Beneficial effect of one HLA haplo- or semi-identical transfusion versus three untyped blood units on alloimmunization and acute rejection episodes in first renal allograft recipients.

Acute allograft rejection is the major risk factor of renal function decline and graft loss. Beside histocompatibility matches and pharmacological immunosuppression, blood transfusion is empirically used to detect responder subjects and to induce immune tolerance. Alloimmunization associated with blood transfusions readily detected by anti-HLA antibodies could induce acute vascular rejection episodes during the early period after grafting. Our open prospective study was aimed at analyzing the 1 year follow-up of 105 successive first cadaver renal transplant recipients according to the transfusion protocol as assessed by anti-HLA antibody production, acute rejection episodes, and graft survival. Our conventional transfusion protocol involved 3 nonphenotyped blood transfusions set up at least 20 days before grafting in a control cohort (group A) and was compared with a single pretransplant HLA haplo- or semi-identical blood transfusion in a successive group of patients (group B). Our results suggest that both protocols were associated with similar 1-year graft survivals (> 96% in both groups) and number of patients experiencing rejection episodes (20.7% in group A; 9.6% in group B; P NS). HLA haplo- or semi-identical transfusion was significantly beneficial in naive patients without previous alloantigen contact by pregnancy or blood transfusions during dialysis. Naive patients in group B did not develop post-transfusion anti-HLA antibodies compared to naive patients in group A (16.6%; P < 0.001), and they experienced significantly less acute rejection episodes (2.7%) compared to group A naive patients (20.8%; P = 0.02).

Role of ACE inhibitors in patients with diabetes mellitus.

The adjective 'epidemic' is now attributed to the rapidly growing number of patients with diabetes mellitus, mainly type 2. and the specific complications linked to this disorder. Provided they are recognised early enough, these different complications can be treated; in some patients the evolutive course of these complications can be slowed or even stopped. Furthermore, some recent observations suggest that specific tissular lesions may be prevented or even reversed. Although glycaemic control is essential, other therapeutic measures that must also be taken include those to control blood pressure and to lower lipid levels. Of the agents available to control the complications of diabetes mellitus, cardiovascular drugs, and particularly ACE inhibitors, have a pre-eminent place. Experimental and epidemiological data suggest that activation of the renin-angiotensin-aldosterone system plays an important role in increasing in the micro- and macrovascular complications in patients with diabetes mellitus. Not only are ACE inhibitors potent antihypertensive agents but there is a growing body of data indicating that also they have a specific 'organ-protective' effect. For the same degree of blood pressure control, compared with other antihypertensive agents, ACE inhibitors demonstrate function and tissue protection of considered organs. ACE inhibitors have been reported to improve kidney, heart, and to a lesser extent, eye and peripheral nerve function of patients with diabetes mellitus. These favourable effects are the result of inhibition of both haemodynamic and tissular effects of angiotensin II. Finally, there are a growing number of arguments favouring the use of ACE inhibitors very early in patients with diabetes mellitus.

[Mixed cryoglobulinemia with necrotizing angiitis. Apropos of 2 cases]. / Cryoglobulinémies mixtes avec angéites nécrosantes. A propos de deux observations.

Out of a series of 26 personal cases, 2 cases of mixed IgM-IgG cryoglobulinemia, one type II the other type III, are reported because they were associated with histologically proven necrotizing vasculitis. In both cases the numerous symptoms were due to renal damage (the vasculitis was discovered in the kidney) and to peripheral neuropathy. One of the patients died; the other had severely deteriorated general condition and required substitution hemodialysis. Cases of vasculitis associated with mixed cryoglobulinemia have often been published, but there are few reports mentioning necrotizing vasculitis; a search in the literature yielded only 9 cases. This small number does not mean that mixed cryoglobulinemia should not be listed among the causes of necrotizing vasculitis, but it makes it difficult to extract those specific features that would enable to predict which case of mixed cryoglobulinemia is associated or not with necrotizing vasculitis.

[Heterogeneity of nephropathies in type 2 diabetes]. / Hétérogénéité de la néphropathie chez les diabétiques de type 2.

DIVERSE KIDNEY DISORDERS: Patients with type 2 diabetes mellitus who develop nephropathy can have various types of disorders capable of progressively destroying the kidneys. It is now clear that the same type of diffuse or nodular glomerulosclerosis develops irrespective of the type of diabetes, i.e. the pathophysiology of hyperglycemia. HETEROGENEITY: There is however a certain degree of heterogeneity in terms of clinical presentation, clinical course and response to treatment. Heterogeneity is due to age, the number of different accumulated risk factors and disease states, genetic factors that are in the process of being identified, and finally, lesions to the urologic apparatus, the arteries, and the renal parenchyma itself that are not directly caused by diabetes. PRACTICAL IMPACT: Mixed lesions, due to both diabetic and non-diabetic causes, may therefore exist in the same kidney. These different possibilities should be systematically considered in order to adopt an individualized investigative and therapeutic attitude for each new patient.

