Thiazide diuretics and risk of knee replacement surgery among patients with knee osteoarthritis: a general population-based cohort study.

OBJECTIVE: Thiazide diuretic use is associated with higher bone mineral density (BMD) and possibly lower serum magnesium levels than loop diuretic use, and both high BMD and low serum magnesium have been linked to high prevalent knee osteoarthritis. This study aimed to compare the risk of a clinically relevant endpoint, knee replacement (KR) surgery, among initiators of thiazide and loop diuretics. DESIGN: Among patients aged ≥50 years with a diagnosis of knee osteoarthritis in The Health Improvement Network (THIN) in United Kingdom, we conducted a propensity score-matched cohort study to examine the relation of thiazide diuretic initiation vs loop diuretic initiation to the risk of KR over 5 years. RESULTS: Among thiazide and loop diuretic initiators (n = 3,488 for each group; mean age: 73 years; female ratio: 59%), 359 (28.6/1,000 person-years) and 283 (24.1/1,000 person-years) KRs occurred during the follow-up period, respectively. The hazard ratio (HR) of KR for thiazide diuretic initiation vs loop diuretic initiation was 1.26 (95% confidence interval [CI]: 1.08-1.47). The adherence-adjusted HR of KR for continuous use of thiazide diuretics was 1.44 (95% CI: 1.21-1.72). CONCLUSIONS: In this population-based cohort of patients with knee osteoarthritis, thiazide diuretic use was associated with a higher risk of KR than loop diuretic use. This association may potentially be due to thiazide diuretics' effect on BMD and serum magnesium.

Disseminated adenovirus infection in renal transplant recipients: the role of cidofovir and intravenous immunoglobulin.

Disseminated adenovirus (ADV) infection in solid organ transplant patients is associated with high mortality. Limited studies have shown benefit from using cidofovir (CDV), as well as intravenous immunoglobulin (IVIG). In this study, we report 2 renal transplant patients who presented with fever and pulmonary infiltrates. Both patients continued to worsen despite antibiotic therapy. Bronchoalveolar lavage viral culture and serum polymerase chain reaction (PCR) were positive for ADV. Patients were treated with CDV, IVIG, and reduction in immunosuppression. A progressive decline in serum ADV DNA by PCR correlated with clinical improvement and pulmonary infiltrates improved. Both patients recovered. Allograft function was preserved although reversible acute kidney injury was observed in both patients. To the best of our knowledge, this is the first successful use of CDV and IVIG in renal transplant patients with disseminated ADV infection.

Renovascular hypertension: clinical concepts.

Systemic hypertension is a common disorder in clinical practice and causes significant morbidity and premature death. A small percentage (< 5%) of patients with hypertension may have renovascular hypertension. Strictly speaking, the term renovascular hypertension should be applied only when the blood pressure rises as a consequence of renal ischemia. Thus, the mere presence of renal artery stenosis is not synonymous with renovascular hypertension. Treatment strategies should be directed at ''renovascular hypertension'' rather than an anatomic renal artery stenosis (which may be discovered accidentally). Management of renal artery stenosis/renovascular hypertension is imprecise at best. This article discusses the patho-physiology of renovascular hypertension and how to approach a patient with renal artery stenosis.

Improving survival of octogenarian patients selected for haemodialysis.

