BACKGROUND AND OBJECTIVES:Enteric overabsorption of oxalate may lead to hyperoxaluria and subsequent acute oxalate nephritis (AON). AON related to chronic pancreatitis is a rare and poorly described condition precluding early recognition and treatment. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:We collected the clinical characteristics, treatment, and renal outcome of 12 patients with chronic pancreatitis-associated AON followed in four French renal units. RESULTS:Before AON, mild to moderate chronic kidney disease was present in all patients, diabetes mellitus in eight (insulin [n = 6]; oral antidiabetic drugs [n = 2]), and known chronic pancreatitis in only eight. At presentation, pancreas imaging showed gland atrophy/heterogeneity, Wirsung duct dilation, calcification, or pseudocyst. Renal findings consisted of rapidly progressive renal failure with tubulointerstitial profile. Acute modification of glomerular filtration preceded the AON (i.e., diarrhea and diuretics). Increase in urinary oxalate excretion was found in all tested patients and hypocalcemia in nine (<1.5 mmol/L in four patients). Renal biopsy showed diffuse crystal deposits, highly suggestive of oxalate crystals, with tubular necrosis and interstitial inflammatory cell infiltrates. Treatment consisted of pancreatic enzyme supplementation, oral calcium intake, and an oxalate-free diet in all patients and renal replacement therapy in five patients. After a median follow-up of 7 months, three of 12 patients reached end-stage renal disease. CONCLUSION:AON is an under-recognized severe crystal-induced renal disease with features of tubulointerstitial nephritis that may occur in patients with a long history of chronic pancreatitis or reveal the pancreatic disease. Extrinsic triggering factors should be prevented.

Kidney injury during HIV infection encompasses a wide variety of disorders, including acute interstitial nephritis. We report a case of acute granulomatous interstitial nephritis related to a mycobacterial-triggered immune reconstitution inflammatory syndrome (IRIS) in an HIV-infected patient. IRIS is an emerging health concern during HIV infection and should be considered in the diagnostic frame of acute renal failure during immune restoration.

Axillary arterio-arterial graft interposition has been described as a reasonable haemodialysis access in selected patients. In a patient with this unusual access, we measured and calculated effective clearance at different extracorporeal blood flows (Qb). Effective clearance increased with increasing blood flow and reached a maximum at a Qb of ∼200 mL/min but then decreased when Qb was increased further. As this type of access typically provides low access flow, one has to be aware that local recirculation will easily occur. Therefore, a Qb above access flow has to be avoided since any increase beyond that threshold reduces effective clearance.

Polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes (POEMS) syndrome is a systemic condition related to plasma cell dyscrasia. Increased vascular permeability is responsible for some of the hallmarks of this disorder that may include renal microangiopathy. Several lines of evidence suggest that vascular endothelial growth factor (VEGF) is central to the pathogenesis of POEMS syndrome. Thus, specifically targeting VEGF over-expression seems to be a promising treatment. Anti-VEGF therapies are yielding conflicting results. We report on a patient with POEMS syndrome treated with bevacizumab, an anti-VEGF monoclonal antibody. Sequential monitoring of serum VEGF showed sustained normalization of serum VEGF levels, without any beneficial effect on the patient's condition. Indications of this treatment should be chosen carefully.

Membranous glomerulopathy (MG) is a rare cause of chronic kidney disease. However, after kidney transplantation (KT), despite immunosuppression, it often relapses on the allograft. Herein, we report on a male kidney-transplant patient, aged 27 years, who developed overt nephrotic syndrome 11 months after KT. This was related to relapsing MG, as evidenced by the allograft biopsy, which, in addition, showed CD3 (+) and CD20 (+) interstitial lymphocyte infiltration. The patient was treated with rituximab: 375 mg/m(2)/week for 4 consecutive weeks, followed by one additional injection every 3 months for one year. Remission was observed before the third rituximab injection. After a follow-up of 42 months, the patient was still in remission, i.e., microalbuminuria of 107 mg/day.