[Mesenteric ischemia in hemodialyzed patients]. / L'ischémie mésentérique chez le sujet dialysé.

OBJECTIVES: Mesenteric ischemia is uncommon in the general population but is frequently encountered in chronic hemodialysis patients. We present here four cases which occurred in our unit within one year while only six cases had been observed in the preceding twenty years. OBSERVATIONS: Four chronic hemodialysis patients (age: 57 to 76 years) with renal failure due to diffuse atheromatous disease, presented non-occlusive mesenteric ischemia. One patient died and one underwent resection of the colon. For the final two patients, prophylactic therapy was initiated. DISCUSSION: Mesenteric ischemia is a severe condition which appears to occur more frequently in end-stage renal disease. In the chronic hemodialysis patient excessive ultrafiltration or a too rapid filtration rate can favor ischemia. Prophylactic measures must be taken at the first sign of ischemia, especially since clinical and biological features of mesenteric ischemia remain largely non-specific.

[How does one explain the very good performance of Spanish nephrology]. / Comment expliquer les très bonnes performances de la néphrologie espagnole actuelle?

Spain is a highly performing country in nephrology with 2000 kidney grafts a year (50 pmp); 42% of end stage renal disease patients have a functioning kidney graft (338 pmp); the highest level worldwide of organ donors (33.9 pmp) and very few living donors and finally one of the lowest level in Europe of "late referral to nephrologists" (18%). Amongst various explanations emerge the fact that the number of nephrologist is high in this 40 millions inhabitants country (more than one thousand) when they are less than the thousand for 60 millions inhabitants in France.

[Aggravation of anemia in a hypertensive hemodialysis patient by captopril treatment]. / Aggravation de l'anémie chez un sujet hémodialysé hypertendu par un traitement au captopril.

We report here the case of an hypertensive chronic hemodialysis patient treated by captopril. Captopril treatment has been effective in normalizing blood pressure but induced a severe anemia necessitating frequent transfusions. Captopril withdrawal eliminated transfusion needs.

Epidemiology, development and treatment of end-stage renal failure in type 2 (non-insulin-dependent) diabetes mellitus. The case of mainland France and of overseas French territories.

The prevalence of diabetes mellitus among patients treated for end-stage renal failure by dialysis in France was studied in two stages (UREMIDIAB Study). The first stage consisted of a questionnaire which was mailed to all dialysis centres in mainland France. The response rate was 80.8%, resulting in a study population of 12,903 patients. Of these patients 884 were declared diabetic (6.9%). Later 295 of them were interviewed by seven specially-trained physicians who checked the medical records together with the nephrologist in charge. Plasma C-peptide was measured in almost all of the patients. Effectively, 1.4% were found to have Type 1 diabetes and 5.5%, Type 2. Diabetic nephropathy was found to be the only primary renal diagnosis among 93.9% of Type 1 diabetic patients and 36.8% of Type 2. Of the latter 51.6% had a non-diabetic cause of renal failure. In the second stage a survey was later conducted in 13 of 14 dialysis centres located in the remote overseas French territories. Among 934 patients 1.04% were Type 1 diabetic and 19.67% Type 2 (22.9% altogether). Type 2 diabetic patients treated overseas were essentially non-Caucasians (92.6%). The sex ratio was 0.54 in the overseas territories vs 1.4 in the mainland. We conclude that the prevalence of diabetes among people on dialysis is low in mainland France. But there are striking differences in the prevalence of Type 2 diabetes among dialysis patients in mainland France and its overseas territories. These differences are not related to access to dialysis facilities.

Does ACE inhibition slow progression of glomerulopathy in patients with Type 2 diabetes mellitus?

