Hypophosphataemia: an easy strategy for diagnosis and treatment in HIV patients.

Because HIV infection has become a chronic disease, it is crucial that metabolic complications secondary to HIV infection or prolonged therapy be diagnosed and managed appropriately over time. Therefore the optimal follow-up becomes complex and time consuming. Our review aimed to provide physicians in charge of HIV-infected patients with key data helping them to diagnose and understand hypophosphataemia in HIV patients. Hypophosphataemia is frequent and sometimes secondary to renal phosphate wasting. It is very rarely a component of a complex proximal tubular disorder, such as Fanconi syndrome. When isolated, hypophosphataemia is easy to rule out and treat. In rare cases, prolonged hypophosphataemia, when related to renal phosphate wasting and tubular dysfunction, might have potential consequences on bone outcome, however, more studies are needed. HIV infection by itself might be a risk factor for bone metabolism abnormalities; antiretroviral drugs might also be involved. Therefore, it seems valuable for patients that the minimal screening should be performed routinely, in order to prevent long-term disabilities.

Renal safety of gadolinium-based contrast media in patients with chronic renal insufficiency.

Contrast medium (CM)-induced nephropathy (CIN), defined as acute renal failure after administration of CM when alternative causes of renal damage have been excluded, is the third leading cause of acute renal injury necessitating hospitalization. However, the pathophysiology of CIN is complex and not fully understood. Gadolinium chelates, originally introduced as intravenous CM for magnetic resonance imaging and regarded as nonnephrotoxic, have been recommended to replace iodinated contrast agents in patients at risk for acute renal failure. Since then, some gadolinium-based CM have been reported to be associated with CIN, especially in patients with advanced renal disease. However, the biochemical and physicochemical properties of the gadolinium-chelates that are responsible for such nephrotoxicity have not been clearly defined, and the issue of gadolinium-induced nephrotoxicity remains controversial. This review surveys the literature with the purpose of clarifying the renal effects of gadolinium-based CM in patients with renal insufficiency.

Antiretroviral drug dosing errors in HIV-infected patients undergoing hemodialysis.

BACKGROUND: Several studies have revealed the frequency of antiretroviral (ARV) drug prescription errors. We analyzed highly active antiretroviral therapy (HAART) prescribing practices for human immunodeficiency virus (HIV)-infected patients undergoing hemodialysis in France. METHODS: Prescribed ARV drug doses in our cohort (consisting of all HIV-infected patients who underwent hemodialysis from 1 January 2002 and were prospectively followed up until 1 January 2004) were compared with the recommended doses for patients undergoing hemodialysis. The log-rank test was used to compare the outcomes among different groups of treated patients. RESULTS: One hundred seven of the 129 patients in our cohort received a total of 317 ARV drugs, 59% of which were improperly prescribed. The dosing was too low for 18% of the patients and too high for 39% of the patients. Twenty-eight patients (26%) did not receive any of their ARV drugs at the recommended dose. The lowest prescribed dose (8% of the daily recommended dose) was observed with indinavir and zidovudine, and the highest prescribed dose (1000% of the recommended dose) was observed with stavudine. Among patients who received HAART, those who were prescribed an insufficient dose of a protease inhibitor had more-severe HIV disease and worse 2-year survival than did the other patients (mean rate of survival+/-standard deviation, 79.5%+/-7.5% vs. 95.4%+/-2.6%, respectively; P<.02). For dialyzable ARV drugs, the delay between ARV drug receipt by the patients and dialysis sessions was not respected in 9% of cases, and in 73% of cases, it was not known whether the patients took the ARV drugs before or after dialysis sessions. CONCLUSION: This is, to our knowledge, the first study to show a significant association between ARV drug prescription errors and survival in patients undergoing dialysis.

Renal tubular drug transporters.

