Fabry disease: detection of undiagnosed hemodialysis patients and identification of a "renal variant" phenotype

BACKGROUND: Fabry disease is an X-linked recessive lysosomal storage disease resulting from deficient alpha-galactosidase A (alpha-Gal A) activity. Renal failure is a major debilitating complication in classically affected males. To determine if this disorder is underdiagnosed in patients with end-stage renal disease (ESRD), the frequency of unrecognized males with Fabry disease on chronic hemodialysis was determined. METHODS: Plasma alpha-Gal A activity was measured in 514 consecutive males with ESRD on hemodialysis. Patients with low alpha-Gal A activity were evaluated clinically and their alpha-Gal A mutations were determined. RESULTS: Six (1.2%) of 514 hemodialysis patients had low plasma alpha-Gal A activities and a previously identified (E66Q, A97V, M296I) or novel (G373D) missense mutation. At ages 30 to 68 years, five patients lacked the classic manifestations of angiokeratoma, acroparesthesias, hypohidrosis, and ocular opacities, while the sixth lacked angiokeratoma and ocular changes. Five had left ventricular hypertrophy (LVH). CONCLUSION: The clinical spectrum of Fabry disease includes a "renal variant" phenotype in patients without classic symptoms who develop ESRD. Affected males undergoing hemodialysis or renal transplantation can be readily diagnosed by plasma alpha-Gal A assays. These patients and their family members may benefit from enzyme replacement therapy for the later, life-threatening cardiovascular and cerebrovascular complications of Fabry disease.     

Renal Transplantation With Expanded Criteria Donors: The Experience of One Portuguese Center

Background

The shortage of kidneys available for transplantation has led to enlarged criteria donors (ECD): namely, donors older than 60 years or aged between 50 and 59 years with 2 of the following characteristics-hypertension, predonation serum creatinine level higher than 1.5 mg/dL or cerebrovascular disease as the cause of death. The aim of this study was to analyze renal transplants using ECD compared with standard criteria donors (SCD) concerning the incidences of delayed graft function (DGF), acute rejection episodes (ARE), and patient and graft survivals.

Materials and Methods

This retrospective study of 409 cadaveric renal transplants over the last 4 years identified ECD in contrast with SCD.

Results

Of the transplants, 24.4% used ECD. The baseline characteristics of recipients of ECD versus SCD kidneys were similar, except for age and cold ischemia time. Comparing ECD and SCD, we observed an higher incidence of DGF (35% vs 18%), occurrence of ARE (34.4% vs 16.6%), average serum creatinine levels at 6 (1.87 vs 1.4 mg/dL), and 12 months (1.88 vs 1.43 mg/dL) as well as lower graft survival at 1 (82% vs 91%) and 3 years (75% vs 84%) after transplantation. Recipient survival at 1 year was not different. Multivariate analysis identified recipient age, cold ischemia time, ARE, and DGF as risk factors for graft failure.

Conclusions

Renal transplantation with grafts from ECD shows significantly worse outcomes with higher rates of DGF and ARE, worse graft function, and lower graft survival.     

Renal function in patients with cadaveric kidney transplants treated with tacrolimus or cyclosporine

INTRODUCTION: Renal function predicts graft survival in kidney transplant patients. This study compared the 2-year evolution of renal function in patients treated with cyclosporine or tacrolimus in combination with mycophenolate mofetil (MMF) and prednisone. METHODS: We studied 1558 cadaveric renal transplant recipients from 14 Spanish hospitals between January 2000 and December 2002. Of these, 1168 were treated with tacrolimus and 390 with cyclosporine. The primary efficacy endpoint was long-term renal function. Renal function was measured by serum creatinine and glomerular filtration rate (GFR) by creatinine clearance calculated from the Cockcroft-Gault formula. This report summarizes the 2-year results. RESULTS: At 24 months the tacrolimus group showed significantly better serum creatinine (1.5 +/- 0.7 vs 1.8 +/- 0.8 mg/dL, P < .001) and GFR (60.5 +/- 20.9 mL/min vs 47.9 +/- 10.0, P < .001) than the cyclosporine group. Additionally, recipients with ideal graft donors (23.5 +/- 2.8 vs 24.0 +/- 2.9 years) had a better serum creatinine at 2 years (1.23 +/- 0.2 vs 1.5 +/- 0.4 mg/dL, P < .05). Multivariate analysis showed that tacrolimus was an independent factor associated with better renal function: odds ratio 1.6, 95% confidence interval (1.2 to 2.2), P < .001. CONCLUSIONS: Patients with a renal transplant treated with tacrolimus in combination with MMF and prednisone displayed better renal function at 2 years than those who received cyclosporine.     