AIMS: To examine the effect of ACE inhibition on glomerular structure in Type 2 diabetic patients with nephropathy. METHODS: Twenty-two patients were randomized to receive either perindopril (PE) or placebo (PO) and biopsied at baseline and after 2 years. Nineteen patients completed the study and data on interstitial changes, examined by light microscopy, have already been published. Only 11 patients (five PE, six PO) had sufficient tissue at baseline and follow-up to provide material for detailed electron microscopic examination. RESULTS: At baseline, mean +/- sd age (PE vs. PO) was 48 +/- 12 vs. 45 +/- 7 years; creatinine clearance 116 +/- 24 vs. 128 +/- 68 ml/min; median (range) proteinuria 0.7 (0.1-1.0) vs. 0.5 (0.07-3.9) g/24 h (P = NS for all). This cohort of 11 patients showed the same interstitial changes as the whole group. Between-group analysis showed that the change in interstitial volume fraction was significantly greater in the PO compared with PE group (0.10 +/- 0.07 vs. -0.001 +/- 0.04, P = 0.020). There were no significant changes in proteinuria or glomerular structural parameters (mesangial volume fraction PO 0.40 +/- 0.17 to 0.42 +/- 0.21; PE 0.29 +/- 0.08 to 0.28 +/- 0.14) in either treatment group. CONCLUSIONS: Interstitial changes appear to be more sensitive to ACE inhibition than glomerulopathy. Larger patient groups and longer treatment periods are necessary in order to detect any possible impact of ACE inhibition on the glomerular changes in Type 2 diabetes mellitus.

Inter-regulated balance between gelatinases and tissue inhibitor (TIMP-1) in isolated human glomeruli.

Leukocyte infiltration inside glomeruli necessitates basement membrane collagen i.v. breakdown and leads to mesangiolysis, cell proliferation and extracellular matrix synthesis during the repair process as observed in the course of acute glomerulonephritis, vasculitis and acute graft rejection. Two matrix metalloproteinases, MMP-2 and MMP-9 gelatinases, are expressed and co-secreted in balance with the tissue inhibitor of metalloproteinases-1 (TIMP-1) by activated neutrophils as well as by glomerular cells and are aimed to control basement membrane collage i.v. deposition. Using a conventional double mesh sieving method, pure populations of glomeruli were isolated from fresh human cortex specimen and maintained in short-term cultures. ELISA, zymography and immunoblotting of conditioned serum-free media revealed glomerular MMP-2, MMP-9 and TIMP-1 secretion and activity while reverse transcription-polymerase chain reaction amplification of cellular RNA demonstrated glomerular transcripts coding for these enzymes and their inhibitor. When purified neutrophils were allowed to adhere onto Transwell apparatus in contact with glomerular suspensions, neutrophil 92 kDa gelatinase seemed apparently inhibited mainly because the production of TIMP-1 was enhanced on both sides of the insert. Glomerular 72 kDa and 92 kDa gelatinases were activated shortly (1 to 6 h) after neutrophils had interacted with glomeruli and furthermore upon activation by inflammatory or vasoactive mediators such as phorbol. Decreased neutrophil MMP-9 activity together with reduced MMP-9 mRNA levels and protracted TIMP-1 transcription and secretion during cell-cell interaction could participate to cell detachment from degraded basement membranes and to increased collagen i.v. deposition leading to glomerulosclerosis after initial glomerular injury by inflammatory cells.

Proteinuria and the expression of the podocyte slit diaphragm protein, nephrin, in diabetic nephropathy: effects of angiotensin converting enzyme inhibition.

AIMS/HYPOTHESIS: Proteinuria, reflecting increased glomerular permeability to macromolecules is a characteristic feature of diabetic nephropathy. Nephrin, a 1241-residue transmembrane protein is a key component of the podocyte slit pore membrane and a major contributor of the glomerular filtration barrier. We investigated the expression of nephrin in human kidney tissue from patients with diabetic nephropathy to elucidate its relationship with proteinuria and the effects of anti-proteinuric therapy with angiotensin converting enzyme inhibition. METHODS: Renal biopsies were examined from 14 patients with Type II (non-insulin-dependent) diabetes mellitus and proteinuria who had been randomised to receive treatment with the ACE inhibitor, perindopril (4 mg/day) or placebo for the preceding 2 years. These specimens were compared with control human tissue sections, obtained from areas of normal renal cortex following nephrectomy for malignancy. Proteinuria was measured, specimens were examined histologically for injury and the expression of nephrin messenger RNA was assessed by quantitative in situ hybridisation. RESULTS: Glomeruli from placebo-treated patients with diabetic nephropathy, showed a 62% reduction in nephrin expression compared with control subjects (p=0.0003). In contrast, nephrin RNA in glomeruli from perindopril treated patients was similar to that in the non-diabetic control group. In both placebo and perindopril treated patients, a close inverse correlation was noted between the magnitude of nephrin gene expression and the degree of proteinuria (placebo: r=0.86, p=0.013, perindopril: r=0.91, p=0.004). CONCLUSION/INTERPRETATION: Modulation in nephrin expression is related to the extent of proteinuria in diabetic nephropathy. These changes define, at a molecular level alterations in the glomerulus that occur in relation to proteinuria in diabetes and the effects of anti-proteinuric treatment with ACE inhibition.

