Incidence and risk factors for posttransplant subcapsular cataract: a long-term retrospective cohort study.

BACKGROUND: The occurrence and risk factors for posterior subcapsular cataract (PSC) after renal transplantation have received little attention. OBJECTIVES: To analyze the cumulative incidence of PSC after renal transplantation and identify risk factors for the development of PSC. METHODS: Retrospective review of the records of the patients who underwent kidney transplantation between May 1986 and December 2008. RESULTS: We included 94 renal transplant recipients who showed PSC incidence at 5, 10, and 15 years of 3.5%, 40.5%, and 50.1%, respectively. Cumulative incidence of PSC during the follow-up was 37.2%. On multivariate analysis, age, body mass index (BMI) and cumulative corticosteroid dose were significantly associated with PSC. Recipient age above 50 years (hazard ratio [HR] = 2.88, 95% confidence interval [CI]: 1.42-5.83; P = .003), BMI above 25 kg/m(2) (HR = 2.28, CI: 1.09-4.78; P = .029), and prednisolone dose above 3 mg/kg/mo (HR = 7.79, CI: 3.34-18.99; P < .001) were independent risk factors for PSC. Diabetes, renal diagnosis, duration, and type of dialysis and posttransplant immunosuppressive regimen did not influence the occurrence of PSC. CONCLUSION: The risk of PSC was low during the first years after transplantation reaching a plateau at 15 years posttransplantation. Among the risk factors for PSC, cumulative corticosteroid dose and body weight were the only modifiable risk factors.

Long-term evolution of the mineral metabolism after renal transplantation: a prospective, single-center cohort study.

BACKGROUND: Abnormalities in bone and mineral metabolism are common after renal transplantation (RT) but information on their long-term time course is scarce. OBJECTIVES: (1) Evaluate the time course of biochemical parameters of bone and mineral metabolism over 60 months after RT; (2) identify predictors for persistent hyperparathyroidism (HPT). DESIGN: Prospective, longitudinal, single-center cohort study. METHODS: We determined serum levels (mean values ± standard deviations) of intact parathyroid hormone (iPTH), calcium (Ca), phosphorus (P), magnesium (Mg), alkaline phosphatase (APh), calcitriol, and creatinine (Cr) preoperatively as well as 6, 12, 24, 36, 48, and 60 months after cadaveric RT in 49 patients. We in addition recorded demographic, clinical, and therapeutic data. RESULTS: Pretransplantation iPTH stabilized from 194.2 ± 273.5 to 71.5 ± 50.7 ng/L at 6 months. Serum Ca (9.5 ± 1.1 mg/dL) and APh (81.9 ± 42.1 U/L) did not change. Baseline serum P (5.7 ± 1.8 mg/dL) and serum Mg (2.4 ± 0.4 mg/dL) decreased to normal ranges from month 6 onward. Low baseline calcitriol (22.4 ± 21.8 pmol/L) normalized slowly by 12 months (95.4 ± 46.7 pmol/L). Stable graft function (53.2 ± 15.8 mL/min) was achieved from 6 months onward. By 60 months, 26.5% of patients had a serum Ca above 9.8 mg/dL and serum P below 2.7 mg/dL; 22.4%, an Mg below 1.7 mg/dL and 8.2%, a serum iPTH more than 2.5-fold the upper limit of normal. Upon multiple regression analyses the iPTH at 60 months was influenced by a dialysis duration ≥ 2 years (ß = 0.259, P = .003), body mass index > 25 kg/m(2) (ß = 0.257, P = .006), baseline iPTH (ß = 0.182, P = .036), serum Cr (ß = 0.268, P = .002) and Mg (ß = -0.242, P = .006). CONCLUSIONS: Hypercalcemia, hypophosphatemia, hypomagnesemia, and elevated iPTH persist in a subset of post-RT patients. Pretransplantation iPTH and obesity, dialysis duration, and posttransplant serum creatininemia and hypomagnesemia independently contribute to persistent HPT.

Posttransplantation diabetes mellitus: a long-term retrospective cohort study.