alpha-Galactosidase A deficiency in Dutch patients on dialysis: a critical appraisal of screening for Fabry disease.

INTRODUCTION: Fabry disease or alpha-galactosidase A (alpha-Gal A) deficiency is an X-linked lysosomal storage disorder that often leads to renal insufficiency in males and occasionally in females. The disease is rare, but its prevalence may be underestimated due to its variable clinical picture. Enzyme supplementation therapy with rHu-alphaGal A is currently available. Limited experience has so far shown that therapy may at best stabilize renal function. Despite these preliminary findings, much effort is being put into screening high-risk groups for undiagnosed alpha-Gal A deficiency. We studied the prevalence of alpha-Gal A deficiency in a Dutch dialysis cohort to establish possible underdiagnosis. We discuss the benefits of screening for Fabry disease. METHODS: Activity of alpha-Gal A in whole blood was measured in a group of 508 male Dutch dialysis patients. RESULTS: Of the 508 patients studied only one patient, already known with Fabry disease, had a alpha-Gal A deficiency, a prevalence of 0.22% (95 CI 0-1.1%). CONCLUSIONS: No undiagnosed Fabry patients were found, indicating that in our studied cohort there is no large-scale underestimation of its prevalence. Even though screening of dialysis patients for Fabry disease might identify patients who remain otherwise unrecognized, screening of high-risk populations for alpha-Gal A deficiency should be carried out with caution since long-term efficacy of treatment is currently unknown.     

The grafted kidney takes over: disappearance of the nephrotic syndrome after preemptive pancreas-kidney and kidney transplantation in diabetic nephropathy

This report describes the rapid and complete reversal of proteinuria after preemptive transplantation in diabetic nephropathy. Case 1 was a 42-year-old woman with type 1 diabetes (before pancreas-kidney graft: serum creatinine 1.6 mg/dL and proteinuria 9.1 g/day; 1 month after pancreas-kidney graft: proteinuria 0.3 g/day and creatinine 1.3 mg/dL). Case 2 was a 48-year-old man with type 2 diabetes (before kidney graft: creatinine 2 mg/dL and proteinuria 5.9 g/day; 1 month after: proteinuria 0.7 g/day and creatinine 1.1 mg/dL). The proteinuria pattern changed (pre: glomerular nonselective, tubular complete; post: physiologic). Renal scintiscan (99mTC-MAG3) demonstrated functional exclusion of the native kidneys, despite high pretransplant clearance (> 50 mL/min). The effect was not linked to euglycemia or readily explainable by pharmacologic effects (no difference in renal parameters after pancreas transplantation with the same protocols). These data confirm the efficacy of preemptive kidney and kidney-pancreas transplantation in diabetic nephrotic syndrome and indicate that a regulatory hemodynamic effect should be investigated.     

Early Focal Segmental Glomerulosclerosis as a Cause of Delayed Graft Function With Combined Acute Antibody Rejection: A Case Report

Focal segmental glomerulosclerosis (FSGS) is the most common form of post-transplant glomerulonephritis. We describe a case where a biopsy proved that early recurrence of FSGS on postoperative day 1 was the cause of delayed graft function. A 39-year-old man, on hemodialysis for 15 years due to polycystic kidney disease, received a cadaveric renal transplantation. On postoperative day 1, his hourly urine output decreased from 700–800 mL to 50 mL. The graft biopsy showed a mild acute kidney injury confusing nephrotic syndrome. On postoperative day 45, his creatinine level increased to 3.02 mg/dL with severe proteinuria. A kidney biopsy showed focal segmental glomerulosclerosis. On postoperative day 120, his creatinine level elevated again, concomitant with proteinuria. A kidney biopsy showed FSGS with antibody-mediated rejection. After plasmapheresis, his creatinine level decreased to 1.3 mg/dL with mild proteinuria. Once active in the allograft, de novo FSGS is a potentially aggressive process. In this case, it could be managed because of an accurate diagnosis and appropriate treatment.     

