Benefits of Selective Vitamin D Receptor Activators in Kidney Transplanted Patients

Severe chronic kidney disease may lead to disturbances, such as hyperphosphatemia, increased secretion of fibroblast growth factor -23 (FGF -23) and vitamin D deficiency. These may increase plasmatic levels of parathyroid hormone, and decrease plasmatic levels of calcium. Altogether, these may contribute to the development of secondary hyperparathyroidism, and to abnormalities in mineral metabolism. Kidney transplantation is the best option to improve longevity and quality of life in end -stage chronic kidney disease patients. Vitamin D deficiency has been associated with cardiovascular disease, which is the leading cause of death in chronic kidney disease. Therefore, diagnosing this deficiency may be pivotal for minimizing mortality in chronic kidney disease, because pharmacological treatments for this deficiency may be prescribed. Calcitriol is indicated for the treatment of vitamin D deficiency, both in chronic kidney disease and in kidney transplanted patients. However, calcitriol may increase the plasmatic levels of calcium and phosphorous, which can lead to vascular calcifications, that have been associated with cardiovascular mortality. Selective vitamin D receptor activators are indicated for the treatment of vitamin D deficiency in chronic kidney disease. These have the advantage of being associated with lower increases of plasmatic levels of calcium and phosphorous. These drugs also seem to have additional effects that may minimise patient morbidity and mortality, especially due to potentially reducing cardiovascular events. Unfortunately, there are few studies about the use of these drugs in kidney transplanted patients. Here we present a review about the physiology of vitamin D, the consequences of its deficiency in chronic kidney disease and in kidney transplanted patients, and about the diagnosis and treatment of this deficiency. Finally, we discuss the new line of research about the efficacy and safety of selective vitamin D receptor activators in kidney transplanted patients.

A new surgical approach for treating dilated cardiomyopathy with mitral regurgitation

OBJECTIVE: To evaluate the early outcome of mitral valve prostheses implantation and left ventricular remodeling in 23 patients with end-stage cardiomyopathy and secondary mitral regurgitation (NYHA class III and IV). METHODS: Mitral valvular prosthesis implantation with preservation of papillary muscles and chordae tendinae, and plasty of anteriun cuspid for remodeling of the left ventricle. RESULTS: The surgery was performed in 23 patients, preoperative ejection fraction (echocardiography) varied from 13% to 44% (median: 30%). In 13 patients associated procedures were performed: myocardial revascularization (9), left ventricle plicature repair (3) and aortic prosthese implantation (1). Early deaths (2) occurred on the 4th PO day (cardiogenic shock) and on the 20th PO day (upper gastrointestinal bleeding), and a late death in the second month PO (ventricular arrhythmia). Improvement occurred in NYHA class in 82.6% of the patients (P<0.0001), with a survival rate of 86.9% (mean of 8.9 months of follow-up). CONCLUSION: This technique offers a promising therapeutic alternative for the treatment of patients in refractory heart failure with cardiomyopathy and secondary mitral regurgitation.

Mitral Valve Replacement and Remodeling of the Left Ventricle in Dilated Cardiomyopathy with Mitral Regurgitation: Initial Results

OBJECTIVE: This study evaluated the effects of a new method of mitral valve replacement on left ventricular (LV) remodeling and heart failure functional class. METHODS: Eight patients (6 men) with severe mitral regurgitation from end-stage dilated cardiomyopathy underwent surgery. Five patients were in functional class (FC) IV, 2 were in FC III and 1 was in FC III/IV. Age ranged from 33 to 63 years. Both the anterior and posterior leaflets of the mitral valve were divided into hemileaflets. The resultant 4 pedicles were displaced under traction toward the left atrium and anchored between the mitral annulus and an implanted valvular prosthesis. The beating heart facilitated ideal chordae tendineae positioning. RESULTS: All patients survived and were discharged from the hospital. After a mean follow-up period of 6.5 months (1-12 m), 5 patients were in FC I; 2 in FC I/II; and 1 in FC II. The preoperative ejection fraction ranged from 19% to 30% (mean: 25.7±3.4 %), and the postoperative ejection fraction ranged from 21% to 40% (mean: 31.1± 5.8%). Doppler echocardiography showed evidence of LV remodeling in 4 patients, including lateral wall changes and a tendency of the LV cavity to return to its elliptical shape. CONCLUSION: This technique of mitral valve replacement, involving new positioning of the chordae tendineae, allowed LV remodeling and improvement in FC during this brief follow-up period.

