Polycystic kidney size and outcomes on peritoneal dialysis: comparison with haemodialysis.

BACKGROUND: For many nephrologists, patients with polycystic kidney disease (PKD) have an increased risk of complications and technique failure on peritoneal dialysis (PD) due to enlarged kidneys. The literature showed that PD can be as good a therapeutic option as haemodialysis (HD) for patients with PKD. However, no study has focused on the impact of polycystic kidney size on outcomes for patients on PD. METHODS: This is a retrospective monocentric study. Fifty-eight patients with PKD started dialysis between January 2000 and December 2010: 24 on PD and 34 on HD. Kidney size assessed by abdominal computed tomography scans was available for 45 patients (19 on PD and 26 on HD). PD technique survival, specific PKD complications and mechanical and infectious PD complications, as need for pre-transplant nephrectomy and kidney transplantation, were considered. RESULTS: The two cohorts were similar in terms of age and body surface area. The median kidney size was not significantly different between PD and HD patients [19.1 cm (12.5-32.5) versus 16.5 cm (11.8-33.8), respectively, P = 0.13]. However, we identified an increased number of PD patients with larger kidneys [(>25 cm) (27.8% on PD versus 7.7% on HD (P = 0.07)]. Neither cystic (infection or haemorrhage) nor mechanical complications (hernias and leaks) were different in PD or HD. Ten patients experienced PD-related peritonitis, mainly due to non-enteric bacterial pathogens. The main reason for stopping PD and HD was transplantation. Six PD patients underwent nephrectomy in order to access the transplant programme. Among them, five were maintained on PD after surgical procedure with good adequacy dialysis criteria. CONCLUSIONS: We observed no deleterious impact of kidney size on outcomes on PD when compared with HD. A large kidney size in patients with PKD is not a contraindication to PD. Patients for whom a pre-transplant nephrectomy is mandatory can also safely opt for PD as a dialysis method.

CT in predicting abdominal cocoon in patients on peritoneal dialysis.

AIM: To evaluate the computed tomography (CT) signs of encapsulating peritoneal sclerosis (EPS) in patients on peritoneal dialysis (PD) as predictive factors for the evolution to abdominal cocoon (AC). MATERIALS AND METHODS: Clinical features and CT signs of 90 patients on PD were retrospectively reviewed. According to the clinical features, they were divided into three groups (asymptomatic, moderate, or severe). Clinical results were correlated with previously reported CT signs of EPS, i.e., peritoneal thickening, peritoneal calcifications, loculated fluids, small bowel faeces sign, small bowel obstruction, clustered bowel loops, pseudo sac, signs of bowel ischaemia or necrosis. AC was defined at CT by the association of clustered bowel loops and a pseudo sac. Statistical analysis was performed using the Fisher's exact test and the t-test. RESULTS: Although demonstrated in symptomatic patients (p=0.041), the occurrence of AC was not correlated with the severity of the symptoms (p=0.16). Among the CT signs, the presence of loculated fluids (p=0.011), a small bowel faeces sign (p=0.002); and small bowel obstruction (p=0.0001) were found to be statistically correlated with the appearance of an AC. Moreover, the association of loculated fluids, small bowel faeces sign, small bowel obstruction was extremely sensitive and specific in the development of AC (sensitivity=67%, specifity=100%, positive predictive value=100%, negative predictive value=96%). CONCLUSION: CT should be carried out in every symptomatic patient on PD. Indeed, the association of loculated fluid, small bowel faeces sign, and small bowel obstruction enables the prediction of the development of AC, which is likely to curtail PD and require surgery.

Hypertension in renal transplantation: donor and recipient risk factors.

AIMS: To determine the respective roles of donor and recipient factors in the subsequent development of hypertension after renal transplantation. PATIENTS AND METHODS: All the patients transplanted between January 1990 and December 1999 who still had a functioning graft 1 year post-transplant (n = 321) were retrospectively studied. Blood pressure was assessed at 1 year post-transplant. Hypertension was defined as a systolic BP > or equal 140 mmHg or diastolic BP > or equal 90 mmHg, or use of antihypertensive medication. Relevant donor and recipient characteristics were recorded. RESULTS: Two-hundred-and-sixty-three patients (82%) were hypertensive. In multivariate analysis, pretransplant hypertension (RR, 1.74, 95% CI, 1.07 to 2.87), anticalcineurin use (RR, 2.59, 95% CI, 1.13 to 5.92), urinary protein excretion (RR, 1.84, 95% CI, 1.06 to 3.18), BMI (RR, 1.08, 95% CI, 1.01 to 1.16), donor age (RR, 1.28,95% CI, 1.05 to 1.59, for each 10-year increase in donor age) and donor aortorenal atheroma (OR, 2.34; 95% CI, 1.24 to 4.46) were associated with hypertension. Among patients under calcineurin inhibitors, those receiving cyclosporine were more prone to have hypertension than those receiving tacrolimus (88.7% vs 78%; p = 0.04). CONCLUSION: Both recipient and donor factors contribute to hypertension in RTR.