Post-transplant renal function in the first year predicts long-term kidney transplant survival

BACKGROUND: Improvements in long-term kidney graft survival have been recently noted. However, the reasons for this were unclear. This study examined post-transplant renal function within the first year as an independent variable influencing long-term survival. METHODS: The influence of demographic characteristics (age, sex, race); transplant variables (cadaver versus living donor, cold ischemia time, HLA mismatching, delayed graft function and transplant year), and post-transplant variables (immunosuppressive agents for the prevention of acute rejection, clinical acute rejection and post-transplant renal function in the first year) on graft survival were analyzed for 105,742 adult renal transplants between 1988 and 1998. Renal function in the first year was expressed as serum creatinine at six months and one year and delta creatinine (change in serum creatinine between 6 months and 1 year). Graft half-life was used to measure long-term survival. RESULTS: During this 11-year period, the one-year serum creatinine values for cadaver recipients steadily improved, from 1.82 +/- 0.82 mg/dL in 1988 to 1.67 +/- 0.82 mg/dL in 1998 (P < 0.001), as did the graft half-life. There was a progressive decline in graft half-life for each incremental increase of six month, one year and Delta creatinine for living and cadaver donor transplants as well for cadaver transplants with donor age > and < or =50 years. The Relative Hazard (RH) for graft failure was 1.63 (1.61, 1.65; P < 0.0001) with each increment of 1.0 mg/dL of serum creatinine at one year post-transplant and it increased to 2.26 (2.2, 2.31; P < 0.0001) when the Delta creatinine was 0.5 mg/dL. The RH reduction for graft failure was substantially lower for the years 1993, 1996, 1997 and 1998 when post-transplant renal function was not included in the model (P < 0.05). However, the RH reduction per year was not different when post-transplant creatinine was included in the model, 1.01 (0.94 to 1.05; P = 0.89). CONCLUSION: In conclusion, one-year creatinine and Delta creatinine values predict long-term renal graft survival. Recent improvements in graft half-life are related to conservation of renal function within the first year post-transplantation.     

Impact of fluvastatin on hyperlipidemia after renal transplantation

BACKGROUND: Renal transplant recipients are at increased risk of atherosclerotic vascular disease with hyperlipidemia. Many recipients have preexisting cardiovascular disease at the time of transplantation, and immunosuppressive therapy may aggravate existing risk factors or promote development of new risk factors, notably hyperlipidemia and hypertension. Fluvastatin is one of the statins, an HMG-CoA reductase inhibitor, which has been shown to be effective in lowering cholesterol levels. We treated hyperlipidemia after renal transplantation with Fluvastatin for more than 6 months.We attempted to clarify the efficacy of fluvastatin on hyperlipidemia in renal transplant recipients. MATERIALS: Forty-five renal transplant recipients with hyperlipidemia were enrolled in this study. The mean age was 44.2 years, with 23 men and 22 women. Thirty-seven transplantations were from a living related donors and eight from cadaveric donors. Thirty-three recipients were ABO-compatible, seven recipients had minor mismatches, and five recipients were ABO-incompatible. The dose of fluvastatin was 20 mg per day. Levels of total cholesterol (TC), triglyceride (TG), HDL cholesterol (HDL-C), LDL cholesterol (LDL-C), serum creatinine (s-Cr), ALT, ALP, uric acid (UA), hematocrit (Ht), CPK, and blood pressure were examined in all recipients before treatment as well as 1, 3, and 6 months after Fluvastatin administration. RESULTS: The mean levels of TC and TG were significantly reduced from 256, to 224 and 215 mg/dL, and from 188 to 170 and 147 mg/dL at 1 and 6 months after treatment, respectively. The mean levels of HDL-C were 72 mg/dL before treatment, 81 mg/dL at 1 month, and 80 mg/dL at 6 months after treatment. The mean levels of LDL-C were 153 mg/dL before treatment, 145 mg/dL at 1 month, and 145 mg/dL at 6 months after treatment. Fluvastatin significantly produced a reduction rate in TC of 16%, TG of 22%, and LDL-C of 5% after 6 months of treatment, respectively. The mean levels of HDL-C of were increased 10% after 6 months of treatment. The serum creatinine and CPK were not significantly different. There were no clinically significant differences in other factors. No significant adverse effects were observed. CONCLUSIONS: Fluvastatin seemed to be safe and highly effective to control TC, TG, LDL-C, and HDL-C in renal transplant recipients.     