BACKGROUND:In hepatitis C virus (HCV) positive kidney transplant (KT) patients, the use of alpha-interferon (alphaIFN) is contraindicated due to the risk of acute rejection (AR). Conversely, if these HCV(+) KT patients lose their allograft, re-transplantation might be contemplated provided alphaIFN therapy has been attempted.METHODS:Between 01/01/1989 and 31/12/1994, 261 kidney transplantations were performed; of these 174 were HCV(-) (group I) and 87 were HCV(+) (group II).RESULTS:At last follow-up (2006), in group I, the number of patients with a functioning graft, the number of patients who died with a functioning graft, and the number of patients who lost their graft before or after month (M) 12 were 92 (52.8%), 14 (8%), 20 (11.5%) and 48 (27.7%), respectively. In group II, the corresponding figures were 22 (25.3%; P < 0.0001), 8 (9.1%; ns), 9 (10.3%; ns) and 48 (55.3%; P < 0.0001). In group I, 19 of 48 (39.5%) patients with failed allografts after M12 underwent transplantectomy (TX) compared to 14 of 48 (29%; ns) in group II. In group II, 11 of 48 (23%) patients were offered alphaIFN therapy after their allograft failed: of these, four (36.3%) developed AR during alphaIFN therapy leading to TX. Histology, in addition to chronic allograft lesions, showed acute cellular and vascular lesions. In patients who were not offered alphaIFN therapy, TX was performed less frequently, i.e. in only six cases (16.2%).CONCLUSIONS:We conclude that even alphaIFN-treated KT patients with a failed allograft can experience acute allograft rejection that requires transplantectomy during therapy.

Renal disease is rare in children with juvenile idiopathic arthritis, although a number of associated nephropathies have been described, including mesangial glomerulonephritis. We report the presence of mesangial glomerulonephritis, revealed by a nephrotic syndrome, in a paediatric patient with juvenile idiopathic arthritis. Short-term steroid treatment induced a rapid remission of the nephrotic syndrome, but the presence of anti-nuclear antibodies, 1:320 in a homogeneous pattern, irregular deposits of C1q in a renal biopsy, and a mother with episodes of cutaneous lupus suggested an uncertain renal evolution for this infant.

BACKGROUND:Many etiologies lead to thrombotic microangiopathy (TMA), amongst which are antineoplastic chemotherapies. Gemcitabine, a nucleoside analogue, has been approved for the treatment ofbladder and advanced non-small cell lung carcinomas (NSCLC). The reported incidence of gemcitabine-associated TMA in the literature is low, ranging from 0.015-0.31%.METHODS:Herein, we describe the first reported case of gemcitabine-induced TMA in a renal transplant patient. This occurred in a 54-year-old male transplant recipient undergoing sirolimus-based immunosuppression. In February 2005, he was diagnosed to have NSCLC, for which he received dual chemotherapy, including carboplatin and gemcitabine. After the third cycle he developed TMA.RESULTS:On admission, he presented with weakness, edema, normal blood pressure, leucopenia (2440/mm3), thrombopenia (11,000/mm3), hemolytic anemia with hemoglobin at 8 g/dl, schistocytes between 18-33% per hundred, increase in lactate dehydrogenase at 600 IU/l (N <380), and decreased haptoglobin at 0.29 g/l. Renal function was stable: serum creatinine was 1.3 mg/dl, albuminemia 30 g/l, proteinuria was present at 3 g/l in association with microscopic hematuria, and sirolimus trough level was 6.4 ng/ml. Treatment included infusions of fresh frozen plasma, withdrawal of sirolimus, which was replaced by mycophenolate mofetil, and suspension of chemotherapy. He fully recovered from TMA within 4 weeks. The concomitant use of sirolimus, which inhibits vascular endothelial growth factor, plus gemcitabine may have resulted in TMA.