The kidney plays an important role in the elimination of numerous hydrophilic xenobiotics, including drugs, toxins, and endogenous compounds. It has developed high-capacity transport systems to prevent urinary loss of filtered nutrients, as well as electrolytes, and simultaneously to facilitate tubular secretion of a wide range of organic ions. Transport systems for organic anions and cations are primarily involved in the secretion of drugs in renal tubules. The identification and characterization of organic anion and cation transporters have been progressing at the molecular level. To date, many members of the organic anion transporter, organic cation transporter, and organic anion-transporting polypeptide families have been found to mediate the transport of diverse organic ions. It has also been suggested that ATP-dependent primary active transporters such as MDR1/P-glycoprotein and the multidrug resistance-associated protein family function as efflux pumps of renal tubular cells for more hydrophobic molecules and anionic conjugates. Tubular reabsorption of peptide-like drugs such as beta-lactam antibiotics across the brush-border membranes appears to be mediated by two distinct H+/peptide cotransporters: PEPT1 and PEPT2. Renal disposition of drugs occurs through interaction with these diverse secretory and absorptive transporters in renal tubules. Studies of the functional characteristics, such as substrate specificity and transport mechanisms, and of the localization of drug transporters could provide information regarding the cellular network involved in renal handling of drugs. Detailed information concerning molecular and cellular aspects of drug transporters expressed in the kidney has facilitated studies of the mechanisms underlying renal disposition as well as transporter-mediated drug interactions.

[Statins in patients with kidney failure: efficacy, tolerance, and prescription guidelines in patients with chronic kidney disease and renal transplant]. / Prescription des statines en cas d'insuffisance rénale: efficacité, tolérance et maniement chez le patient insuffisant rénal et chez le patient transplanté rénal.

BACKGROUND: Chronic kidney disease (CKD) is extremely common in adults, although often undiagnosed and thus untreated. Cardiovascular disease is the leading cause of death among patients with CKD and reducing its risk in this population is an important priority. Dyslipidemia is almost always present when proteinuria is above 3 gr/24 hours. Roughly two thirds of all patients with end-stage renal failure and kidney transplants suffer from dyslipidemia and should receive lipid-lowering therapy, as suggested by recent Afssaps (French drug agency) and NKF-K/DOQI (National Kidney Foundation-Kidney Disease Outcomes Quality Initiative) guidelines. We reviewed recent studies on efficacy, tolerability and prescription recommendations of statins in CKD and renal transplant patients. METHODS: We searched Medline, the international medical database, to conduct a systematic review of the literature on the efficacy and tolerability of statins in CKD and renal transplant patients and on specific recommendations for dosage adjustments in this population. RESULTS: The efficacy of statins in decreasing total cholesterol and LDL-cholesterol levels in dialysis and renal transplant patients is similar to that in the general population. On the other hand, large-scale randomized clinical trials among CKD (4D) and renal transplant (ALERT) patients do not demonstrate that statins significantly decrease rates of cardiovascular disease. They have a beneficial effect on proteinuria and lower the rate of kidney function deterioration in patients with dyslipidemia. Early introduction of a statin in transplant patients did not lead to improved kidney function or prevent loss of the graft. Although most statins are not excreted by the kidneys, the dosage of some must be adapted in CKD patients because of pharmacokinetic modifications induced by renal impairment. CONCLUSION: Statins at appropriately adapted doses have the same efficacy in CKD patients as in subjects with normal kidney function, and tolerance is not a problem. Their effectiveness in cardiovascular prevention in this population has not been demonstrated to date. Results about statin-induced kidney protection are encouraging but further and more specific studies are needed.

[Drud-induced nephrotoxicity: Bibliography from January 2003 to December 2005]. / Néphrotoxicité des médicaments: veille bibliographique janvier 2003-décembre 2005.

Drug-induced kidney injury is a major side effect in clinical practice. Renal injury associated with drugs may involve several components of the kidney: glomerulus, tubules, interstitium, and blood vessels. Acute renal failure may occur as a major reaction to many drugs. Moreover, therapeutic agents may induce an allergic reaction leading to interstitial inflammation and tubular damage. In this article, we present an updated version of the bibliography containing the case reports of nephrotoxicity published in the international literature from January 2003 to December 2005.

Treatment of pain in patients with renal insufficiency: the World Health Organization three-step ladder adapted.

The World Health Organization established official recommendations for managing pain in cancer patients. Since then, this stepladder approach has been widely adopted as a conceptual framework to treat all types of pain. However, those guidelines have not been critically evaluated for use in patients with renal insufficiency. In these patients, the questions of drug dosage adjustment and renal toxicity must be considered. This article reviews the pharmacokinetics of major analgesic drugs and data on their use and/or behavior in renal failure and considers their potential nephrotoxicity. Finally, according to available data in the international literature on pharmacokinetics, recommendations for dosage adjustment in patients with renal failure, and their potential nephrotoxicity, the World Health Organization three-step ladder for the treatment of pain was modified and adapted for patients with impaired renal function. Perspective This well-known treatment strategy now adapted for use in patients with renal insufficiency should secure and rationalize pain treatment in those patients.