Results in Laparoscopic Living Donor Nephrectomy: A Multicentric Experience

ObjectiveRenal transplantation is the most successful therapy to improve survival and quality of life for patients with end-stage renal disease. Living donors have been used as an alternative to reduce the stay on the waiting list. Laparoscopic living donor nephrectomy has become the standard procedure for renal transplantation. Minimally invasive surgery involves less postoperative pain with less analgesic requirements allowing shorter hospital stay for the donor.Material and MethodsWe retrospectively analyzed demographic and intraoperative data and surgical complications for 46 patients who underwent laparoscopic living donor nephrectomy between March 2001 and March 2011.ResultsMean donor age was 41 years. Mean operative time was 170 ± 45 minutes. The average cold ischemic time was 40 minutes and warm ischemic time was 26 minutes. Twenty-one patients were donors for pediatric receptors. Fourty patients underwent left laparoscopic nephrectomy, the other 6 patients underwent right laparoscopic nephrectomy due to vascular anatomic variant. Right laparoscopic nephrectomy was converted in 1 case (2.2%) due to renal vein laceration without donor morbidity and without compromise of graft function. Renal function at the second day post donor nephrectomy was measured using serum creatinine averaged 1.2 mg/dL with a mean increase of 0.4 mg/dL from baseline, with normalization after 30 days. No patient required blood transfusion, and there were no immediate surgical complications, infections, or mortality. One patient developed an incisional hernia in relation to the site of kidney removal. The mean hospital stay was 5 ± 1 days.ConclusionsLaparoscopic nephrectomy in our experience is a safe technique without postoperative morbidity or mortality. It is associated with low levels of pain, early discharge and early return to physical activity and work, good sense of aesthetic results, and long-term graft function comparable to traditional nephrectomy and cadaveric grafts.     

First A2-to-O renal transplantation in the 21st Century: a step in the transplantation history of Turkey

Renal transplantation is the best treatment modality for patients with end-stage renal disease. Turkey is a country with limited cadaveric donor organ programs. Herein we have reported the first A2-to-O living donor kidney transplantation in Turkey. A 20-year-old female patient was admitted for a living related renal transplantation from her only potential donor her mother. She was blood group O and her mother was blood group A2. Three plasmapheresis sessions followed by intravenous immunoglobulin (IVIG) were performed every other day in the week prior to transplantation. Daclizumab was administered at the time of transplantation with an additional four doses every 2 weeks after the procedure. The immunsuppressive regimen included tacrolimus, mycophenolate mofetil, and prednisolone. Eight plasmapheresis sessions followed by IVIG were performed in the first 2 weeks posttransplant. Six months after transplantation, the serum creatinine was 1 mg/dL. Our experience showed that A2-to-O renal transplantation can be safely performed and may expand the pool of living kidney donors in Turkey.     