BACKGROUND Salmonella enteritidis-associated acute renal failure has often been described and is usually a result of dehydration or of rhabdomyolysis. A few cases of acute renal failure with glomerular syndrome, caused by S. enteritidis infection, have been reported in the literature, but none have been proven by histological findings. METHODS Herein, we report on a case of S. enteritidis-related glomerulonephritis that occurred in a 42-year-old male transplant recipient. He was admitted with fever, signs of urinary infection, diarrhea, and nephritic syndrome, i.e. edema, hypertension, increase in serum creatinine, microscopic hematuria, proteinuria. His urine culture tested positive for S. enteritidis. RESULTS Under light microscopy, the graft biopsy showed proliferative and exudative endocapillary glomerulonephritis. In addition, there was polymorphonuclear infiltration of the interstitium, and extra-capillary proliferation in one glomerulus. Immunofluorescence showed granular deposits of C3 in the mesangium. Electron microscopy showed electron-dense deposits typical of humps. He fully recovered on a double antibiotic therapy that included ofloxacin and amikacin. CONCLUSION Although acute renal failure related to non-typhoidal Salmonella infections are often related to dehydration or rhabdomyolysis, this case report shows that it might also be related to immune complex-mediated glomerulonephritis manifesting as nephritic syndrome.

Polyomavirus-associated nephropathy (PVAN) affects 1-10% of kidney-transplant (KT) patients, with graft failure/loss in approximately 90% of cases. Reducing immunosuppression is the key treatment option, but addition of leflunomide may improve BK Virus (BKV) clearance and graft survival. In a prospective open-labeled study, 12 KT patients with biopsy-proven PVAN were treated with reduced immunosuppression and leflunomide. BKV viremia and graft function were followed. PVAN was diagnosed at 6 months (3-192) post-transplant; median serum creatinine concentration (sCC) was 189 micromol/l (92-265). After 16 months (8-30) of follow-up, the sCC was 150 micromol/l (90-378, NS). Renal function improved in six cases (50%), remained stable in two (16.6%) and deteriorated in four (33.4%), with graft loss in two (17%). Clearance of BKV viremia was observed in five (42%) cases. Side effects included anemia in six cases leading to leflunomide withdrawal in two patients, and mild thrombocytopenia. In KT patients diagnosed with PVAN, leflunomide plus reduced immunosuppression improved graft function in 66.6%, cleared BKV viremia in 42%, and resulted in side effects in 17%. This limited efficacy contrasts with other reports and falls short of expectation. We conclude that active screening, earlier diagnosis and intervention remain the cornerstones of treatment.

Linezolid is a recent oral antibiotic used in drug-resistant Gram-positive cocci infections. Herein, we report on the first case of linezolid-related acute renal failure in a kidney-transplant patient. A 60-year-old male having autosomic polycystic kidney disease with liver involvement, on cyclosporin A, mycophenolate mofetil and very low dose prednisolone, presented with an Enterococcus faecium abscess of a huge liver cyst, which was treated by percutaneous drainage and linezolid therapy. Eight days after starting linezolid, he presented with acute renal failure, i.e. serum creatinine increased from 136- 221 micromol/l, associated with mild hypereosinophilia, anemia and thrombocytopenia. There was no skin rash, arthralgia, eosinophiluria or proteinuria. The transplant kidney biopsy, performed 15 days after the beginning of linezolid therapy, showed interstitial nephritis and focal tubular atrophy. After linezolid withdrawal and increasing prednisolone daily dose to 20 mg/d, within a few days, serum creatinine had decreased; after 2 and 4 weeks post linezolid withdrawal, his serum creatinine was 166 and 159 micromol/l, respectively. Because of the potential side effects of linezolid, i.e. myelosuppression and possibly nephrotoxicity, we recommend close monitoring of these parameters when linezolid therapy is attempted in kidney transplant patients.