Options chirurgicates pour l'insuffisance cardiaque terminale [Surgical options for terminal heart failure]

Terminal heart failure can be the cause or the result of major dysfunctions of the organisms. Although, the outcome of the natural history is the same in both situations, it is of prime importance to differentiate the two, as only heart failure as the primary cause allows for successful mechanical circulatory support as bridge to transplantation or towards recovery. Various objective parameters allow for the establishment of the diagnosis of terminal heart failure despite optimal medical treatment. A cardiac index <2.0 l/min, and a mixed venous oxygen saturation <60%, in combination with progressive renal failure, should trigger a diagnostic work-up in order to identify cardiac defects that can be corrected or to list the patient for transplantation with/without mechanical circulatory support.

Severe rhabdomyolysis following venlafaxine overdose.

Venlafaxine is a recently developed serotoninergic antidepressant whose reported toxicity at overdose levels includes central nervous system depression, seizures, and cardiovascular toxicity. The authors now present a case of venlafaxine overdose in a young woman complicated by a rise in plasma creatine kinase activity up to 52,600 U/L. Immediate therapy with intravenous fluids, bicarbonate, and furosemide was administered, and there were no further complications, notably no renal failure. This case supports the notion that venlafaxine can induce direct skeletal muscle toxicity leading to severe rhabdomyolysis. Therefore, clinicians should monitor muscle enzymes in patients with venlafaxine overdose to detect the development of rhabdomyolysis at an early stage and to initiate appropriate therapy rapidly.

Transplantation rénale pédiatrique: expérience lausannoise de 1971 à 1998 [Pediatric renal transplantation: Experience in Lausanne 1971 to 1998].

AIMS OF THE STUDY: Analysis of indications and results of paediatric renal transplantation in a single centre, before and after the introduction of cyclosporine A (CSA). METHODS: Historical retrospective study. RESULTS: 19 transplantations were performed in 14 patients (5 second grafts) between 1971 and 1987 (group I). 13 patients were transplanted between 1988 and 1998 (no second transplant) (group II). In group II, all the patients had immunosuppression with CSA, but none in group I. Group II, with CSA, showed better renal survival than patients without CSA. In group I, obstructive uropathies (posterior urethral valves, pyelo-ureteral junction stenosis, vesico-ureteral reflux) represent a common cause (35%) of terminal chronic renal failure (TCRF), whereas in group II they represent only 15% of the causes and chronic glomerulonephritis is the most common cause (69%) of TCRF. Acute and chronic graft rejections were the cause of 9 and 1 graft losses in group I and II respectively. Living related donors account for 14% of all renal transplantations in group I and 46% in group II. CONCLUSIONS: The incidence of paediatric patients referred to Lausanne for TCRF is stable. We have observed a constant and steady decrease in obstructive uropathies leading to TCRF and renal transplantations, whereas glomerulonephritis are increasingly frequent. Graft survival has much improved since the introduction of cyclosporine A, without an increase in morbidity. In carefully selected cases, intrafamilial renal transplantation provides good results and helps to shorten the time spent on dialysis.

Insuficiència renal i mortalitat dels pacients cirròtics amb peritonitis bacteriana espontània i baix risc de mortalitat no tractats amb albúmina

L’expansió amb albúmina disminueix la incidència d’insuficiència renal i la mortalitat dels pacients cirròtics amb peritonitis bacteriana espontània (PBE). Però no està ben establert si caldria administrar-la a tots aquests pacients. Aquest estudi determina la incidència i evolució de la insuficiència renal i mortalitat en una sèrie no seleccionada de pacients cirròtics amb PBE i baix risc de mortalitat (urea&11mmol/l i bilirrubina&68µmol/l) no tractats amb albúmina. La baixa mortalitat i la bona evolució de la funció renal observades en els pacients amb PBE i baix risc de mortalitat no tractats amb albúmina, suggereixen que en aquests pacients no caldria administrar albúmina.

Le syndrome hépatorénal chez le patient cirrhotique [Hepatorenal syndrome in patients with liver cirrhosis].