BACKGROUND: The incidence of end-stage renal disease (ESRD) among patients over the age of 80 has nearly tripled in the last decade, making the 'old-old' the fastest growing ESRD demographic group. Despite this, very little information is available on the characteristics and survival of patients who initiate haemodialysis (HD) after reaching this age. METHODS: We performed a retrospective study on all patients who entered an outpatient HD programme after the age of 80, from January 1988 to September 1998. A total of 106 charts were reviewed from a single nephrology practice group. Eleven patients were excluded due to incomplete data. The survival probability was calculated using the Kaplan-Meier method. RESULTS: The characteristics of 95 patients were as follows: mean age at initiation of dialysis, 83.7 years; female, 50.5%; Caucasian, 40.0%, African-American, 30.0%; Hispanic, 10.0%; Asian, 4.3%; polytetrafluorethylene grafts, 80.0%; primary fistulas, 5.6%; tunnelled catheters, 5.6%; mean established Kt/V, 1.68; urea reduction ratio (URR), 0.74; estimated dry weight (EDW), 60.3 kg. ESRD was attributed to hypertension in 37%, diabetes in 22% and analgesic use in 8%. The 1-, 2- and 5-year survival probability of the entire group was 82.6+/-4.0%, 64.0+/-5.6%, and 19.6+/-6.0%, respectively. The median survival was 29 months. When comparing survival probability of patients who were in the highest quartiles of URR and EDW to those in the lowest quartile there was no discernible difference. However, the 2-year survival probability of patients initiated after January 1, 1995 (76.9+/-8.4) was significantly better than those initiated from 1988-1994 (47.8+/-6.5; P<0.05). CONCLUSIONS: From analysis of this cohort, we conclude that: (i) elderly patients selected for outpatient HD programmes have substantially better survival than previously reported; (ii) Kt/V does not correlate with survival in this demographic group; and (iii) contemporary dialysis practice is associated with better likelihood of survival of elderly patients in outpatient HD programmes.

Membranous glomerulonephritis associated with Graves' disease.

Renal involvement in thyroid diseases is an unusual event. Antineutrophil cytoplasmic antibody (ANCA) associated vasculitis has been reported in propylthiouracil-treated patients. Membranous glomerulonephritis has been reported in association with both antithyroglobulin and thyroid antimicrosomal antibodies. The development of membranous glomerulonephritis may be associated with administration of 131I. We present a patient who developed membranous glomerulonephritis after administration of 131I. The clinical and pathological features of renal involvement in thyroid diseases are reviewed.

Fibromuscular dysplasia of the renal arteries.

Although renovascular hypertension is less common than primary hypertension, it is important for clinicians to recognize this clinical entity because of its distinct pathophysiology and specific therapy. It is estimated that about 5% of the overall hypertensive population have renovascular hypertension. Whereas most renovascular lesions are caused by atherosclerosis, stenosis due to fibrous dysplasia is an important disease. In children and young adults, fibromuscular dysplasia of the renal arteries is the most common cause of renovascular hypertension. This review deals with the pathology, clinical characteristics, diagnosis, and therapy of renovascular hypertension associated with fibromuscular dysplasias.

Intermittent fever and pancytopenia in a young Mexican man.

We report a case of brucellosis in a young Mexican man who had weight loss, fever, and nausea. Physical examination revealed hepatosplenomegaly, and examination of the blood showed pancytopenia. This case illustrates the need for a high index of suspicion when patients living in the southern United States have these symptoms.

Anaritide in acute tubular necrosis. Auriculin Anaritide Acute Renal Failure Study Group.

BACKGROUND: Atrial natriuretic peptide, a hormone synthesized by the cardiac atria, increases the glomerular filtration rate by dilating afferent arterioles while constricting efferent arterioles. It has been shown to improve glomerular filtration, urinary output, and renal histopathology in laboratory animals with acute renal dysfunction. Anaritide is a 25-amino-acid synthetic form of atrial natriuretic peptide. METHODS: We conducted a multicenter, randomized, double-blind, placebo-controlled clinical trial of anaritide in 504 critically ill patients with acute tubular necrosis. The patients received a 24-hour intravenous infusion of either anaritide (0.2 microgram per kilogram of body weight per minute) or placebo. The primary end point was dialysis-free survival for 21 days after treatment. Other end points included the need for dialysis, changes in the serum creatinine concentration, and mortality. RESULTS: The rate of dialysis-free survival was 47 percent in the placebo group and 43 percent in the anaritide group (P = 0.35). In the prospectively defined subgroup of 120 patients with oliguria (urinary output, < 400 ml per day), dialysis-free survival was 8 percent in the placebo group (5 of 60 patients) and 27 percent in the anaritide group (16 of 60 patients, P = 0.008). Anaritide-treated patients with oliguria who no longer had oliguria after treatment benefited the most. Conversely, among the 378 patients without oliguria, dialysis-free survival was 59 percent in the placebo group (116 of 195 patients) and 48 percent in the anaritide group (88 of 183 patients, P = 0.03). CONCLUSIONS: The administration of anaritide did not improve the overall rate of dialysis-free survival in critically ill patients with acute tubular necrosis. However, anaritide may improve dialysis-free survival in patients with oliguria and may worsen it in patients without oliguria who have acute tubular necrosis.