Idiopathic membranous glomerulonephritis (MGN) is a rare cause of end-stage renal failure, which can lead to chronic hemodialysis. This glomerulopathy can recur after renal transplantation despite immunosuppressive therapy. To date, there is no confirmed therapy for treatment of renal grafts after recurrence of MGN. Herein, we report on a 27-year-old man who underwent cadaveric renal transplantation for MGN in September 2001. At 2 months posttransplant, a renal biopsy showed membranous deposition on immunofluorescence staining evocative of recurrence of MGN. Proteinuria developed progressively and, at one year, was estimated at 7.65 g/24 h, with hypoalbuminemia of 24 g/l. This persisted despite symptomatic treatment with anti-proteinuric agents (enalapril 20 mg/day and irbesartan 75 mg/day) and atorvastatin (10 mg/day). By March 2004, his proteinuria was 11 g/day; therefore, therapy with rituximab (monoclonal anti-CD20) at 375 mg/m(2) weekly was initiated for four consecutive weeks, followed by the same dosage every four months for one year. Biological controls performed two weeks after the fourth infusion of rituximab showed a fall in proteinuria, assessed at 1 g/24 h, with albuminemia of 29 g/l and normalized lipidic results. A renal biopsy performed 6 months after the first infusion was unchanged. Follow-up at 30 months showed consistent remission of membranous nephropathy, demonstrated by a serum creatinine level of 150 mumol/L, microalbuminuria of 107 mg/24 h and normal albuminemia of 43.7 g/l. There were no side effects; in particular, no infectious complications occurred, despite CD19 lymphocytes being still negative after 30 months. Monoclonal CD-20 antibodies have shown efficacy against MGN compared to conventional therapies in native kidneys. It has recently been shown that CD20 mRNA is overexpressed in the renal interstitium in patients suffering from MGN and that the interstitial infiltrates is mainly composed of B-cell lymphocytes in these patients. These data may explain the efficiency of rituximab in these circumstances.

Idiopathic membranous glomerulonephritis (MGN) is a rare cause of end-stage renal failure, which can lead to chronic hemodialysis. This glomerulopathy can recur after renal transplantation despite immunosuppressive therapy. To date, there is no confirmed therapy for treatment of renal grafts after recurrence of MGN. Herein, we report on a 27-year-old man who underwent cadaveric renal transplantation for MGN in September 2001. At 2 months post-transplant, a renal biopsy showed membranous deposition on immunofluorescence staining evocative of recurrence of MGN. Proteinuria developed progressively and, at one year, was estimated at 7.65 g/24 h, with hypoalbuminemia of 24 g/l. This persisted despite symptomatic treatment with anti-proteinuric agents (enalapril 20 mg/day and irbesartan 75 mg/day) and atorvastatin (10 mg/day). By March 2004, his proteinuria was 11 g/day; therefore, therapy with rituximab (monoclonal anti-CD20) at 375 mg/m(2) weekly was initiated for four consecutive weeks, followed by the same dosage every four months for one year. Biological controls performed two weeks after the fourth infusion of rituximab showed a fall in proteinuria, assessed at 1 g/24 h, with albuminemia of 29 g/l and normalized lipidic results. A renal biopsy performed 6 months after the first infusion was unchanged. Follow-up at 30 months showed consistent remission of membranous nephropathy, demonstrated by a serum creatinine level of 150 mu mol/L, microalbuminuria of 107 mg/24 h and normal albuminemia of 43.7 g/l. There were no side effects; in particular, no infectious complications occurred, despite CD19 lymphocytes being still negative after 30 months. Monoclonal CD-20 antibodies have shown efficacy against MGN compared to conventional therapies in native kidneys. It has recently been shown that CD20 mRNA is overexpressed in the renal interstitium in patients suffering from MGN and that the interstitial infiltrates is mainly composed of B-cell lymphocytes in these patients. These data may explain the efficiency of rituximab in these circumstances. (C) 2007 Elsevier Masson SAS et Association Societe de Nephrologie. Tous droits reserves.

A pilot study was performed on eight consecutive renal-transplant (RT) patients presenting with acute humoral rejection (AHR) to assess the efficacy of monoclonal anti-B cell antibodies, such as rituximab (375 mg/m weekly) for 3 to 5 consecutive weeks, in addition to plasma exchange (PE), steroids, mycophenolate mofetil, and tacrolimus. AHR was associated with increased serum creatinine, the appearance of donor-specific alloantibodies (DSA), and the presence of C4d in a transplant biopsy. After a follow-up of 10 months (range 7-23), patient and graft survivals were 100% and 75%, respectively. Renal function improved in six cases in which serum creatinine decreased from 297+/-140 to 156+/-53 micromol/L (P=0.015); graft loss occurred in two cases; and four patients had infectious complications. At last follow-up, DSA had disappeared or decreased in four cases. Rituximab therapy, in addition to PE, might be of benefit for RT patients presenting with AHR.