Use of pentoxifylline in membranous nephropathy.

Urinary TNF-alpha excretion correlates with proteinuria in patients with membranous nephropathy (MGN). Pentoxifylline suppresses or reduces the production of TNF-alpha. Between April, 1999 and August, 2000, we did a single-centre, prospective, pilot study to assess the effects of pentoxifylline (1200 mg/day) on proteinuria in patients with idiopathic MGN. Ten patients were included and treated for 6 months. Pentoxifylline significantly decreased proteinuria from 11 g/day [range 4.6-27] to 1.8 (0-10.9); p=0.001). Pentoxifylline may be a safe and effective adjunct to steroids and immunosuppressants in patients with MGN.

T-cell immune defect and B-cell activation in renal transplant recipients with monoclonal gammopathies.

Monoclonal immunoglobulins (molg) have repeatedly been described in organ and bone marrow transplantation. Although their exact significance is not known, their occurrence is often associated with intensive immunosuppression. We investigated whether molg reflect T-cell immune defect and B-cell activation in renal transplant recipients. Immunofixations and lymphocyte subset analysis (CD4, CD8, CD19) were performed in 182 renal transplant recipients. Soluble CD23 concentrations were measured in patients with molg and in control transplant patients without molg. Monoclonal immunoglobulins were identified in 54 patients (29.6 %). Transplant endurance was shorter (62 +/- 53 months vs 81 +/- 47 months; P < 0.02) and age was older (53 +/- 13 years vs 46 +/- 13 years; P < 0.005) in patients with molg. Maintenance immunosuppression did not differ between patients with and without molg. Mean CD4-cell count was significantly lower in patients with molg (387 +/- 286/mm(3) vs 538 +/- 341/mm(3); P < 0.005). Both CD8- and CD19-cell counts were similar for the 2 groups. Soluble CD23 concentrations were higher in patients with abnormal immunoglobulin values than in patients with normal immunofixation (12.8 +/- 8 vs 1.9 +/- 1.8 microg/l; P < 0. 005). Our study provides new evidence that molg reflect T-cell immune defect in renal transplant recipients. Further studies are required to determine whether CD4-cell count and sCD23 may help to predict the risk of lymphoma in transplant patients with molg.

Polycystic kidney disease as a risk factor for post-transplant diabetes mellitus.

BACKGROUND: Insulin resistance with compensatory hyperinsulinaemia has been reported in adult polycystic kidney disease (APKD) patients. Diabetes mellitus is a common complication following transplantation and previous studies have demonstrated that inadequate insulin secretion was a prerequisite for the development of post-transplant diabetes mellitus (PTDM). We conducted a retrospective study to determine whether APKD is a risk factor for PTDM. METHODS: Twenty-six consecutive patients transplanted because of end-stage renal disease due to APKD were studied. A control patient matched for age, gender, immunosuppressive therapy and transplant year was selected for each APKD patient. PTDM was defined by fasting glycaemia exceeding 7.8 mmol/l and the need for insulin or oral antidiabetic therapy. RESULTS: Age, renal function, immunosuppressive regimen, number of acute rejection, cumulative dose of steroids and haemodialysis duration before transplantation were similar in both groups. PTDM occured in 10 APKD patients and four controls (34.6% vs 15.3%; P < 0.005). Among diabetic patients, six APKD patients and two controls required insulin therapy (60% vs 50%; P = n.s.). Diabetic patients were significantly older (55.8 +/- 7 years vs 50.2 +/- 11 years; P < 0.05). CONCLUSION: Although retrospective, this study suggests that APKD confers an increased risk of PTDM.

Dialysis adequacy and homocyst(e)ine concentrations in peritoneal dialysis patients.