BACKGROUND: Posttransplantation diabetes mellitus (PTDM) is a serious complication of transplantation which is caused by immunosuppressive drugs and adversely affects the survival of the transplant recipient and the long-term survival of the graft. In this study, we assessed the incidence of PTDM and the factors associated with its development during long-term follow-up of renal transplant recipients. We also investigated the influence of PTDM on the cardiovascular risk (CVR) profile. METHODS: We retrospectively reviewed the records of the patients who underwent renal transplantation at our center between 1986 and January 2007. Diabetes was diagnosed according to American Diabetes Association criteria. The CVR factors were analyzed at the time of transplantation as well as at 1 and 3 years follow-up. RESULTS: We included 136 nondiabetic transplant recipients. The PTDM incidences at 1, 3, 5, and 10 years were 9%, 12%, 13%, and 16.4%, respectively. The cumulative incidence during follow-up was 17.6%. On both univariate and multivariate analyses body mass index (BMI) was significantly associated with PTDM. Patients with BMI 25 = 30 kg/m(2) had an odds ratio [OR] of 3.53 (95% confidential interval [CI] 1.26-9.90; P = .017) and those with BMI >30 kg/m(2) had an OR of 4.58 (95% CI 1.4-14.01; P = .012). There were no significant differences in gender distribution, age, pretransplant dialysis period, acute rejection rate, or immunosuppressive regimens between patients with (n = 24) versus without (n = 112) PTDM. CONCLUSION: The risk of PTDM increased continuously with time after transplantation. BMI was an independent predictor of PTDM. Among all of the risk factors for PTDM, obesity is the only modifiable risk factor before transplantation. PTDM was associated with a worse traditional CVR profile; a better control of CVR factors should be performed to prevent long-term morbidity and mortality in this population.

Reduced-exposure cyclosporine is safe and efficacious in de novo renal transplant recipients treated with enteric-coated mycophenolic acid and basiliximab.

BACKGROUND: The lower limit of exposure to calcineurin inhibitors has not yet been established in de novo renal transplant patients receiving mycophenolic acid therapy with basiliximab. METHODS: A 12-month, multicenter, randomized, open-label trial was carried out in which de novo renal transplant patients received enteric-coated mycophenolate sodium, cyclosporine microemulsion, steroids and basiliximab. Patients were randomized to receive standard-exposure (n = 45) or reduced-exposure (n = 44) cyclosporine, based on differing C2 target ranges, after the first month post-transplant. RESULTS: Cyclosporine exposure gradually increased over the first month and was lower than previously recommended. Mean calculated creatinine clearance (primary end-point) was similar in the standard-exposure and reduced-exposure groups at month 6 (55.3+/-3.2 ml/min and 61.5+/-3.7 ml/min respectively, n.s.). There were 4 deaths but no death-censored graft losses, resulting in 95.5% patient and graft survival at one year in both groups. At 6 and 12 months, the incidence of biopsy-proven acute rejection was 17.8% and 17.8% in the standard-exposure group, and 13.6% and 15.9% in the reduced-exposure group. Adverse events were similar between treatment groups. Exploratory analyses could not identify a lower limit for the optimal CsA exposure range, but results suggested that high exposure at one year was associated with deteriorating renal function. CONCLUSIONS: These results indicate that enteric-coated mycophenolate sodium with reduced-exposure cyclosporine, steroids and basiliximab induction has an excellent therapeutic effect and is safe in de novo kidney transplant recipients. Lower C2 targets than previously recommended, particularly early post-transplant, do not appear to be associated with compromised efficacy.

Severe diarrhea in renal transplant patients: results of the DIDACT study.

Diarrhea is common in transplant recipients. While the majority of cases are mild and transient, some are severe and prolonged, which can threaten graft survival through dehydration. While it is known that some immunosuppressive agents can elicit diarrhea, there does not appear to be any consensus on the role that other nonimmunosuppressive causes can play in transplant patients. The aim of the present open, nonrandomized, multicenter study was to identify nonimmunosuppressive factors involved in severe diarrhea in renal transplant patients. Patients (n = 108) with severe diarrhea (>/=3 stools/day for >/=7 days) were enrolled from 16 Belgian transplant centers. Patients were diagnosed according to an agreed flowchart that consisted of identification of possible infections, followed by changes in empirical and immunosuppressive treatment. Approximately 50% of patients experienced resolution of severe diarrhea following treatment for infections, dietary problems or diarrhea-causing concomitant medications. In conclusion, a large proportion of the severe diarrhea observed in renal transplant recipients is not associated with immunosuppressive therapy and can be treated through anti-infectives, changes to concomitant medication and other empirical treatments. Correct diagnosis of the cause of severe diarrhea in such patients should help to protect graft survival in transplant recipients.