[Is dialysis efficient in the prevention of ionic contrast agent-induced nephropathy?]. / Néphropathie induite par les produits de contraste iodés, l'epuration extrarénale est-elle efficace en prévention?

UNLABELLED: A FREQUENT AND EXPENSIVE PROBLEM: Ninety percent of contrast media nephrotoxicity (CMN) occur in patients with pre-existing kidney failure. Its aggravation may require early chronic dialysis. PREVENTIVE MEASURES: CMN prophylaxis is important in these patients. Pre- and post-hydration, with infusion of isotonic saline solution or sodium bicarbonate, and reduction of contrast medium (CM) volume to the strict minimum are essential for preventing CM-induced kidney failure. THE INTEREST OF PROPHYLACTIC HEMODIALYSIS AND HEMOFILTRATION: An interesting approach in preventing CMN is the early elimination of the CM with dialysis techniques. Preventive hemodialysis does not reduce the risk of CMN, but hemofiltration has shown significant efficacy in a population of patients with kidney failure. THE INTEREST OF IMMEDIATE HEMODIALYSIS IN CHRONIC HEMODIALYSIS PATIENTS: Although nephrotoxicity is no longer a problem in patients undergoing chronic hemodialysis, CM, especially in high-dose injections, may be responsible for fluid and electrolyte abnormalities and/or volemic expansion. No data yet justify a conclusion that a hemodialysis session immediately after injection of a CM in chronic dialysis patients might be helpful.

[Drug-induced nephrotoxicity: bibliography from January 2003 to December 2004]. / Néphrotoxicité des médicaments : veille bibliographique janvier 2003-décembre 2004.

Drug-induced kidney injury is a major side effect in clinical practice. Renal injury associated with drugs may involve several components of the kidney: glomerulus, tubules, interstitium and blood vessels. Acute renal failure may occur as a major reaction to many drugs. Moreover, therapeutic agents may induce an allergic reaction leading to interstitial inflammation and tubular damage. In this article, we present an updated version of the bibliography containing the case reports of nephrotoxicity published in the international literature from January 2003 to December 2004.

[Drugs renal toxicity]. / Toxicité rénale des médicaments.

Drug-induced renal dysfunction is frequent in clinical practice. Outcomes may be severe, with increased morbidity and mortality. Kidneys are particularly vulnerable to drug toxicity, especially since they are highly vascularized, thus receiving about 25% of cardiac output. Furthermore, interstitial accumulation of toxic agents in papilla and the medulla often occurs due to the existence of a corticomedullary osmotic gradient. Moreover, the key role played by the renal tubule in the reabsorption processes of a number of endogenous and exogenous substances further increases the exposure of the kidney to high concentrations of potentially toxic agents, both in the tubular lumen and cells. As a result, drugs may be toxic to all of the four structures of the kidney: glomerulus, tubule, interstitium, and blood vessels. This chapter reviews the main mechanisms of drug-induced renal toxicity and then focuses on the nephrotoxicity of anti-infectious drugs: antibacterial drugs, antifungal agents, antimalariae, and antiviral drugs. NSAID and anticancer drugs renal toxicity are detailed elsewhere in this textbook. Methods used to prevent drug-induced nephrotoxicity, when known, are detailed. Risk factors are also listed, such as high-risk populations, identification and elimination of risk factors, and drug dosage adjustment in patients with baseline abnormal renal function.

Prevalence of nephrogenic systemic fibrosis in renal insufficiency patients: results of the FINEST study.