A single center experience in preemptive kidney transplantation

Transplantation is recognized as preemptive if it takes place before the initiation of chronic dialysis. This maneuver has the potential to avoid the morbidity and burden of chronic dialysis. From November 2003 to April 2005, 15 (7 male, 8 female) end-stage renal failure patients of mean age 40 +/- 14.8 years received preemptive grafts from 2 living-related and 13 cadaveric donors, constituting 11.5% of all kidney transplantations performed in our center at that time. The period on the waiting list for preemptive recipients, namely, 2 weeks to 6 months (mean, 2.4 months), was significantly shorter than that of other patients (mean, 13.8 months). The mean creatinine clearance calculated from the Cockroft Gault formula and the mean plasma creatinine level in preemptive recipients before transplantation were 12.7 +/- 3.1 mL/min and 6.6 +/- 0.8 mg/dL, respectively. The donors for preemptive and non-preemptive groups of recipients did not differ significantly in respect to age, gender, and renal function. The mean number of mismatches of 3.73 and 3.25 and the mean total ischemic times of 9.53 +/- 5 and 11.2 +/- 5 hours, in preemptive and non-preemptive groups of recipients, respectively. The incidence of delayed graft function (dialysis in the first week after transplantation) was significantly lower among preemptive recipients (20% versus 42%, respectively). The groups did not differ either in respect to the occurrence of acute rejection episodes or graft and patient survivals. In preemptive patients the mean plasma creatinine levels at 3 and 12 months were 1.37 +/- 0.3 and 1.09 +/- 0.3 mg/dL, and in non-preemptive patients 1.7 +/- 0.5 and 1.4 +/- 0.4 mg/dL. In conclusion, these results are promising, confirming the notion that preemptive kidney transplantation is the optimal treatment for end-stage renal disease patients.     

Donor affected by hemosiderosis: is kidney transplantation possible? A case report

Marginal donors (advanced age, comorbidities, and so on) provide an increasing contribution to the kidneys used to alleviate the relative organ shortage. We describe the evaluation process and clinical outcome of two kidneys with hemosiderosis used as a double graft. The donor was a 59-year-old hypertensive man, known to have a mechanical mitral valve, who died from a cerebral hemorrhage, with a normal serum creatinine (SCr) and kidneys with normal appearances at sonography. A protocol donor biopsy showed a Karpinsky score of 5 for both kidneys. A double graft was therefore scheduled. The recipient was a 59-year-old man, on dialysis because of chronic glomerulonephritis. HLA match was incompatibility 4/6; immunosuppression was based on steroids, cyclosporine, and mycophenolate mofetil with basiliximab as induction therapy. The grafts showed delayed function with dialysis treatments performed from postoperative day (POD) 1. On POD 2, a magnetic resonance imaging (MRI) study showed the typical appearance of siderosis. Pearl's staining performed on a protocol biopsy confirmed the presence of widespread iron deposits. On POD 5, a recipient renal biopsy showed a superimposed severe acute tubular necrosis. Renal function recovered slowly; SCr at discharge on POD 22 was still 4.2 mg/dL. Two months later, the SCr was 2.2 mg/dL. A second MRI performed at 3 years and 6 months after transplantation confirmed a progressive removal of iron overload while the patient had stable renal function (glomerular filtration rate) of 33 mL/min and SCr: 2.3 mg/dL. We concluded that donors with hemosiderosis should be treated as marginal donors and may be grafted based on a pretransplant biopsy.     

Improved renal function in sirolimus-treated renal transplant patients after early cyclosporine elimination