Effect of ramipril on blood pressure and protein excretion rate in normotensive nondiabetic patients with proteinuria.

Angiotensin-converting enzyme inhibitors reduce proteinuria in both normotensive and hypertensive patients with proteinuric renal disease. However, the mechanism of the antiproteinuric effect has not been clarified. We performed a prospective, double-blind, placebo-controlled, randomized crossover trial to test the hypothesis that the antiproteinuric effect of ramipril was due to an improvement in glomerular permselectivity independent of blood pressure and glomerular filtration rate. The effect of low-dose (1.25 mg/d) and high-dose (5 mg/d) ramipril was assessed in 15 normotensive nondiabetic patients with proteinuria (> 150 mg/d). The study was divided into four 12-week periods: placebo, high- or low-dose ramipril, crossover to low- or high-dose ramipril, and placebo. Blood pressure, glomerular filtration rate, renal plasma flow rate, urinary protein excretion rate, and plasma angiotensin II levels were measured at the end of each period. Mean arterial pressure, urine protein to creatinine ratio, and albumin excretion rate decreased significantly during low- and high-dose ramipril. Glomerular filtration rate and renal plasma flow rate were not changed significantly. Plasma angiotensin II levels decreased with both low- and high-dose ramipril. There were no episodes of hypotension and only one subject developed cough during ramipril that did not require discontinuation of the study drug. In conclusion, administration of ramipril in both low and high doses lowered blood pressure and reduced proteinuria in this cohort of normotensive patients with a variety of proteinuric renal diseases. The antiproteinuric effect of ramipril is probably mediated by a reduction in glomerular capillary pressure.

Beer potomania: two cases and review of the literature.

The association of severe hyponatremia and the ingestion of large quantities of beer, termed beer potomania, has been known for several years. We report two new cases, and review 20 others from the medical literature. These patients usually have a history of binge beer drinking, poor dietary intake, and then present with severe hyponatremia and various mental status changes or seizures. Typical laboratory findings include hyponatremia, hypokalemia, and a very dilute urine. The patients respond quickly to the administration of sodium chloride containing i.v. fluids. We propose that the pivotal pathophysiologic mechanism in beer potomania syndrome is the minimal intake of solute and the hypoosmolality of the beer ingested. This will lead to the inability to excrete sufficient amounts of free water to keep up with the ingestion of large quantities of the hyposmolar beer. Treatment with isotonic sodium chloride results in the rapid clearance of the accumulated excess free water.

Deferoxamine therapy and mucormycosis in dialysis patients: report of an international registry.

Fifty-nine cases of mucormycosis in dialysis patients have been reported to the registry (25 new cases and 34 previously reported cases). The presenting forms of mucormycosis included disseminated in 44%, rhinocerebral in 31%, and other forms in 25%. The diagnosis was made during life in only 39%, while the diagnosis was discovered at autopsy in 61% of the cases. The fungus, cultured in only 36%, was always Rhizopus. The infection was fatal in 86% of cases. No known risk factors for fungal infections, eg, diabetes mellitus, liver disease, splenectomy, neutropenia, steroid therapy, or other immunosuppressive therapy, were present in 70% of patients, but 78% of patients were being treated with deferoxamine. The role played by this drug and more particularly by its iron chelate, feroxamine, in the pathogenesis of mucormycosis in these patients is underscored. Because of this risk, deferoxamine therapy in dialysis patients should be limited to severe aluminum toxicity, the deferoxamine should be given at the lowest possible dose, and dialytic methods to augment the removal of feroxamine should be studied.

