Transcatheter embolization of biopsy-related vascular injuries in renal allografts. Long-term technical, clinical and biochemical results.

PURPOSE: Biopsy-related vascular injuries in renal transplants are rare, but they can lead to dramatic clinical symptoms prompting immediate treatment. Transcatheter embolization is a known minimally invasive technique to treat some form of arterial bleeding. This study evaluated the efficacy of this technique in iatrogenic biopsy-related vascular lesions in renal allografts. MATERIAL AND METHODS: Between 1993 and 2001, 13 patients were treated by percutaneous transcatheter intervention. Indications for embolization were hypovolemic shock due to perinephric hematoma (n = 5), persistent macroscopic hematuria (n = 7) and an asymptomatic large intrarenal pseudoaneurysm in 1 patient. Selective angiography revealed an arteriovenous fistula (n = 7), a pseudoaneurysm (n = 6), and perinephric contrast extravasation (n = 4). RESULTS: In all patients, successful embolization of the feeding artery could be performed; in 11 patients it was performed in one session, in 2 patients an additional session was needed. In 1 patient thrombosis of a segmental artery occurred immediately after embolization, but was successfully treated by short-term in situ thrombolysis. Clinical symptoms disappeared in all patients. Serum creatinine levels (determined 30 and 60 days after embolization, compared to the level before embolization) decreased significantly in 10 patients; a progressive deterioration of the renal function was observed in 3 patients. CONCLUSIONS: Transcatheter embolization is a safe and effective endovascular technique to treat biopsy-related vascular injuries in renal transplants. In the vast majority of cases an immediate clinical success and significant benefit in renal function can be obtained and the longevity of the allograft after successful embolization mainly depends on the natural (medical) outcome.

Modifier effect of ENOS in autosomal dominant polycystic kidney disease.

A significant phenotypical variability is observed in autosomal dominant polycystic kidney disease (ADPKD). ADPKD is associated with altered endothelial-dependent vasodilation and decreased vascular production of nitric oxide (NO). Thus, ENOS, the gene coding for the endothelial nitric oxide synthase (eNOS), could have a modifier effect in ADPKD. In order to test this hypothesis, we genotyped 173 unrelated ADPKD patients from Belgium and the north of France for the Glu298Asp, intron 4 VNTR and T-786C polymorphisms of ENOS and looked for their influence on the age at end-stage renal disease (ESRD). In males (n = 93), the Glu298Asp polymorphism was associated with a lower age at ESRD (Glu/Asp + Asp/Asp: 49.0 +/- 1.2 years, n = 53; Glu/Glu: 53.5 +/- 1.5 years, n = 40; simple regression, P = 0.02; multiple regression, P = 0.006). This effect was confirmed in a subset of males linked to PKD1 and reaching ESRD before age 45, and by a cumulative renal survival analysis in PKD1-linked families. Further studies demonstrated that NO synthase (NOS) activity was decreased in renal artery samples from ADPKD males harbouring the Asp298 allele, in association with post-translational modifications and partial cleavage of eNOS. No significant effect of the other polymorphisms was found in males, and no polymorphism influenced the age at ESRD in females. In conclusion, the frequent Glu298Asp polymorphism of ENOS is associated with a 5 year lower mean age at ESRD in this subset of ADPKD males. This effect could be due to a decreased NOS activity and a partial cleavage of eNOS, leading to a further decrease in the vascular production of NO.

Posttransplantation diabetes mellitus in FK-506-treated renal transplant recipients: analysis of incidence and risk factors.

BACKGROUND: The development of posttransplantation diabetes mellitus has a major impact on the quality of life and long-term outcome. METHODS: One hundred thirty-nine patients without known glucose metabolism abnormalities and treated with FK-506, methylprednisolone, and mycophenolate mofetil/azathioprine were analyzed for incidence of and risk factors for developing impaired fasting glycemia (IFG) and diabetes mellitus (DM). RESULTS: Using the American Diabetes Association criteria, 15% developed IFG and 32% developed DM in the first year after transplantation. High trough levels of FK-506 during the first month after transplantation (especially >15 ng/ml) and high body mass index (BMI) were significant risk factors for IFG or DM. Patients with (steroid-treated) acute rejections in addition to high trough levels of FK-506 were most prone to develop DM, whereas high BMI conferred risk of developing IFG. Patients with posttransplantation glycemic abnormalities also had higher levels of serum triglycerides at the time of transplantation, but they needed a lower dose of FK-506 to obtain higher trough levels of FK-506, suggesting metabolic differences already present before transplantation. The only risk factor retained for persistent IFG or DM beyond the first year was a higher number of trough levels of FK-506 >15 ng/ml during the first month after transplantation. CONCLUSIONS: Induction with an FK-506 based immunosuppressive regimen resulted in a high incidence of glucose metabolism disorders in renal transplantation recipients. Higher trough levels of FK-506 during the first month, acute rejections, and higher BMI were the most obvious risk factors.