BACKGROUND: Sirolimus (Rapamune; SRL) in combination with cyclosporine (CsA) reduces the incidence of acute rejection episodes in renal allograft recipients. This study evaluated whether renal function could be improved by elimination of CsA from an SRL-based regimen. METHODS: This phase 2, open-label, controlled, randomized study was conducted at 17 centers in the United States and Europe. Two hundred forty-six first cadaveric renal allograft recipients were enrolled, and 197 were randomized to full-dose CsA (microemulsion) plus fixed-dose SRL (2 mg/day; group A, n=97) or reduced-dose CsA plus concentration-controlled SRL (troughs 10-20 ng/mL; group B, n=100). Most patients with acute tubular necrosis-delayed graft function that resolved later than posttransplantation day 7 were not randomized but were assigned to a third group (nonrandomized, n=49) and received up to 5 mg per day of SRL as part of their individualized treatment regimen. All patients received standard doses of corticosteroids. At the end of posttransplantation month 2, eligible patients (those not treated for rejection within 3 weeks) in group B had CsA tapered and eliminated over the subsequent 4 to 6 weeks. RESULTS: At 12 months after transplantation, renal function was significantly better in the CsA-elimination arm. In patients who were on therapy and who had not experienced an acute rejection episode before month 6, serum creatinine level was significantly lower (1.38 mg/dL vs. 1.82 mg/dL, P < 0.001) and calculated glomerular filtration rate (Nankivell method) was significantly higher (73.5 mL/min vs. 57.1 mL/min, P < 0.001) in group B than in group A. In the intention-to-treat population, rates of biopsy-confirmed acute rejection at 12 months were similar between groups A and B (18.6% vs. 22.0%, respectively; P = 0.598). In addition, graft survival (92.8% and 95.0%) and patient survival (96.9% and 96.0%) rates at 12 months were not significantly different between groups A and B, respectively. Furthermore, there were no significant differences between black and nonblack recipients within treatment groups in terms of rejection rates and graft survival at 12 months. Black recipients in group B had better serum creatinine levels at 12 months compared with black recipients in group A (1.55 mg/dL vs. 2.69 mg/dL, respectively, P = 0.011), as did nonblack recipients in group B compared with nonblack recipients in group A (1.53 mg/dL vs. 1.75 mg/dL, respectively, P = 0.055). Black patients in group A had higher mean serum creatinine levels (2.69 mg/dL) than nonblack patients in group A (1.75 mg/dL, P = 0.028). Hypertension, edema, hypomagnesemia, and dyspnea were reported significantly less frequently in patients randomly assigned to undergo CsA elimination compared with patients in group A (P < 0.05); group B patients had a significantly greater (P < 0.05) incidence of abnormal liver function tests, diarrhea, hypokalemia, and thrombocytopenia. CONCLUSION: Concentration-controlled SRL with early elimination of CsA is safe and results in improved renal function. Reduced exposure to CsA does not result in a clinically significant increase in the incidence of acute rejection episodes. This is true for both black and nonblack recipients. SRL may be used to reduce the exposure of renal allograft recipients to the nephrotoxic effects of CsA.     

Fabry disease: diagnosis and treatment

Fabry disease is an X-linked lysosomal storage disorder that results from a deficiency of the enzyme alpha-galactosidase A (alpha-Gal A). The lack of alpha-Gal A causes an intracellular accumulation of glycosphingolipids, mainly globotriaosyceramide (GL3). Affected organs include, among others, the vascular endothelium, heart, brain, and kidneys, leading to end-stage renal disease (ESRD). Since Fabry disease cannot be cured at present, clinical management is symptomatic. Enzyme replacement therapy (ERT) with recombinant alpha-Gal A has been introduced as a new therapeutic option for the treatment of Fabry patients. Short-term (one year) clinical studies have positively correlated ERT with improvement of clinical symptoms and microvascular endothelial cell clearance. Treatment outcome concerning severe organ manifestations such as proteinuria and renal function impairment, left ventricular hypertrophy, and heart failure in the long run has yet to be shown. In our studies we used sensitive and noninvasive techniques such as ultrasound-based strain rate imaging and magnetic resonance imaging (MRI), combined with MR-spectroscopy (MR-S), for the quantification of functional abnormalities at an early stage of the disease and during long-term follow-up. Future issues should determine the appropriate timing to start therapy and how children and heterozygous females should be managed. Given the diagnostic and therapeutic potential today, it is of importance to identify patients at an early stage and to start therapeutic intervention before progression of organ damage is inevitable.     

Acute Anti-A/B Antibody-Mediated Rejection After ABO-Incompatible Kidney Transplantation Treated With Bortezomib and Plasmapheresis: A Case Report

