patients, frequent relapse in 13, persistent nonnephrotic proteinuria in 5, and persistent nephrotic syndrome in 17; 2 patients had stable renal failure and 8 had progressive renal failure, 5 of them evolving to end-stage renal failure (ESRF). Resistance to prednisone was recorded in 76.6% of patients. The use of cyclophosphamide plus prednisone was of benefit in 42.8% of patients; 22.2% of the prednisone-resistant patients achieved remission of the nephrotic syndrome. A Kaplan-Meier analysis revealed a survival rate of 92% after 5 years, 86% after 10 years, and 76% after 15 years. Using both univariate and multivariate analysis, persistent nephrotic syndrome was associated with progression to ESRF and the remission of proteinuria with maintenance of renal function. As the outcome of the nephrotic syndrome in FSGS is significantly improved by remission of proteinuria, it is conceivable that immunosuppressive medication may be used in conjunction with prednisone in patients with steroid resistance.