INTRODUCTION: Determinants of hyperhomocysteinaemia in peritoneal dialysis patients have been recently reported but there is still conflicting data on the influence of dialysis adequacy on homocysteine (Hcy). METHODS: We studied 46 consecutive new continuous ambulatory peritoneal dialysis (CAPD) patients to determine the variation of Hcy before and 1 and 6 months after dialysis. The variation in Hcy was analysed with respect to dialysis adequacy, factors known to influence its metabolism, and Hcy peritoneal clearance. RESULTS: Hcy was 31.9+/-9 micromol/l before dialysis. It was significantly higher before dialysis than 1 month after the onset of PD (31.9+/-9 micromol/l vs 23.2+/-6.9 micromol/l, P < 0.0005). Weekly PD Hcy clearance was 14.3+/-5.4 1. There was no relationship between pre-dialysis Hcy and 1 month post-dialysis Hcy (r=0.176, P=0.15). There was a strong relationship between PD Hcy clearance and both PD creatinine clearance (r=0.502, P<0.005) and Kt/V (r=0.42, P<0.005). There was no relationship between Hcy and PD creatinine clearance (r= -0.221, P=0.11). In contrast, the decrease in tHcy at 1 month was related to PD Hcy clearance (r=0.487, P<0.01), to PD creatinine clearance (r= 0.349, P<0.02) and to Kt/V (r=0.32, P<0.02). Multivariate analysis confirmed the relationship between the decrease in Hcy and dialysis adequacy. Eleven patients (24%) experienced arteriosclerotic complications. Fasting Hcy concentrations in this population were significantly higher before and 1 month-post-dialysis than in patients without cardiovascular complications. CONCLUSIONS: We observed a significant and prolonged reduction in Hcy concentrations by peritoneal dialysis in end-stage renal disease patients. The decrease in Hcy concentration was positively related to dialysis adequacy. This study suggests the possibility that dialysis adequacy may influence arteriosclerotic outcomes through an Hcy-lowering effect.

Prevalence and clinical significance of antiphospholipid antibodies in renal transplant recipients.

BACKGROUND: The prevalence and clinical significance of antiphospholipid antibodies (APAs) have not been extensively studied in non-systemic lupus erythematosus (non-SLE) renal transplant recipients. METHODS: To further define the prevalence and clinical significance of APAs in non-SLE renal transplant recipients and the appearance of dialysis-related APAs after renal transplantation, we conducted a retrospective study on 178 renal transplant recipients. Documentation of anticardiolipin antibodies (ACAs) and lupus anticoagulant in non-SLE renal transplant recipients, retrospective documentation of ACAs on pretransplant frozen plasma and standardized collection of demographic characteristics and posttransplant history of thrombosis were assessed. RESULTS: Fifty of 178 patients (28.1%) had APAs. Transplant duration was shorter and hemodialysis duration was longer in patients with APAs. A posttransplant history of both venous and arterial thrombosis was more frequent in patients with posttransplant APAs (respectively, 18% vs. 6.2% [P<0.001] and 8% vs. 2.3% [P<0.001]). Pretransplant sera were available from 55 patients. Most of patients with posttransplant ACAs had ACAs in the pretransplant period (85%). Pretransplant ACAs were associated with a posttransplant history of venous thrombosis (P<0.001). CONCLUSIONS: Our study demonstrates a high prevalence of APAs in non-SLE renal transplant recipients. Most of them have been acquired in the pretransplant period. Both pretransplant ACAs and posttransplant APAs are associated with posttransplant episodes of thrombosis. Further studies are required to determine the interest of prophylactic measures.

Prevalence, determinants, and clinical significance of hyperhomocyst(e)inaemia in renal-transplant recipients.