[Atypical Cogan's syndrome. Based on a case]. / Le syndrome de Cogan atypique. A propos d'un cas.

Cogan's syndrome is a systemic inflammatory disease that associates typical (interstitial keratitis) and atypical (such as anterior uveitis) ocular manifestations to vestibulo-auditory dysfunction. It has also a systemic vascular association of vasculitis type. We report a case of a 64 years old woman who presented an atypical form with anterior uveitis.

Relapsing ascites and uremia due to urinary bladder leakage.

A 62-year-old female was admitted for a new episode of ascites, complicated by uremia. She had been treated 6 years earlier for bladder cancer with partial cystectomy and postoperative radiotherapy. At the work-up for both previous episodes of ascites, 6 and 24 months earlier, no definite diagnosis was made, and each time the ascites disappeared spontaneously. Also, at the third episode, the uremia resolved. Finally, explorative laparoscopy demonstrated urinary leakage from the superior portion of the bladder. This feature of vanishing and relapsing ascites is explained by intermittent covering by overlying abdominal structures and subsequent spontaneous healing. The pseudo-renal failure is caused by reabsorption of urine through the peritoneum. Only nine cases of recurring ascites and eight cases of bladder perforation after radiotherapy have been described in the literature.

Hydroxyethyl starch does not impair immediate renal function in kidney transplant recipients: a retrospective, multicentre analysis.

BACKGROUND: The effect of hydroxyethyl starch (HES) on early allograft function was examined retrospectively in a cohort of 119 renal transplantations realized by local organ exchange between four cooperating centres. METHODS: After exclusions, 109 transplant procedures were subdivided in three groups according to donor colloid loading: (i) HS-group (Haes steril 6%, mean volume (SD): 979 (946) ml, n = 20); (ii) PS-group [Plasmasteril, mean volume (SD): 769 (411) ml, n = 16]; and (iii) control group (gelatin albumin, n=73). RESULTS: Delayed graft function (DGF), defined as the need for dialysis during the first post-transplant week, occurred in 3/20 (15%) cases in the HS-group, in 5/16 (31%) cases in the PS-group and in 14/73 (19%) cases in the control group (P = 0.450). Uni- and multivariate analysis revealed older donor age (P = 0.001) and kidney preservation with histidine-tryptophan-ketoglutarate (HTK) (P = 0.001) as the only factors associated with a higher incidence of DGF. CONCLUSIONS: Renal function as measured by daily serum creatinine concentration and 24 h urinary output up to 14 days post-transplantation in the HS-group was comparable with that of controls. The higher serum creatinine observed during the first seven post-transplant days in the PS-group could be related to higher donor age and haemodynamic instability, and recipient male preponderance, rather than to HES itself.

Fixed low-dose perindopril-indapamide combination in hypertensive patients with chronic renal failure.

The angiotensin converting enzyme inhibitor perindopril and the diuretic indapamide have been shown to be effective antihypertensive agents in patients with chronic renal failure. A fixed low-dose combination of these two agents has been proposed in the treatment of hypertension. We evaluated this combination in 26 patients with mild to moderate essential hypertension and mild to severe chronic renal failure that did not require dialysis. This was a multicenter, open trial consisting of a 2-week single-blind placebo washout period followed by 12 weeks of active treatment. At week 0, the patients received 2 mg perindopril/0.625 mg indapamide once a day or every other day, with the possibility of dosage adjustment to perindopril 4 mg/indapamide 1.25 mg at week 2, week 4, or week 8. A pharmacokinetic analysis using a population pharmacokinetic approach was performed at week 8. Twenty-three patients completed the 12-week study, at which time 14 patients were receiving 2 mg perindopril/0.625 mg indapamide daily, three were receiving 2 mg perindopril/0.625 mg indapamide every other day, and six perindopril 4 mg/indapamide 1.25 mg. Blood pressure readings (supine) decreased from 170.4+/-19.2 / 101.5+/-6.7 mm Hg before active treatment to 146.5+/-19.7 / 86.5+/-10.6 mm Hg at the end of treatment (P < .0001). Pharmacokinetic analysis showed that for indapamide and perindoprilat (the active metabolite of perindopril) the area under the curve (AUC24) increased with the severity of renal failure. No interaction was noted between the two drugs. Mean serum creatinine and sodium and serum potassium levels remained stable during the study. Impairment of renal function occurred in one patient and was considered unrelated to treatment. We conclude that a fixed low-dose perindopril-indapamide combination as first-line treatment has a good safety/efficacy ratio in hypertensive patients with chronic renal failure.