Hepatorenal syndrome is a particular form of functional renal failure which may develop in patients with liver cirrhosis. On a clinical standpoint, precise diagnostic criteria have been established to clearly define this entity, whereas recent advances in the understanding of the biology of vasoactive mediators and the physiology of microcirculation have allowed to better anticipate its pathophysiological mechanisms. During the course of cirrhosis, sinusoidal portal hypertension leads to splanchnic and systemic vasodilation, responsible for a reduction of effective arterial blood volume. As a result, a state of intense renal vasoconstriction develops, leading to renal failure in the absence of any organic renal disease. At this stage, liver transplantation is the only definitive therapy able to reverse renal dysfunction. In recent years, innovative therapies have shown promise to prolong survival in patients with hepatorenal syndrome, including the administration of analogs of vasopressin (mainly terlipressin), the insertion of transjugular intrahepatic portosystemic shunts and the use of novel techniques of dialysis. On a preventive viewpoint, several simple measures have been shown to reduce the risk of hepatorenal syndrome in cirrhotic patients, including the appropriate use of diuretics, the avoidance of nephrotoxic drugs, the prophylaxis of spontaneous bacterial peritonitis and optimal fluid management in patients undergoing large volume paracentesis.

Vitaminas B y homocisteína en la insuficiencia renal crónica

Metabolic, biochemical, and hormonal changes occur in chronic renal failure usually associated with hyponutrition states. In predialysis patients, knowing the nutritional state about water-soluble vitamins such as thiamine, riboflavin, pyridoxine, cianocobalamine, and folic acid is becoming more and more important since some of the manifestations of chronic renal failure may be due to the deficiency of some of these water-soluble vitamins. The metabolic pathways in which most of these vitamins participate are interrelated and it is difficult to understand how the individual deficits of each vitamin affect renal pathology. This work aims at reviewing not only this issue but also the status of these water-soluble vitamins that different authors have found in groups of predialysis patients. On the other hand, the issue on the high prevalence of hyperhomocysteinemia in chronic renal failure as the main mortality risk factor due to cardiovascular pathologies as well as the implication of these vitamins in the metabolism of homocysteine, and consequently in plasma levels of this metabolite in predialysis patients is reviewed.

The appropriateness of renal angioplasty: the ANPARIA software: a multidisciplinary expert panel approach

Percutaneous transluminal renal angioplasty (PTRA) is an invasive technique that is costly and involves the risk of complications and renal failure. The ability of PTRA to reduce the administration of antihypertensive drugs has been demonstrated. A potentially greater benefit, which nevertheless remains to be proven, is the deferral of the need for chronic dialysis. The aim of the study (ANPARIA) was to assess the appropriateness of PTRA to impact on the evolution of renal function. A standardized expert panel method was used to assess the appropriateness of medical treatment alone or medical treatment with revascularization in various clinical situations. The choice of revascularization by either PTRA or surgery was examined for each clinical situation. Analysis was based on a detailed literature review and on systematically elicited expert opinion, which were obtained during a two-round modified Delphi process. The study provides detailed responses on the appropriateness of PTRA for 1848 distinct clinical scenarios. Depending on the major clinical presentation, appropriateness of revascularization varied from 32% to 75% for individual scenarios (overal 48%). Uncertainty as to revascularization was 41% overall. When revascularization was appropriate, PTRA was favored over surgery in 94% of the scenarios, except in certain cases of aortic atheroma where sugery was the preferred choice. Kidney size [7 cm, absence of coexisting disease, acute renal failure, a high degree of stenosis (C70%), and absence of multiple arteries were identified as predictive variables of favorable appropriateness ratings. Situations such as cardiac failure with pulmonary edema or acute thrombosis of the renal artery were defined as indications for PTRA. This study identified clinical situations in which PTRA or surgery are appropriate for renal artery disease. We built a decision tree which can be used via Internet: the ANPARIA software (http://www.chu-clermontferrand.fr/anparia/). In numerous clinical situations uncertainty remains as to whether PTRA prevents deterioration of renal function.

Estimation de la fonction rénale par l'equation MDRD: intérêt et limites pour l'adaptation des doses de médicaments [Renal function estimation by MDRD equation: interest and limitations for drug dosing].