[Twenty one years of hemodialysis in a patient with primary hyperoxaluria]. / Vingt et un ans d'hémodialyse chez un patient atteint d'hyperoxalurie primitive.

We report a male patient with primary hyperoxaluria from childhood who survived more than 21 years on conventional haemodialysis. Despite the severity of his bone disease, he was married and actively employed up until 2 years before his death. His condition really worsened a few months before his death. He presented with only renal and bone involvement and had hardly any cardiovascular complications, that was probably a reason for his prolonged survival. Such an evolution is very unusual and we speculate that the length of haemodialysis sessions in addition to the large surface of the membrane probably contributed to such an outcome. During the time period on HD, anemia was transiently controlled by recombinant erythropoietin despite oxalate involvement of the marrow. He was refused a liver-kidney transplant and died from malnourishment at 43 years of age. To our knowledge, such an outcome has not yet been reported. It shows that careful prolonged hemodialysis sessions should be helped in admet patients without severe cardiovascular involvement.

Expansion of cortical interstitium is limited by converting enzyme inhibition in type 2 diabetic patients with glomerulosclerosis. The Diabiopsies Group.

Renal interstitial expansion is now considered a useful marker of progression of several nephropathies. This study describes a multicenter, prospective, double-blind, placebo-controlled, randomized trial of the effects of Perindopril (4 mg/d) on kidney structure and function over 2 yr in 26 type 2 diabetic patients with proteinuria ranging from 70 to 4210 mg/d and relatively preserved GFR (creatinine clearance >60 ml/min). All patients underwent baseline renal biopsy, but four (15%) were not randomized because of the presence of nondiabetic nephropathy. The remaining 22 were randomized ( 11 to Perindopril [PE], 11 to placebo [PO]), and 19 (9 PE, 10 PO) underwent follow-up biopsy at 2 yr. BP was controlled equally in both groups throughout. Proteinuria increased in PO patients (+1562 mg/d) but declined in PE patients (-156 mg/d) (P < 0.05). Morphometric analysis was performed by light microscopy using a Biocom computer. Over the 2 yr, mean cortical interstitial fractional volume identical at baseline increased significantly in PO patients (31.7 +/- 5.3 versus 40.2 +/- 11.1%; P = 0.001) but was unchanged in PE patients (33.8 +/- 4.9 versus 34.7 +/- 6.6%; P = 0.50). It is concluded that: (1) nondiabetic nephropathy is present in approximately 15% of albuminuric type 2 diabetic patients; and (2) Perindopril prevents interstitial expansion in hypertensive patients with biopsy-proven diabetic glomerulopathy. These results support a role of angiotensin II in the progression of interstitial changes in type 2 diabetic patients with nephropathy.

[Ophthalmologic manifestations of dialysis. Retrospective study on 81 patients]. / Manifestations ophtalmologiques du dialysé. Etude rétrospective sur 81 patients.

In this work, we looked at the results of a retrospective study carried out in our unit on the ocular manifestations in the dialysed chronic renal failure patient. Eighty-one of our 189 patients had an ophtalmic examination. Thirty-six showed a retinopathy, 26 suffered from a corneoconjunctival alterations, 19 from a cataract, 6 a vascular thrombosis, 4 a glaucoma and one motor-ocular paralysis. There was no significant difference for age and sex between the 81 patients and the group of 108 who did not have an ophtalmic examination. But this difference was positive for duration of time on dialysis (p = 0.01). There is a correlation between the presence of a cataract and the age of the patients (p = 0.01). There was no link between the different types of ophtalmic problems on the one hand, and the age, sex, time on dialysis, type of dialysis, original nephropathy, hypertensive history or anterior renal transplantation on the other hand.

[Short- (1 session) and long-term (6 months) course of the serum level of zinc in 33 hemodialysis patients]. / Evolution du taux sérique du zinc à court (1 séance) et moyen terme (6 mois) chez 33 hémodialysés.

In patients with chronic renal insufficiency undergoing hemodialysis, the seric zinc level was significantly lower than in normal subjects. In 7 patients this was even more marked prior to their first hemodialysis session. Following hemodialysis this level increased, but by comparing the zinc level to that of the binding proteins it could be seen that this result was a reflection of the hemo-concentration phenomenon. During hemodialysis there was no change in the zinc level of dialysate. Finally, a significant increase in the seric level of the 7 new patients was noted after 6 months of hemodialysis treatment. This increase reached the mean level observed in the 26 other patients who had been undergoing hemodialysis from between 8 and 87 months, but pre-dialysis normalization of seric zinc levels was not attained. The reasons for this increase in the 7 recently hemodialysed patients receiving no zinc treatment are discussed.