BACKGROUND: Previous studies have demonstrated that hyperhomocyst(e)inaemia is present in patients with impaired renal function and is correlated with cardiovascular disease. Because conflicting data are available on the prevalence, determinants, and clinical significance of hyperhomocyst(e)inaemia in renal-transplant recipients, we conducted the largest cross-sectional study on homocysteine determinants and clinical correlates in renal transplant recipients. METHODS: Plasma homocyst(e)ine concentrations and factors known to influence homocysteine metabolism were analysed in 224 renal transplant recipients. Atherosclerotic complications were evaluated with respect to plasma homocysteine concentrations. RESULTS: Mean plasma homocyst(e)ine was 21.3+/-9.7 micromol/l. After adjusting for age, gender, transplant duration, and creatinine clearance, patients with and without cyclosporin A (CsA) had similar plasma homocyst(e)ine concentrations (16.9+/-5.9 micromol/l in CsA(+) patients vs 16.3+/-5.2 micromol/l in CsA(-) patients; P=0.3). We found a significant inverse relationship between plasma homocyst(e)ine and folate concentrations in both CsA(+) (r=-0.243; P<0.005) and CsA(-) (r=-0.396; P<0.05) patients. Patients with a past history of cardiovascular events had higher plasma homocyst(e)ine concentrations (25.2+/-11.7 mmol/l vs 20.5+/-8.9 mmol/l; P<0.005). CONCLUSION: Homocyst(e)inaemia is closely related to renal function and folate concentration in renal-transplant recipients. CsA does not seem to have direct effects on homocysteine metabolism. Hyperhomocyst(e)inaemia is associated with cardiovascular disease in renal-transplant recipients. Prospective placebo-controlled homocysteine-lowering therapy studies are required in this patient category.

Long-term follow-up of renal transplant recipients treated with losartan for post-transplant erythrosis.

Post-transplant erythrosis (PTE) develops in 9%-22% of all renal transplant recipients. Defined as a persistently elevated hematocrit (> 0.51), it occurs most commonly during the first 2 years post-transplantation in hypertensive males with excellent allograft function. Several studies have focused on a major role for angiotensin II in PTE pathogenesis, and some case reports have suggested that losartan is an effective treatment for PTE. Nevertheless, its long-term safety and efficiency have not been reported in renal transplant recipients suffering from PTE. We describe four patients successfully treated with losartan for PTE. Hematocrit remained normal for 21, 18, 15, and 15 months, respectively, after the beginning of losartan therapy. Mean erythropoietin concentration was not modified by treatment (17 +/- 3.7 mU/ml vs 17 +/- 3.8 mU/ml) and serum creatinine concentration remained stable. We conclude that losartan is a safe and effective long-term treatment for PTE.

Mycophenolate mofetil in renal transplant recipients with cyclosporine-associated nephrotoxicity: a preliminary report.

BACKGROUND: There is a great concern over cyclosporine (CsA) nephrotoxicity in renal transplant recipients, and the effects of conversion from CsA to azathioprine (AZA) remain controversial. Large studies have demonstrated that mycophenolate mofetil (MMF), the morpholinoethyl ester of mycophenolic acid, is superior to AZA as a posttransplant immunosuppressant. METHODS: Six patients with isolated biopsy-proven CsA nephrotoxicity were converted from CsA-AZA to MMF. RESULTS: Mean follow-up was 12+/-2 months. No patient experienced acute rejection. The mean serum creatinine concentration decreased from 225+/-58 to 159+/-66 micromol/L (P<0.0005). Hyperlipidemia and blood pressure improved after CsA withdrawal. CONCLUSION: In a selected transplant population with biopsy-proven CsA nephrotoxicity, CsA withdrawal with a concomitant switch from AZA to MMF seems to be safe and allows a significant improvement of renal function.

Recurrence of hemolytic-uremic syndrome in renal transplant recipients: a meta-analysis.

BACKGROUND: Recurrence of hemolytic-uremic syndrome (HUS) in the allograft is associated with a very poor renal prognosis. Meta-analysis of previous trials may allow us to better estimate its real frequency, to identify risk factors for recurrence, and to predict the outcome of patients with definite recurrence. METHODS: An exhaustive search was conducted of HUS recurrence in renal transplantation from January 1977 to June 1997 using MEDLINE. RESULTS: Ten studies comprising 159 grafts in 127 patients were identified. The rate of recurrence was 27.8%. One-year graft survival was 76.6% in patients without recurrence and 33.3% in patients with recurrence (P<0.001). Older age at onset of HUS (16.96+/-7.6 years vs. 9.95+/-6.55 years; P<0.02), shorter mean interval between HUS and transplantation (2.51+/-2.7 years vs. 6.03+/-6.4 years; P<0.01), shorter mean interval between HUS and end-stage renal disease (0.79+/-0.39 years vs. 2.78+/-2.47 years; P<0.01), living-related donors, and the use of calcineurin inhibitors were associated with recurrence. CONCLUSION: Risk factors for HUS recurrence in renal transplantation could be identified through this meta-analysis.