OBJECTIVE:The aim of this study was to assess the effects of tacrolimus in combination with either sirolimus (n = 10) or mycophenolate mofetil (n = 7) on renal function and renal histopathologic factors 6 and 12 months after kidney transplantation.MATERIALS AND METHODS:Renal function was assessed by the glomerular filtration rate (as measured by the inulin clearance rate) and by determining renal functional reserve. A renal allograft biopsy was performed at the time of transplantation and 6 and 12 months later.RESULTS:Serum creatinine levels tended to be higher in the sirolimus group 12 months after transplantation. In contrast, inulin clearance and renal functional reserve were similar in both groups 6 and 12 months after transplantation. With respect to histopathologic findings, only mononuclear-cell interstitial inflammation was significantly higher in the sirolimus group than in the mycophenolate mofetil group 12 months after transplantation. However, the progression of tubular atrophy, interstitial fibrosis, and vascular fibrous intimal thickening within the first postoperative year was significantly greater in the sirolimus group.CONCLUSIONS:In the long term, the addition of sirolimus to treatment with tacrolimus in de novo renal transplant patients might more adversely affect renal allograft survival than might the addition of mycophenolate mofetil to tacrolimus therapy.

BACKGROUND:Switching from calcineurin inhibitors (CNIs) to sirolimus might improve renal function in chronic renal transplant patients. METHODS:In a prospective study, we assessed long-term efficacy and safety parameters in 43 renal transplant recipients who were switched from a CNI (cyclosporin A, 65%; and tacrolimus, 35%) to sirolimus for either chronic allograft dysfunction (n = 38) or recurrent cutaneous cancers (n = 5). A kidney biopsy was done in 79% of patients prior to conversion, and showed either chronic allograft nephropathy (n = 26) or CNI nephrotoxicity (n = 7). Conversion was either abrupt or progressive, with CNI withdrawal over 3 weeks. All patients also received steroids with or without mycophenolate mofetil or azathioprin. Patient data were recorded at baseline (D0), at 1 (D30) and 6 months (D180), and at 1, 1.5 and 2 years post-conversion. RESULTS:After a mean post-conversion follow-up of 27+/-1.5 months, 58% of the patients were still on sirolimus. The survival of intent to treat patients and grafts was 95.3 and 93%, respectively. Overall, there was significant improvement in renal function, creatinine clearance increasing from 49.4+/-14.9 to 53+/-16.3 ml/min at D30 (P = 0.01), and to 54.7+/-20 ml/min at D180 (P = 0.01). Thereafter, creatinine clearance was not different from baseline, i.e. 54.7+/-21.7, 52.8+/-20 and 51.7+/-20.3 ml/min at years 1, 1.5 and 2, respectively. We divided the patients into two groups: responders (n = 29), those with an increase in creatinine clearance at 6 months post-conversion compared with D0, and non-responders (n = 14), those with a decrease in creatinine clearance at 6 months post-conversion compared with D0. In univariate analysis, factors predictive of response included proteinuria at D0 and the magnitudes of the differences between D30 and D0 for serum creatinine and lactate dehydrogenase. The conversion was associated with (i) significant decreases in serum calcium, phosphorus and uric acid, and in haemoglobin levels; (ii) significant increases in serum alkaline phosphatase, total cholesterol, parathyroid hormone, and the number of patients on statin and recombinant erythropoietin therapies; and (iii) the appearance of de novo proteinuria of >1 g/day in 28% of patients (P < 0.0009), which was >2 g/day in 12% of the entire cohort. Kidney biopsies in 17 patients 2 years after conversion showed the same Banff scores as observed at baseline. We identified three independent predictive factors for a renal response to the switch: absence of proteinuria, presence of antihypertensive therapy at D0 and serum lactate dehydrogenase level at D30. CONCLUSION:Conversion from CNIs to sirolimus in renal transplant patients with chronic allograft nephropathy was associated with improved renal function; however, 33% of the patients developed overt proteinuria.