Prevalence of histological beta2-microglobulin amyloidosis in CAPD patients compared with hemodialysis patients.

BACKGROUND: The prevalence of beta2-microglobulin amyloidosis (Abeta2m) in patients on continuous ambulatory peritoneal dialysis (CAPD) is unknown. METHODS: We prospectively obtained a median of 2 (range 1 to 4) joint samples from 26 CAPD patients aged 44 to 93 (median 73) years at post-mortem evaluation after 4.5 to 126 (median 27) months solely on CAPD (N = 19) or primarily on CAPD (that is, < or = 10% and < or = 1 year of renal replacement therapy time on other modalities; N = 7). The diagnosis of Abeta2m rested on Congo red staining (typical birefringence) and positive immunostaining of amyloid deposits by a monoclonal anti-beta2m antibody. RESULTS: Abeta2m was diagnosed in 8 of 26 patients (31%). Prevalence ranged from 20% (2 of 10 patients) within < or = 24 months CAPD to 30% (3 of 10 patients) after 24 to 48 months and 50% (3 of 6 patients) after 49 to 126 months (P = 0.11). The prevalence of Abeta2m was similar in patients without or with one or more peritonitis episodes. No significant difference in prevalence (P = 0.118) was found between CAPD patients (8+/26; 31%) and hemodialysis patients (13+/26; 50%) carefully matched for time on dialysis and age at the onset of dialysis. CONCLUSIONS: The prevalence of histological Abeta2m reaches 31% after a median duration of 27 months of CAPD. This prevalence is not significantly different from that observed in a group of HD patients matched for age and dialysis duration.

Odour perception in chronic renal disease.

BACKGROUND: The sense of smell plays an important role in the quality of life. Many studies have shown a declining odour perception in the elderly, as well as in subjects in poor health or nutritional state. Considering the high prevalence of poor nutritional state in renal disease and the importance of odour perception in nutrition and health, the relationship between renal function, nutritional state, and odour perception is explored in this study. METHODS: A total of 101 patients with chronic renal failure participated in the study. Thirty-eight haemodialysis patients (mean age = 64.3 years) were evaluated both before and after dialysis. Sixteen patients on peritoneal dialysis treatment (mean age = 64.0 years), 28 transplanted patients (mean age = 53.5 years, mean creatinine clearance = 64.0 ml/min) and 19 patients with varying degrees of renal insufficiency were also included (mean age = 63.7 years, mean creatinine clearance = 29.5 ml/min). Patients with cognitive deficits or upper respiratory airway diseases were excluded. A validated objective procedure was used to measure odour perception, by determining the detection threshold for isoamyl acetate (banana odour) as the lowest detectable odour concentration. RESULTS: Healthy control persons had significantly lower odour thresholds compared to patients on peritoneal (P = 0.001) and haemodialysis (P = 0.002). No significant difference was observed in odour perception between patients on peritoneal and haemodialysis (P = 0.779) and for patients on haemodialysis before and after a dialysis session. Transplanted patients had significantly better odour perception compared to matched patients on dialysis (P < 0.001). Odour perception of transplanted patients and matched healthy control persons was similar (P = 0.81). In patients with varying degrees of renal insufficiency, including healthy controls and transplanted patients, a significant positive correlation was found between odour perception and creatinine clearance (P = 0.02). A significant negative correlation was found between odour perception and serum concentration of urea (P < 0.001), serum phosphorus (P = 0.022) and protein catabolic rate (P < 0.05). Other parameters measuring nutritional status (albumin, BMI) were not correlated with odour perception. CONCLUSION: Our results show that the ability to smell is severely impaired in patients with chronic renal failure and is related to the degree of renal impairment and the degree of accumulation of uraemic toxins. After renal transplantation, patients have a normal odour perception, indicating the capacity of the olfactory system to recover once the concentration of uraemic toxins remains below a critical threshold. Acute removal of uraemic toxins by dialysis does not correct olfactory disturbances, suggesting a long lasting effect of uraemia on olfactory function.