CD4 lymphocytopenia as a risk factor for skin cancers in renal transplant recipients.

BACKGROUND: Renal transplant recipients are at increased risk of developing skin cancer. It remains difficult to establish the actual influence of overimmunosuppression in the development of skin cancers. We investigated whether lymphocyte subset count may predict the risk of developing skin cancer in long-term renal transplant recipients. METHODS: One hundred fifty long-term renal transplant recipients were followed for a mean period of 26 months. Each patient was examined at least annually by a dermatologist. Lymphocyte subsets were measured annually. RESULTS: Fifteen patients exhibited skin cancers. Patients with and without skin cancer did not differ in age, gender, transplant duration, hemodialysis duration before transplantation, immunosuppressive regimen, and serum creatinine concentration. CD4 cell counts were significantly lower in patients with skin cancers (330+/-179/mm3 vs. 503+/-338/mm3; P<0.01), whereas total lymphocyte and CD8 and CD19 cell counts were similar between the two groups. CONCLUSIONS: CD4 cell depletion is associated with skin cancer in long-term renal transplant recipients.

Hyperhomocyst(e)inemia in renal transplant recipients with and without cyclosporine.

Studies have demonstrated that hyperhomocyst(e)inemia is present in renal transplant recipients and is correlated with cardiovascular disease. It is still unclear whether hyperhomocyst(e)inemia observed in renal transplant recipients solely depends on the moderate reduction of renal function in these patients or if additional mechanisms are operative in this patient category. A recent study suggested that cyclosporine (CsA) increased plasma homocyst(e)ine concentration in interfering with folate-assisted remethylation of homocysteine. To confirm this hypothesis, we studied plasma homocyst(e)ine folic acid and cobalamin concentrations in 122 renal transplant recipients (104 on CsA and 18 not receiving CsA). After adjusting for age, gender, transplant duration and serum creatinine concentration, patients with and without CsA had similar plasma homocyst(e)ine concentrations (17.9 +/- 6.1 mumol/l in CsA(+)patients vs 17.1 +/- 5.6 mumol/l in CsA(-)patients; p = 0.3). Moreover, we found a significant inverse relationship between plasma homocyst(e)ine and folic acid concentrations in both CsA(+) (r = 0.218; p < 0.01) and CsA(-) (r = -0.678; p < 0.05) patients. Patients with a past history of cardiovascular incidents had higher plasma homocyst(e)ine concentrations than those without cardiovascular antecedent (20.5 +/- 7.8 mumol/l vs. 18.01 +/- 9.9 mumol/l; p < 0.05. To conclude: 1, We did not find any influence of CsA on plasma homocyst(e)ine concentrations. 2. We demonstrated that as in other patient category, plasma folic acid and homocyst(e)ine concentrations are significantly correlated in CsA(+) patients. 3. Homocyst(e)ine-lowering therapy would be prescribed in CsA(+) patients to allow correction of hyperhomocyst(e)inemia.

Colchicine myopathy in renal transplant recipients on cyclosporin.

Few data are available about the muscle status in renal transplant recipients. Moreover, the list of myotoxic drugs is growing longer and some of them are likely to be prescribed in renal transplant patients. These conditions may act as confounding factors in case reports of both cyclosporin and colchicine myopathies. Moreover no study has evaluated the frequency of myopathy in patients on both colchicine and cyclosporin. We conducted a retrospective study including all renal transplant recipients followed in our unit in whom colchicine was prescribed since January 1994. Clinical and biological data of patients on both colchicine and cyclosporin were analysed. Secondly case subjects were compared with matched controls not receiving colchicine but cyclosporin. Ten patients received colchicine in association with cyclosporin. Five patients (50%) experienced muscular symptoms and when performed, muscular histology showed vacuolar myopathy. All five patients improved after colchicine withdrawal. Cases with and without muscular symptoms did not differ in age, transplant duration, and serum creatinine level. Mean duration of colchicine therapy was 12.2 +/- 4.4 months in cases with muscular symptoms and 6.8 +/- 4.6 months in cases without muscular symptoms (P < 0.05). No control complained of either muscular pain nor weakness (P < 0.0005). Only one patient (3.3%) had elevated serum creatine phosphokinase concentration (P < 0.0005). We conclude that myopathy is very frequent in patient on both colchicine and cyclosporin. Muscular symptoms improve in all patients after colchicine withdrawal.