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

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

Fatal Rhizopus infections in hemodialysis patients receiving deferoxamine.

Four hemodialysis patients receiving deferoxamine for metal overload had fatal rhinocerebral rhizopus infections. Serious fungal infections are not commonly seen in patients on dialysis, and none of these patients had the usual risk factors for rhizopus infection. Deferoxamine is being used with increased frequency in dialysis patients for aluminum and iron overload states. We propose that there is a link between the deferoxamine therapy and this unusual infection. Deferoxamine may serve as a specific growth factor for Rhizopus species or may alter host immune function. We suggest searching for fungal organisms in patients with unexplained illnesses receiving deferoxamine.

Carpal tunnel syndrome with cystic bone lesions secondary to amyloidosis in chronic hemodialysis patients.

Carpal tunnel syndrome (CTS) is increasingly recognized in patients undergoing chronic hemodialysis. Although the etiology remains obscure, angioaccess-related vascular engorgement and edema, and ischemic neuropathy are two likely possibilities. Amyloidosis is a relatively rare cause of CTS and had previously been thought to occur almost exclusively in patients with multiple myeloma. We report seven patients on chronic hemodialysis who developed CTS and were shown to have amyloid deposition within the synovium. Amyloid was demonstrated by characteristic staining with Congo red on polarizing microscopy and confirmed by electron microscopy. Six patients also exhibited radiolucent carpal bone cysts which were histologically shown to be due to bone replacement by an amyloid-positive synovitis. The average age of the patient and time on dialysis were 59.1 and 7.9 years, respectively. Serum and urine immunoelectrophoresis and bone marrow aspirates showed no evidence for plasma cell dyscrasia in six patients, while one patient did manifest a monoclonal IgA spike. Autopsies in three patients and liver biopsy in another showed no other evidence for disseminated amyloid. These hemodialysis patients exhibited a unique syndrome of CTS, lytic lesions of the carpal bones, and amyloid deposition in the synovium and within the bone cysts.

Legionnaires' disease associated with acute renal failure: a report of two cases and review of the literature.

Renal involvement is a well described complication of Legionnaires' disease and is often manifested as mild, transient azotemia, hematuria, proteinuria, pyuria or cylinduria. Acute renal failure complicating Legionnaires' disease has also been described, and some patients have required hemodialysis. Renal morphology has only been described in a few cases. We report two cases of Legionnaires' disease who developed acute renal failure. The serotype of the Legionella pneumophilia isolated from one of the patients had never been isolated from humans before. This patient expired and at autopsy the kidney revealed acute tubular necrosis, but there was no evidence for interstitial or glomerular disease. Renal morphology in six previously reported cases revealed acute tubulointerstitial nephritis in three cases and acute tubular necrosis in the other three. We conclude that acute renal failure may accompany severe Legionnaires' disease, and the development of the renal failure is not related to hemodynamic factors, while nephrotoxic antibiotics may be a contributing factor.

Lithium intoxication associated with acute renal failure.

Lithium can produce transient natriuresis, nephrogenic diabetes insipidus, and partial distal renal tubular acidosis. Lithium intoxication is commonly associated with mild renal insufficiency and may produce acute renal failure. We have described a case of acute renal failure in a patient with severe lithium intoxication, as well as cardiac arrhythmias and hypothyroidism, both of which have been reported to occur with lithium toxicity. Treatment with daily hemodialysis eventually produced complete recovery. Lithium clearance occurs quickly with hemodialysis, but a rebound effect occurs as lithium in intracellular water equilibrates with extracellular fluid. Prolonged dialysis may be required to reduce the blood lithium level to the therapeutic range. We conclude that lithium intoxication may produce severe reversible renal failure as a result of direct tubular epithelial damage.