The MDRD (Modification of diet in renal disease) equation enables glomerular filtration rate (GFR) estimation from serum creatinine only. Thus, the laboratory can report an estimated GFR (eGFR) with each serum creatinine assessment, increasing therefore the recognition of renal failure. Predictive performance of MDRD equation is better for GFR < 60 ml/min/1,73 m2. A normal or near-normal renal function is often underestimated by this equation. Overall, MDRD provides more reliable estimations of renal function than the Cockcroft-Gault (C-G) formula, but both lack precision. MDRD is not superior to C-G for drug dosing. Being adjusted to 1,73 m2, MDRD eGFR has to be back adjusted to the patient's body surface area for drug dosing. Besides, C-G has the advantage of a greater simplicity and a longer use.

Haben selektive COX-2-Hemmer unerwünschte renale und kardiovaskuläre Wirkungen [Do selective COX-2 inhibitors have adverse renal and cardiovascular effects?].

Selective cyclooxygenase-2-inhibitors (COX-2) were developed as an alternative to the non-steroidal anti-inflammatory drugs (NSAID) in order to reduce their known gastrointestinal and renal toxicity. Several recent studies have shown the complex mechanism of the cyclooxygenase-2. The inhibition of the COX-2 has effects on renal hemodynamics, renal salt and water retention and may increase the thromboembolic and therefore the cardiovascular risk. The renal toxicity of the COX-2 inhibitors is similar to that of traditional NSAID. Regarding these data, COX-2 inhibitors should be prescribed with much caution to high risk patients, that is, patients with renal failure and/or cardiovascular diseases.

Glucosurie rénale [Renal glucosuria].

The occurrence of glucosuria in the absence of hyperglycemia is distinctive for renal glucosuria. SGLT2 mutations provoke familial renal glucosuria characterized by persistent glucosuria in the absence of any other renal tubular dysfunction. Renal glucosuria associated with others proximal tubular dysfunctions points to Fanconi syndrome. This generalized dysfunction of proximal tubule needs to be treated and may progress regarding its aetiology to chronic renal failure. The development and study of models of Fanconi syndrome has recently contributed to a better knowledge of the mechanisms implicated in the tubular transport of glucose and low-molecular-weight-proteins. This article reviews these recent developments.

Troubles du sommeil chez des patients présentant une insuffisance rénale chronique [Sleep disorders in patients with chronic renal insufficiency].

Sleep disorders, especially insomnia, daytime sleepiness, sleep apnea syndrome and restless legs syndrome are very frequently encountered in patients with chronic renal failure whether or not they undergo renal replacement therapy. The causes of sleep disorders are multifactorial and not only linked to the renal disease itself, but also to its treatment and its associated psychosocial factors. This article discusses the prevalence and physiopathology of the most frequently encountered sleep disorders in chronic renal failure patients, and highlights the actually available therapeutic options.

La néphropathie ischémique par athérosclérose aortorénale : diagnostic [Atherosclerotic renal artery disease diagnosis update].

Atherosclerotic renal artery disease represents a cause of which little is known but not a cause to be neglected for hypertension and renal insufficiency. Even though its occurrence remains badly defined, atherosclerotic renal artery disease is constantly on the rise due to the aging population, the never prevailing hypertension and diabetes mellitus. This review aims to give a clinical profile of patients presenting with atherosclerotic renal artery disease and to discuss, in the light of study results, which diagnostic evaluation should be used considering the sequence and the benefit and risk of each in order to initiate a personalized treatment. Patients affected by atherosclerotic renal artery disease are likely to have more complications and more extensive target-organ damage than patients without renal artery stenosis. The evolution of the atherosclerotic renal artery disease is in general slow and progressive. Nevertheless, certain clinical cases manifest themselves with the onset of acute renal failure bought upon by the administration of blockers of the rennin-angiotensin-aldosterone system, or by some other causes responsible for a sudden drop in renal plasma flow (e.g., thrombosis of the renal artery). The relationship between atherosclerotic renal artery disease and atherosclerosis is complex, and mediators implicated in the pathophysiology of renovascular disease may also contribute to the progression of cardiovascular damage. An early assumption of the atherosclerotic renal artery stenosis is warranted to determine the adapted treatment (i.e., medical treatment, revascularisation...) just as the assumption and the correction of the more general cardiovascular risk factors.