EMC - Néphrologie最新文献

Diabetic nephropathy is the most serious problem among current issues in nephrology, as 40 % of the cases of end-stage renal disease are due to this entity. The close relationship between type 2 diabetes and hypertension makes the problem even more severe. The knowledge of the intrarenal effects of angiotensin II and the greater effect of angiotensin converting enzyme inhibitors (ACEI) on reducing albuminuria suggested in the past a trend toward preferable use of these drugs in diabetic nephropathy. The first relevant clinical trials yielded rather poor conclusions because of lack of blind randomization and short duration. Subsequent double-blind studies with adequate numbers of patients and sufficient duration underlined the importance of blood pressure (BP) control as well as the rather poor response of diabetic nephropathy to any treatment. In most of these studies, the changes in albuminuria or microalbuminuria were a substitute end point for the renal function. Three clinical trials using angiotensin II receptor blockers (ARB), planned specifically to monitor the progression of renal damage, have been recently published. They showed better renal protection by ARB, as compared with placebo or calcium channel blockers (CCB), beyond or independently of the BP reduction. Nevertheless, these recent trials, like the previous ones with similar results, invariably demonstrate slightly better control of BP in the groups of the active drug. Another issue is that the vast majority of the patients need so many nonstudy drugs to keep their pressure under control, that the isolation of advantageous effects of certain drugs seems unrealistic.

Despite major improvements in immunosuppressive therapy during the past decade, infections and cancers remain a frequent complication after renal transplantation. Infections are generally due to bacteria during the first post-transplant month (wound, pulmonary, urinary infections) and to opportunistic agents from month 2 to month 6 post-transplant : viruses (herpes-virus particularly cytomegalovirus (CMV), bacteria (nocardia, listeria, mycobacteria) of fungi (candida, pneuymocyistis carinii). After month 6, urinary and pulmonary infections are frequent and those recipients with over-immunosuppression and/or unsatisfactory graft function may experience opportunistic infections. Since the availability of antiviral drugs, particularly ganciclovir used for prophylaxis or treatment of CMV infection, the incidence and the severity of viral diseases had significantly decreased. However, due to higher efficacy of new immunosuppressive drugs, “new” viral infections (polyomavirus, parvovirus, west-nile virus) had emerged in the transplant population. BK virus nephropathy is now a new cause of graft dysfunction. Maligrances occur much more frequently in the transplant than in the general population ; twenty ears post-transplant, incidence of cancer may be as high as 40 %. The main cause of cancer in the transplant population is chronic replication of oncogenic viruses promoted by immunosuppression. In fact, the most frequent malignancies are skin cancers due to papillomaviruses, post-transplant lymphoproliferative disorders (PTLD) due to Epstein-Barr virus, Kaposi sarcoma associated with HHV-8 and hepatocarcinomas associated with B or C hepatitis viruses. In HHV-8 or EBV donor positive/recipient negative pairs, regular monitoring of viremia should provide a mean of detecting patients at risk of developing Kaposi sarcoma or PTLD in order to prevent malignancies.

Recurrent and de novo glomerulonephritis is an important cause of renal dysfunction after renal allografting. It is known to negatively impact the transplant graft survival. In the present review, we describe the incidence, clinical features, histological characteristics, risk factors, prognosis, and treatment of the different types of recurrent and de novo glomerulonephritis in allografted patients. Diagnosis is based on histological examination of renal biopsy samples by optic and, if needed, electron microscopy. Recurrent glomerulopathy is the most frequent condition. However, it is uncommon in systemic lupus erythematosus. De novo glomerulonephritis is less frequent. Chronic transplant glomerulopathy may cause a late graft loss. It is thought to be the only post-transplant glomerulopathy intrinsically due to alloimmunisation.

Nephrosclerosis is the renal disease which appears as a consequence of long-standing (and generally poorly treated) hypertension. It is manifested as a slowly progressive renal failure that may eventually lead to end-stage renal failure. It is considered responsible for more than 20% of patients entering dialysis in the United States. In fact, nephrosclerosis is relatively frequent in the Afro-American population, but it seems very rare in other groups. Hypertension results in vascular, glomerular, then interstitial lesions of the kidney. Hypertensive renal damage is more pronounced when systemic blood pressure is transmitted to the glomerular circulation, due to altered self-regulation. The frequency of nephrosclerosis is obviously overestimated, due to the lack of renal biopsy; moreover the precession of hypertension on renal disease is rarely established. Doubt has been cast on this concept. The alternative hypothesis is that the primary abnormality is renal, mostly congenital, and responsible for the elevation of blood pressure. Blood pressure and renal injury are then engaged in a vicious circle, aggravating each other. Anyway, lowering blood pressure is the only therapeutic measure able to stop the self-aggravation loop. Some antihypertensive drugs, especially those inhibiting the renin angiotensin system, have a direct action on renal haemodynamics, and seem to be nephroprotective beyond the lowering of blood pressure.

These past years, many causes and mechanisms of inherited renal kidney diseases have been identified. The study of the mutations identified has improved our knowledge in renal tubule physiology. The identification of new proteins and the disruption of the genes encoding these proteins in mouse unravelled the cause of diseases described many years ago. The physiopathology of most tubular disorders is now known. The accurate analysis of patients' phenotype, based on the knowledge in renal physiology, allowed identifying the tubular part(s) involved in the abnormalities observed. We briefly summarise the main functions of each tubule segment, and describe the inherited disorders currently identified together with their pathophysiology. We describe the dysfunctions of proximal tubule (glycosuria, renal phosphate leak, aminoaciduria, tubular acidosis, urate excretion), thick ascending limb (Bartter's syndrome, hypercalciuria, hypermagnesuria…), distal tubule (Gitelman's syndrome, Gordon's syndrome…), collecting duct (distal tubular acidosis, salt wasting or retention syndrome…). Diabetes insipidus is not included.