BackgroundABO-incompatible kidney transplantation (KTP) is effective for avoiding transplantation-related issues. It is a viable alternative to ABO-compatible KTP, as both techniques have similar patient and graft survival rates. However, anti-A/B antibody-mediated rejection (AMR) can occur, resulting in poor long-term graft survival.CaseA 45-year-old man with end-stage renal disease presented with a serum creatinine level of 10.2 mg/dL. We decided to perform KTP with spousal donation. He had panel-reactive antibody class I and II and cross matching test negativity, a 3/6 mismatch on human leukocyte antigen typing, an ABO antibody titer of 1:256, and no donor-specific antibodies. The patient and donor blood types were O+ and A+, respectively. The anti-A/B antibody titer was reduced preoperatively with rituximab (200 mg/body), plasmapheresis, and intravenous immunoglobulin (0.2 mg/kg). Basiliximab and methylprednisolone were used for induction immunosuppression, and tacrolimus, mycophenolate mofetil, and prednisolone were used for maintenance immunosuppression. KTP was successful, and graft function was initially normal. On postoperative day (POD) 5, the serum creatinine level and anti-A/B antibody titer increased from 0.9 mg/dL to 1.9 mg/dL and 1:16 to 1:64, respectively. Graft biopsy revealed acute AMR and tubular injury. We started steroid pulse therapy, plasmapheresis, and subcutaneous bortezomib (2.6 mg, twice a day, every 3 days) with no side effects. The serum creatinine level decreased from 5.7 mg/dL to 1.5 mg/dL on POD 28. Graft biopsy showed no rejection, and normal function was maintained for 40 months.ConclusionsAcute, early anti-A/B AMR was successfully treated with plasmapheresis and bortezomib.     

Hydronephrosis in the early stage of pregnancy after renal transplantation

A 28-year-old woman with end-stage renal disease due to congenital hypoplasia and vesicoureteric reflux in the bilateral kidneys received a renal transplant from her 52-year-old mother. She became pregnant 3 years later. The serum creatinine level was 1.6 mg/dL with a creatinine clearance of 27.3 mL/min/1.48 m(2) just prior to pregnancy. Her graft showed hydronephrosis at 12 weeks of pregnancy. At 25 weeks a double J-type stent catheter was placed, without exposure to radiation, because of progressive deterioration of the graft hydronephrosis. Hydronephrosis partially improved, but her serum creatinine level further increased to 2.3 mg/dL. She delivered a healthy boy by routine caesarean section at 34 weeks of pregnancy. Computed tomography demonstrated the ureter wedged between the gravid uterus and the graft. The catheter was removed 10 days postpartum. Six months later, ultrasonographic study did not show hydronephrosis and the serum creatinine level was 2.0 mg/dL.     

Cyclosporine toxicity: the effect of combined therapy using cyclosporine, azathioprine, and prednisone

Forty-nine patients among 360 who received renal transplants under cyclosporine (CsA)/prednisone (Pred) immunosuppression required alteration of the immunosuppressive regimen because of intractable nephrotoxicity. Twenty-five patients, converted totally to azathioprine (Aza)/Pred, suffered intractable nephrotoxicity with no associated evidence suggesting ongoing rejection. The results with Aza/Pred conversion were disappointing because of an unacceptably high incidence of rejection and allograft loss. Twenty-four patients with intractable CsA nephrotoxicity were, therefore, treated using an alternative approach combining Aza with aggressive CsA dose reduction, and continued Pred therapy. All patients tolerated initiation of Aza without complication; allograft rejection was not common. Renal function improved for 23 of the 24 (96%) CsA/Aza/Pred patients with mean serum creatinine levels falling from 3.5 +/- 0.5 mg/dL to 2.2 +/- 0.4 mg/dL after a mean follow-up of 14 months (P less than .001). Among 18 patients observed at least 12 months, seven (39%) enjoyed serum creatinine values less than or equal to 2 mg/dL. Nine CsA/Aza/Pred-treated patients (37.5%) required hospitalization because of infectious complications, all of which resolved with temporary reduction of immunosuppression and specific antimicrobial therapy when indicated. One patient sustained acute allograft rejection as a result of patient noncompliance, and one patient on a seemingly appropriate CsA/Aza/Pred dose responded initially to steroid pulse antirejection therapy; however, renal function again worsened. Two patients developed progressive renal dysfunction due to chronic rejection, and returned to dialysis 13 and 17 months, respectively, following initiation of CsA/Aza/Pred. Overall, the actuarial graft survival for CsA/Aza/Pred-treated patients was 100% at 1 year, and 84% at 2 years.(ABSTRACT TRUNCATED AT 250 WORDS)     

Successful kidney transplantation from a cadaveric donor unsuitable for other centers due to acute renal failure: a case report