Histological prevalence of beta 2-microglobulin amyloidosis in hemodialysis: a prospective post-mortem study.

The histological prevalence of beta-2 microglobulin amyloidosis (A beta 2m) was evaluated in a prospective study of joint samples obtained at autopsy in 54 patients on hemodialysis (HD) for 2 to 163 (median 47) months, aged 20 to 80 (median 63) years at HD onset. Carpal tunnel syndrome surgery or radiological signs of A beta 2m were present in 2 and 4% of them, respectively. A control group of 34 patients without end-stage renal disease, autopsied during the same period was used as a reference. The 153 sampled joints (1 to 8, median 2 per patient) were sternoclavicular joints (N = 77), shoulders (N = 35), knees (N = 28), others (N = 13). A beta 2m was diagnosed (positive Congo red with typical birefringence and positive immunostaining of deposits for beta 2m) in 26 of 54 (48%) patients. Prevalence reached respectively 21%, 33%, 50%, 90% and 100% within two years, after 2 to 4 years, 4 to 7 years, 7 to 13 years and more than 13 years HD. The calculated sensitivity of the various joints for A beta 2m detection is significantly higher (P < 0.03) for sternoclavicular joints (97%) and knees (91%) than for shoulders (57%). Multivariate stepwise logistic regression with discriminant analysis identified both HD duration (P = 0.0008) and age at HD onset (P = 0.0093) but not diabetic nephropathy (P = 0.23) or gender (P = 0.25) as independent risk factors for A beta 2m. The probability of joint A beta 2m was quantitated as a function of age and HD duration. In conclusion, A beta 2m may be observed in the large joints early after HD onset. Overall prevalence reaches 48% of the patients on HD for a median of 47 months. It is much higher than that reported on the basis of clinical or radiological evidence. The sternoclavicular and knee joints are more frequently (P < 0.03) involved than the shoulder. The easily accessible sternoclavicular joint therefore appears to be the best site for the early detection of A beta 2m. Both HD duration and age at HD onset, but not diabetic nephropathy, are independent risk factors for A beta 2m.

Hemophagocytic syndrome and T-cell lymphoma after kidney transplantation: a case report.

Lymphoma in immunocompromised transplant patients is a feared cause of morbidity and mortality. Superimposed on the lymphoma and the transplantation immunosuppression is a rare condition: hemophagocytic syndrome (HS). HS is characterized by fever, hepatosplenomegaly and lymphadenopathy, skin rashes, jaundice, coagulopathy, and phagocytosis of blood elements with pancytopenia. Here we describe a rare but fatal case of a kidney transplant patient who developed T-cell lymphoma and HS, without evidence of EBV replication. A short review of the diagnosis, treatment, and prognosis of HS is given.

Divergent effects of calcium channel and angiotensin converting enzyme blockade on glomerulotubular function in cyclosporine-treated renal allograft recipients.