PURPOSE: Nephrogenic systemic fibrosis (NSF) is characterized by widespread tissue fibrosis, mainly affecting the skin. Gadolinium chelates have been implicated in the onset of NSF in patients with renal impairment (RI). The FINEST study (FIbrose Néphrogénique SysTémique) was designed to determine the prevalence of NSF after magnetic resonance imaging (MRI) in French RI patients. MATERIALS AND METHODS: We studied all patients with RI who had at least one MRI examination during a one-year period, with or without gadolinium chelate administration. Data were collected retrospectively from 9 Nephrology Departments in France, and included sex, age, renal function, type of gadolinium administered, and subsequent cutaneous disorders. If a patient presented a cutaneous disorder, a skin biopsy was performed to confirm the diagnostic. RESULTS: The 308 eligible patients had a mean age of 59.9 years, 59% were men, and 54% had stage 5 RI. 75% of those 308 patients received a Gadolinium chelate. Among those patients who received a gadolinium chelate, 76% received gadoterate, 20% gadopentetate, 3% gadodiamide and 1% gadobenate. No cutaneous disorders were recorded after MRI. CONCLUSION: These results confirm that NSF is a rare disease. Based on a reported frequency, approximately 3.5% in patients with glomerular filtration rate <30ml/min/1.73m(2)), some cases should have been observed in our study which included 308 patients. Most patients received gadoterate, a macrocyclic gadolinium chelate for which no case of NSF has been observed worldwide. This suggests that more stable macrocyclic agents may be less likely to induce NSF.

[Chemotherapy and renal toxicity]. / Chimiothérapie et toxicité rénale.

Antineoplastic drugs used in the treatment of cancers present with variable renal tolerance profiles. Among drugs with a potential for renal toxicity, platinum salts, methotrexate, and gemcitabine are well-known. The mechanisms of their renal toxicity and the means of its prevention are presented in this article. Anti-angiogenic drugs, recently marketed or still under clinical development, may also interact with the kidneys. In general, optimising the renal tolerance of anticancer drugs requires an appropriate evaluation of patients'renal function, before and during treatment, at each course. Serum creatinine alone is not a reliable index of renal function. Its evaluation must be performed with the use of Cockcroft-Gault or aMDRD formulae. In patients with abnormal renal function, dosage adjustment is often required to improve the renal tolerance, and also to limit the risk of extra-renal toxicities (such as haematological toxicities) induced by a drug overdosage, in those patients with reduced drug-elimination.

Drug-induced glomerulopathies.

Normal renal function depends upon an intact glomerular apparatus. Many drugs and chemicals are capable of damaging the glomerulus, causing its increased permeability to large molecules. Glomerular lesions are usually responsible for proteinuria and the nephrotic syndrome. This also holds true for the drug-induced glomerulopathies, of which membranous glomerulo-nephritis is the most frequent type of lesion encountered. Apart from this, several cases of different glomerular changes such as focal segmental glomerulosclerosis and crescentic glomerulonephritis have also been reported. The drug-induced glomerulopathies are probably immune mediated. This is, for instance, reflected in the fact that patients with drug-induced nephritic syndrome frequently have the HLA-B8 and DR3 antigens. In depth information is provided for the previously mentioned disorders.

Outcome and prognosis factors in HIV-infected hemodialysis patients.

HIV-infected patients who are on hemodialysis have a worse prognosis than noninfected patients who are on hemodialysis. Their outcome in the highly active antiretroviral therapy (HAART) era remains unclear. Outcomes in patients who were enrolled in the French Dialysis in HIV/AIDS (DIVA) cohort were determined in a 2-yr prospective follow-up. All HIV-infected patients who were on hemodialysis in France on January 1, 2002, were included and followed prospectively until January 1, 2004. Patients' survival was examined by Kaplan-Meier method, and mortality risk factors were examined using uni- and multicovariate analyses. Survival was compared with that of 584 hemodialysis patients who did not have HIV or diabetes and were enrolled in the French Dialysis Outcomes and Practice Patterns Study II (DOPPS II) in the same period (after standardization for the average age, gender, and ethnicity of the DIVA cohort). A total of 27,577 patients were receiving hemodialysis in France at the beginning of the study; 164 (0.59%) were infected with HIV, 72% were male, mean age was 44.8 +/- 10.9 yr, and 65% were black. The 2-yr survival rate was 89 +/- 2% and statistically indistinguishable from the survival of the French cohort extracted from the DOPPS II study. Significant mortality risk factors were low CD4 cell count (hazard ratio [HR] 1.4/100 CD4 cells per mm(3) lower), high viral load (HR 2.5/1 Log per ml), absence of HAART (HR 2.7), and a history of opportunistic infection (HR 3.7), the last two being independent (HR 2.6 and 3.6, respectively). Survival of HIV-infected patients who are hemodialysis has greatly improved. A prospective cohort of paired hemodialysis patients with and without HIV is required to compare better their mortality in the HAART era.