Persistent hyperparathyroidism after kidney transplantation requiring parathyroidectomy.

INTRODUCTION: Successful kidney transplantation (KT) is believed to cure secondary hyperparathyroidism, but persistent disease has emerged in a significant number of allograft recipients. Parathyroidectomy (PTX) is ultimately required in some of these patients. AIM: To provide an in-depth analysis of 42 patients who required surgical treatment for persistent hyperparathyroidism after successful renal transplantation and to identify risk factors for PTX present at the time of transplantation. DESIGN: Retrospective case controlled study. METHODS: Charts of 1332 kidney allograft recipients, transplanted between 1989 and 2000, were reviewed. Patients requiring a PTX after a first successful kidney transplantation (serum creatinine < 2.5 mg/dl) were identified. Their charts were checked for various demographic, clinical and biochemical variables. The data were compared with data obtained from a control group closely matched for time of transplantation. RESULTS: Persistent hyperparathyroidism after successful KT requiring PTX occurred in 55 (4.1%) patients. Because of insufficient follow-up data only 42 recipients were eligible for further analysis. The age of the patients was 52 +/- 2.1 years (mean +/- SEM). The time between transplantation and PTX was 416 +/- 61 days. The mean serum creatinine at the time of PTX amounted to 1.6 +/- 0.1 mg/dl. Persistent hypercalcemia, albeit asymptomatic in most patients, was the main indication for PTX. Enlarged parathyroid glands were visualised by ultrasonography in 74% of the cases. Subtotal parathyroidectomy was the procedure of choice. The operative morbidity was negligible and the incidence of persistent or recurrent hyperparathyroidism was low, being 15%. In comparison to the control group, the patients with persistent hyperparathyroidism had a significant longer duration of pre-transplantation dialysis treatment (36.3 vs. 23.0 months, p < 0.01) and significant higher values of intact parathyroid hormone (iPTH) (268.1 vs. 96.0 ng/l, p < 0.001), total serum calcium (10.6 vs. 9.4 mg/dl, p < 0.001), and serum alkaline phosphatases (185.5 vs. 132.0 U/L, p < 0.001) at the time of transplantation. No relationship with the mode of dialysis treatment was observed. CONCLUSION: Persistent hyperparathyroidism requiring PTX after successful KT is a common clinical problem. Patients who spent a long time on dialysis and/or patients with a high pre-transplant level of iPTH, serum calcium and alkaline phosphatases are especially at risk.

A comparative prospective study on the use of low concentrate citrate lock versus heparin lock in permanent dialysis catheters.

We prospectively evaluated the efficacy and safety of a low concentrate citrate lock versus heparin lock in permanent single lumen hemodialysis catheters. The frequency of clot formation, complete catheter occlusion, flow problems and the use of urokinase as well as catheter infection episodes were monitored during 1370 dialysis sessions in 19 patients, randomised in two study groups. There was a significantly higher number of dialysis sessions with clot formation in the citrate group but regarding the need for urokinase bolus or infusion, complete obstruction of the catheter or local infections, there were no statistically significant differences between groups. The higher incidence of clotting in the citrate locked catheters had no repercussion on dialysis efficiency, effective blood flow or on the use of thrombolytic therapy. We found that low concentrate citrate is as safe as heparin for long-term interdialytic anticoagulation of permanent single lumen hemodialysis catheters but is more efficient from a pharmaco-economic viewpoint.

Crescentic glomerulonephritis complicating the course of a hypocomplementemic urticarial vasculitis.

The authors report a case of crescentic glomerulonephritis leading to end-stage renal failure in a patient affected by a hypocomplementemic urticarial vasculitis (HUV). The patient's clinical course was characterized by the survey of several episodes of extra-renal vasculitis. We emphasize that HUV commonly considered as a limited form of vasculitis might in some cases have a dramatic evolution.

Limited cutaneous systemic sclerosis associated with MPO-ANCA positive renal small vessel vasculitis of the microscopic polyangiitis type.