The effects of amlodipine and perindopril on renal hemodynamics and tubular function in cyclosporine-treated hypertensive renal allograft recipients were evaluated in a randomized, double-blind crossover fashion. Ten patients were studied after a 2-week placebo run-in and, after 8 weeks of active treatment, allowing a 2-week placebo washout between treatments. At the end of each period, glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured as 51Cr-EDTA and 123I-hippuran clearance, respectively, and tubular function evaluated by the lithium clearance technique was determined. Both drugs maintained GFR and ERPF and lowered mean arterial pressure (MAP, mm Hg) to a similar extent (time x treatment, P = 0.466): amlodipine from 126.9 +/- 2.5 to 115.9 +/- 2.2; perindopril from 126.9 +/- 2.5 to 117.9 +/- 3.9 (time effect of all treatments together, P = 0.003). Accordingly, renal vascular resistance (RVR, mm Hg/mL/min/1.73 m2) was equally reduced (time x treatment, P = 0.955): amlodipine from 0.36 +/- 0.03 to 0.30 +/- 0.02; perindopril from 0.36 +/- 0.03 to 0.32 +/- 0.01 (time effect all treatments together, P = 0.043). Sodium clearance and fractional excretion of sodium were not affected by either drug. Output of fluid from the proximal tubules measured as clearance of lithium (CLi, mL/min) and uric acid (CUr, mL/min) was higher after amlodipine than after perindopril (CLi 19.1 +/- 2.1 v 16.5 +/- 1.7, P =0.036 and CUr 7.0 +/- 0.6 v 5.9 +/- 0.4, P = 0.007). As a consequence, after amlodipine, distal absolute reabsorption of sodium was higher (DARNa 2.57 +/- 0.28 v 2.19 +/- 0.22 mEq/min, P = 0.027) and serum uric acid was lower (5.9 +/- 0.3 v 6.7 +/- 0.4 mg/dL, P = 0.001) in comparison with perindopril. In cyclosporine-treated renal allograft hypertensives, amlodipine and perindopril lower blood pressure equally and reduce RVR to the same extent. Overall sodium excretion is not affected by either agent. Urate clearance is higher and serum uric acid lower on amlodipine as compared with perindopril.

Effect of treatment with 1.25 and 1.75 mmol/l calcium dialysate on bone mineral density in haemodialysis patients.

The effect of two different dialysate solutions with a calcium concentration of 1.25 and 1.75 mmol/l was evaluated in 14 patients, using a cross-over design. Patients were treated with each solution during a period of 6 months. Treatment with calcium supplements, vitamin D and aluminium hydroxide was adapted weekly, according to the results of blood chemistry. PTH, SAP, and ionized calcium were determined monthly, bone density with DXA and QCT before and after 6 months of treatment. During treatment with both 1.25 and 1.75 calcium dialysate (cad), the control of serum calcium and phosphate was similar. PTH did not change during either treatment. SAP decreased during treatment with 1.75, but remained stable with 1.25 mmol/l cad. Bone density evaluated with DXA remained unchanged during both treatments. QCT measured bone density increased from 101.29 +/- 13.50 to 106.79 +/- 13.14 mg/ml in the 1.75 cad group, while it did not vary in the 1.25 cad group, (107.75 +/- 13.48 versus 108.97 +/- 13.40 mg/ml). It is concluded that lowering the calcium content of the dialysate does not negatively influence the control of serum calcium and phosphate, nor does it aggravate hyperparathyroidism when vitamin D is administered simultaneously. Under the present conditions, osteopenia and possibly bone mineralization improve only in the group dialysed with 1.75 Ca.

Serum soluble interleukin 2 receptor in hemodialysis patients treated with recombinant human erythropoietin.

The cell-mediated immunity was studied in 14 hemodialysis patients by determination of the serum levels of soluble interleukin 2 receptor (sIL-2R) before (hemoglobin 7.9 +/- 0.6 g/dl) and after 16 months of recombinant human erythropoietin (rHuEPO) administration (hemoglobin 10.3 +/- 1.1 g/dl) and compared with 14 hemodialysis patients not receiving the drug (hemoglobin 9.7 +/- 1.4 g/dl). The sIL-2R level was higher in severely anemic patients starting rHuEPO than in patients not receiving the drug (9,414 +/- 2,822 vs. 5,001 +/- 2,905 pg/ml; p < 0.05). At the end of the 16-month observation period, a decrease in sIL-2R of about 48% was observed following raising hemoglobin with rHuEPO, whereas untreated patients exhibited a further increase in sIL-2R, amounting to 59% (p < 0.001). There was a correlation between sIL-2R and hemoglobin (r = -0.40; p < 0.02) at the start of the study and between sIL-2R and hemoglobin (r = -0.43; p < 0.02) and monocyte number (r = 0.48; p < 0.01) at the end of the observation period. Elevated serum sIL-2R levels, a characteristic finding of the altered cell-mediated immunity of hemodialysis patients, may be influenced by the increase in hemoglobin concentration following rHuEPO administration rather than by the hormone itself.