The demand for kidney transplantation due to improved recipient outcomes has stimulated surgeons to expand the criteria for usable donors, but still the use of organs from deceased donors with terminal acute renal failure is uncommon. We report 2 kidney transplant recipients from a cadaveric donor who was not accepted by other centers because of acute renal failure. The donor, a 24-year-old man with an intracerebral hemorrhage, displayed a serum creatinine (SCr) value of 0.6 mg/dL on hospital admission, which increased to 7.3 mg/dL on the fourth hospital day. After the diagnosis of brain death and refusal of the kidneys by other regional centers, we decided to transplant the 2 kidneys. Recipient 1, a 31-year-old man on an 11-year dialysis program, discontinued hemodialysis after 7 days of delayed graft function. The SCr level decreased gradually and was stable at 1.08 mg/dL on postoperative day (POD) 45. The contralateral graft was transplanted into a 30-year-old man (recipient 2) undergoing dialysis treatment for 7 years. After 10 days of delayed graft function, the SCr decreased gradually with continued hemodialysis until POD 24. The SCr level has been stable at 1.34 mg/dL on POD 52. At the end of the third month the SCr levels in recipients 1 and 2 were 1.1 mg/dL and 1.4 mg/dL, respectively. In conclusion, one may safely expand the donor pool with kidneys from deceased donors with acute renal failure (ARF) with good short-term outcomes.     

Conversion to sirolimus from cyclosporine may induce nephrotic proteinuria and progressive deterioration of renal function in chronic allograft nephropathy patients

Antiproliferative and non-nephrotoxic properties of sirolimus have been exploited for treatment of patients with chronic graft dysfunction. In this paper we point to the possible association of nephrotic syndrome and renal impairment with rapid conversion from cyclosporine (CsA) to sirolimus in patients with chronic nephropathy. Five male patients, ages 34 to 56 years, with chronic renal failure in the course of glomerulonephritis, were transplanted between 1997 and 1999. For the first 49 to 65 months, the immunosuppressive regimen consisted of CsA, azathioprine (AZA), and prednisone. Thereafter, due to chronic nephropathy evidenced by biopsy, conversion to sirolimus was performed with sharp withdrawal of CsA. The serum creatinine level prior to conversion was 1.9 +/- 0.3 mg/dL. Trace to 86 mg/dL proteinuria was found in 3 patients, while 2 patients had about 200 mg/dL. After 2 to 4 months of sirolimus treatment the proteinuria progressed (558 +/- 183 mg/dL); edema, hypoproteinemia, hypoalbuminemia, and hyperlipidemia developed; and the serum creatinine increased to 3.5 +/- 0.8 mg/dL. Biopsies performed in three patients revealed new pathologic changes. After 4 to 5 months, we performed reconversion to calcineurin inhibitor. Proteinuria decreased to 0 to 150 mg/dL; nevertheless the serum creatinine was continuously rising. Six to 15 months after the conversion, 3 patients returned to dialysis. The fourth patient, who was earlier reconverted, has a serum creatinine level of 2.0 mg/dL after 15 months. In conclusion, conversion from CsA to sirolimus may induce nephrotic syndrome with progressive deterioration of renal function. Converted patients require careful monitoring of proteinuria and renal function. Early reconversion to calcineurin inhibitor may prevent progressive deterioration of graft function.     

N-acetylcysteine as salvage therapy in cisplatin nephrotoxicity

N-acetylcysteine (NAC) repletes intracellular stores of reduced glutathione and may be a scavenger of oxygen free radicals. We report a 52-year-old female who developed acute renal insufficiency after administration of one dose of 150 mg of cisplatin for treatment of squamous cell cancer of the esophagus. Her blood urea nitrogen and creatinine rose from 12 and 0.7 mg/dL, respectively, to 24 and 1.8 mg/dL on day 5 after cisplatin. On that day the patient was begun on NAC, starting with a loading dose of 140-mg/kg-body weight followed by 70mg/kg every 4h for 4 days. Two days after starting NAC her renal function began to improve, and although she failed to complete a full course of the drug, by day 10 her serum creatinine had fallen to 0.8 mg/dL. A previous report showed that N-acetylcysteine might reverse cisplatin-induced renal toxicity. Our case supports this hypothesis.