Renal disease in systemic sclerosis may present in various patterns. A 66-year-old woman with a history of longstanding limited cutaneous systemic sclerosis of the CREST syndrome variant presented with a sudden left foot drop and rapidly progressive renal insufficiency associated with mild proteinuria, a nephritic urine sediment, and a urinary output of 900 mL/d. There was no history of intake of D-penicillamine, and there were no signs of malignant arterial hypertension or microangiopathic hemolytic anemia. Renal histology showed a small vessel vasculitis of the microscopic polyangiitis type. Serologic tests showed a marked increase of antineutrophil cytoplasmic antibodies with a perinuclear pattern and an elevated titer of antimyeloperoxidase antibodies. No clinical or laboratory signs of Sjögren's syndrome were present. This clinical report adds new information to the spectrum of renal disease in systemic sclerosis. It discusses the association between systemic sclerosis and small vessel vasculitis of the microscopic polyangiitis type as well as the possible meaning of serologic markers.

Granulomatous renal pseudotumor in Wegener's granulomatosis: imaging findings in one case.

Wegener's granulomatosis is a clinicopathological entity characterized by necrotizing granulomatous angiitis involving the upper- and/or lower respiratory tract and the kidneys. Renal involvement is usually characterized by a rapidly progressive necrotizing glomerulonephritis. A case is presented of a patient who developed renal failure and presented a solitary pseudotumoral lesion in the upper pole of the left kidney. Imaging characteristics on US, CT and MR imaging are discussed. The diagnosis was confirmed with ultrasound-guided needle biopsy.

Adult Fanconi syndrome secondary to light chain gammopathy. Clinicopathologic heterogeneity and unusual features in 11 patients.

Fifty-seven cases of Ig light chain-associated Fanconi syndrome (FS) have been reported so far, mostly as isolated reports. The pioneering work by Maldonado and associates (35), who reviewed the first 17 cases in 1975, led to the unifying concept that patients with FS and Bence Jones proteinuria have a special form of plasma cell dyscrasia characterized by slow progression of the tumor and by prominent crystal formation in proximal tubule cells, in the absence of myeloma casts in the distal tubule. We carefully reappraised these characteristics in a series of 11 patients. Ten renal biopsy specimens were available for electron microscopy, adding to the 15 previously reported cases with ultrastructural studies. Moreover, 10 of the kappa light chains could be entirely or partially sequenced and tested for their resistance to cathepsin B, a lysosomal protease present in proximal tubule cells. Our series showed an unexpected clinicopathologic heterogeneity. Seven patients presented with the typical clinical and pathologic features of FS and low-mass myeloma or monoclonal gammopathy of undetermined significance (MGUS), in keeping with Maldonado et al's description. Crystals in bone marrow cells were detected in patients of this group, only. Three patients who presented with full-blown FS exhibited, however, the characteristic features of myeloma cast nephropathy in the setting of high-mass myeloma. One patient of this group also had numerous crystals in proximal tubule cells. The eleventh patient had complete FS with MGUS, but no crystals in proximal tubule cells even after electron microscopy. Contrasting with the clinicopathologic heterogeneity, genetic and biochemical analyses of the light chains showed a striking homogeneity. First, they all were of the kappa type. Second, 8 of 9 belonged to the V kappa I variability subgroup, which indicates that FS light chains are related by the sequence of their variable regions. Third, the 8 V kappa I light chain sequences most likely originated from only 2 germline genes, LCO2/012 and LCO8/018. Fourth, all 5 LCO2/012-derived sequences presented an unusual hydrophobic or nonpolar residue at position 30. These sequence peculiarities may account for unusual physicochemical properties of the light chains including the resistance of their variable domain V kappa to proteolysis by cathepsin B, observed in 7 of 9 patients in our series, while light chains isolated from patients with myeloma cast nephropathy are completely digested. Resistance of V kappa to proteolysis in FS patients can explain the accumulation of the light chain in the endocytotic compartment of the proximal tubule cells, leading to impairment of proximal tubule functions.

Splenic lymphoma presenting as necrotizing glomerulonephritis.

The authors report a case of necrotizing glomerulonephritis, with granular immune deposits, leading to the etiologic diagnosis of splenic non-Hodgkin's Lymphoma (NHL). The serum creatinine, initially markedly elevated, decreased under steroids and chlorambucil. Unfortunately, the patient died from septic complications. The importance of a careful search for a (localized) NHL in case of necrotizing glomerulonephritis with granular immune deposits is emphasized.